hydrocodone/homatropine (Rx)

Brand and Other Names:Tussigon
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

hydrocodone/homatropine

tablet: Schedule II

  • 5mg/1.5mg (Tussigon)
  • Generic available

oral solution: Schedule II

  • (5mg/1.5mg)/5mL (Hydromet)
  • Generic available

Cough

5 mg/1.5 mg (1 tablet) PO q4-6hr

Not to exceed 30 mg/9 mg (6 tablets) in 24 hr

Dosing considerations

Advise patients not to increase dose or dosing frequency; serious adverse events such as respiratory depression may occur with overdosage; the dosage should not be increased if cough fails to respond; an unresponsive cough should be reevaluated for possible underlying pathology

Prescribe for shortest duration consistent with individual patient treatment goals

Monitor patients closely for respiratory depression, especially within first 24-72 hours of initiating therapy [

Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease

If a patient requires a refill, reevaluate cause of cough and assess need for continued treatment; the relative incidence of adverse reactions, and development of addiction, abuse, or misuse

Do not abruptly discontinue in a physically-dependent patient; when a patient who has been taking drug regularly and may be physically dependent no longer requires therapy, taper dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal

If patient develops these signs or symptoms, raise dose to previous level and taper more slowly, either by increasing interval between decreases, decreasing amount of change in dose, or both

Limitations of use

Because of risks of addiction, abuse, and misuse with opioids, even at recommended doses reserve medication for use in adult patients for whom benefits of cough suppression are expected to outweigh risks, and in whom an adequate assessment of etiology of cough has been made

Dosage Forms & Strengths

hydrocodone/homatropine

tablet: Schedule II

  • 5mg/1.5mg (Tussigon)
  • Generic available

oral solution: Schedule II

  • (5mg/1.5mg)/5mL (Hydromet)
  • Generic available

Cough

Adolescents ≥18 years: 5 mg/1.5 mg (1 tablet) PO q4-6hr, up to 30 mg/9 mg (6 tablets) in 24 hr

Dosing considerations

Advise patients not to increase dose or dosing frequency; serious adverse events such as respiratory depression may occur with overdosage; the dosage should not be increased if cough fails to respond; an unresponsive cough should be reevaluated for possible underlying pathology

Prescribe for shortest duration consistent with individual patient treatment goals

Monitor patients closely for respiratory depression, especially within first 24-72 hours of initiating therapy [

Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease

If a patient requires a refill, reevaluate cause of cough and assess need for continued treatment; the relative incidence of adverse reactions, and development of addiction, abuse, or misuse

Do not abruptly discontinue in a physically-dependent patient; when a patient who has been taking drug regularly and may be physically dependent no longer requires therapy, taper dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal

If patient develops these signs or symptoms, raise dose to previous level and taper more slowly, either by increasing interval between decreases, decreasing amount of change in dose, or both

Limitations of use

Not indicated for pediatric patients <18 years

Contraindicated in pediatric patients <6 years

Because of risks of addiction, abuse, and misuse with opioids, even at recommended doses reserve medication for use in adult patients for whom benefits of cough suppression are expected to outweigh risks, and in whom an adequate assessment of etiology of cough has been made

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Interactions

Interaction Checker

and hydrocodone/homatropine

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            Contraindicated (1)

            • alvimopan

              alvimopan, hydrocodone. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

            Serious - Use Alternative (125)

            • alfentanil

              hydrocodone, alfentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • alprazolam

              hydrocodone, alprazolam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • amobarbital

              hydrocodone, amobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              amobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • arbaclofen

              hydrocodone, arbaclofen. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • aripiprazole

              hydrocodone, aripiprazole. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • asenapine

              hydrocodone, asenapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • atracurium

              hydrocodone, atracurium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • baclofen

              hydrocodone, baclofen. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • bremelanotide

              bremelanotide will decrease the level or effect of hydrocodone by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

            • buprenorphine

              buprenorphine decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

              hydrocodone, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • buprenorphine buccal

              buprenorphine buccal decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

            • buprenorphine subdermal implant

              buprenorphine subdermal implant decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

            • buprenorphine transdermal

              buprenorphine transdermal decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

              hydrocodone, buprenorphine transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

            • buspirone

              hydrocodone, buspirone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • butabarbital

              hydrocodone, butabarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • butalbital

              hydrocodone, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • butorphanol

              butorphanol decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients.

              hydrocodone, butorphanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • calcium/magnesium/potassium/sodium oxybates

              hydrocodone, calcium/magnesium/potassium/sodium oxybates. Either increases levels of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • cariprazine

              hydrocodone, cariprazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • carisoprodol

              hydrocodone, carisoprodol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • chloral hydrate

              hydrocodone, chloral hydrate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • chlordiazepoxide

              hydrocodone, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • chlorpromazine

              hydrocodone, chlorpromazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • chlorzoxazone

              hydrocodone, chlorzoxazone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • cisatracurium

              hydrocodone, cisatracurium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • clonazepam

              hydrocodone, clonazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • clonidine

              clonidine, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

            • clorazepate

              hydrocodone, clorazepate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • clozapine

              hydrocodone, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • codeine

              hydrocodone, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • cyclobenzaprine

              hydrocodone, cyclobenzaprine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • dantrolene

              hydrocodone, dantrolene. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • desflurane

              hydrocodone, desflurane. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • dexmedetomidine

              hydrocodone, dexmedetomidine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • diazepam

              hydrocodone, diazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • diazepam intranasal

              diazepam intranasal, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • doxylamine

              hydrocodone, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • estazolam

              hydrocodone, estazolam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • eszopiclone

              hydrocodone, eszopiclone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ethanol

              hydrocodone, ethanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • etomidate

              hydrocodone, etomidate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • fentanyl

              hydrocodone, fentanyl. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fentanyl intranasal

              hydrocodone, fentanyl intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fentanyl transdermal

              hydrocodone, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fentanyl transmucosal

              hydrocodone, fentanyl transmucosal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fexinidazole

              fexinidazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fluphenazine

              hydrocodone, fluphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • flurazepam

              hydrocodone, flurazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • haloperidol

              hydrocodone, haloperidol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • hydromorphone

              hydrocodone, hydromorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • iloperidone

              hydrocodone, iloperidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • isocarboxazid

              isocarboxazid increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • isoflurane

              hydrocodone, isoflurane. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • ivosidenib

              ivosidenib will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketamine

              hydrocodone, ketamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • levorphanol

              hydrocodone, levorphanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • linezolid

              linezolid increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

            • lorazepam

              hydrocodone, lorazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • loxapine

              hydrocodone, loxapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • loxapine inhaled

              hydrocodone, loxapine inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • lurasidone

              hydrocodone, lurasidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • meperidine

              hydrocodone, meperidine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • meprobamate

              hydrocodone, meprobamate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • metaxalone

              hydrocodone, metaxalone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • methadone

              hydrocodone, methadone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • methocarbamol

              hydrocodone, methocarbamol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • methohexital

              hydrocodone, methohexital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • methylene blue

              methylene blue increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • metoclopramide intranasal

              hydrocodone, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • midazolam

              hydrocodone, midazolam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • molindone

              hydrocodone, molindone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • morphine

              hydrocodone, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • nalbuphine

              nalbuphine decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients.

              hydrocodone, nalbuphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • olanzapine

              hydrocodone, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • olopatadine intranasal

              hydrocodone and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • orphenadrine

              hydrocodone, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • oxazepam

              hydrocodone, oxazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • oxycodone

              hydrocodone, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • oxymorphone

              hydrocodone, oxymorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ozanimod

              ozanimod and hydrocodone both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • paliperidone

              hydrocodone, paliperidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pancuronium

              hydrocodone, pancuronium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pentazocine

              pentazocine decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients.

              hydrocodone, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pentobarbital

              hydrocodone, pentobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • perphenazine

              hydrocodone, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • phenelzine

              phenelzine increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • phenobarbital

              hydrocodone, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pimavanserin

              hydrocodone, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pimozide

              hydrocodone, pimozide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pramlintide

              pramlintide, homatropine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Synergistic inhibition of GI motility.

            • primidone

              hydrocodone, primidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • procarbazine

              procarbazine increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • prochlorperazine

              hydrocodone, prochlorperazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • propofol

              hydrocodone, propofol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • quazepam

              hydrocodone, quazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • quetiapine

              hydrocodone, quetiapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ramelteon

              hydrocodone, ramelteon. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • rasagiline

              rasagiline increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • remifentanil

              hydrocodone, remifentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • risperidone

              hydrocodone, risperidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • rocuronium

              hydrocodone, rocuronium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • secobarbital

              hydrocodone, secobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • selegiline

              selegiline increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • selegiline transdermal

              selegiline transdermal increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • selinexor

              selinexor, hydrocodone. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • sevoflurane

              hydrocodone, sevoflurane. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • sodium oxybate

              hydrocodone, sodium oxybate. Either increases levels of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • succinylcholine

              hydrocodone, succinylcholine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • sufentanil

              hydrocodone, sufentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • sufentanil SL

              hydrocodone, sufentanil SL. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              sufentanil SL, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • suvorexant

              hydrocodone, suvorexant. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tapentadol

              hydrocodone, tapentadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tasimelteon

              hydrocodone, tasimelteon. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • temazepam

              hydrocodone, temazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • thioridazine

              hydrocodone, thioridazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • thiothixene

              hydrocodone, thiothixene. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tramadol

              tramadol, hydrocodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

              hydrocodone, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tranylcypromine

              tranylcypromine increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • triazolam

              hydrocodone, triazolam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • trifluoperazine

              hydrocodone, trifluoperazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • tucatinib

              tucatinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • umeclidinium bromide/vilanterol inhaled

              homatropine, umeclidinium bromide/vilanterol inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Concomitant use with other anticholinergic-containing drugs may lead to additive anticholinergic adverse effects.

            • vecuronium

              hydrocodone, vecuronium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            Monitor Closely (222)

            • abobotulinumtoxinA

              abobotulinumtoxinA increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects. .

            • aclidinium

              homatropine and aclidinium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • almotriptan

              hydrocodone, almotriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • alosetron

              hydrocodone, alosetron. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • amantadine

              homatropine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced CNS side effects.

            • amiodarone

              amiodarone will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • amitriptyline

              hydrocodone, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

              homatropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • amoxapine

              hydrocodone, amoxapine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

              homatropine and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • amphetamine

              hydrocodone, amphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • anticholinergic/sedative combos

              anticholinergic/sedative combos and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • apalutamide

              apalutamide will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • aripiprazole

              homatropine decreases levels of aripiprazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of aripiprazole by pharmacodynamic antagonism. Use Caution/Monitor.

              aripiprazole increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • asenapine

              asenapine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • atazanavir

              atazanavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • atracurium

              atracurium and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • atropine

              atropine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • atropine IV/IM

              atropine IV/IM and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • belladonna alkaloids

              belladonna alkaloids and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • belladonna and opium

              homatropine and belladonna and opium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • benperidol

              homatropine decreases levels of benperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of benperidol by pharmacodynamic antagonism. Use Caution/Monitor.

              benperidol increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • benztropine

              benztropine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use.

            • bethanechol

              bethanechol increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • bosentan

              bosentan will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • brexanolone

              brexanolone, hydrocodone. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • bupropion

              bupropion will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, bupropion. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • carbachol

              carbachol increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbamazepine

              carbamazepine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • celecoxib

              celecoxib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • cenobamate

              cenobamate will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • cevimeline

              cevimeline increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chloroquine

              chloroquine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • chlorpromazine

              homatropine decreases levels of chlorpromazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of chlorpromazine by pharmacodynamic antagonism. Use Caution/Monitor.

              chlorpromazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • cimetidine

              cimetidine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • cisatracurium

              cisatracurium and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • citalopram

              hydrocodone, citalopram. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • clarithromycin

              clarithromycin will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • clobazam

              hydrocodone, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clomipramine

              homatropine and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              hydrocodone, clomipramine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • clozapine

              homatropine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.

              clozapine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • cobicistat

              cobicistat will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • conivaptan

              conivaptan will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • cyclizine

              cyclizine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • cyclobenzaprine

              cyclobenzaprine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • dabrafenib

              dabrafenib will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • daridorexant

              hydrocodone and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • darifenacin

              darifenacin will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              darifenacin and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • darunavir

              darunavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • desipramine

              homatropine and desipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • desipramine

              hydrocodone, desipramine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, desvenlafaxine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • dexamethasone

              dexamethasone will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • dextroamphetamine

              hydrocodone, dextroamphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • dichlorphenamide

              dichlorphenamide and hydrocodone both decrease serum potassium. Use Caution/Monitor.

            • dicyclomine

              dicyclomine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • difelikefalin

              difelikefalin and hydrocodone both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              diphenhydramine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • donepezil

              donepezil increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • doxepin

              hydrocodone, doxepin. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • donepezil transdermal

              donepezil transdermal, homatropine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

            • dosulepin

              homatropine and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • doxepin

              homatropine and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • droperidol

              homatropine decreases levels of droperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of droperidol by pharmacodynamic antagonism. Use Caution/Monitor.

              droperidol increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • duloxetine

              duloxetine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, duloxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • echothiophate iodide

              echothiophate iodide increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • elagolix

              elagolix decreases levels of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eletriptan

              hydrocodone, eletriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • encorafenib

              encorafenib, hydrocodone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enzalutamide

              enzalutamide will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • escitalopram

              hydrocodone, escitalopram. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • esketamine intranasal

              esketamine intranasal, hydrocodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • etravirine

              etravirine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • fedratinib

              fedratinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fesoterodine

              fesoterodine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • flavoxate

              flavoxate and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • flibanserin

              hydrocodone, flibanserin. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • fluoxetine

              hydrocodone, fluoxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • fluphenazine

              homatropine decreases levels of fluphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of fluphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              fluphenazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • fluvoxamine

              fluvoxamine and hydrocodone both increase serotonin levels. Use Caution/Monitor. If concomitant use warranted, carfully observe patient, particularly during treatment initiation and dose adjustment

            • fosamprenavir

              fosamprenavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • fosphenytoin

              fosphenytoin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • frovatriptan

              hydrocodone, frovatriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • gabapentin

              gabapentin, hydrocodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, hydrocodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • galantamine

              galantamine increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ganaxolone

              hydrocodone and ganaxolone both increase sedation. Use Caution/Monitor.

            • glycopyrrolate

              glycopyrrolate and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • glycopyrrolate inhaled

              glycopyrrolate inhaled and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • grapefruit

              grapefruit will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • haloperidol

              homatropine decreases levels of haloperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of haloperidol by pharmacodynamic antagonism. Use Caution/Monitor.

              haloperidol increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              haloperidol will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • henbane

              henbane and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • idelalisib

              idelalisib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • huperzine A

              huperzine A increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hyoscyamine

              homatropine and hyoscyamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • hyoscyamine spray

              homatropine and hyoscyamine spray both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • iloperidone

              homatropine decreases levels of iloperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of iloperidone by pharmacodynamic antagonism. Use Caution/Monitor.

              iloperidone increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • imatinib

              imatinib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              imatinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • imipramine

              hydrocodone, imipramine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

              homatropine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • indinavir

              indinavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • ipratropium

              homatropine and ipratropium both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

            • isoniazid

              isoniazid will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • istradefylline

              istradefylline will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ketoconazole

              ketoconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • lasmiditan

              lasmiditan, hydrocodone. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant, hydrocodone. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • letermovir

              letermovir increases levels of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression.

            • levoketoconazole

              levoketoconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • levomilnacipran

              hydrocodone, levomilnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • lisdexamfetamine

              hydrocodone, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • lofepramine

              homatropine and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • lopinavir

              lopinavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • lorcaserin

              hydrocodone, lorcaserin. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • lorlatinib

              lorlatinib will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • loxapine

              homatropine decreases levels of loxapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of loxapine by pharmacodynamic antagonism. Use Caution/Monitor.

              loxapine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • loxapine inhaled

              loxapine inhaled increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              homatropine decreases levels of loxapine inhaled by pharmacodynamic antagonism. Use Caution/Monitor.

            • lumefantrine

              lumefantrine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • lurasidone

              lurasidone, hydrocodone. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              hydrocodone, maprotiline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

              homatropine and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • maraviroc

              maraviroc will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • meclizine

              homatropine and meclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • marijuana

              marijuana will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • methamphetamine

              hydrocodone, methamphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • methscopolamine

              homatropine and methscopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • methylphenidate

              hydrocodone, methylphenidate. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • midazolam intranasal

              midazolam intranasal, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • mifepristone

              mifepristone will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • milnacipran

              hydrocodone, milnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • mirtazapine

              hydrocodone, mirtazapine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • mitotane

              mitotane will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • nafcillin

              nafcillin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • naratriptan

              hydrocodone, naratriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • nefazodone

              nefazodone will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

              hydrocodone, nefazodone. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • nelfinavir

              nelfinavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • neostigmine

              neostigmine increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • nicardipine

              nicardipine will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • nilotinib

              nilotinib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Careful monitoring of hydrocodone therapeutic and adverse effects (including potentially fatal respiratory depression) recommended when coadministered. Reduce hydrocodone dose if necessary.

            • nortriptyline

              homatropine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              hydrocodone, nortriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • olanzapine

              homatropine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              olanzapine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • oliceridine

              oliceridine, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • oliceridine

              homatropine increases toxicity of oliceridine by Other (see comment). Use Caution/Monitor. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

            • onabotulinumtoxinA

              onabotulinumtoxinA and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • orphenadrine

              homatropine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • oxybutynin

              homatropine and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin topical

              homatropine and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin transdermal

              homatropine and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • paliperidone

              homatropine decreases levels of paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor.

              paliperidone increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • pancuronium

              homatropine and pancuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • parecoxib

              parecoxib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • paroxetine

              paroxetine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, paroxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • pegvisomant

              hydrocodone will decrease the level or effect of pegvisomant by unknown mechanism. Use Caution/Monitor. Prescribing information describes higher pegvisomant doses are required to control insulinlike growth factor levels when coadministered with opioids.

            • pentobarbital

              pentobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • perphenazine

              homatropine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              perphenazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              perphenazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • phenobarbital

              phenobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • physostigmine

              physostigmine increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenytoin

              phenytoin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression.

            • pilocarpine

              pilocarpine increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pimozide

              homatropine decreases levels of pimozide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of pimozide by pharmacodynamic antagonism. Use Caution/Monitor.

              pimozide increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • posaconazole

              posaconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • pralidoxime

              homatropine and pralidoxime both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • pregabalin

              pregabalin, hydrocodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • prochlorperazine

              homatropine decreases levels of prochlorperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of prochlorperazine by pharmacodynamic antagonism. Use Caution/Monitor.

              prochlorperazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • promethazine

              homatropine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

              promethazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • propafenone

              propafenone will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • propantheline

              homatropine and propantheline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • protriptyline

              homatropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              hydrocodone, protriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • pyridostigmine

              pyridostigmine increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quinacrine

              quinacrine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • quetiapine

              homatropine decreases levels of quetiapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of quetiapine by pharmacodynamic antagonism. Use Caution/Monitor.

              quetiapine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • quinidine

              quinidine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • ranolazine

              ranolazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • rapacuronium

              homatropine and rapacuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • remimazolam

              remimazolam, hydrocodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • ribociclib

              ribociclib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • rifampin

              rifampin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • rifapentine

              rifapentine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • risperidone

              homatropine decreases levels of risperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of risperidone by pharmacodynamic antagonism. Use Caution/Monitor.

              risperidone increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • ritonavir

              ritonavir will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              ritonavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • rizatriptan

              hydrocodone, rizatriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • rocuronium

              homatropine and rocuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • safinamide

              hydrocodone, safinamide. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • saquinavir

              saquinavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • scopolamine

              homatropine and scopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May also enhance CNS depressant effect of hydrocodone

            • sertraline

              sertraline will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, sertraline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • St John's Wort

              St John's Wort will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

              hydrocodone, St John's Wort. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • solifenacin

              homatropine and solifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • stiripentol

              stiripentol, hydrocodone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol, hydrocodone. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • succinylcholine

              succinylcholine increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sumatriptan

              hydrocodone, sumatriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • sumatriptan intranasal

              hydrocodone, sumatriptan intranasal. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • tazemetostat

              tazemetostat will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • thioridazine

              thioridazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              thioridazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              homatropine decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • thiothixene

              homatropine decreases levels of thiothixene by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of thiothixene by pharmacodynamic antagonism. Use Caution/Monitor.

              thiothixene increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • tipranavir

              tipranavir will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              tipranavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • tiotropium

              homatropine and tiotropium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • tolterodine

              homatropine and tolterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • trazodone

              homatropine and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.

              hydrocodone, trazodone. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • trifluoperazine

              homatropine decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor.

              trifluoperazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • trimipramine

              hydrocodone, trimipramine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • trihexyphenidyl

              homatropine and trihexyphenidyl both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

            • trimipramine

              homatropine and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • trospium chloride

              homatropine and trospium chloride both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • umeclidinium bromide

              umeclidinium bromide and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor. If possible, avoid coadministration of additional anticholinergic agents

            • vecuronium

              homatropine and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • venlafaxine

              venlafaxine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, venlafaxine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • voriconazole

              voriconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • ziprasidone

              homatropine decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor.

              ziprasidone increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • zolmitriptan

              hydrocodone, zolmitriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • zotepine

              homatropine decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              homatropine decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor.

            Minor (5)

            • dimenhydrinate

              dimenhydrinate increases toxicity of homatropine by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • donepezil

              donepezil decreases effects of homatropine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • galantamine

              galantamine decreases effects of homatropine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • levodopa

              homatropine, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .

            • ziconotide

              ziconotide, hydrocodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

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            Adverse Effects

            Frequency Not Defined

            Hydrocodone

            • Bradycardia, anticholinergic effects (dry mouth, palpitation, tachycardia)
            • Angina, arrhythmias, cardiac arrest, myocardial infarction, QT-interval prolongation, pectoris, syncope, severe cardiac ST segment elevation, ventricular tachycardia
            • Agitation, coma, dizziness, mental clouding/depression, dysphoria, euphoria, faintness, restlessness, nervousness, weakness, sedation, seizures, visual disturbances
            • Flushing, sweating, pruritus, urticaria, warmness of the face/neck/upper thorax
            • Constipation, nausea, vomiting
            • Urinary retention, oliguria
            • Respiratory/circulatory depression, respiratory arrest, shock, cardiac arrest

            Homatropine

            • Edema
            • Vascular congestion
            • Exudate
            • Eczematoid dermatitis
            • Increased IOP
            • Follicular conjunctivitis
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            Warnings

            Black Box Warnings

            Addiction, Abuse, and Misuse

            • Tussigon exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death; reserve for use in adult patients for whom benefits of cough suppression expected to outweigh risks, and in whom an adequate assessment of etiology of the cough has been made
            • Assess each patient's risk prior to prescribing drug; prescribe therapy for shortest duration consistent with individual patient treatment goals; monitor all patients regularly for development of addition or abuse, and refill only after reevaluation of need for continued treatment

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur with use; monitor for respiratory depression, especially during initiation of drug therapy or when used in patients at higher risk

            Accidental Ingestion

            • Accidental ingestion of even one dose of drug, especially by children, can result in fatal overdose of hydrocodone

            Risk of Medication Errors

            • Ensure accuracy when prescribing, dispensing, and administering drug; dosing errors can result in accidental overdose and death

            Cytochrome P450 3A4 Interaction

            • Concomitant use with all cytochrome P450 3A4 inhibitors may result in increased hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression
            • In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in increased hydrocodone plasma concentration
            • Avoid use of drug in patients taking a CYP3A4 inhibitor or inducer

            Risks from concomitant use with benzodiazepines or other CNS depressants

            • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
            • Avoid use of in patients taking benzodiazepines, other CNS depressants, or alcohol

            Interaction with Alcohol

            • Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while taking medication; the co-ingestion of alcohol with Tussigon may result in increased plasma levels and a potentially fatal overdose of hydrocodone

            Neonatal Opioid Withdrawal Syndrome

            • Therapy not recommended for use in pregnant women; prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • If used for a prolonged period in a pregnant woman, advise patient of risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Contraindications

            Children <6 years

            Significant respiratory depression

            Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment

            Known or suspected gastrointestinal obstruction, including paralytic ileus

            Hypersensitivity to hydrocodone, homatropine, or any of inactive primary glaucoma or a predisposition to glaucoma

            Cautions

            The hydrocodone in the medication may increase the frequency of seizures in patients with seizure disorders, and may increase risk of seizures occurring in other clinical settings associated with seizures; monitor patients with a history of seizure disorders for worsened seizure control during therapy

            Severe hypotension

            • Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics)
            • Monitor these patients for signs of hypotension after initiating therapy; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid use of medication in patients with circulatory shock

            Neonatal Opioid Withdrawal Syndrome

            • This medication is not recommended for use in pregnant women; prolonged use during pregnancy can result in withdrawal in the neonate; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly; advise pregnant women using opioids for a prolonged period of risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Adrenal insufficiency

            • Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use; presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure
            • If adrenal insufficiency is suspected, confirm diagnosis with diagnostic testing as soon as possible; if adrenal insufficiency diagnosed, treat with physiologic replacement doses of corticosteroids
            • Wean patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers
            • Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency; the information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency

            Addiction, Abuse, and Misuse

            • Medication contains hydrocodone, a Schedule II controlled substance; as an opioid, medication exposes users to risks of addiction, abuse, and misuse
            • Although risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed with the medication; addiction can occur at recommended dosages and if drug is misused or abused
            • Risks are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression); opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion
            • Consider risks when prescribing or dispensing medication; strategies to reduce these risks include prescribing drug in smallest appropriate quantity and advising patient on proper disposal of unused drug
            • Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression reported with use of opioids, including hydrocodone, one of active ingredients in the drug combination; hydrocodone produces dose-related respiratory depression by directly acting on brain stem respiratory center that controls respiratory rhythm and may produce irregular and periodic breathing
            • Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death; management of respiratory depression includes discontinuation of therapy, close observation, supportive measures, and use of opioid antagonists (eg, naloxone), depending on patient’s clinical status
            • Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate sedating effects of opioids; while serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, risk is greatest during initiation of therapy, when drug combination is used
            • concomitantly with other drugs that may cause respiratory depression in patients with chronic pulmonary disease or decreased respiratory reserve, and in patients with altered pharmacokinetics or altered clearance (eg, elderly, cachectic, or debilitated patients)
            • To reduce risk of respiratory depression, proper dosing is essential; monitor patients closely, especially within first 24-72 hr of initiating therapy or when used in patients at higher risk; overdose of hydrocodone in adults has been associated with fatal respiratory depression, and use of hydrocodone in children younger than 6 years of age has been associated with fatal respiratory depression when used as recommended
            • Accidental ingestion of even one dose, especially by children, can result in respiratory depression and death

            Pediatric population

            • Children are particularly sensitive to respiratory depressant effects of hydrocodone; because of risk of life-threatening respiratory depression and death, the drug is contraindicated in children <6 years
            • Use in children also exposes them to risks of addiction, abuse, and misuse, which can lead to overdose and death; because benefits of symptomatic treatment of cough associated with allergies or common cold do not outweigh risks of use of hydrocodone in pediatric patients, this medication is not indicated for use in patients <18 years

            Use in other at-risk population

            • Dosage should not be increased if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease
            • Use in patients with acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment is contraindicated
            • Opioid analgesics and antitussives, including hydrocodone, one of the active ingredients, should not be used in patients with acute febrile illness associated with productive cough or in patients with chronic respiratory disease where interference with ability to clear the tracheobronchial tree of secretions would have a deleterious effect on patient’s respiratory function
            • Treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages
            • Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients
            • Because of risk of respiratory depression, avoid use of opioid antitussives in patients with compromised respiratory function, patients at risk of respiratory failure, and in elderly, cachectic, or debilitated patients; monitor such patients closely, particularly when initiating therapy and when the medication is given concomitantly with other drugs that depress respiration

            Accidental overdose and death due to medication errors

            • Dosing errors can result in accidental overdose and death; to reduce risk of overdose and respiratory depression, ensure that the dose is communicated clearly and dispensed accurately
            • Advise patients to always use an accurate milliliter measuring device when measuring and administering oral solution; inform patients that household teaspoon is not an accurate measuring device and such use could lead to overdosage and serious adverse reactions
            • For prescriptions where a measuring device is not provided, a pharmacist can provide an appropriate calibrated measuring device and can provide instructions for measuring the correct dose

            Mental alertness

            • Hydrocodone, one of the active ingredients in the medication, may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery
            • Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination taking the medication
            • Avoid concurrent use of the medication with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur

            Cytochrome P450 3A4 Inhibitors and Inducers

            • Concomitant use with a CYP3A4 inhibitor, such as macrolide antibiotics (eg, erythromycin), azole-antifungal agents (eg, ketoconazole), and protease inhibitors (eg, ritonavir), may increase plasma concentrations of hydrocodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of the medication is achieved
            • Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, may increase hydrocodone plasma concentrations and prolong opioid adverse reactions
            • Concomitant use of the medication with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease hydrocodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to hydrocodone
            • Avoid use in patients who are taking a CYP3A4 inhibitor or inducer; if concomitant use of the medication with a CYP3A4 inhibitor or inducer necessary, monitor patients for signs and symptoms that may reflect opioid toxicity and opioid withdrawal

            Concomitant Use with Benzodiazepines or other CNS Depressants

            • Concomitant use of opioids with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
            • Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol
            • Advise both patients and caregivers about the risks of respiratory depression and sedation if drug is used with benzodiazepines, alcohol, or other CNS depressants
            • Patients must not consume alcoholic beverages, or prescription or non-prescription products containing alcohol, while on therapy; the co-ingestion of alcohol may result in increased plasma levels and a potentially fatal overdose of hydrocodone

            Patients with Gastrointestinal Conditions

            • Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; the use of hydrocodone in the medication may obscure diagnosis or clinical course of patients with acute abdominal conditions
            • Concurrent use of anticholinergics may produce paralytic ileus; the hydrocodone in the drug combination may result in constipation or obstructive bowel disease, especially in patients with underlying intestinal motility disorders
            • Use with caution in patients with underlying intestinal motility disorders; the hydrocodone in the medication may cause spasm of the sphincter of Oddi, resulting in an increase in biliary tract pressure
            • Opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms

            Patients with head injury, impaired consciousness, increased intracranial pressure, or brain tumors

            • Avoid use in patients with head injury, intracranial lesions, or a pre-existing increase in intracranial pressure; in patients who may be susceptible to intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), the medication may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure
            • Furthermore, opioids produce adverse reactions that may obscure clinical course of patients with head injuries
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            Pregnancy & Lactation

            Pregnancy

            Not recommended for use in pregnant women, including during or immediately prior to labor; prolonged use of opioids during pregnancy may cause neonatal opioid withdrawal syndrome

            There are no available data with use in pregnant women to inform a drug-associated risk for adverse developmental outcomes; published studies with hydrocodone have reported inconsistent findings and have important methodological limitations

            Reproductive toxicity studies have not been conducted; however, studies are available with individual active ingredients or related active ingredients

            Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in neonate and neonatal opioid withdrawal syndrome shortly after birth

            Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight

            The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn

            Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Labor or delivery

            • Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates
            • An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; opioids can prolong labor through actions which temporarily reduce strength, duration, and frequency of uterine contractions
            • However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor; monitor neonates exposed to opioids during labor for signs of excess sedation and respiratory depression

            Infertility

            • Chronic use of opioids, such as hydrocodone may cause reduced fertility in females and males of reproductive potential; it is not known whether these effects on fertility are reversible

            Animal data

            • In animal reproduction studies, hydrocodone administered by subcutaneous route to pregnant hamsters during period of organogenesis produced a teratogenic effect at dose approximately 45 times maximum recommended human dose (MRHD)
            • Based on animal data, advise pregnant women of potential risk to a fetus

            Lactation

            Because of potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, advise patients that breastfeeding is not recommended during treatment

            There are no data on presence of the drugs in human milk, effects on breastfed infant, or on milk production; however, data are available with hydrocodone and homatropine

            Hydrocodone is present in breast milk; published cases report variable concentrations of hydrocodone and hydromorphone (an active metabolite) in breast milk with administration of immediate-release hydrocodone to nursing mothers in early post-partum period with relative infant doses of hydrocodone ranging between 1.4 and 3.7%

            There are case reports of excessive sedation and respiratory depression in breastfed infants exposed to hydrocodone; no information is available on effects of hydrocodone on milk production.

            No information is available on the levels of homatropine in breast milk or on milk production; the published literature suggests that homatropine may decrease milk production based on its anticholinergic effects

            Infants exposed to the drugs through breast milk should be monitored for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid is stopped, or when breastfeeding is stopped

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Hydrocodone: Antitussive; narcotic agonist analgesic

            Homatropine: Anticholinergic agent adjunct to hydrocodone bitartrate added in subtherapeutic amount to suppress deliberate overdosage

            Pharmacokinetics

            Hydrocodone

            • Half-life: 3.3-4.4 hr
            • Duration of action: 4-8 hr
            • Peak plasma time: 1.3 hr
            • Metabolism: liver (O-demethylation, N-demethylation, 6-keto reduction); hepatic P450 enzyme CYP2D6
            • Excretion: Urine (mainly)

            Homatropine

            • Duration of action: 6 hr
            • Excretion: Urine
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            Administration

            Oral Administration

            Administer medication by oral route only; always use an accurate milliliter measuring device when administering oral solution to ensure that dose is measured and administered accurately

            A household teaspoon is not an accurate measuring device and could lead to overdosage

            For prescriptions where a measuring device not provided, a pharmacist can provide an appropriate measuring device and can provide instructions for measuring correct dose; do not overfill; rinse measuring device with water after each use

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.