hydrocodone (Rx)

Brand and Other Names:Zohydro ER, Hysingla ER, more...Vantrela ER
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule, extended-release (Zohydro ER): Schedule II

  • Abuse-deterrent product (BeadTek technology)
  • 10mg
  • 15mg
  • 20mg
  • 30mg
  • 40mg
  • 50mg

tablet, extended-release (Hysingla ER): Schedule II

  • Abuse-deterrent product (RESISTEC)
  • 20mg
  • 30mg
  • 40mg
  • 60mg
  • 80mg
  • 100mg
  • 120mg

Chronic Pain

Indicated for the management of pain severe enough to require daily, around-the-clock, long-term treatment and for which alternative treatment options are inadequate

Initial dosing

  • Should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain
  • Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse
  • Monitor patients closely for respiratory depression, especially within the first 24-72 hr of initiating therapy

Opioid naïve or first opioid analgesic

  • Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
  • Zohydro ER
    • Zohydro ER: 10 mg PO q12hr initially
    • A single dose of Zohydro ER >40 mg, Zohydro ER 50 mg capsules, or a total daily dose greater than 80 mg are only for patients in whom tolerance to an opioid of comparable potency is established
  • Hysingla ER
    • Hysingla ER: Administer once daily as 20 mg PO q24h initially
    • Daily doses of Hysingla ER ≥80 mg/day are only for use in opioid tolerant patients

Opioid tolerant

  • See prescribing information for conversion table from existing opioid analgesic to hydrocodone extended-release
  • Opioid tolerance definition
    • Defined as patients who are receiving the following opioids (or an equianalgesic dose of another opioid) for 1 week or longer
    • morphine 60 mg/day PO
    • transdermal fentanyl 25 mcg/hr
    • oxycodone 30 mg/day
    • hydromorphone 8 mg/day PO
    • oxymorphone 25 mg/day PO

Titration, maintenance, discontinuation

  • Zohydro ER: Increase by increments of 10 mg q12hr q3-7d as needed to achieve adequate analgesia
  • Hysingla ER: Increase by increments of 10-20 mg/day q3-5d as needed to achieve adequate analgesia
  • Assess pain frequently for toxicity, breakthrough pain, or need for short-acting rescue analgesia
  • Discontinue by a gradual downward titration every 2-4 days; do not withdraw abruptly

Dosage Modifications

Hepatic impairment

  • Severe: Initiate with lowest dose, 10 mg (Zohydro ER) or 50% of initial dose (Hysingla ER) and monitor closely for signs of respiratory depression and excessive sedation

Renal impairment

  • Patients with renal impairment may have higher plasma concentrations than those with normal function
  • Moderate-to-severe and ESRD: Initiate therapy with a low initial dose (Zohydro ER) or 50% of initial dose (Hysingla ER) and monitor closely for respiratory depression and sedation

Dosing Considerations

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve use for patients for whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain

Not indicated for acute pain or as an as-needed (prn) analgesic

Access to naloxone for opioid overdose

  • Assess need for naloxone upon initiating and renewing treatment
  • Consider prescribing naloxone
    • Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
    • Household members (including children) or other close contacts at risk for accidental ingestion or overdose
  • Consult patients and caregivers on the following:
    • Availability of naloxone for emergency treatment of opioid overdose
    • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)

Safety and efficacy not established

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Interactions

Interaction Checker

and hydrocodone

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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 (126)

            • 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.

            • 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.

            • 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.

            • 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.

            • voxelotor

              voxelotor will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • zaleplon

              hydrocodone, zaleplon. 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.

            • ziprasidone

              hydrocodone, ziprasidone. 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.

            • zolpidem

              hydrocodone, zolpidem. 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 (135)

            • 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.

            • 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.

            • 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.

            • 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.

            • 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

            • 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

            • 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.

            • 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.

            • 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.

            • 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.

            • 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

              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.

            • 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

            • 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

            • 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.

            • 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

              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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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

              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.

            • 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

            • 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.

            • 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

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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

            • 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.

            • nortriptyline

              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.

            • 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.

            • 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

            • 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

              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.

            • 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

            • 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.

            • 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

            • 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

            • 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.

            • protriptyline

              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.

            • 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.

            • 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.

            • 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

            • 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.

            • 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

            • 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.

            • 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.

            • 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 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

              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

            • trazodone

              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.

            • 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.

            • 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

            • 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.

            Minor (1)

            • 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

            >10%

            Zohydro ER

            • Constipation (8-11%)

            1-10%

            Zohydro ER

            • Nausea (7-10%)
            • Vomiting (3-5%)
            • Somnolence (1-5%)
            • UTI (1-5%)
            • Headache (4%)
            • Fatigue (1-4%)
            • Back pain (1-4%)
            • Dry mouth (3%)
            • Pruritus (3%)
            • Tremor (3%)
            • Dizziness (2-3%)
            • Peripheral edema (1-3%)
            • URI infection (1-3%)
            • Muscle spasms (1-3%)

            1-10% (Hysingla ER)

            • Nausea (8%)
            • Constipation (3%)
            • Vomiting (6%)
            • Dizziness (3%)
            • Insomnia (3%)
            • Influenza (3%)
            • Decreased appetite (2%)
            • Headache (2%)
            • Tinnitus (2%)
            • Somnolence (1%)
            • Fatigue (1%)
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            Warnings

            Black Box Warnings

            Addiction, abuse, and misuse

            • Long-acting hydrocodone exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death
            • Assess each patient’s risk prior to prescribing, and monitor all patients regularly for the development of these behaviors or conditions

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation or following a dose increase
            • Instruct patients to swallow capsules/tablets whole; crushing, chewing, or dissolving the extended-release dosage forms can cause rapid release and absorption of a potentially fatal dose of hydrocodone

            Accidental exposure

            • Accidental consumption of even 1 dose of hydrocodone, especially by children, can result in a fatal overdose of hydrocodone

            Neonatal opioid withdrawal syndrome

            • For patients who require opioid therapy while pregnant, be aware that infants may require treatment for neonatal opioid withdrawal syndrome
            • Prolonged maternal use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening and requires management according to protocols developed by neonatology experts

            Interaction with CNS depressants

            • Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
            • Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate
            • Limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation
            • Coingestion of Zohydro ER with alcohol may increase hydrocodone plasma levels and result in a potentially fatal overdose (alters release of drug from capsule)

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, Food and Drug Administration (FDA) has required a REMS for these products; under the requirements of REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare
            • Providers; healthcare providers are strongly encouraged to complete a REMS-compliant education program, counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products, emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety

            Interaction with CYP3A4 inhibitors

            • Initiation of CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of hydrocodone from hydrocodone ER

            Contraindications

            Hypersensitivity

            Significant respiratory depression

            Acute or severe bronchial asthma or hypercarbia

            Suspected paralytic ileus

            Cautions

            Do not prescribe for acute pain or as needed (prn) pain relief; only for severe chronic pain requiring continuous, around-the-clock opioid analgesia

            Hydrocodone is an opioid agonist and a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone

            Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if concomitant use with benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose

            If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response; follow patients closely for signs and symptoms of respiratory depression and sedation

            Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper

            Monitor carefully in elderly, cachectic, debilitated patients, and those with chronic pulmonary disease because of increased risk for life-threatening respiratory depression

            Monitor patients with head injury or increased ICP for sedation and respiratory depression; avoid use in patients with impaired consciousness or coma susceptible to intracranial effects of CO2 retention

            May cause severe hypotension, including orthostatic hypotension and syncope; added risk to individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone

            May cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

            Coadministration with CYP3A4 inhibitors may increase hydrocodone systemic exposure and result in toxicity; if co-administration with CYP3A4 necessary, monitor patients closely who are currently taking, or discontinuing, CYP3A4 inhibitors or inducers; evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved

            Caution must be used with potentially hazardous activities

            Avoid use of mixed agonist/antagonist analgesics (ie, pentazocine, nalbuphine, butorphanol) when taking full opioid agonist analgesics

            Do not abruptly discontinue therapy in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain

            Hydrocodone ER may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings; monitor patients with a history of seizure disorders for worsened seizure control during hydrocodone ER therapy

            Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of 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

            Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected

            Patient access to naloxone for emergency treatment of opioid overdose

            • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
            • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
            • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
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            Pregnancy & Lactation

            Pregnancy

            Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome; there are no available data in pregnant women to inform a drug associated risk for major birth defects and miscarriage; published studies with morphine use during pregnancy have not reported a clear association with opioids and major birth defects

            Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; 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 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 neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that 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 dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression

            Lactation

            Drug is present in breast milk; published lactation studies report variable concentrations of drug in breast milk with administration of immediate-release formulation to nursing mothers in early postpartum period

            The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

            Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding 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

            Mu opioid receptor agonist; interacts with other opioid receptors at higher doses; activates opioid receptors at sites in the peri-aquaductal and peri-ventricular gray matter, the ventro-medial medulla and the spinal cord to produce analgesia

            Also elicits euphoric, respiratory depressant, and physiologic dependence properties of mu receptors within the CNS

            Absorption

            Zohydro ER

            • Extended-release provided by spheroidal oral drug absorption system (SODAS) technology (ie, multi-particulate formulation of coated carrier beads in hard gelatin capsules); contains rate-controlling polymers and drug release by diffusion
            • Peak plasma time: 5 hr
            • Peak plasma concentration increased by 27% when administered with a high fat meal

            Hysingla ER

            • Peak plasma time (mean): 14-16 hr (range 6-30 hr)
            • AUC and peak plasma concentration increase linearly with doses
            • Peak plasma concentration (median): 14.6-110 ng/mL
            • AUC (median): 284-1787 ng•hr/mL
            • Peak plasma concentration increased by 20% when administered with a high fat meal

            Vantrela ER

            • Peak plasma time: 8 hr (single dose); 5 hr (steady-state)
            • Peak plasma concentration (single doses): 12.6-62.5 ng/mL
            • AUC (single doses): 199-1189 ng•hr/mL

            Distribution

            Protein bound: ~19% (Zohydro ER); 36% (Hysingla ER); 19-45% (Vantrela ER)

            Vd: 402 L (Hysingla ER); 1300-1400 L (Vantrela ER)

            Metabolism

            Metabolized in liver by CYP2D6 (minor) via O-demethylation, CYP3A4 (major) via N-demethylation, and 6-keto reduction

            Metabolites: CYP3A4 mediated N-demethylation to norhydrocodone is the primary metabolic pathway; CYP2D6 to hydromorphone (active metabolite with higher binding capacity to mu opioid receptor)

            Elimination

            Half-life: 8 hr (Zohydro ER); 7-9 hr (Hysingla ER); 11-12 hr (Vantrela ER)

            Excretion: Primarily by kidneys

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            Administration

            Oral Administration

            Swallow capsule/tablet whole; crushing, chewing, or dissolving the extended-release dosage form will result in uncontrolled delivery of hydrocodone and can lead to overdose or death

            Must be taken whole, 1 capsule/tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Zohydro ER oral
            -
            50 mg capsule
            Zohydro ER oral
            -
            40 mg capsule
            Zohydro ER oral
            -
            30 mg capsule
            Zohydro ER oral
            -
            15 mg capsule
            Zohydro ER oral
            -
            10 mg capsule
            Hysingla ER oral
            -
            120 mg tablet
            Hysingla ER oral
            -
            100 mg tablet
            Hysingla ER oral
            -
            80 mg tablet
            Hysingla ER oral
            -
            60 mg tablet
            Hysingla ER oral
            -
            40 mg tablet
            Hysingla ER oral
            -
            30 mg tablet
            Hysingla ER oral
            -
            20 mg tablet
            hydrocodone bitartrate oral
            -
            50 mg capsule
            hydrocodone bitartrate oral
            -
            40 mg capsule
            hydrocodone bitartrate oral
            -
            10 mg capsule
            hydrocodone bitartrate oral
            -
            30 mg capsule
            hydrocodone bitartrate oral
            -
            15 mg capsule

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            hydrocodone bitartrate oral

            HYDROCODONE EXTENDED-RELEASE TABLET - ORAL

            (HYE-droe-KOE-done)

            COMMON BRAND NAME(S): Hysingla ER

            WARNING: Hydrocodone has a risk for abuse and addiction, which can lead to overdose and death. Hydrocodone may also cause severe, possibly fatal, breathing problems. To lower your risk, your doctor should have you take the smallest dose of hydrocodone that works, and take it for the shortest possible time. See also How to Use section for more information about addiction.The risk for severe breathing problems is higher when you start this medication and after a dose increase, or if you take the wrong dose/strength. Taking this medication with alcohol or other drugs that can cause drowsiness or breathing problems may cause very serious side effects, including death. Also, other medications can affect the removal of hydrocodone from your body, which may affect how hydrocodone works. Be sure you know how to take hydrocodone and what other drugs you should avoid taking with it. See also Drug Interactions section. Get medical help right away if any of these very serious side effects occur: slow/shallow breathing, unusual lightheadedness, severe drowsiness/dizziness, difficulty waking up.Do not crush, chew, or dissolve this medication. Taking crushed, chewed, or dissolved forms of extended-release hydrocodone could cause a fatal overdose.Before using this medication, women of childbearing age should talk with their doctor(s) about the risks and benefits. Tell your doctor if you are pregnant or if you plan to become pregnant. During pregnancy, this medication should be used only when clearly needed. It may slightly increase the risk of birth defects if used during the first two months of pregnancy. Also, using it for a long time or in high doses near the expected delivery date may harm the unborn baby. To lessen the risk, take the smallest effective dose for the shortest possible time. Babies born to mothers who use this drug for a long time may develop severe (possibly fatal) withdrawal symptoms. Tell the doctor right away if you notice any symptoms in your newborn baby such as slow/shallow breathing, irritability, shaking, persistent crying, vomiting, diarrhea, poor feeding, or difficulty gaining weight.Keep this medicine in a safe place to prevent theft, misuse, or abuse. If someone accidentally swallows this drug, get medical help right away.

            USES: Hydrocodone is used to help relieve severe ongoing pain. Hydrocodone belongs to a class of drugs known as opioid analgesics. It works in the brain to change how your body feels and responds to pain.Do not use the extended-release form of hydrocodone to relieve pain that is mild or that will go away in a few days. This medication is not for occasional ("as needed") use.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking hydrocodone and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication on a regular schedule as directed by your doctor, not as needed for sudden (breakthrough) pain. Take this medication by mouth as directed by your doctor, usually once daily (24 hours apart). Do not pre-soak, lick, or otherwise wet the tablet before placing it in your mouth, since it may make it harder to swallow the tablet. If your dose is for more than one tablet, you should take one tablet at a time. Take each tablet with enough water to make sure you completely swallow it right after placing it in your mouth.Do not crush or chew extended-release tablets. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing.You may take this drug with or without food. If you have nausea, it may help to take this drug with food. Ask your doctor or pharmacist about other ways to decrease nausea (such as lying down for 1 to 2 hours with as little head movement as possible).The dosage is based on your medical condition and response to treatment. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase. Properly stop the medication when so directed.Pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has worsened, the medication may not work as well.Before you start using this medication, ask your doctor or pharmacist if you should stop or change how you use your other opioid medication(s). Other pain relievers (such as acetaminophen, ibuprofen) may also be prescribed. Ask your doctor or pharmacist about using hydrocodone safely with other drugs.Suddenly stopping this medication may cause withdrawal, especially if you have used it for a long time or in high doses. To prevent withdrawal, your doctor may lower your dose slowly. Tell your doctor or pharmacist right away if you have any withdrawal symptoms such as restlessness, mental/mood changes (including anxiety, trouble sleeping, thoughts of suicide), watering eyes, runny nose, nausea, diarrhea, sweating, muscle aches, or sudden changes in behavior.When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.Though it helps many people, this medication may sometimes cause addiction. This risk may be higher if you have a substance use disorder (such as overuse of or addiction to drugs/alcohol). Take this medication exactly as prescribed to lower the risk of addiction. Ask your doctor or pharmacist for more details.Tell your doctor if your pain does not get better or if it gets worse.

            SIDE EFFECTS: See also Warning section.Nausea, vomiting, constipation, lightheadedness, dizziness, or drowsiness may occur. Some of these side effects may decrease after you have been using this medication for a while. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.To prevent constipation, eat dietary fiber, drink enough water, and exercise. You may also need to take a laxative. Ask your pharmacist which type of laxative is right for you.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: interrupted breathing during sleep (sleep apnea), mental/mood changes (such as agitation, confusion, hallucinations), stomach/abdominal pain, difficulty urinating, signs of your adrenal glands not working well (such as loss of appetite, unusual tiredness, weight loss).Get medical help right away if you have any very serious side effects, including: fainting, fast/irregular heartbeat, severe dizziness, seizure, slow/shallow breathing, severe drowsiness/difficulty waking up.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking hydrocodone, tell your doctor or pharmacist if you are allergic to it; or to other opioids (such as benzhydrocodone, codeine, hydromorphone); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), gallbladder disease, kidney disease, liver disease, mental/mood disorders (such as confusion, depression, thoughts of suicide), personal or family history of a substance use disorder (such as overuse of or addiction to drugs/alcohol), stomach/intestinal problems (such as blockage, constipation, diarrhea due to infection, paralytic ileus), disease of the pancreas (pancreatitis), difficulty urinating (such as due to enlarged prostate), trouble swallowing.Hydrocodone may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using hydrocodone, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using hydrocodone safely.This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Children may be more sensitive to the side effects of this drug, especially slow/shallow breathing, trouble swallowing, and choking.Older adults may be more sensitive to the side effects of this drug, especially confusion, dizziness, drowsiness, slow/shallow breathing, QT prolongation (see above).During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor. (See also Warning section.)This drug passes into breast milk and may have undesirable effects on a nursing infant. Tell the doctor right away if your baby develops unusual sleepiness, difficulty feeding, or trouble breathing. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also Warning section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug are: certain pain medications (mixed opioid agonist-antagonists such as pentazocine, nalbuphine, butorphanol), naltrexone.Other medications can affect the removal of hydrocodone from your body, which may affect how hydrocodone works. Examples include azole antifungals (such as ketoconazole), macrolide antibiotics (such as erythromycin), mifepristone, HIV medications (such as ritonavir), rifamycins (such as rifabutin, rifampin), certain drugs used to treat seizures (such as carbamazepine, phenytoin), among others.The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is taken with other products that may also cause drowsiness or breathing problems. Tell your doctor or pharmacist if you are taking other products such as other opioid pain or cough relievers (such as codeine, oxycodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.This medication may interfere with certain lab tests (such as amylase/lipase levels), possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, give them naloxone if available, then call 911. If the person is awake and has no symptoms, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: slow breathing, slow heartbeat, coma.

            NOTES: Do not share this medication with others. Sharing it is against the law.This medication has been prescribed for your current condition only. Do not use it later for another condition unless your doctor directs you to do so. A different medication may be necessary in that case.Ask your doctor or pharmacist if you should have naloxone available to treat opioid overdose. Teach your family or household members about the signs of an opioid overdose and how to treat it.

            MISSED DOSE: If you miss a dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets. See also Warning section.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. For more details, read the Medication Guide, or consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            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.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
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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.