methenamine/hyoscyamine/methylene blue/phenyl salicylate/sodium phosphate monobasic (Rx)

Brand and Other Names:Uribel, Uticap, more...Utrona-C, Uretron D/S
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Dosing & Uses

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Dosage Forms & Strengths

methenamine/hyoscyamine/methylene blue/phenyl salicylate/sodium phosphate monobasic

tablet

  • 81mg/0.12mg/10mg/32mg/41mg (Uro-458)
  • 81mg/0.12mg/10mg/36mg/41mg (Phosphasal, Urin DS, Utira-C)

tablet, capsule

  • 120mg/0.12mg/10mg/36mg/41mg (Uribel, Uro-MP, UroAv-B, Ustell, Vilamit MB, Uticap)

Urinary Tract Irritative Voiding Symptoms

Symptoms resulting from urinary tract infection or diagnostic procedures: 1 tablet/capsule PO q6hr with liberal fluid intake

Dosage Forms & Strengths

methenamine/hyoscyamine/methylene blue/phenyl salicylate/sodium phosphate monobasic

tablet

  • 81mg/0.12mg/10mg/32mg/41mg (Uro-458)
  • 81mg/0.12mg/10mg/36mg/41mg (Phosphasal, Urin DS, Utira-C)

tablet, capsule

  • 120mg/0.12mg/10mg/36mg/41mg (Uribel, Uro-MP, UroAv-B, Ustell, Vilamit MB, Uticap)

Urinary Tract Irritative Voiding Symptoms

≤6 years: Safety and efficacy not established

>6 years: Symptoms resulting from urinary tract infection or diagnostic procedures: 1 tablet/capsule PO q6hr with liberal fluid intake

Avoid except in short-term settings; high incidence of anticholinergic effects may occur (Beers criteria)

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Interactions

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            Contraindicated (5)

            • cyproheptadine

              methylene blue, cyproheptadine. Other (see comment). Contraindicated. Comment: MAO inhibitors may prolong and intensify the anticholinergic effects of antihistamines. Cyproheptadine may diminish the serotonergic effect of MAO inhibitors.

            • desvenlafaxine

              methylene blue and desvenlafaxine both increase serotonin levels. Contraindicated. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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

            • deutetrabenazine

              methylene blue, deutetrabenazine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Contraindicated. Deutetrabenazine should not be used in combination with an MAOI, or within 14 days of discontinuing therapy with an MAOI. If methylene blue must be used emergently, discontinue deutetrabenazine and monitor for adverse effects. Deutetrabenazine may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • fluoxetine

              methylene blue and fluoxetine both increase serotonin levels. Contraindicated. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue fluoxetine immediately and monitor for CNS toxicity. Fluoxetine may be resumed 24 hours after last methylene blue dose or after 5 weeks of monitoring, whichever comes first.

            • vortioxetine

              methylene blue increases toxicity of vortioxetine by serotonin levels. Contraindicated. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be urgently administered, discontinue vortioxetine immediately and monitor for serotonin syndrome. Monitor for serotonin syndrome for 3 weeks or 24 hr after last methylene blue dose, whichever comes first. Vortioxetine may be resumed 24 hr after last methylene blue dose.

            Serious - Use Alternative (92)

            • 5-HTP

              methylene blue and 5-HTP both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue 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.

            • acetazolamide

              acetazolamide, methenamine. Other (see comment). Contraindicated. Comment: This combination may form an insoluble precipitate in the urine, decreasing the effects of both agents.

            • alfentanil

              methylene blue and alfentanil both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • almotriptan

              almotriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • amitriptyline

              methylene blue and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • amoxapine

              amoxapine and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • belladonna alkaloids

              methylene blue and belladonna alkaloids both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • belladonna and opium

              methylene blue and belladonna and opium both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • benzhydrocodone/acetaminophen

              methylene blue increases toxicity of benzhydrocodone/acetaminophen 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.

            • buprenorphine

              methylene blue and buprenorphine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • bupropion

              bupropion and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • buspirone

              methylene blue and buspirone both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • butalbital

              methylene blue and butalbital both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • butorphanol

              methylene blue and butorphanol both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • cholera vaccine

              methenamine, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.

            • citalopram

              methylene blue and citalopram both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • clomipramine

              methylene blue and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • cocaine

              methylene blue and cocaine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. Cocaine inhibits presynaptic reuptake of serotonin. Monitor for CNS toxicity.

            • codeine

              methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • cyclobenzaprine

              methylene blue and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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

            • desipramine

              methylene blue and desipramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • dexfenfluramine

              methylene blue and dexfenfluramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • dextroamphetamine

              methylene blue and dextroamphetamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • dextromethorphan

              methylene blue and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • dihydroergotamine

              methylene blue and dihydroergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • dihydroergotamine intranasal

              methylene blue and dihydroergotamine intranasal both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • doxepin

              methylene blue and doxepin both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • doxepin cream

              methylene blue and doxepin cream both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • doxylamine

              methylene blue and doxylamine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • duloxetine

              methylene blue and duloxetine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • eletriptan

              eletriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • ergotamine

              methylene blue and ergotamine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • escitalopram

              methylene blue and escitalopram both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • fentanyl

              methylene blue and fentanyl both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • fluvoxamine

              fluvoxamine increases toxicity of methylene blue by serotonin levels. Avoid or Use Alternate Drug.

            • frovatriptan

              frovatriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • glucagon

              glucagon increases toxicity of hyoscyamine by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of anticholinergic drugs and glucagon increase the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. .

            • glucagon intranasal

              glucagon intranasal increases toxicity of hyoscyamine by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of anticholinergic drugs and glucagon increase the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. .

            • glycopyrronium tosylate topical

              glycopyrronium tosylate topical, hyoscyamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

            • hydrocodone

              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.

            • hydromorphone

              methylene blue and hydromorphone both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • imipramine

              methylene blue and imipramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • isocarboxazid

              methylene blue and isocarboxazid both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • isoniazid

              methylene blue and isoniazid both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue and isoniazid may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue isoniazid immediately and monitor for CNS toxicity. Isoniazid may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • L-tryptophan

              methylene blue and L-tryptophan both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • levodopa

              methylene blue and levodopa both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • levomilnacipran

              methylene blue and levomilnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • levorphanol

              methylene blue and levorphanol both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • linezolid

              methylene blue and linezolid both increase serotonin levels. Avoid or Use Alternate Drug. Both drugs increase serotonin as a result of MAO-A inhibition. Avoid coadministration if possible. If coadministered, monitor for CNS toxicity.

            • lsd

              methylene blue and lsd both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity.

            • maprotiline

              methylene blue and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • meperidine

              methylene blue and meperidine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • metformin

              methylene blue will increase the level or effect of metformin by unspecified interaction mechanism. Avoid or Use Alternate Drug.

            • methadone

              methylene blue and methadone both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • milnacipran

              methylene blue and milnacipran both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • mirtazapine

              methylene blue and mirtazapine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • morphine

              methylene blue and morphine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue morphine (if possible) and monitor for CNS toxicity. Morphine may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • naratriptan

              naratriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • nefazodone

              methylene blue and nefazodone both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • nortriptyline

              methylene blue and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • oxycodone

              methylene blue and oxycodone both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • paroxetine

              methylene blue and paroxetine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • pentazocine

              methylene blue and pentazocine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue pentazocine (if possible) 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.

            • phenelzine

              methylene blue and phenelzine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • pramlintide

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

            • procarbazine

              methylene blue and procarbazine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • promethazine

              methylene blue and promethazine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • protriptyline

              methylene blue and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • rasagiline

              methylene blue and rasagiline both increase serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and rasagiline may increase serotonin as a result of MAO-A inhibition. 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.

            • remifentanil

              methylene blue and remifentanil both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • revefenacin

              revefenacin and hyoscyamine both decrease cholinergic effects/transmission. Avoid or Use Alternate Drug. Coadministration may cause additive anticholinergic effects.

            • rizatriptan

              rizatriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • safinamide

              methylene blue, safinamide. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and safinamide may increase serotonin as a result of MAO-A inhibition. If IV 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.

            • SAMe

              methylene blue and SAMe both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • secretin

              hyoscyamine decreases effects of secretin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Concomitant use of anticholinergic drugs may cause a hyporesponse to stimulation testing with secretin. Discontinue anticholinergic drugs at least 5 half-lives before administering secretin.

            • selegiline

              selegiline and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and selegiline may increase serotonin as a result of MAO-A inhibition. 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.

            • selegiline transdermal

              selegiline transdermal and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Both methylene blue and selegiline may increase serotonin as a result of MAO-A inhibition. 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.

            • sertraline

              methylene blue and sertraline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • St John's Wort

              methylene blue and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • sufentanil SL

              methylene blue increases toxicity of sufentanil SL 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.

            • sulfadiazine

              methenamine, sulfadiazine. Other (see comment). Contraindicated. Comment: This combination may form an insoluble precipitate in the urine, decreasing the effects of both agents.

            • sulfamethoxazole

              methenamine, sulfamethoxazole. Other (see comment). Contraindicated. Comment: This combination may form an insoluble precipitate in the urine, decreasing the effects of both agents.

            • sulfisoxazole

              methenamine, sulfisoxazole. Other (see comment). Contraindicated. Comment: This combination may form an insoluble precipitate in the urine, decreasing the effects of both agents.

            • sumatriptan

              sumatriptan and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • sumatriptan intranasal

              sumatriptan intranasal and methylene blue both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • tedizolid

              tedizolid, methylene blue. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase levels of serotonin; increased risk of serotonin syndrome.

            • tramadol

              methylene blue and tramadol both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • tranylcypromine

              methylene blue and tranylcypromine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • trazodone

              methylene blue and trazodone both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • trimipramine

              methylene blue and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. 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.

            • umeclidinium bromide/vilanterol inhaled

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

            • valbenazine

              methylene blue, valbenazine. Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of valbenazine with MAOIs may increase monoamine neurotransmitter concentration in synapses, potentially increasing risk of serotonin syndrome or attenuating valbenazine effect.

            Monitor Closely (65)

            • abobotulinumtoxinA

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

            • aclidinium

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

            • amantadine

              hyoscyamine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

            • amitriptyline

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

            • amoxapine

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

            • anticholinergic/sedative combos

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

            • aripiprazole

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

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

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

            • artesunate

              methylene blue will increase the level or effect of artesunate by decreasing metabolism. Use Caution/Monitor. Coadministration may increase active artesunate metabolite (DHA) by inhibiting UGT. Monitor for increased adverse effects.

            • atracurium

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

            • atropine

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

            • atropine IV/IM

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

            • belladonna alkaloids

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

            • belladonna and opium

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

            • benperidol

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

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

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

            • benztropine

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

            • bethanechol

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

            • buprenorphine subdermal implant

              methylene blue, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • buprenorphine, long-acting injection

              methylene blue, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

              buprenorphine, long-acting injection increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • carbachol

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

            • lasmiditan

              methylene blue increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

            • cevimeline

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

            • chlorpromazine

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

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

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

            • cisatracurium

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

            • clomipramine

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

            • clozapine

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

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

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

            • cyclizine

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

            • cyclobenzaprine

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

            • darifenacin

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

            • desipramine

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

            • dicyclomine

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

            • diphenhydramine

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

            • donepezil

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

            • dosulepin

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

            • doxepin

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

            • droperidol

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

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

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

            • echothiophate iodide

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

            • fesoterodine

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

            • flavoxate

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

            • fluphenazine

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

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

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

            • galantamine

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

            • glycopyrrolate

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

            • glycopyrrolate inhaled

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

            • haloperidol

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

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

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

            • henbane

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

            • homatropine

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

            • huperzine A

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

            • iloperidone

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

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

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

            • imipramine

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

            • ipratropium

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

            • levodopa

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

            • levodopa inhaled

              levodopa inhaled increases effects of methylene blue by dopaminergic effects. Use Caution/Monitor. Coadministration of selective MAO-B inhibitors with levodopa may be associated with orthostatic hypotension.

            • lofepramine

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

            • loxapine

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

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

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

            • loxapine inhaled

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

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

            • maprotiline

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

            • meclizine

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

            • methoxsalen

              methoxsalen, methylene blue. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

            • methscopolamine

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

            • metoclopramide intranasal

              hyoscyamine will decrease the level or effect of metoclopramide intranasal by Other (see comment). Use Caution/Monitor. Coadministration of metoclopramide intranasal with drugs that impair GI motility may decrease systemic absorption of metoclopramide. Monitor for reduced therapeutic effect.

            • neostigmine

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

            • nortriptyline

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

            • olanzapine

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

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

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

            • oliceridine

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

              methylene blue, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

            • onabotulinumtoxinA

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

            • tapentadol

              methylene blue and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            Minor (3)

            • dimenhydrinate

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

            • donepezil

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

            • galantamine

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

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            Adverse Effects

            >10%

            Hyoscyamine

            • Dry skin

            Methylene blue

            • Urine and stool discoloration
            • Limb pain
            • Skin discoloration
            • Feeling hot

            1-10%

            Methenamine

            • Pruritus
            • Rash
            • Dyspepsia
            • Nausea
            • Vomiting

            Hyoscyamine

            • Blurred vision
            • Constipation
            • Dysphagia
            • Dysguesia

            Methylene blue

            • Headache
            • Paresthesia
            • Musculoskeletal pain

            <1%

            Methenamine

            • Increased serum ALT (reversible)
            • Increased AST (reversible)

            Hyoscyamine

            • Headache
            • Tachycardia

            Methylene blue

            • Serotonin syndrome

            Frequency Not Defined

            Cardiovascular: Flushing

            Central nervous system: Dizziness, drowsiness

            Genitourinary: Difficult micturition, acute urinary retention

            Gastrointestinal: Dry mouth

            Respiratory: Shortness of breath or trouble breathing

            Anaphylactic reactions (itching, rash, severe dizziness, swelling, or trouble breathing)

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            Warnings

            Contraindications

            Hypersensitivity to drugs or excipients

            Cautions

            Use with caution in patients with a history of intolerance to salicylates or belladona alkaloids

            Do not exceed dosage; discontinue use immediately if tachycardia, blurred vision, or tachycardia occurs

            Delay in gastric emptying may complicate management of gastric ulcers

            Hypersensitivity to any of the ingredients is possible; carefully consider risk and benefits in the presence of cardiac disease (especially cardiac arrhythmias, congestive heart failure, coronary heart disease, and mitral stenosis)

            Use caution in patients with gastrointestinal tract obstructive disease, glaucoma, or myasthenia gravis; acute urinary retention may be precipitated in obstructive uropathy (eg, bladder neck obstruction due to prostatic hypertrophy)

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            Pregnancy & Lactation

            Pregnancy

            Reproduction studies not conducted with this drug combination; methenamine and hyoscyamine are known to cross the placenta; not known whether drug combination causes fetal harm when administered to a pregnant woman or if it can affect reproduction capacity; administer therapy to a pregnant woman only if clearly needed

            Lactation

            Problems in humans have not been documented; methenamine and traces of hyoscyamine are excreted in breast milk; administer therapy to a nursing mother with caution and only if clearly needed

            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

            Hyosciamine sulfate is a parasympatholytic that relaxes smooth muscles, which, in turn, produces an antispasmodic effect; it is well absorbed from the gastrointestinal tract and is rapidly distributed throughout body tissues; most is excreted in the urine within 12 hours, 13-50% being unchanged; undergoes hepatic metabolism; protein binding is moderate

            Methanamine degrades in an acidic urine environment, releasing formaldehyde, which provides bactericidal or bacteriostatic action; well absorbed from the gastrointestinal tract; 70-90% reaches urine unchanged, at which point it is hydrolyzed if urine is acidic; within 24 hours, it is almost completely (90%) excreted; of this at a pH of 5, approximately 20% is formaldehyde; some formaldehyde is bound to substances in the urine and surrounding tissues; it is freely distributed to body tissue and fluids but is not clinically significant as it does not hydrolyze at pH greater than 6.8

            Methylene blue possesses weak antiseptic properties; well absorbed by the gastrointestinal tract and rapidly reduced to leukomethylene blue, which is stabilized in some combination form in the urine; 75% is excreted unchanged

            Phenyl salicylate releases salicylate, a mild analgesic for pain

            Sodium phosphate monobasic is an acidifier; helps to maintain an acid pH in the urine necessary for the degradation of methenamine

            Note: The pharmacokinetic parameters described below are for each agent administered as monotherapy; the values may differ when administered in combination but have not been provided by the manufacturer

            Absorption

            Hyosciamine

            • Well absorbed (100%)
            • Onset: 20-30 min
            • Duration: ~4hr
            • Peak plasma time: 2.5 hr

            Methenamine

            • Readily absorbed from the gastrointestinal track
            • Rime to peak: 1-2 hr
            • Peak plasma time: 3-8 hr
            • Onset: 30 min

            Methylene blue

            • Peak plasma concentration: 2.817 ng/mL
            • AUC: 13.977 ng.hr/mL

            Distribution

            Hyoscyamine

            • Protein bound: 50%
            • Vd: 1.2-1.9 L/kg (adults); 1.1-3.7 L/kg (children 4-16 years)

            Methenamine

            • Vd: 0.56 L/kg

            Methylene blue

            • Vd: 255 L
            • Protein bound: 94%

            Metabolism

            Hyoscyamine

            • Hepatic

            Methenamine

            • ~20% hydrolyzed to formaldehyde and ammonia

            Methylene blue

            • Metabolized by CYPs 1A2, 2C19, and 2D6 in vitro; however, the predominant in vitro pathway appears to be UGT-mediated conjugation by multiple UGT enzymes, including UGT1A4 and UGT1A9

            Elimination

            Hyoscyamine

            • Half-life: 3.5 hr
            • Excretion: Urine

            Methenamine

            • Half-life: ~4.3hr
            • Excretion: Urine (70-90%) within 24 hr

            Methylene blue

            • Half-life: 24 hr
            • Excretion: 40% unchanged in urine
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            Patient Handout

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

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            NC NOT COVERED – Drugs that are not covered by the plan.
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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.