Dosing & Uses
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)
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

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 (93)
- 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 topical
methylene blue and cocaine topical 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
- microbiota oral
methenamine decreases effects of microbiota oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Microbiota oral contains bacterial spores. Antibacterial agents may decrease efficacy if coadministered. Complete antibiotic regimens 2-4 days before initiating microbiota oral. .
- 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 (67)
- 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.
- donepezil transdermal
donepezil transdermal, hyoscyamine. Either decreases effects of the other by pharmacodynamic antagonism. 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.
- hydroxyzine
hydroxyzine and hyoscyamine both decrease cholinergic effects/transmission. 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.
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)
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)
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.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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Formulary
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