Drug Interactions between hyoscyamine / methenamine / methylene blue / sodium biphosphate and Paxil

CONTRAINDICATED: Coadministration of methylene blue with serotonergic agents may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Current research suggests that methylene blue has structural properties similar to monoamine oxidase inhibitors (MAOIs). As such, it may enhance serotonergic effects by inhibiting serotonin metabolism. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. Serotonin syndrome has been reported when methylene blue was administered intravenously at dosages ranging from 1 to 8 mg/kg to patients exposed to drugs that interfere with serotonin reuptake. Several cases required admission to the intensive care unit. The risk of administering methylene blue intravenously at dosages less than 1 mg/kg or by non-intravenous routes (e.g., orally or by local injection) is unclear, although the potential for interaction with serotonergic agents should be considered.

MANAGEMENT: Serotonergic agents should not be used in patients receiving methylene blue intravenously. Most serotonergic psychiatric drugs should be stopped 1 to 2 weeks (i.e., 4 to 5 half-lives) prior to treatment with methylene blue if possible, while others such as fluoxetine may require discontinuation up to 5 weeks in advance due to its prolonged half-life. Treatment with serotonergic medications may be resumed 24 hours after the last dose of methylene blue. In patients receiving methylene blue who require urgent treatment of a psychiatric condition, other interventions including hospitalization should be considered. Conversely, when urgent treatment with methylene blue is required (e.g., methemoglobinemia, ifosfamide-induced encephalopathy, cyanide poisoning) in patients receiving serotonergic agents, the benefit of methylene blue treatment should be weighed against the risk of serotonin toxicity. If a decision is made to use methylene blue, the serotonergic drug must be immediately stopped, and the patient closely monitored for emergent symptoms of CNS toxicity for two weeks (five weeks if fluoxetine was taken; three weeks if vortioxetine was taken) or until 24 hours after the last dose of methylene blue, whichever comes first. Patients and/or their caregivers should be advised to seek medical attention if potential symptoms of serotonin syndrome develop.

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MONITOR: The following interaction applies only to products containing sodium biphosphate that are used for bowel cleansing. It does not apply to products containing sodium biphosphate that are used for other, non-laxative related purposes.

The risk of seizures induced by the use of bowel cleansing preparations may be increased in patients on concomitant medications that can lower the seizure threshold such as selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), systemic steroids, carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, and theophylline. Rare cases of generalized tonic-clonic seizures and/or loss of consciousness in association with low serum osmolality and electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, hypomagnesemia) have been reported with the use of bowel cleansing products in patients with no prior history of seizures. The condition resolved with correction of fluid and electrolyte abnormalities.

MANAGEMENT: Caution is advised when bowel cleansing preparations are prescribed in patients treated with agents that can lower the seizure threshold. Bowel cleansing preparations should not be used if these patients have impaired renal function or perfusion, dehydration, or uncorrected electrolyte abnormalities. Baseline and postprocedure labs including serum electrolytes, calcium, phosphate, BUN, and creatinine should be considered, particularly in the elderly. Patients should be advised not to exceed the recommended dosage of their bowel cleansing preparation and to drink sufficient quantities of clear fluids before, during, and after the bowel preparation process. Administration of an electrolyte rehydration solution may help attenuate the electrolyte abnormalities and hypovolemia.

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