Drug Interactions between Eskalith-CR and hyoscyamine / methenamine / methylene blue / sodium biphosphate

MONITOR: The following interactions apply only to products containing sodium biphosphate that are used for bowel cleansing. They do 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, including psychotherapeutic agents (antidepressants; neuroleptics; lithium), fluoroquinolones, some antimalarial agents (chloroquine; hydroxychloroquine; mefloquine), and some narcotic analgesics. 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.

The use of bowel cleansing preparations may increase the risk of ventricular arrhythmia, particularly torsade de pointes, in patients treated with drugs that can prolong the QT interval, including psychotherapeutic agents (antidepressants; neuroleptics; lithium), fluoroquinolones, some antimalarial agents (chloroquine; mefloquine; halofantrine; lumefantrine), and some narcotic analgesics (methadone; propoxyphene). Severe and potentially fatal cases of electrolyte disorders and arrhythmias have been reported in elderly patients using bowel cleansing products. Electrolyte disturbances such as hypokalemia and hypomagnesemia are known risk factors for torsade de pointes associated with QT interval prolongation.

MANAGEMENT: Caution is advised when bowel cleansing preparations are prescribed in patients treated with agents that can lower the seizure threshold and/or prolong the QT interval. 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, 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. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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MONITOR: Concomitant administration of lithium with drugs that can impair the metabolism of serotonin (e.g., monoamine oxidase inhibitors, or MAOIs) may precipitate serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. 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.

MANAGEMENT: Close monitoring is advised when lithium is used with MAOIs or drugs that have MAOI activity. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

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