Drug Interaction Report

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.

ADJUST DOSING INTERVAL: Bowel cleansing products can increase the gastrointestinal transit rate. Oral medications administered within one hour of the start of administration of the bowel cleansing solution may be flushed from the gastrointestinal tract and not properly absorbed.

MANAGEMENT: Patients should be advised that absorption of oral medications may be impaired during bowel cleansing treatment. Oral medications (e.g., anticonvulsants, oral contraceptives, antidiabetic agents, antibiotics) should not be administered during and within one hour of starting bowel cleansing treatment whenever possible. However, if concomitant use cannot be avoided, monitoring for reduced therapeutic effects may be advisable.

GENERALLY AVOID: The oral bioavailability of quinolone and tetracycline antibiotics may be reduced by concurrent administration of preparations containing polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc. Therapeutic failure may result. The proposed mechanism is chelation of quinolone and tetracycline antibiotics by di- and trivalent cations, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. Reduced gastrointestinal absorption of the cations should also be considered.

MANAGEMENT: Concomitant administration of oral quinolone and tetracycline antibiotics with preparations containing aluminum, calcium, iron, magnesium, and/or zinc salts should generally be avoided. Otherwise, the times of administration should be staggered by as much as possible to minimize the potential for interaction. Quinolones should typically be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation preparations, depending on the quinolone and formulation. Likewise, tetracyclines and polyvalent cation preparations should typically be administered 2 to 4 hours apart. The prescribing information for the antibiotic should be consulted for more specific dosing recommendations.