Drug Interactions between allopurinol and hyoscyamine / methenamine / methylene blue / phenyl salicylate / sodium biphosphate

MONITOR CLOSELY: 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.

Coadministration with agents that affect renal function or perfusion such as diuretics, ACE inhibitors, angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy associated with the use of bowel-cleansing phosphate solutions. The risk and/or severity of fluid and electrolyte disturbances may also be increased, which can lead to serious adverse events including cardiac arrhythmias, seizures, and renal impairment. Acute phosphate nephropathy is a rare adverse event that presents as acute renal failure with minimal proteinuria and a bland urine sediment. Renal biopsy findings are consistent with nephrocalcinosis and include acute and/or chronic renal tubular injury, calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histological injury. The risk of acute phosphate nephropathy stems from the large phosphate load, fluid shifts, and decreased intravascular volume, which can be exacerbated in the presence of medications that affect renal perfusion or function. In reported cases, acute renal failure was typically diagnosed within two to five months of colonoscopy. These cases often resulted in permanent impairment of renal function, some requiring long-term dialysis.

MANAGEMENT: Caution is advised when bowel-cleansing phosphate preparations are prescribed in patients treated with agents that affect renal function or perfusion, particularly if they are frail or elderly. Bowel-cleansing phosphate preparations should not be used in patients who have impaired renal function or perfusion, dehydration, or uncorrected electrolyte abnormalities. In patients at risk for acute phosphate nephropathy, baseline and postprocedure labs including serum electrolytes, calcium, phosphate, BUN, and creatinine should be performed. Patients should be advised not to exceed the recommended dosage of their bowel-cleansing preparation and to drink sufficient quantities of clear fluids during before, during, and after bowel cleansing. Limited data suggest that administration of an electrolyte rehydration solution may attenuate the electrolyte abnormalities and hypovolemia. Hospitalization and intravenous fluid hydration may be appropriate for frail or elderly patients who may be unable to drink an adequate volume of fluid.

MONITOR: Coadministration with alcohol or other central nervous system (CNS) depressants may enhance the sedative effects of allopurinol and increase the likelihood and/or severity of central nervous system (CNS) side effects, such as drowsiness, somnolence, vertigo, and ataxia.

MANAGEMENT: Caution for increased CNS adverse effects is advised if allopurinol is coadministered with alcohol, other CNS depressants, or agents that cause dizziness or vertigo. Patients should not drive, operate machinery, or engage in hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them.

The renal excretion allopurinol's active metabolite, oxypurinol, may be increased when coadministered with probenecid and/or large doses of salicylates (e.g., aspirin). At the same time, both probenecid and large doses of salicylates may have a hypouricemic effect; allopurinol may also inhibit probenecid metabolism. The clinical significance of this interaction is unknown. Patients should be monitored for altered effects of both allopurinol and probenecid.