Drug Interaction Report

MONITOR: Coadministration with tolvaptan can potentiate the risk of hyperkalemia in patients treated with other drugs that are known to increase serum potassium. Tolvaptan alone can increase serum potassium by causing an acute reduction of the extracellular fluid volume. In clinical studies, adverse reactions of hyperkalemia were approximately 1% to 2% higher when tolvaptan was used concomitantly with ACE inhibitors, angiotensin II receptor antagonists, or potassium sparing diuretics compared to administration of these medications with placebo.

MANAGEMENT: Serum potassium levels should be checked regularly during concomitant therapy with tolvaptan and other agents that can increase serum potassium such as ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, aldosterone antagonists, and miscellaneous agents like cyclosporine, heparin, tacrolimus, and trimethoprim. Particular caution is warranted in patients with renal impairment, diabetes, old age, severe or worsening heart failure, or dehydration. Patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat.

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: Grapefruit juice may significantly increase the plasma concentrations of tolvaptan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration of tolvaptan with grapefruit juice resulted in a 1.8-fold increase in tolvaptan systemic exposure. The clinical significance is unknown, although increased pharmacologic effects may be expected. Too rapid correction of hyponatremia increases the risk of osmotic demyelination syndrome, which is associated with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death.

MANAGEMENT: Patients treated with tolvaptan should avoid consumption of grapefruits and grapefruit juice.