Drug Interactions between HalfLytely and Bisacodyl and neratinib

ADJUST DOSING INTERVAL: By increasing gastric pH, antacids may reduce the resistance of the enteric coating of bisacodyl tablets, resulting in earlier release of bisacodyl and gastric irritation and dyspepsia.

MANAGEMENT: The administration of antacids and bisacodyl should be separated by at least one hour.

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of neratinib. The solubility of neratinib is pH-dependent and increases as neratinib becomes protonated at acidic pH, thus an increase in pH may interfere with its absorption. According to the product labeling, neratinib is sparingly soluble at pH 1.2 (32.90 mg/mL) and insoluble at approximate pH 5.0 and above (0.08 mg/mL or less). When a single 240 mg dose of neratinib was administered to 15 healthy adult subjects on day 5 of treatment with lansoprazole 30 mg orally once daily for 7 days, mean neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 71% and 65%, respectively, compared to neratinib administered alone. Concomitant use with other pH lowering agents was not studied, but a decrease in neratinib AUC is also considered likely.

MANAGEMENT: Concomitant use of neratinib with drugs that increase gastric pH should generally be avoided. If acid-suppression therapy is required, short-acting antacids should be considered, with neratinib dosing separated by at least three hours after antacid administration.

GENERALLY AVOID: Concomitant use of stimulant laxatives (e.g., bisacodyl, sodium picosulfate) may increase the risk of serious gastrointestinal adverse effects associated with certain osmotic laxatives (e.g., polyethylene glycol (PEG), oral sulfate solution), such as colonic mucosal ulcerations or ischemic colitis. There have been isolated case reports of ischemic colitis occurring with the use of PEG-based bowel cleansing products in combination with higher dosages of bisacodyl (usually greater than 10 mg). Bisacodyl can cause colonic ischemia due to transient reduction in splanchnic blood flow. When administered in conjunction with an osmotic laxative such as PEG, increased intramural pressure secondary to increased peristalsis may lead to ischemic colitis and perforation.

MANAGEMENT: The manufacturers for some osmotic bowel cleansing products recommend avoiding the concurrent use of stimulant laxatives. However, stimulant laxatives, in particular bisacodyl and sodium picosulfate, are sometimes used with PEG in certain bowel cleansing regimens to help reduce dose volume and improve patient tolerability and acceptance. Please consult individual product labeling for specific recommendations and guidance. Patients using osmotic bowel cleansing products and stimulant laxatives who present with sudden abdominal pain, rectal bleeding, or other symptoms of ischemic colitis should be evaluated promptly.