Drug Interaction Report

MONITOR: The use of fumaric acid esters in combination with medications that can cause nephrotoxicity (e.g., aminoglycosides, diuretics, nonsteroidal anti-inflammatory drugs, cyclosporine, lithium, methotrexate) may increase the potential for adverse renal reactions. In clinical trials in patients with multiple sclerosis treated with dimethyl fumarate, a fumaric acid ester that is converted to the active metabolite monomethyl fumarate, adverse events of proteinuria were reported at slightly higher frequencies than in patients receiving placebo. The clinical significance of these observations is unknown. Cases of Fanconi syndrome have been reported for a medicinal product containing dimethyl fumarate in combination with other fumaric acid esters. Renal toxicity, including tubular changes and/or interstitial fibrosis, has been observed in animal studies with dimethyl fumarate and diroximel fumarate.

MANAGEMENT: The use of fumaric acid esters in patients who receive concomitant treatment with potentially nephrotoxic agents, particularly for longer durations, has not been evaluated and should be approached with caution. Assessment of renal function (e.g., serum creatinine, blood urea nitrogen, urinalysis) is recommended prior to initiating treatment with fumaric acid esters and as clinically indicated during treatment.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of alectinib and its major active metabolite, M4. According to the manufacturer, a high-fat, high-calorie meal increased the combined systemic exposure (AUC) of alectinib and M4 by 3.1-fold following oral administration of a single 600 mg dose of alectinib.

MANAGEMENT: To ensure maximal oral absorption, alectinib should be administered with food.