Basic Information
ID DDInter633 and DDInter661
Interaction Coadministration with moderate inducers of CYP450 2C9 or 3A4 may decrease the plasma concentrations and therapeutic effects of erdafitinib. The mechanism is induction of CYP450 2C9- or 3A4-mediated metabolism of erdafitinib, which has been shown to be metabolized by these isoenzymes.
Management According to the manufacturer, if a moderate CYP450 2C9 or 3A4 inducer is coadministered at the start of erdafitinib therapy, the recommended dose of erdafitinib should be administered. If a moderate CYP450 2C9 or 3A4 inducer is coadministered after the initial dose increase period, the dose of erdafitinib may be increased up to 9 mg once daily based on serum phosphate levels and tolerability. When a moderate CYP450 2C9 or 3A4 inducer is discontinued, the current dose of erdafitinib may be continued in the absence of erdafitinib toxicity.
References [1] "Product Information. Balversa (erdafitinib)." Janssen Products, LP, Horsham, PA. [2] Cronk GA, Wheatley WB, Fellers GF, Albright H "The relationship of food intake to the absorption of potassium alpha-phenoxyethyl penicillin and potassium phenoxymethyl penicillin from the gastrointestinal tract." Am J Med Sci 240 (1960): 219-25 [3] Neuvonen PJ, Elonen E, Pentikainen PJ "Comparative effect of food on absorption of ampicillin and pivampicillin." J Int Med Res 5 (1977): 71-6 [4] Klein JO, Sabath LD, Finland M "Laboratory studies on oxacillin. I: in vitro activity against staphylococci and some other bacterial pathogens. II: absorption and urinary excretion in normal young." Am J Med Sci 245 (1963): 399-411 [5] Welling PG, Huang H, Koch PA, Madsen PO "Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects." J Pharm Sci 66 (1977): 549-52 [6] McCarthy CG, Finland M "Absorption and excretion of four penicillins." N Engl J Med 263 (1960): 315-26 [7] Neu HC "Antimicrobial activity and human pharmacology of amoxicillin." J Infect Dis 129 (1974): s123-31
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Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.