Drug Interactions between primidone and ropeginterferon alfa-2b

MONITOR: Coadministration with ropeginterferon alfa-2b may increase the plasma concentrations of drugs that are metabolized by CYP450 pathways. The formation of hepatic CYP450 enzymes is down-regulated by increased levels of certain proinflammatory cytokines including interferons, thus treatment with ropeginterferon alfa-2b can effectively suppress CYP450 enzymes resulting in increased exposures of some CYP450 substrates. Clinical data demonstrating the interaction are currently lacking. Ropeginterferon alfa-2b did not inhibit CYP450 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes. However, since interferons may influence CYP450 enzymes via mechanisms that require an extended duration to exert effect (e.g., by modulating transcription factors and altering protein expression and/or structure), enzyme inhibition cannot be evaluated by in vitro assays.

MANAGEMENT: Caution is advised when ropeginterferon alfa-2b is coadministered with drugs that are CYP450 substrates, particularly those with narrow therapeutic ranges (e.g., antiarrhythmics, anticonvulsants, immunosuppressants, theophylline) or sensitive substrates where increases in plasma levels may be significant or undesirable (e.g., statins, benzodiazepines, opioids). Clinical and/or laboratory monitoring should be considered following the initiation or withdrawal of ropeginterferon alfa-2b, and the dosage(s) of the CYP450 substrate(s) adjusted accordingly. Clinicians should note that the effects of interferons on CYP450 activities may persist for several weeks after stopping therapy.