Drug Interactions between Actemra and crizotinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: The use of interleukin blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections.

MANAGEMENT: Concomitant use of interleukin blockers with other immuno- or myelosuppressive agents should be avoided if possible.

MONITOR: Plasma concentrations of drugs that are CYP450 substrates may decrease following the initiation of interleukin inhibitors in patients with chronic inflammatory diseases. Because the formation of hepatic CYP450 enzymes is down-regulated during infection and chronic inflammation by increased levels of certain cytokines (e.g., interleukins-1, -6, and -10; tumor necrosis factor alpha; interferons), treatment with interleukin inhibitors may restore or normalize CYP450 enzyme levels resulting in increased metabolism of these drugs. In vitro studies showed that tocilizumab, an inhibitor of interleukin-6, has the potential to impact expression of various hepatic microsomal enzymes including CYP450 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4. Its effects on CYP450 2C8 or transporters is unknown. In vivo studies with omeprazole (a substrate of CYP450 2C19 and 3A4) and simvastatin (a substrate of CYP450 3A4) showed decreases of up to 28% and 57% in systemic exposure, respectively, one week following a single dose of tocilizumab. A role for other interleukins such as IL-12, IL-17A, or IL-23 in the regulation of CYP450 enzymes has not been established, and it is not known whether antagonists of these interleukins (e.g., ixekizumab, secukinumab, ustekinumab) would similarly affect CYP450 metabolism.

MANAGEMENT: Caution is advised when interleukin inhibitors are prescribed to patients receiving concomitant drugs that are CYP450 substrates, particularly those with narrow therapeutic ranges such as immunosuppressants or antineoplastic agents. Clinical and/or laboratory monitoring should be considered following the initiation or withdrawal of interleukin inhibitor therapy, and the dosage(s) of these drugs adjusted accordingly. Clinicians should note that the effects of interleukin inhibitors on CYP450 activities may persist for several weeks after stopping therapy.