Livtencity Drug Interactions

Effect of other medicinal products on maribavir: Maribavir is primarily metabolised by CYP3A, and medicinal products that induce or inhibit CYP3A are expected to affect the clearance of maribavir (see Pharmacology: Pharmacokinetics under Actions). Concomitant administration of strong CYP3A inducers, such as rifampicin, rifabutin, and St John's wort, should be avoided, as significant decreases in maribavir plasma concentrations may occur which may result in decrease in efficacy. Alternative antimicrobial or anti-tuberculosis therapy with a lower CYP3A induction potential should be considered (see Pharmacology: Pharmacokinetics under Actions).
Co-administration with carbamazepine, phenobarbital, and phenytoin (strong or moderate CYP3A inducers) is likely to decrease maribavir concentrations, and therefore, the maribavir dose should be increased according to Table 10 (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Co-administration of maribavir with other strong or moderate CYP3A inducers has not been evaluated, but decreased maribavir concentrations are expected. If co-administration with other strong or moderate CYP3A inducers cannot be avoided, a maribavir dose increase up to 1,200 mg twice daily should be considered (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Co-administration of maribavir and medicinal products that are inhibitors of CYP3A may result in increased plasma concentrations of maribavir (see Pharmacology: Pharmacokinetics under Actions). However, no dose adjustment is needed when maribavir is co administered with CYP3A inhibitors.
Effect of maribavir on other medicinal products: Maribavir is contraindicated with valganciclovir/ganciclovir. Maribavir may antagonize the antiviral effect of ganciclovir and valganciclovir by inhibiting human CMV UL97 serine/threonine kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir (see Contraindications and Pharmacology: Pharmacodynamics under Actions).
At therapeutic concentrations, clinically significant interactions are not expected when maribavir is co-administered with substrates of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2E1, 2D6, and 3A4; UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B7; bile salt export pump (BSEP); multidrug and toxin extrusion protein (MATE)1/2K; organic anion transporters (OAT)1 and OAT3; organic cation transporters (OCT)1 and OCT2; organic anion transporting polypeptide (OATP)1B1 and OATP1B3 based on in vitro and clinical drug interaction results (see Table 10 and Pharmacology: Pharmacokinetics under Actions) except the following medicinal products. In vitro, Breast Cancer Resistance Protein (BCRP) indicated higher potential for drug interactions with drugs transported by this transporter at clinically relevant concentrations. The primary metabolite VP44469 was not a CYP inhibitor at clinically relevant concentrations.
Co-administration of maribavir increased plasma concentrations of immunosuppressants, including tacrolimus (see Table 10). When the immunosuppressants tacrolimus, cyclosporin, everolimus, or sirolimus are co-administered with maribavir, frequently monitor immunosuppressant drug levels throughout treatment with maribavir, especially following initiation and after discontinuation of maribavir and adjust dose, as needed (see Precautions and Table 10).
Co-administration of maribavir with rosuvastatin, a sensitive BCRP substrate, is expected to increase rosuvastatin concentration. Rosuvastatin is associated with the occurrence of myopathy and rhabdomyolysis (see Precautions and Table 10).
Maribavir inhibited P-gp transporter in vitro at clinically relevant concentrations. In a clinical study, co-administration of LIVTENCITY increased plasma concentrations of digoxin (see Table 10). Therefore, caution should be exercised when LIVTENCITY and sensitive P-gp substrates (e.g., digoxin) are co administered. Serum digoxin concentrations should be monitored, and dose of digoxin may need to be reduced, as needed (see Table 10).
General Information: If dose adjustments of concomitant medicinal products are made due to treatment with LIVTENCITY, doses should be readjusted after treatment with LIVTENCITY is completed. Table 10 provides a listing of established or potentially clinically significant medicinal product interactions. The medicinal product interactions described are based on studies conducted with LIVTENCITY or are predicted medicinal product interactions that may occur with LIVTENCITY (see Precautions and Pharmacology: Pharmacokinetics under Actions). (See Tables 10a and 10b.)

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