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).
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.
Concomitant administration of strong or moderate CYP3A inducers, (such as rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin, efavirenz and St John's wort), is expected to significantly decrease maribavir plasma concentrations, which may result in decrease in efficacy. Therefore, alternative medicinal products with no CYP3A induction potential should be considered. Co-administration of maribavir with strong cytochrome P450 3A (CYP3A) inducers rifampicin, rifabutin or St. John's wort is not recommended.
If co-administration of maribavir with other strong or moderate CYP3A inducers (e.g., carbamazepine, efavirenz, phenobarbital and phenytoin) cannot be avoided, the maribavir dose should be increased to 1,200 mg twice daily (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Effect of maribavir on other medicinal products: Co-administration of maribavir with valganciclovir and ganciclovir is contraindicated (see Contraindications). LIVTENCITY may antagonise 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 relevant interactions are not expected when maribavir is co-administered with substrates of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2E1, 2D6, and 3A4; UGT1A1, 1A4, 1A6, 1A9, 2B7; bile salt export pump (BSEP); multidrug and toxin extrusion protein (MATE)/2K; organic anion transporters (OAT)1; organic cation transporters (OCT)1 and OCT2; organic anion transporting polypeptide (OATP)1B1 and OATP1B3 based on in vitro and clinical interaction results (see Table 6 and Pharmacology: Pharmacokinetics under Actions).
Maribavir acted as an inducer of CYP1A2 enzyme in vitro. There are no clinical data available to exclude an interaction risk via CYP1A2 induction in vivo. Therefore, the concomitant administration of maribavir and medicinal products that are sensitive substrates of CYP1A2 with a narrow therapeutic window (e.g., tizanidine and theophylline) should be avoided due to the risk for lack of efficacy of CYP1A2 substrates.
Co-administration of maribavir increased plasma concentrations of tacrolimus (see Table 6). When the immunosuppressants tacrolimus, cyclosporine, everolimus or sirolimus are co-administered with maribavir, immunosuppressant levels should be frequently monitored throughout treatment with maribavir, especially following initiation and after discontinuation of maribavir and dose adjusted, when needed (see Precautions and Table 6).
Maribavir inhibited P-gp transporter in vitro at clinically relevant concentrations. In a clinical study, co-administration of maribavir increased plasma concentrations of digoxin (see Table 6). Therefore, caution should be exercised when maribavir and sensitive P-gp substrates (e.g., digoxin, dabigatran) are co-administered. Serum digoxin concentrations should be monitored, and dose of digoxin may need to be reduced, as needed (see Table 6).
Maribavir inhibited BCRP transporter in vitro at clinically relevant concentrations. Therefore, co-administration of maribavir with sensitive BCRP substrates such as rosuvastatin, is expected to increase their exposure and lead to undesirable effects.
In vitro, maribavir inhibits OAT3, therefore, plasma concentrations of medicinal products transported by OAT3 may be increased (e.g.: ciprofloxacin, imipenem, and cilastatin).
In vitro, maribavir inhibits MATE1. There are no clinical data available whether the co-administration of maribavir with sensitive MATE1 substrates (e.g., metformin) could potentially lead to clinically relevant interactions.
General information: If dose adjustments of concomitant medicinal products are made due to treatment with maribavir, doses should be readjusted after treatment with maribavir is completed. Table 6 provides a listing of established or potentially clinically significant medicinal product interactions. The medicinal product interactions described are based on studies conducted with maribavir or are predicted medicinal product interactions that may occur with maribavir (see Precautions and Pharmacology: Pharmacokinetics under Actions). (See Table 6.)

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Paediatric population: Interaction studies have only been performed in adults.