Interactions : אינטראקציות

7   DRUG INTERACTIONS
7.1 Reduced Antiviral Activity When Coadministered with Ganciclovir or Valganciclovir LIVTENCITY is not recommended to be coadministered with valganciclovir/ganciclovir (vGCV/GCV).
LIVTENCITY may antagonize the antiviral activity of ganciclovir and valganciclovir by inhibiting human CMV pUL97 kinase, which is required for activation/phosphorylation of ganciclovir and valganciclovir [see Warnings and Precautions (5.1) and Microbiology (12.4)].
7.2 Potential for Other Drugs to Affect LIVTENCITY
Maribavir is a substrate of CYP3A4. Coadministration of LIVTENCITY with strong inducers of CYP3A4 is not recommended, except for selected anticonvulsants [see Dosage and Administration (3.2) and Drug Interactions (7.3)].
7.3 Potential for LIVTENCITY to Affect Other Drugs
Maribavir is a weak inhibitor of CYP3A4, and an inhibitor of P-gp and breast cancer resistance protein (BCRP).
Coadministration of LIVTENCITY with drugs that are sensitive substrates of CYP3A, P-gp and BCRP may result in a clinically relevant increase in plasma concentrations of these substrates (see Table 4). Table 4 provides a list of established or potentially clinically significant drug interactions, based on either clinical drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or decrease in efficacy [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)].



Table 4: Established and Other Potentially Significant Drug Interactionsa 
Effect on
Concomitant Drug Class: Drug Name                          Clinical Comments Concentration
Antiarrhythmics
Use caution when LIVTENCITY and digoxin are coadministered.
Digoxinb                                ↑ Digoxin        Monitor serum digoxin concentrations. The dose of digoxin may need to be reduced when coadministered with LIVTENCITY.c
Anticonvulsants
A dose adjustment of LIVTENCITY to 800 mg twice daily is
Carbamazepine                           ↓ Maribavir recommended when coadministered with carbamazepine.
A dose adjustment of LIVTENCITY to 1,200 mg twice daily is
Phenobarbital                           ↓ Maribavir recommended when coadministration with phenobarbital.
A dose adjustment of LIVTENCITY to 1,200 mg twice daily is
Phenytoin                               ↓ Maribavir recommended when coadministration with phenytoin.
Antimycobacterials
Coadministration of LIVTENCITY and rifabutin is not recommended
Rifabutin                               ↓ Maribavir due to potential for a decrease in efficacy of LIVTENCITY.
Coadministration of LIVTENCITY and rifampin is not recommended
Rifampinb                               ↓ Maribavir due to potential for a decrease in efficacy of LIVTENCITY.
Herbal Products
Coadministration of LIVTENCITY and St. John’s wort is not
St. John’s wort                         ↓ Maribavir      recommended due to potential for a decrease in efficacy of LIVTENCITY.
HMG-CoA Reductase Inhibitors
The patient should be closely monitored for rosuvastatin-related
Rosuvastatinc                           ↑ Rosuvastatin events, especially the occurrence of myopathy and rhabdomyolysis.c
Immunosuppressants
Frequently monitor cyclosporine levels throughout treatment with
Cyclosporine                            ↑ Cyclosporine   LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY and adjust dose, as needed.c
Frequently monitor everolimus levels throughout treatment with
Everolimus                              ↑ Everolimus     LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY and adjust dose, as needed.c
Frequently monitor sirolimus levels throughout treatment with
Sirolimus                               ↑ Sirolimus      LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY and adjust dose, as needed.c
Frequently monitor tacrolimus levels throughout treatment with
Tacrolimusb                             ↑ Tacrolimus     LIVTENCITY, especially following initiation and after discontinuation of LIVTENCITY and adjust dose, as needed.c
↓=decrease, ↑=increase.
a
This table is not all inclusive.
b
The interaction between LIVTENCITY and the concomitant drug was evaluated in a clinical study [see Clinical Pharmacology (12.3)].
c
Refer to the respective prescribing information.



7.4 Drugs without Clinically Significant Interactions with LIVTENCITY No clinically significant interactions were observed in clinical drug-drug interaction studies of LIVTENCITY and ketoconazole, antacid, caffeine, warfarin, voriconazole, dextromethorphan, or midazolam [see Clinical Pharmacology (12.3)].