Co-administration of INCIVEK with drugs that are substrates for P-gp transport may result in increased plasma concentrations of such drugs, which could increase or prolong their therapeutic effect and adverse reactions (see Table 5). If dose adjustments of concomitant medications are made during INCIVEK treatment, they should be re-adjusted after administration of INCIVEK is completed.
7.2 Potential for Other Drugs to Affect INCIVEK
INCIVEK is a substrate of CYP3A and P-gp; therefore, drugs that induce CYP3A and/or P-gp may decrease INCIVEK plasma concentrations and reduce the therapeutic effect of INCIVEK. Co-administration of INCIVEK with drugs that inhibit CYP3A and/or P-gp may increase INCIVEK plasma concentrations.
7.3 Established and Other Potentially Significant Drug Interactions
Table 5 provides effect of concentration of INCIVEK or concomitant drug with INCIVEK. These recommendations are based on either drug interaction studies (indicated with *) or predicted interactions due to the expected magnitude of interaction and potential for serious adverse events or loss of efficacy.
Table 5: Established and Other Potentially Significant Drug Interactions: Alterations in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction [See Clinical Pharmacology (12.3) (Tables 6 and 7) for Magnitude of Interaction.] Concomitant Drug Class:
Drug Name Effect on concentration of INCIVEK or Concomitant Drug Clinical Comment
The direction of the arrow (↑ = increase, ↓ = decrease, ↔ = no change) indicates the direction of the change in PK.
ANTIARRHYTHMICS
lidocaine (systemic), amiodarone, bepridil, flecainide, propafenone, quinidine ↑ antiarrhythmics
Co-administration with telaprevir has the potential to produce serious and/or life-threatening adverse events and has not been studied. Caution is warranted and clinical monitoring is recommended when co-administered with telaprevir.
digoxin* ↑ digoxin Concentrations of digoxin were increased when co-administered with telaprevir. The lowest dose of digoxin should be initially prescribed. The serum digoxin concentrations should be monitored and used for titration of digoxin dose to obtain the desired clinical effect.
ANTIBACTERIALS
clarithromycin
erythromycin
telithromycin ↑ telaprevir
↑ antibacterials Concentrations of both telaprevir and the antibacterial may be increased during co-administration. Caution is warranted and clinical monitoring is recommended when co-administered with telaprevir. QT interval prolongation and Torsade de Pointes have been reported with clarithromycin and erythromycin. QT interval prolongation has been reported with telithromycin.
ANTICOAGULANT
warfarin ↑ or ↓ warfarin Concentrations of warfarin may be altered when co-administered with telaprevir. The international normalized ratio (INR) should be monitored when warfarin is co-administered with telaprevir.
ANTICONVULSANTS
carbamazepine
phenobarbital
phenytoin ↓ telaprevir
↑ carbamazepine
↑ or ↓ phenytoin
↑ or ↓ phenobarbital
Concentrations of the anticonvulsant may be altered and concentrations of telaprevir may be decreased. Caution should be used when prescribing carbamazepine, phenobarbital, and phenytoin.
Telaprevir may be less effec |
