ng their therapeutic and adverse effects. Boceprevir does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 in vitro. In addition, boceprevir does not induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 or CYP3A4/5 in vitro.
Boceprevir is a potential inhibitor of p-glycoprotein (P-gp) based on in vitro studies. The potential for a drug interaction with sensitive substrates of p-glycoprotein (e.g., digoxin) has not been eva luated in a clinical trial.
7.2 Potential for Other Drugs to Affect VICTRELIS
Boceprevir is primarily metabolized by aldo-ketoreductase (AKR). In drug interaction trials conducted with AKR inhibitors diflunisal and ibuprofen, boceprevir exposure did not increase to a clinically significant extent. VICTRELIS may be coadministered with AKR inhibitors.
Boceprevir is partly metabolized by CYP3A4/5. It is also a substrate for p-glycoprotein. Coadministration of VICTRELIS with drugs that induce or inhibit CYP3A4/5 could decrease or increase exposure to boceprevir.
7.3 Established and Other Potential Significant Drug Interactions
Table 5 provides recommendations based on established or potentially clinically significant drug interactions. VICTRELIS is contraindicated with drugs that are potent inducers of CYP3A4/5 and drugs that are highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or life-threatening events [see Contraindications (4)].
Table 5 Established and Other Potentially Significant Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration of Boceprevir or Concomitant Drug Recommendations
Antiarrhythmics: amiodarone, bepridil, flecainide, propafenone, quinidine
↑ antiarrhythmics
Coadministration with VICTRELIS has the potential to produce serious and/or life-threatening adverse events and has not been studied. Caution is warranted and therapeutic concentration monitoring of these drugs is recommended if they are used concomitantly with VICTRELIS.
digoxin ↑ digoxin Digoxin concentrations may be increased with VICTRELIS. Use the lowest dose initially with careful titration and monitoring of serum digoxin concentrations.
Anticoagulant: warfarin ↑ or ↓ warfarin Concentrations of warfarin may be altered when co-administered with VICTRELIS. Monitor INR closely.
Antidepressants: trazadone, desipramine ↑ trazadone
↑ desipramine Plasma concentrations of trazadone and desipramine may increase when administered with VICTRELIS, resulting in adverse events such as dizziness, hypotension and syncope. Use with caution and consider a lower dose of trazadone or desipramine.
Antifungals: ketoconazole, itraconazole, posaconazole, voriconazole ↑ boceprevir*
↑ itraconazole
↑ ketoconazole
↑ posaconazole
↑ voriconazole Plasma concentrations of ketoconazole, itraconazole, voriconazole or posaconazole may be increased with VICTRELIS. When coadministration is required, doses of ketoconazole and itraconazole should not exceed 200 mg/day.
Anti-gout: colchicine ↑ colchicine Significant increases in colchicine levels are expected; fatal colchicine toxicity has been reported with other strong CYP3A4 inhibitors.
Patients with renal or hepatic impairment should not be given colchicine with VICTRELIS.
Treatment of gout flares (during treatment |
