e highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (narrow therapeutic index). INCIVEK is contraindicated when combined with drugs that strongly induce CYP3A and thus may lead to lower exposure and loss of efficacy of INCIVEK. Contraindicated drugs are listed below in Table 3 [also see Drug Interactions (7), Table 5 and Clinical Pharmacology (12.3), Tables 6 and 7 ].
Table 3: Drugs that are Contraindicated with INCIVEK Drug Class Drugs within Class that are Contraindicated with INCIVEK Clinical Comments
Alpha 1-adrenoreceptor antagonist Alfuzosin Potential for hypotension or cardiac arrhythmia
Antimycobacterials Rifampin Rifampin significantly reduces telaprevir plasma concentrations.
Ergot derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine Potential for acute ergot toxicity characterized by peripheral vasospasm or ischemia
GI Motility Agent Cisapride Potential for cardiac arrhythmias
Herbal products St. John's wort (Hypericum perforatum) Plasma concentrations of telaprevir can be reduced by concomitant use of the herbal preparation St. John's wort.
HMG CoA reductase inhibitors Atorvastatin, lovastatin, simvastatin Potential for myopathy including rhabdomyolysis
Neuroleptic Pimozide Potential for serious and/or life-threatening adverse reactions such as cardiac arrhythmias secondary to increases in plasma concentrations of antiarrhythmics
PDE5 inhibitor Sildenafil (Revatio®) or tadalafil (Adcirca®) [for treatment of pulmonary arterial hypertension]* Potential for PDE5 inhibitor-associated adverse events, including visual abnormalities, hypotension, prolonged erection, and syncope
Sedatives/hypnotics Orally administered midazolam†, triazolam Prolonged or increased sedation or respiratory depression
*See Drug Interactions, Table 5 for co-administration of sildenafil and tadalafil when dosed for erectile dysfunction.
†See Drug Interactions, Table 5 for parenterally administered midazolam.
5 WARNINGS AND PRECAUTIONS
5.1 Pregnancy: Use with Ribavirin and Peginterferon Alfa
Ribavirin may cause birth defects and/or death of the exposed fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy.
Because INCIVEK must be used in combination with peginterferon alfa and ribavirin, the contraindications and warnings applicable to those drugs are applicable to combination therapy. Female patients of childbearing potential and their male partners as well as male patients and their female partners must use 2 effective contraceptive methods during treatment and for 6 months after all treatment has ended. Female patients should have monthly pregnancy tests during treatment and during the 6-month period after stopping treatment. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients as significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin [see Contraindications (4), Use in Specific Populations (8.1), and Patient Counseling Information (17.1) ]. Refer also to the prescribing information for ribaviri |
