laprevir 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
5 WARNINGS AND PRECAUTIONS
5.1Pregnancy: 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 ribavirin.
Female Patients
Hormonal contraceptives may be continued but may not be reliable during INCIVEK dosing and for up to two weeks following cessation of INCIVEK [see Drug Interactions (7)]. During this time, female patients of childbearing potential should use two effective non-hormonal methods of contraception. Examples may include barrier methods or intrauterine devices (IUDs) [see also Use in Specific Populations: Pregnancy (8.1) and Patient Counseling Information (17.1)]. Two weeks after completion of INCIVEK treatment, hormonal contraceptives are again appropriate as one of the two required effective methods of birth control; however, specific prescribing information recommendations should be followed for the contraceptives.
5.2Serious Skin Reactions
Serious skin reactions, including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome (SJS) were reported in less than 1% of subjects who received INCIVEK combination treatment compared to none who received peginterferon alfa and ribavirin alone. These serious skin reactions required hospitalization, and all patients recovered. The presenting signs of DRESS may include rash, fever, facial edema, and evidence of internal organ involvement (e.g., hepatitis, nephritis). Eosinophilia may or may not be present. The pre
