Indication

INCIVEK^® (telaprevir), in combination with peginterferon alfa and ribavirin, is indicated for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including cirrhosis, who are treatment naïve or who have previously been treated with interferon-based treatment, including prior null responders, partial responders, and relapsers.

• INCIVEK must not be administered as monotherapy and must only be prescribed with both peginterferon alfa and ribavirin
• A high proportion of previous null responders (particularly those with cirrhosis) did not achieve a Sustained Virologic Response (SVR) and had telaprevir resistance–associated substitutions emerge on treatment with INCIVEK combination treatment
• INCIVEK efficacy has not been established for patients who have previously failed therapy with a treatment regimen that includes INCIVEK or other HCV NS3/4A protease inhibitors

Important safety information

Contraindications

Contraindications to peginterferon alfa and ribavirin also apply to INCIVEK combination treatment.

INCIVEK combination treatment is contraindicated in women who are or may become pregnant. Ribavirin may cause fetal harm when administered to a pregnant woman. If ribavirin is used during pregnancy or in the event of a pregnancy while on treatment, inform the patient of the potential hazard to a fetus. INCIVEK combination treatment is also contraindicated in men whose female partners are pregnant.

INCIVEK is contraindicated when combined with drugs that 1) are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events and 2) strongly induce CYP3A and thus may lead to lower exposure and loss of efficacy of INCIVEK. Contraindicated medications are alfuzosin, rifampin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, St. John's wort, atorvastatin, lovastatin, simvastatin, pimozide, sildenafil (Revatio^®) or tadalafil (Adcirca^®) for pulmonary arterial hypertension, oral midazolam, and/or triazolam.

Warnings and precautions

• Warnings and Precautions to peginterferon alfa and ribavirin also apply to INCIVEK combination treatment
• Pregnancy: 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 just before initiation of 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 combination 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 all treatment. Female patients may continue hormonal contraceptives but they may not be reliable during INCIVEK dosing and for up to two weeks after stopping INCIVEK. During this time, female patients of childbearing potential should use 2 effective non-hormonal methods of contraception
  
  A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes in patients exposed to ribavirin
• 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 receiving INCIVEK combination treatment compared to none with peginterferon alfa and ribavirin alone. These serious reactions required hospitalization and all patients recovered. Presenting signs of these reactions may include rash, fever, facial edema, target lesions, mucosal ulcerations, and evidence of internal organ involvement. If serious skin reactions occur, all components of INCIVEK combination treatment must be discontinued immediately and the patient referred for urgent medical care
• Rash developed in 56% of patients who received INCIVEK combination treatment compared to 34% with peginterferon alfa and ribavirin alone. Severe rash was reported in 4% of patients treated with INCIVEK combination treatment compared to <1% with peginterferon alfa and ribavirin alone. Severe rash may have a prominent eczematous component. Patients with mild to moderate rash should be followed for progression of rash or development of systemic symptoms. If rash becomes severe or systemic symptoms develop, discontinue INCIVEK. Peginterferon alfa and ribavirin may be continued. If improvement is not observed within 7 days of discontinuing INCIVEK, consider sequential or simultaneous interruption or discontinuation of ribavirin and/or peginterferon alfa; earlier interruption or discontinuation may be medically indicated. Monitor patients until the rash has resolved. INCIVEK must not be reduced or restarted if discontinued due to rash. Treatment of rash with oral antihistamines and/or topical corticosteroids may provide symptomatic relief but effectiveness of these measures has not been established. Treatment of rash with systemic corticosteroids is not recommended
• Anemia has been reported with peginterferon alfa and ribavirin treatment. Adding INCIVEK is associated with additional decrease in hemoglobin compared to peginterferon alfa and ribavirin alone. Hemoglobin values of ≤10 g/dL were observed in 36% of subjects, and <8.5 g/dL in 14% of subjects who received INCIVEK combination treatment compared to 17% and 5%, respectively, with peginterferon alfa and ribavirin alone. Hemoglobin should be monitored at baseline and at weeks 2, 4, 8, and 12, or as clinically appropriate. Use the labeled ribavirin dose modification guidelines to manage anemia; if ribavirin dose reductions are inadequate, consider discontinuing INCIVEK. If ribavirin is permanently discontinued, INCIVEK must also be permanently discontinued. The dose of INCIVEK must not be reduced and must not be restarted if discontinued
• Certain drugs are contraindicated for use with INCIVEK due to potentially life-threatening adverse events or potential loss of therapeutic effect to INCIVEK. See INCIVEK Prescribing Information Table 3 for contraindicated drugs, and Table 5 for established and other potentially significant drug interactions
• Monitor HCV-RNA levels at Weeks 4 and 12 and as clinically indicated. Use a sensitive real-time RT-PCR assay to monitor HCV RNA during treatment (lower limit of quantification should be ≤25 IU/mL and limit of detection approximately 10–15 IU/mL). To assess response-guided therapy eligibility, an "undetectable" HCV-RNA result is required; a confirmed "detectable but below limit of quantification" should not be considered equivalent to an "undetectable" result
• Hematology and chemistry evaluations are recommended at weeks 2, 4, 8, and 12 or as clinically appropriate
• INCIVEK must not be administered as monotherapy and must only be prescribed with both peginterferon alfa and ribavirin. There are no clinical data on retreating patients who have failed an HCV NS3/4A protease inhibitor-based treatment and no data on repeated courses of INCIVEK
• INCIVEK is not recommended for patients with moderate or severe hepatic impairment (Child-Pugh B or C, score ≥7) or patients with decompensated liver disease
• The safety and efficacy of INCIVEK combination treatment has not been established in co-infected HCV/HIV and HCV/HBV patients, pediatric patients, or in solid organ transplant patients

Adverse reactions

• Adverse reactions to peginterferon alfa and ribavirin also apply to INCIVEK combination treatment
• The most common adverse reactions seen with an incidence ≥5% with INCIVEK over controls were rash (56% vs 34%), fatigue (56% vs 50%), pruritus (47% vs 28%), nausea (39% vs 28%), anemia (36% vs 17%), diarrhea (26% vs 17%), vomiting (13% vs 8%), hemorrhoids (12% vs 3%), anorectal discomfort (11% vs 3%), dysgeusia (10% vs 3%), and anal pruritus (6% vs 1%)

Please see the accompanying full Prescribing Information.

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