WARNING: SERIOUS SKIN REACTIONS

Fatal and non-fatal serious skin reactions, including Stevens Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with INCIVEK combination treatment. Fatal cases have been reported in patients with progressive rash and systemic symptoms who continued to receive INCIVEK combination treatment after a serious skin reaction was identified. For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, INCIVEK, peginterferon alfa, and ribavirin must be discontinued immediately. Discontinuing other medications known to be associated with serious skin reactions should be considered. Patients should be promptly referred for urgent medical care.


Welcome Healthcare Professionals

This website provides an overview of efficacy, safety, and dosing information for U.S. healthcare professionals prescribing INCIVEK combination treatmentINCIVEK combination treatment = INCIVEK + pegIFN-RBV for 12 weeks, and an additional 12 or 36 weeks of pegIFN-RBV alone., including:

    • Treatment-naïveTreatment-naïve = received no prior therapy for HCV, including interferon or pegylated interferon monotherapy. patients
    • Prior relapsersRelapser = undetectable HCV RNA at the end of a prior pegIFN-RBV regimen, but detectable HCV RNA within 24 weeks of follow-up.
    • Prior partial respondersPartial responder = ≥2 log10 reduction in HCV RNA at Week 12, but not achieving undetectable HCV RNA at the end of a prior pegIFN-RBV therapy.
    • Prior null respondersNull responder = <2 log10 reduction in HCV RNA at Week 12 during a prior pegIFN-RBV therapy.

HCV = hepatitis C virus. INCIVEK combination treatment = INCIVEK + pegIFN-RBV for 12 weeks, and an additional 12 or 36 weeks of pegIFN-RBV alone. pegIFN = peginterferon alfa. RBV = ribavirin. SVR (virologic cure) = sustained virologic response; defined as HCV RNA <25 IU per mL at last observation within the SVR visit window (i.e., weeks 32-78 for patients assigned to 24 weeks of treatment and weeks 56-78 for patients assigned to 48 weeks of treatment). eRVR = undetectable HCV RNA (Target Not Detected) at Weeks 4 and 12. Treatment-naïve = received no prior therapy for HCV, including interferon or pegylated interferon monotherapy. Partial responder = ≥2 log10 reduction in HCV RNA at Week 12, but not achieving undetectable HCV RNA at the end of a prior pegIFN-RBV therapy. Relapser = undetectable HCV RNA at the end of a prior pegIFN-RBV regimen, but detectable HCV RNA within 24 weeks of follow-up. Null responder = <2 log10 reduction in HCV RNA at Week 12 during a prior pegIFN-RBV therapy.

Reference

  1. Patient Regimens Monthly Report, IMS Health, NPA through November 2012, extracted December 2012.

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.

The following points should be considered when initiating treatment with INCIVEK:
  • 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

WARNING: SERIOUS SKIN REACTIONS

Fatal and non-fatal serious skin reactions, including Stevens Johnson Syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with INCIVEK combination treatment. Fatal cases have been reported in patients with progressive rash and systemic symptoms who continued to receive INCIVEK combination treatment after a serious skin reaction was identified. For serious skin reactions, including rash with systemic symptoms or a progressive severe rash, INCIVEK, peginterferon alfa, and ribavirin must be discontinued immediately. Discontinuing other medications known to be associated with serious skin reactions should be considered. Patients should be promptly referred for urgent medical care.

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 a strong inhibitor of CYP3A. 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, lovastatin, simvastatin, pimozide, sildenafil (Revatio®) or tadalafil (Adcirca®) for pulmonary arterial hypertension, oral midazolam, and/or triazolam

Warnings and precautions

  • See Boxed Warning regarding serious skin reactions at beginning of Important Safety Information
  • In clinical trials, serious skin reactions, including DRESS and SJS were reported in <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 subjects recovered. Presenting signs of these reactions may include rash, fever, facial edema, target lesions, mucosal ulcerations, and evidence of internal organ involvement

    TEN and Erythema Multiforme (EM) have been observed in post-marketing experience

    Rash events (all grades) 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, 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 systemic corticosteroids is not recommended
  • Anemia has been reported with peginterferon alfa and ribavirin treatment. Adding INCIVEK is associated with an additional decrease in hemoglobin compared to peginterferon alfa and ribavirin alone. Hemoglobin values of ≤10 g per dL were observed in 36% of patients, and <8.5 g per dL in 14% of patients who received INCIVEK combination treatment compared to 17% and 5%, respectively, with peginterferon alfa and ribavirin alone

    Hemoglobin should be monitored prior to and at least at weeks 2, 4, 8, and 12 during INCIVEK combination treatment and as clinically appropriate. Earlier and more frequent monitoring for some patients should be considered. 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
  • Pregnancy: Ribavirin may cause 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 2 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
  • 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 per mL and limit of detection approximately 10–15 IU per mL). To assess response-guided therapy eligibility, an "undetectable" HCV RNA (Target Not Detected) result is required; a confirmed "detectable but below limit of quantification" HCV RNA result should not be considered equivalent to an "undetectable" HCV RNA result (reported as "Target Not Detected" or "HCV RNA Not Detected")
  • Hematology and chemistry evaluations are recommended prior to and at weeks 2, 4, 8, and 12, and 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
  • Warnings and Precautions to peginterferon alfa and ribavirin also apply to INCIVEK combination treatment

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 full Prescribing Information, including Boxed Warning.

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