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Telaprevir FDA Label Change Report
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The label for INCIVEK® (telaprevir) has been updated to include a new Boxed Warning stating that fatal and non-fatal serious skin reactions have been reported that were reported to FDA in patients taking the hepatitis C drug Incivek (telaprevir) in combination with the drugs peginterferon alfa and ribavirin (Incivek combination treatment).
Incivek is a hepatic C virus NS3/4A protease inhibitor indicated in combination with peginterferon alfa and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including patients who have cirrhosis, who are treatment-naïve, or who have been previously received interferon-based treatment.
Fatal cases of serious skin reactions have been reported in patients who continued to receive Incivek combination treatment after developing a worsening, or progressive rash and systemic symptoms (symptoms affecting the entire body).
Rash and serious skin reactions are known adverse events associated with Incivek combination treatment, and were previously included in the warnings and precautions section of the label. Because of the severity of the adverse events reported in the postmarketing setting, and the importance of discontinuing Incivek combination treatment in the event of one of these reactions, the information has been given greater prominence through a boxed warning.
In Phase 3 clinical trials, less than 1 percent of people who received INCIVEK combination treatment experienced a serious skin reaction. These serious skin reactions required hospitalization and all patients recovered. For serious skin reactions, INCIVEK combination treatment must be discontinued immediately, and patients should be promptly referred for urgent medical care.
The Boxed warning states the following:
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.
Below is additional information on serious skin reactions from the Prescribing Information:
In clinical trials, serious skin reactions, including DRESS and 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 subjects 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 presenting signs of SJS may include fever, target lesions, and mucosal erosions or ulcerations (e.g., conjunctivae, lips).
TEN and Erythema Multiforme (EM) have been observed in post-marketing experience.
Patients should be instructed to contact their health care provider immediately if they experience any skin changes. Sometimes these skin rashes and other skin reactions can become serious, require treatment in a hospital and may result in death.
The INCIVEK label was also updated to include additional information on the time to onset and management of anemia.
WARNINGS AND PRECAUTIONS
Anemia
· In clinical trials, the median time to onset of hemoglobin less than or equal to 10 g/dL was faster among subjects treated with INCIVEK combination treatment compared to those who received peginterferon alfa and ribavirin: 56 days (range 8-365 days) versus 63 days (range 13-341 days), respectively.
· Anemia requiring ribavirin dose reduction, blood transfusion, and/or erythropoiesis stimulating agent (ESA) has been reported to occur as soon as 10 days following initiation of INCIVEK combination treatment.
· 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.
You can view the complete revised label at DRUGS@FDA.
Incivek is a product of Vertex Pharmaceuticals Incorporated.
Richard Klein
Office of Special Health Issues,
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products,
Food and Drug Administration
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