sábado, 25 de julio de 2015

FDA Hepatitis Update - Approval of Technivie to treat of genotype 4 chronic hepatitis C virus

On July 24, 2015, FDA approved TECHNIVIE, a fixed-dose combination containing ombitasvir, a hepatitis C virus NS5A inhibitor; paritaprevir, a  hepatitis C virus NS3/4A protease inhibitor; and ritonavir, a CYP3A inhibitor. The product is indicated in combination with ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis.
TECHNIVIE in combination with ribavirin is the first drug that has demonstrated safety and efficacy to treat genotype 4 HCV infections without the need for co-administration of interferon, an FDA-approved drug also used to treat HCV infection.
TECHNIVIE is not recommended for use in patients with moderate hepatic impairment (Child-Pugh B) and is contraindicated in patients with severe hepatic impairment (Child-Pugh C).                  
The recommended dosage of TECHNIVIE in adults is two tablets taken orally once daily (in the morning) with a meal without regard to fat or calorie content. TECHNIVIE is intended to be used in combination with ribavirin for 12 weeks. TECHNIVIE administered without ribavirin for 12 weeks may be considered for treatment-naïve patients who cannot take or tolerate ribavirin.
TECHNIVIE is contraindicated:
  • In patients with severe hepatic impairment due to risk of potential toxicity.
  • With drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.
  • With drugs that are moderate or strong inducers of CYP3A and may lead to reduced efficacy of TECHNIVIE.
  • In patients with known hypersensitivity to ritonavir (e.g. toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome).
The safety and efficacy of TECHNIVIE with ribavirin were evaluated in a clinical trial of 135 participants with chronic HCV genotype 4 infections without cirrhosis who were either treatment-naïve (n=86) or did not achieve a virologic response with prior treatment with pegylated interferon/ribavirin (n=49). Previous exposure to HCV direct-acting antivirals was prohibited. Ninety-one participants received TECHNIVIE with ribavirin once daily for 12 weeks. Forty-four participants received TECHNIVIE once daily without ribavirin for 12 weeks.
Results showed that 100 percent of the participants who received TECHNIVIE with ribavirin achieved a sustained virologic response. Of those who received TECHNIVIE without ribavirin, 91 percent achieved sustained virologic response.
Safety information was available for 316 participants with HCV treated with the recommended dose of TECHNIVIE in combination with other anti-HCV drugs in clinical trials. The three drugs included in TECHNIVIE are also included in Viekira Pak, previously approved for the treatment of HCV genotype 1 infection. Additional safety information for those drugs was available from the Viekira Pak trials. The most common side effects of TECHNIVIE with ribavirin were fatigue, weakness (asthenia), nausea, insomnia, itching (pruritus) and other skin reactions. The majority of adverse reactions were mild in severity. None of the subjects who received TECHNIVIE with ribavirin experienced a serious adverse reaction. None of the subjects receiving TECHNIVIE with or without ribavirin discontinued treatment due to an adverse reaction.
TECHNIVIE labeling includes a WARNINGS and PRECAUTIONS that elevations of liver enzymes to greater than five times the upper limit of normal occurred in approximately one percent of clinical trial participants. The elevations occurred more frequently in females taking contraceptives containing ethinyl estradiol. Contraceptives containing ethinyl estradiol must be discontinued prior to starting TECHNIVIE. Hepatic laboratory testing should be performed during the first four weeks of starting treatment, and as clinically indicated thereafter.
The approve product label will be available soon at http://dailymed.nlm.nih.gov/dailymed/, or at drugs@fda
Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration

Kimberly Struble
Division of Antiviral Products
Food and Drug Administration

Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration

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