Bristol-Myers Squibb Company and Gilead Sciences, Inc. announced that Health Canada has approved Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) for the treatment of HIV-1 infection in adults. With this notice of compliance, Atripla becomes the first once-daily single tablet regimen for HIV approved in Canada for use as a stand-alone therapy or in combination with other anti-retrovirals.
Atripla combines Sustiva (efavirenz), manufactured by Bristol-Myers Squibb Company and Truvada (emtricitabine/tenofovir disoproxil fumarate), manufactured by Gilead Sciences. Truvada itself is a fixed-dose product that contains two of Gilead's anti-HIV medications, Viread (tenofovir disoproxil fumarate) and Emtriva (emtricitabine), in a single once-daily tablet for use as part of combination therapy. All three medicines work by blocking reverse transcriptase, an enzyme necessary for HIV replication.
"Atripla represents a milestone in treatment for this disease. I commend the companies involved for joining forces to make Atripla, the first complete three-drug regimen in a single once-daily pill," said Mark Wainberg, MD, director, McGill AIDS Centre and professor of medicine and microbiology at McGill University.
Atripla was developed through a joint venture partnership between Bristol-Myers Squibb Company and Gilead Sciences. The product was approved by the US Food and Drug Administration in July 2006 and has since become the most-prescribed treatment regimen for patients starting HIV therapy in the United States. In Canada, approximately 60,000 people are living with HIV, and around 2,500 new HIV diagnoses are reported each year.
Clinical data support the use of the three-drug regimen contained in Atripla in HIV treatment-naive patients. A randomized, open label, active-controlled, multicenter, non-inferiority study, Study 934, compared a once-daily regimen of Viread, Emtriva and Sustiva, the components of Atripla, with twice-daily Combivir (lamivudine/zidovudine) and once-daily Sustiva in treatment-naive patients with HIV. Through 48 weeks, 84 per cent of patients in the Viread/Emtriva/Sustiva group (n=244) compared to 73 per cent of patients in the Combivir/Sustiva group (n=243) achieved and maintained a viral load of less than 400 copies/mL. This difference largely results from the higher number of discontinuations in the Combivir/Sustiva group due to adverse events (9 per cent vs. 4 per cent in the Viread/Emtriva/Sustiva group) and other reasons including loss to follow-up, patient withdrawal, non-compliance and protocol violation (14 per cent vs. 10 percent in the Viread/Emtriva/Sustiva group).
In addition, 80 per cent and 70 per cent of patients in the Viread/Emtriva/Sustiva group and the Combivir/Sustiva group, respectively, achieved and maintained a viral load less than 50 copies/mL through 48 weeks. Selected treatment-emergent adverse events (Grades 2-4) reported in greater than or equal to 5 per cent of patients in the Viread/Emtriva/Sustiva group through 48 weeks included dizziness, nausea, diarrhea, fatigue, headache and rash.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals.
Emtriva, Viread, Truvada and Atripla are not approved for the treatment of chronic hepatitis B virus (HBV) infection and their safety and efficacy have not been established in patients co-infected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Viread or Emtriva, which are components of Truvada and Atripla. In some of these patients treated with Emtriva, the exacerbations of hepatitis B were associated with liver decompensation and liver failure. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are co-infected with HIV and HBV and discontinue Truvada or Atripla. If appropriate, initiation of anti-hepatitis B treatment may be warranted.
It is important for patients to be aware that anti-HIV medicines including Truvada, Viread, Emtriva, Sustiva and Atripla do not cure HIV infection or AIDS and do not reduce the risk of transmitting HIV to others.
Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate [DF] 300 mg) is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.
Coadministration of Atripla with astemizole, bepridil, cisapride, midazolam, pimozide, triazolam, ergot derivatives, or voriconazole is contraindicated. Concomitant use of Atripla with St. John's wort (Hypericum perforatum) or St. John's wort-containing products is not recommended.
Since Atripla contains efavirenz, emtricitabine, and tenofovir DF, Atripla should not be coadministered with Sustiva (efavirenz), Emtriva (emtricitabine), Viread (tenofovir disoproxil fumarate), or Truvada (emtricitabine/tenofovir DF). Due to similarities between emtricitabine and lamivudine, Atripla should not be coadministered with drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Epivir or Epivir-HBV (lamivudine), Epzicom (abacavir sulfate/lamivudine), or Trizivir (abacavir sulfate/lamivudine/zidovudine).
Serious psychiatric adverse experiences, including severe depression (2.4 per cent), suicidal ideation (0.7 per cent), nonfatal suicide attempts (0.5 per cent), aggressive behavior (0.4 per cent), paranoid reactions (0.4 per cent), and manic reactions (0.2 per cent), have been reported in patients receiving efavirenz. In addition to efavirenz, factors identified in a clinical study that were associated with an increase in psychiatric symptoms included a history of injection drug use, psychiatric history, and use of psychiatric medication. There have been occasional reports of suicide, delusions, and psychosis-like behavior, but it could not be determined if efavirenz was the cause. Patients with serious psychiatric adverse experiences should be evaluated immediately to determine whether the risks of continued therapy outweigh the benefits.
The dose of Atripla is one tablet (containing 600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir DF) once daily taken orally on an empty stomach. Dosing at bedtime may improve the tolerability of nervous system symptoms. Atripla is not recommended for use in patients less than 18 years of age.
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has Canadian offices in Mississauga, Ontario and manufacturing facilities in Edmonton, Alberta. The company also has operations in Europe and Australia.