January 19, 2012
U.S. Food and Drug Administration Approves New Formulations of Viread® for Use by Children Living With HIV
-- Viread Now Available in an Oral Powder and Three Lower-Strength Tablets --
Viread was originally approved by the
The pediatric regulatory applications for Viread were supported by
clinical data from a Phase 3 safety and efficacy study of a
Viread-containing antiretroviral regimen compared to an antiretroviral
regimen containing zidovudine or stavudine in HIV-infected
treatment-experienced children ages 2-12. The safety profile observed in
the study was consistent with that observed in clinical trials in
adults. The applications were submitted to the
“Prenatal HIV testing and antiretroviral interventions during pregnancy
have contributed to a dramatic decline in the number of children born
with HIV in
According to the
Important Safety Product Information About Viread, Including Boxed Warnings
Indication and Usage
Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older.
The following point should be considered when initiating therapy with Viread for the treatment of HIV-1 infection:
- Viread should not be used in combination with Atripla® (efavirenz/emtricitabine/tenofovir disoproxil fumarate), Complera® (emtricitabine/rilpivirine/tenofovir disoproxil fumarate), or Truvada® (emtricitabine/tenofovir disoproxil fumarate).
WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including Viread, in combination with other antiretrovirals. Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including Viread. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
Warnings and Precautions
- New onset or worsening renal impairment: New onset or worsening renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), have been reported with the use of Viread. Assess creatinine clearance (CrCl) before initiating treatment with Viread. Monitor CrCl and serum phosphorus in patients at risk, including those who have previously experienced renal events while receiving Hepsera® (adefovir dipivoxil). Avoid administering Viread with concurrent or recent use of nephrotoxic drugs. Dosing interval adjustment of Viread and close monitoring of renal function are recommended in all patients with CrCl <50 mL/min.
Coadministration with Other Products:
- Do not use with other tenofovir-containing products (eg, Atripla, Complera, or Truvada)
- Do not administer in combination with Hepsera.
- Patients coinfected with HIV-1 and HBV: Due to the risk of development of HIV-1 resistance, Viread should only be used in HIV-1 and HBV co-infected patients as part of an appropriate antiretroviral combination regimen. Testing for the presence of chronic hepatitis B should be offered to all patients with HIV-1 before initiating treatment with Viread.
- Decreases in bone mineral density: Decreases in bone mineral density (BMD) have been observed in HIV-infected patients. Consider monitoring BMD in patients with a history of pathologic fracture or who are at risk for osteopenia. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread.
- Fat Redistribution: In HIV-infected patients redistribution/accumulation of body fat has been observed in patients receiving combination antiretroviral therapy.
- Immune Reconstitution Syndrome: Immune reconstitution syndrome has been reported in HIV-infected patients treated with combination antiretroviral therapy.
- Early Virologic Failure: HIV treatment regimens that only contain three nucleoside reverse transcriptase inhibitors (NRTI) are generally less effective than triple drug regimens containing two NRTIs used with a non-nucleoside reverse transcriptase inhibitor or HIV-1 protease inhibitor. Triple nucleoside regimens should be used with caution and patients should be carefully monitored and considered for treatment modification.
- Clinical Trials in Adults Patients with HIV-1 Infection: In HIV-infected subjects the most common adverse reactions (incidence greater than or equal to 10%, Grades 2 - 4) are rash, diarrhea, headache, pain, depression, asthenia, and nausea.
- Clinical Trials in Pediatric Subjects 2 Years of Age and Older with HIV-1 Infection: In a clinical trial of 89 pediatric subjects treated with Viread (48 who were initially randomized to Viread and 41 who were initially randomized to continue stavudine or zidovudine and then received Viread in the extension phase) for a median exposure of 104 weeks, four subjects discontinued due to adverse reactions consistent with proximal renal tubulopathy.
- Didanosine: Coadministration increases didanosine concentrations. Use with caution and monitor for evidence of didanosine toxicity (eg, pancreatitis, neuropathy). Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions. In adults weighing >60 kg, the didanosine dose should be reduced to 250 mg when it is coadministered with Viread. Data are not available to recommend a dose adjustment of didanosine for patients weighing <60 kg.
- Atazanavir: Coadministration decreases atazanavir concentrations and increases tenofovir concentrations. Use atazanavir with Viread only with additional ritonavir; monitor for evidence of tenofovir toxicity.
- Lopinavir/ritonavir: Coadministration increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity.
Dosage and Administration
Recommended dose of Viread for the treatment of HIV-1 in:
- adult patients is 300 mg once daily without regard to food
- pediatric patients is 8 mg of tenofovir disoproxil fumarate per kilogram of body weight (maximum of 300 mg) once daily.
Dose Adjustment for Patients with Altered Creatinine Clearance
- The dosing interval of Viread should be adjusted (using recommendations in the table below) and renal function closely monitored in patients with creatinine clearance <50 mL/min.
|Dosage Adjustment for Patients with Altered Creatinine Clearance|
Recommended 300 mg
Every 72 to
Every 7 days or after a total of
|Calculated using ideal (lean) body weight.|
|Generally once weekly assuming three hemodialysis sessions a week of approximately 4 hours duration. Viread should be administered following completion of dialysis.|
- The pharmacokinetics of tenofovir have not been evaluated in non-hemodialysis patients with creatinine clearance <10 mL/min; therefore, no dosing recommendation is available for these patients.
- No dose adjustment is necessary for patients with mild renal impairment (creatinine clearance 50-80 mL/min). Routine monitoring of calculated creatinine clearance and serum phosphorus should be performed in these patients.
- No data are available for dosing recommendations in pediatric patients with renal impairment.
Please see full Prescribing Information for Viread (including BOXED WARNINGS).
This press release includes forward-looking statements, within the
meaning of the Private Securities Litigation Reform Act of 1995, that
are subject to risks, uncertainties and other factors, including the
risk that physicians may not see advantages of Viread for the treatment
of HIV infection over other therapies for children, and may therefore be
reluctant to prescribe the product, and payers may be reluctant to
approve or provide reimbursement for the product. These risks,
uncertainties and other factors could cause actual results to differ
materially from those referred to in the forward-looking statements. The
reader is cautioned not to rely on these forward-looking statements.
These and other risks are described in detail in Gilead’s Quarterly
Report on Form 10-Q for the quarter ended
Viread is a registered trademark of
Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Erin Rau, 650-522-5635 (Media)