Emtricitabine and tenofovir disoproxil fumarate: uses, appearance and warnings

HIV-1 Treatment (1.1) Emtricitabine and tenofovir disoproxil fumarate is a two-drug combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), both HIV-1 nucleoside analog reverse transcriptase inhibitors, and is indicated: in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 17 kg. HIV-1 PrEP (1.2): Emtricitabine and tenofovir disoproxil fumarate is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Individuals must have a negative HIV-1 test immediately prior to initiating emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP. 1.1 Treatment of HIV-1 Infection Emtricitabine and tenofovir disoproxil fumarate is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 17 kg [see Clinical Studies (14)] . 1.2 HIV-1 Pre-Exposure Prophylaxis (PrEP) Emtricitabine and tenofovir disoproxil fumarate is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Individuals must have a negative HIV-1 test immediately prior to initiating emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP [see Dosage and Administration (2.2), Warnings and Precautions (5.2)] .

Emtricitabine and tenofovir disoproxil fumarate is available as tablets. Each tablet contains 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil). The tablets are white colored, capsule-shaped, film-coated, engraved TE on one side and plain on the other side. Tablets: 200 mg/300 mg of emtricitabine and tenofovir disoproxil fumarate, respectively. (3)

The white colored, capsule shaped, biconvex, film coated tablets contain 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil), tablets engraved TE on one side and plain on the other side., and are available in unit of use bottles (75CC), containing a dessicant [silica gel canister or sachet] and closed with a child-resistant closure/screw cap of: 30 tablets (NDC-64380-719-04) Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Keep container tightly closed Dispense only in original container Do not use if seal over bottle opening is broken or missing

Emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status [see Warnings and Precautions (5.2)]. Emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status. (4)

Comprehensive management to reduce the risk of acquiring HIV-1 when emtricitabine and tenofovir disoproxil fumarate is used for HIV-1 PrEP: Use as part of a comprehensive prevention strategy including other prevention measures; strictly adhere to dosing schedule. (5.2) Management to reduce the risk of acquiring HIV-1 drug resistance when emtricitabine and tenofovir disoproxil fumarate is used for HIV-1 PrEP: refer to full prescribing information for additional detail. (5.2) New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome. Avoid administering emtricitabine and tenofovir disoproxil fumarate with concurrent or recent use of nephrotoxic drugs. (5.3) Immune reconstitution syndrome during treatment of HIV-1 infection: May necessitate further evaluation and treatment. (5.4) Decreases in bone mineral density (BMD): Consider assessment of BMD in individuals with a history of pathologic fracture or other risk factors for osteoporosis or bone loss. (5.5) Lactic acidosis/severe hepatomegaly with steatosis: Discontinue emtricitabine and tenofovir disoproxil fumarate in individuals who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. (5.6) 5.1 Severe Acute Exacerbation of Hepatitis B in Individuals with HBV Infection All individuals should be tested for the presence of chronic hepatitis B virus (HBV) before or when initiating emtricitabine and tenofovir disoproxil fumarate [see Dosage and Administration (2.1)]. Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in HBV-infected individuals who have discontinued emtricitabine and tenofovir disoproxil fumarate. Individuals infected with HBV who discontinue emtricitabine and tenofovir disoproxil fumarate should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, anti-hepatitis B therapy may be warranted, especially in individuals with advanced liver disease or cirrhosis, since posttreatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure. HBV-uninfected individuals should be offered vaccination. 5.2 Comprehensive Management to Reduce the Risk of Sexually Transmitted Infections, Including HIV-1, and Development of HIV-1 Resistance When Emtricitabine and Tenofovir Disoproxil Fumarate is Used for HIV-1 PrEP Use emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP to reduce the risk of HIV-1 infection as part of a comprehensive prevention strategy that includes other prevention measures, including adherence to daily administration and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). The time from initiation of emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown . Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including but not limited to condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network. Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use, knowledge of partner(s)' HIV-1 status, including viral suppression status, regular testing for STIs that can facilitate HIV-1 transmission). Inform uninfected individuals about and support their efforts in reducing sexual risk behavior. Use emtricitabine and tenofovir disoproxil fumarate to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-negative . HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only emtricitabine and tenofovir disoproxil fumarate, because emtricitabine and tenofovir disoproxil fumarate alone does not constitute a complete regimen for HIV-1 treatment [see Microbiology (12.4)]; therefore, care should be taken to minimize the risk of initiating or continuing emtricitabine and tenofovir disoproxil fumarate before confirming the individual is HIV-1 negative. Some HIV-1 tests only detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP, ask seronegative individuals about recent (in past month) potential exposure events (e.g., condomless sex or condom breaking during sex with a partner of unknown HIV-1 status or unknown viremic status, or a recent STI), and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash). If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection. While using emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP, HIV-1 testing should be repeated at least every 3 months, and upon diagnosis of any other STIs. If an HIV-1 test indicates possible HIV-1 infection, or if symptoms consistent with acute HIV-1 infection develop following a potential exposure event, convert the HIV-1 PrEP regimen to an HIV treatment regimen until negative infection status is confirmed using a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection. Counsel HIV-1 uninfected individuals to strictly adhere to the once daily emtricitabine and tenofovir disoproxil fumarate dosing schedule. The effectiveness of emtricitabine and tenofovir disoproxil fumarate in reducing the risk of acquiring HIV-1 is strongly correlated with adherence, as demonstrated by measurable drug levels in clinical trials of emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP. …

The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B in Patients with HBV Infection [see Warnings and Precautions (5.1)]. New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.3)]. Immune Reconstitution Syndrome [see Warnings and Precautions (5.4)]. Bone Loss and Mineralization Defects [see Warnings and Precautions (5.5)]. Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.6)]. In HIV-1 infected patients, the most common adverse reactions (incidence greater than or equal to 10%) are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. …

Tenofovir disoproxil fumarate increases didanosine concentrations. Dose reduction and close monitoring for didanosine toxicity are warranted. (7.2) Coadministration decreases atazanavir concentrations. When coadministered with emtricitabine and tenofovir disoproxil fumarate, use atazanavir given with ritonavir. (7.2) Coadministration of emtricitabine and tenofovir disoproxil fumarate with certain HIV-1 protease inhibitors or certain drugs to treat HCV increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity. (7.2) Consult Full Prescribing Information prior to and during treatment for important drug interactions. (7.2) 7.1 Drugs Affecting Renal Function FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion [see Clinical Pharmacology (12.3)]. …