Emtricitabine/Tenofovir Disoproxil Fumarate 200mg/300mg for HIV-1 Pre-exposure Prophylaxis (PrEP)

This is a Risk Evaluation and Mitigation Strategy (REMS) Web site. Emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP—in combination with safer sex practices—can help reduce the risk of sexually acquired HIV-1 infection as part of a comprehensive HIV-1 prevention strategy in at-risk adults and adolescents weighing at least 35 kg. Emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP does not replace existing prophylaxis strategies. Review factors that can help healthcare providers identify individuals at risk for sexually acquired HIV-1 infection and important prescribing considerations


Review the online training for prescribers

Report completion of training for emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP

Participate in a Knowledge, Attitude, and Behavior (KAB) survey to assess the use and understanding of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP

REMS Information

A Risk Evaluation and Mitigation Strategy (REMS) is a strategy to manage known or potential serious risks associated with a drug product and is required by the Food and Drug Administration (FDA) to ensure that the benefits of the drug outweigh its risks.

To help ensure emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP is prescribed and taken safely, emtricitabine/tenofovir disoproxil fumarate Sponsor(s) has worked with the FDA to develop materials for the REMS program to educate and inform healthcare providers and uninfected adults and adolescents weighing at least 35 kg who are at risk of HIV-1 acquisition.

Access REMS resources

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Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis (PrEP)

Healthcare Provider Training

HIV-1 Pre-Exposure Prophylaxis (PrEP)

  • Emtricitabine/tenofovir disoproxil fumarate is indicated in combination with safer sex practices for HIV-1 pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing at least 35 kg. Individuals must have a negative HIV-1 test immediately prior to initiating emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP
    • If clinical symptoms consistent with acute viral infection are present and recent (<1 month) exposures are suspected, delay starting HIV-1 PrEP for at least 1 month and reconfirm HIV-1 status or use a test cleared by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection

Factors to Help Identify Individuals At Risk May Include

  • Has a partner known to be HIV-1 infected, or
  • Engages in sexual activity within a high prevalence area or social network and has additional risk factors for HIV-1 acquisition, such as:
    • Inconsistent or no condom use
    • Diagnosis of sexually transmitted infections
    • Exchange of sex for commodities (such as money, food, shelter, or drugs)
    • Use of illicit drugs or alcohol dependence
    • Incarceration
    • Partner(s) of unknown HIV-1 status with any of the factors listed above

When Prescribing Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 PrEP, Healthcare Providers MUST:

  • Use emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP as part of a comprehensive prevention strategy that includes other prevention measures, such as safer sex practices, because emtricitabine/tenofovir disoproxil fumarate is not always effective in preventing acquisition of HIV-1 infection
  • Counsel all uninfected individuals about safer sex practices that include consistent and correct use of condoms, knowledge of their HIV-1 status and that of their partner(s), the importance of virologic suppression in their partner(s) with HIV-1 and regular testing for other sexually transmitted infections that can facilitate HIV-1 transmission (such as syphilis, chlamydia, and gonorrhea)
  • Inform uninfected individuals about and support their efforts in reducing sexual risk behavior
  • Many HIV-1 tests, such as rapid tests, detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP, evaluate seronegative individuals for current or recent signs or symptoms consistent with acute viral infections (e.g., fever, fatigue, myalgia, skin rash) and ask about potential exposure events (e.g., unprotected, or condom broke during, sex with an HIV-1 infected partner) that may have occurred within the last month
  • If clinical symptoms consistent with acute viral infection are present and recent (<1 month) exposures are suspected, delay starting HIV-1 PrEP for at least one month and reconfirm HIV-1 status or use a test approved or cleared by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection

Additional Considerations When Prescribing Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 PrEP in Adolescents

  • The following points should also be considered when prescribing emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP in adolescents:
    • Use of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP as part of a comprehensive HIV prevention strategy for adolescents should include consideration of the ability of the individual to understand the importance of adherence to daily dosing, the need for frequent HIV testing, the need for frequent sexually transmitted infection testing, and the continued risk of pregnancy
    • In a clinical study in adolescents, the percentage of subjects with protective levels of drug declined markedly after subjects switched from monthly to quarterly visits, suggesting that adolescents may benefit from more frequent visits and counseling

BOXED WARNING

  • Emtricitabine/tenofovir disoproxil fumarate used for HIV-1 PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initial use and periodically (at least every 3 months) during use. Drug-resistant HIV-1 variants have been identified with the use of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP if signs or symptoms of acute HIV infection are present unless negative infection status is confirmed

BOXED WARNING (Continued)

  • Severe acute exacerbations of hepatitis B virus (HBV) have been reported in HBV-infected patients who have discontinued emtricitabine/tenofovir disoproxil fumarate. Hepatic function should be monitored closely in HBV-infected patients who discontinue emtricitabine/tenofovir disoproxil fumarate. If appropriate, initiation of anti-hepatitis B therapy may be warranted

Why Use Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 PrEP?

  • By inhibiting HIV-1 from replicating as it enters the body, emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP works to prevent the virus from establishing permanent infection. However, emtricitabine/tenofovir disoproxil fumarate should not be seen as the first line of defense against HIV-1
  • Because emtricitabine/tenofovir disoproxil fumarate is not always effective in preventing the acquisition of HIV-1, emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP must be used in combination with a comprehensive prevention strategy that includes safer sex practices, such as regular and correct condom use, regular HIV testing for themselves (and their sexual partner(s)), and other proven HIV prevention methods to safely and effectively reduce the risk of acquiring HIV-1
    • Emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP must only be prescribed to uninfected individuals at risk who are confirmed to be HIV-1 negative
    • Uninfected individuals who are prescribed emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP should not miss any doses. Missing doses may increase the risk of acquiring HIV-1 infection

Key Findings of the Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 PrEP Studies: The iPrEx Trial

  • In one clinical trial of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP, emtricitabine/tenofovir disoproxil fumarate was shown to reduce the risk of HIV-1 acquisition by 42% for high risk adult men who have sex with men who also received comprehensive prevention services, including monthly HIV-1 testing, condom provision, counseling, and management of other sexually transmitted infections
  • In a post hoc case control study of plasma and intracellular drug levels in about 10% of clinical trial subjects, risk reduction appeared to be the greatest in subjects with detectable intracellular tenofovir. Efficacy was therefore strongly correlated with adherence
  • Intensive risk reduction counseling was provided as part of the study, and self-reported risk behavior among the subjects in this clinical trial declined overall during the study, both in terms of decreases in the number of self-reported sexual partners and increases in condom use

Key Findings of the Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 PrEP Studies: The Partners PrEP Trial

  • In another clinical trial of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP, emtricitabine/tenofovir disoproxil fumarate was shown to reduce HIV-1 acquisition by 75% in uninfected individuals in stable adult heterosexual serodiscordant relationships who also received comprehensive prevention services, including monthly HIV testing, evaluation of adherence, assessment of sexual behavior, and safety evaluations
  • In a post-hoc case control study of plasma drug levels in about 10% of study subjects, risk reduction appeared to be the greatest in subjects with detectable plasma tenofovir. Efficacy was therefore strongly correlated with adherence. Risk reduction increased further in subjects with detectable plasma tenofovir

Important Safety Information: Comprehensive Management to Reduce the Risk of Acquiring HIV-1 and Development of HIV-1 Resistance

  • Use emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP only as part of a comprehensive prevention strategy that includes other prevention measures, such as safer sex practices, because emtricitabine/tenofovir disoproxil fumarate is not always effective in preventing the acquisition of HIV-1 infection
    • Counsel uninfected individuals about safer sex practices that include consistent and correct use of condoms, knowledge of their HIV-1 status and that of their partner(s), the importance of virologic suppression in their partner(s) with HIV-1 and regular testing for other sexually transmitted infections that can facilitate HIV-1 transmission (such as syphilis, chlamydia and gonorrhea)
    • Inform uninfected individuals about and support their efforts in reducing sexual risk behavior

Important Safety Information: Comprehensive Management to Reduce the Risk of Acquiring HIV-1 and Development of HIV-1 Resistance

  • Use emtricitabine/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/tenofovir disoproxil fumarate, because emtricitabine/tenofovir disoproxil fumarate alone does not constitute a complete regimen for HIV-1 treatment; therefore, care should be taken to minimize drug exposure in HIV-infected individuals
  • Many HIV-1 tests, such as rapid tests, detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP, evaluate seronegative individuals for current or recent signs or symptoms consistent with acute viral infections (e.g., fever, fatigue, myalgia, skin rash) and ask about potential exposure events (e.g., unprotected, or condom broke during, sex with an HIV-1 infected partner) that may have occurred within the last month

Important Safety Information: Comprehensive Management to Reduce the Risk of Acquiring HIV-1 and Development of HIV-1 Resistance

  • While using emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP, HIV-1 screening tests should be repeated at least every 3 months, and upon diagnosis of any sexually transmitted infections. Some individuals, such as adolescents may benefit from more frequent visits and counseling
    • If a screening test indicates possible HIV-1 infection, or 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 HIV-1, including acute or primary HIV-1 infection

Important Safety Information: Comprehensive Management to Reduce the Risk of Acquiring HIV-1 and Development of HIV-1 Resistance

  • Counsel uninfected individuals to strictly adhere to the recommended daily emtricitabine/tenofovir disoproxil fumarate dosing schedule. The effectiveness of emtricitabine/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

Important Safety Information: Additional Warnings and Precautions

New Onset or Worsening Renal Impairment

  • Can include acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia)
  • Prior to initiating and during use of emtricitabine/tenofovir disoproxil fumarate, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients
  • In patients with chronic kidney disease, also assess serum phosphorus

Important Safety Information: Additional Warnings and Precautions

New Onset or Worsening Renal Impairment

  • Emtricitabine/tenofovir disoproxil fumarate should be avoided with concurrent or recent use of a nephrotoxic agent. Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported. Some patients required hospitalization and renal replacement therapy. Alternatives to NSAIDs should be considered, if needed, in patients at risk for renal dysfunction
  • Emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP is not recommended in uninfected individuals with an estimated CrCl less than 60 mL/min
    • If a decrease in estimated CrCl is observed while using emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use

Important Safety Information: Additional Warnings and Precautions

Lactic Acidosis/Severe Hepatomegaly with Steatosis

  • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported. Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity

Bone Effects

  • Decreases in bone mineral density (BMD) and mineralization defects, including osteomalacia, have been seen in patients treated with tenofovir disoproxil fumarate. Consider assessment of BMD in individuals with a history of pathologic fracture or other risk factors for osteoporosis or bone loss
  • Persistent or worsening bone pain, pain in extremities, fractures and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients

Important Safety Information: Additional Warnings and Precautions

Severe Acute Exacerbation of Hepatitis B in Patients with HBV Infection

  • All patients should be tested for HBV infection before or when starting emtricitabine/tenofovir disoproxil fumarate
  • HBV-uninfected individuals should be offered vaccination
  • HBV-infected individuals should be monitored closely with both clinical and laboratory follow-up for exacerbation of hepatitis B for at least several months after discontinuing emtricitabine/tenofovir disoproxil fumarate (see BOXED WARNING)

Coadministration with Other Products

  • Do not use emtricitabine/tenofovir disoproxil fumarate with drugs containing emtricitabine, tenofovir disoproxil fumarate, or tenofovir alafenamide, with drugs containing lamivudine, or with adefovir dipivoxil

Important Safety Information: Use of Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 PrEP in Specific Populations

Pregnancy

  • There are no adequate and well controlled trials in pregnant women
  • Published studies indicate an increased risk of HIV-1 infection during pregnancy and an increased risk of mother-to-child transmission during acute HIV-1 infection. In women at risk of acquiring HIV-1, consideration should be given to methods to prevent acquisition of HIV, including continuing or initiating emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP, during pregnancy
  • A pregnancy registry is available. Enroll pregnant women exposed to emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP by calling 1-800-258-4263

Important Safety Information: Use of Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 PrEP in Specific Populations

Lactation

  • It is not known if the components of emtricitabine/tenofovir disoproxil fumarate affect milk production or have effects on the breastfed child
  • In HIV-uninfected women, the developmental and health benefits of breastfeeding and the mother's clinical need for emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP should be considered along with any potential adverse effects on the breastfed child from emtricitabine/tenofovir disoproxil fumarate and the risk of HIV-1 acquisition due to nonadherence and subsequent mother-to-child transmission
  • Women should not breastfeed if acute HIV-1 infection is suspected because of the risk of HIV-1 transmission to the infant

Important Safety Information: Use of Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 PrEP in Specific Populations

Pediatrics

  • Safety, adherence, and resistance were evaluated in a single-arm, open label clinical trial (ATN113) in 67 HIV-1 uninfected at-risk adolescent men who have sex with men received emtricitabine/tenofovir disoproxil fumarate once daily for HIV-1 PrEP
  • In the ATN113 trial, HIV-1 seroconversion occurred in 3 subjects. Tenofovir diphosphate (DP) levels in dried blood spot assays indicate that these subjects had poor adherence
  • Adherence to study drug, as demonstrated by tenofovir DP levels in dried blood spot assays, declined markedly after Week 12 once subjects switched from monthly to quarterly visits, suggesting that adolescents may benefit from more frequent visits and counseling

Important Safety Information: Confirming and Regularly Reconfirming Negative HIV Status

  • Emtricitabine/tenofovir disoproxil fumarate should be used to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-1 negative
    • A negative HIV-1 status should be confirmed before prescribing emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP
    • Individuals should be regularly tested (at least every 3 months) while taking emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP to reconfirm that they are HIV-1 negative. Some individuals, such as adolescents, may benefit from more frequent visits and counseling
    • If a screening test indicates possible infection, or 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 HIV-1, including acute or primary HIV-1 infection

Important Safety Information: Confirming and Regularly Reconfirming Negative HIV Status

Potential for Resistance in Undetected Acute HIV-1 Infection

  • It is important to be alert to the signs of potential acute HIV-1 infection when prescribing emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP. These include fever, headache, fatigue, arthralgia, vomiting, myalgia, diarrhea, pharyngitis, rash, night sweats, and cervical and inguinal adenopathy
  • HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP
    • Although emtricitabine/tenofovir disoproxil fumarate is active against HIV-1, emtricitabine/tenofovir disoproxil fumarate alone does not constitute a complete treatment regimen for HIV-1 infection
    • HIV-1-infected patients taking emtricitabine/tenofovir disoproxil fumarate must take it with other antiretroviral agents to fully suppress virus replication and avoid the development of resistance

Important Safety Information: Drug Interactions and Common Adverse Events

Drug Interactions

  • Coadministration of emtricitabine/tenofovir disoproxil fumarate with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir
  • For further details about emtricitabine/tenofovir disoproxil fumarate drug interactions, please see the Prescribing Information for emtricitabine/tenofovir disoproxil fumarate

Common Adverse Events

  • In HIV-1 uninfected adults in HIV-1 PrEP trials, adverse reactions that were reported by more than 2% of emtricitabine/tenofovir disoproxil fumarate subjects and more frequently than by placebo subjects were headache, abdominal pain and decreased weight

Additional Educational Materials

  • Agreement Form for Initiating Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis (PrEP)
    • Designed for prescribers to use with uninfected individuals to facilitate discussion of appropriate use of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP
    • Form covers safety risks associated with use of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP, the importance of adherence to the recommended daily dosing regimen, regular assessment of HIV-1 test results, and screening for sexually transmitted infections
  • Checklist for Prescribers: Initiation of Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis (PrEP)
    • Checklist of key components for prescribers to consider before starting an uninfected individual on emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP
    • Checklist items include confirming a negative HIV-1 test result, screening for signs or symptoms of acute HIV-1 infection, counseling on safety risks and importance of adherence, and other components to ensure a comprehensive prevention strategy
  • Copies are available from www.ftc-tdf-preprems.com or by filling out the business reply card at the back of the Training Guide for Healthcare Providers booklet

Additional Educational Materials

  • Additional educational materials can be reviewed and downloaded at www.ftc-tdf-preprems.com or requested by hard copy by calling 1-800-625-7471
  • Please confirm completion of training by going to www.ftc-tdf-preprems.com or by filling out the business reply card at back of the Training Guide for Healthcare Providers booklet
  • A survey is being conducted to fulfill an FDA Risk Evaluation and Mitigation Strategy (REMS) requirement to assess prescribers’ knowledge regarding important safety information associated with the use of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP. To participate, please go to www.ftc-tdf-preprems.com

Additional Educational Materials

  • Important Safety Information for Adolescents Who Don't Have HIV
    • Designed as an educational tool for HIV-1 uninfected adolescents
    • Contains similar information as the educational tool written for adults Important Safety Information for Adults Who Don't Have HIV but written to be more easily understood by adolescents
    • Copies are available from www.ftc-tdf-preprems.com or by filling out business reply card at the back of the Training Guide for Healthcare Providers booklet

REMS-SSS-0029
05/18

To help emtricitabine/tenofovir disoproxil fumarate Sponsor(s) and the FDA understand who has viewed this training, please tell us the following


Report completion of training for emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP

Participate in a Knowledge, Attitude, and Behavior (KAB) survey to assess the use and understanding of emtricitabine/tenofovir disoproxil fumarate for HIV-1 PrEP


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