Important Safety Information
Before prescribing TRUVADA for a PrEP indication, please review the complete Important Safety Information. To access a specific section of the Important Safety Information, use the links below:
Important Safety Information About TRUVADA for a PrEP Indication
- TRUVADA for a PrEP indication must only be prescribed to individuals confirmed to be HIV-1 negative immediately prior to initiating and periodically (at least every 3 months) during use. Drug-resistant HIV-1 variants have been identified with the use of TRUVADA for a PrEP indication following undetected acute HIV-1 infection. Do not initiate TRUVADA for a PrEP indication if signs or symptoms of acute HIV infection are present unless negative infection status is confirmed
- TRUVADA is not approved for the treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of hepatitis B have been reported in patients infected with HBV who have discontinued TRUVADA. Therefore, hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in HBV-infected patients who discontinue TRUVADA. If appropriate, initiation of anti-hepatitis B therapy may be warranted
Contraindications: DO NOT PRESCRIBE TRUVADA for pre-exposure prophylaxis in individuals with unknown or positive HIV-1 status. TRUVADA should be used in HIV-1 infected patients only in combination with other antiretroviral agents.
Warnings and Precautions Relating to the Use of TRUVADA for a PrEP Indication
Comprehensive management strategies to reduce potential risks associated with use of TRUVADA for a PrEP indication:
- Strategy to reduce uninfected individual's exposure to HIV-1 infection includes safer sex practices such as consistent and correct use of condoms, an individual knowing their HIV-1 status and that of their partner(s), regular testing for HIV-1 and other sexually transmitted infections, and counseling regarding reducing sexual risk behavior
Strategies to reduce potential for drug resistance: TRUVADA must only be used for PrEP in individuals confirmed to be HIV-1 negative. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only TRUVADA, because TRUVADA alone does not constitute a complete regimen for HIV-1 treatment
- Confirm negative HIV-1 status immediately prior to initiating TRUVADA for PrEP. Do not initiate TRUVADA for PrEP if signs or symptoms of HIV-1 infection are present (e.g., fever, fatigue, myalgia, skin rash, etc.) or if recent exposure (<1 month) is suspected. Alternatively, delay initiating PrEP for at least one month or confirm negative HIV-1 status using a test approved by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection
- Screen for HIV-1 infection at least every three (3) months. Adolescents may benefit from more frequent visits and counseling. If a screening test indicates possible infection, or symptoms of acute infection develop after potential exposure event, convert the PrEP regimen to an HIV treatment regimen until negative HIV-1 status is confirmed using a test approved by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection
- Counsel all uninfected individuals to strictly adhere to their TRUVADA daily dosing schedule because the effectiveness of TRUVADA for PrEP is correlated with adherence and measurable drug levels
New or worsening renal impairment: Acute renal impairment including Fanconi syndrome may occur. Assess estimated creatinine clearance (CrCl) before prescribing and periodically during therapy with TRUVADA. In patients at risk of renal dysfunction, monitor estimated CrCl, serum phosphorus, urine glucose and urine protein before prescribing TRUVADA. Avoid administering TRUVADA with concurrent or recent use of nephrotoxic drugs. Cases of acute renal failure, some requiring hospitalization and renal replacement therapy, have been reported after initiation of high dose or multiple NSAIDs in patients with risk factors for renal dysfunction; consider alternatives to NSAIDs in these patients
- For pre-exposure prophylaxis: Do not prescribe TRUVADA for uninfected individuals with an estimated CrCl below 60 mL/min. If a decrease in estimated CrCl is observed in uninfected individuals while using TRUVADA for PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use
- HBV-uninfected individuals should be offered vaccination
- HBV-infected individuals should be monitored closely for exacerbations of hepatitis B for at least several months after discontinuing TRUVADA (see BOXED WARNING above)
- 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: Consider assessment of bone mineral density (BMD) in individuals with history of bone fractures, 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
- Coadministration with other products: Do not co-administer with other drugs containing emtricitabine, tenofovir disoproxil fumarate, or tenofovir alafenamide, with drugs containing lamivudine, or with adefovir dipivoxil
Common Adverse Reactions
In HIV-1 uninfected adults in PrEP trials, adverse reactions that were reported by more than 2% of TRUVADA subjects and more frequently than by placebo subjects were headache, abdominal pain and decreased weight.
Potential Drug Interactions
Coadministration of TRUVADA with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir
Please see Prescribing Information for more information about potential drug interactions.
Use of TRUVADA for PrEP in Specific Populations
Pregnancy: There are insufficient human data on the use of TRUVADA during pregnancy to inform a drug-associated risk of birth defects and miscarriage. Because the studies in humans cannot rule out the possibility of harm, TRUVADA should be used during pregnancy only if clearly needed. If an uninfected individual becomes pregnant while taking TRUVADA for a PrEP indication, careful consideration should be given to whether use of TRUVADA should be continued, taking into account the potential increased risk of HIV-1 infection during pregnancy
- There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to TRUVADA during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263
- Lactation: It is not known if the components of TRUVADA (emtricitabine and tenofovir disoproxil fumarate) affect milk production or have effects on the breastfed child. Because of the potential risks to the infant are not known, mothers taking TRUVADA for a PrEP indication should be instructed not to breastfeed. If an uninfected individual acquires HIV-1 infection, it is recommended that she not breastfeed to avoid risking postnatal transmission of HIV-1.
- Pediatrics: The safety and effectiveness of TRUVADA for PrEP in adolescents 15 years of age and older is supported by evidence from adequate and well-controlled studies of TRUVADA for PrEP in adults with additional data from safety and pharmacokinetic studies in previously conducted trials with the individual drug products (EMTRIVA and VIREAD).
Safety, adherence, and resistance of TRUVADA for PrEP in adolescents were evaluated in a clinical trial (ATN113) of 67 HIV-1 uninfected adolescent men aged 15 to 18 years who have sex with men., No seroconversion occurred in subjects that had tenofovir diphosphate (DP) levels associated with protection against HIV exposure. The percentage of subjects with protective levels of study drug, evaluated by tenofovir DP and emtricitabine triphosphate levels, declined markedly after subjects switched from monthly to quarterly visits, suggesting that adolescents may benefit from more frequent visits and counseling.
Dosage and Administration
- Adults and adolescents 15 years of age and older: Dosage of TRUVADA for PrEP for adults is one tablet once per day orally with or without food
- Dose Adjustment for Renal Impairment: Do not prescribe TRUVADA for uninfected individuals with an estimated CrCl below 60 mL/min. If a decrease in estimated CrCl is observed in uninfected individuals while using TRUVADA for PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use
Indication and Usage for Pre-exposure Prophylaxis
TRUVADA® (emtricitabine/tenofovir disoproxil fumarate), a combination of EMTRIVA® (emtricitabine) and VIREAD® (tenofovir disoproxil fumarate), is indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents 15 years of age and older at high risk. This indication is based on clinical trials in adult and adolescent men who have sex with men (MSM) at high risk for HIV-1 infection and in adult heterosexual serodiscordant couples.
Factors that may help identify individuals at high risk include:
- Has partner(s) known to be HIV-1 infected, or
Engages in sexual activity within a high prevalence area or social network and one or more of the following:
- 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
- Partner(s) of unknown HIV-1 status with any of the factors listed above
The following points must be considered when prescribing TRUVADA for pre-exposure prophylaxis:
- Prescribe TRUVADA as part of a comprehensive prevention strategy because TRUVADA is not always effective in preventing the acquisition of HIV-1 infection
- Counsel all uninfected individuals to strictly adhere to their TRUVADA daily dosing schedule because the effectiveness of TRUVADA in reducing the risk of acquiring HIV-1 infection is strongly correlated with adherence and measurable drug levels
- Confirm a negative HIV-1 test immediately prior to initiating TRUVADA for a PrEP indication. If clinical symptoms consistent with acute viral infection are present and recent (<1 month) exposures are suspected, delay starting PrEP for at least 1 month and reconfirm HIV-1 status or use a test approved by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection
- Screen uninfected individuals for HIV-1 infection at least once every 3 months while taking TRUVADA for PrEP. Adolescents may benefit from more frequent visits and counseling
Do not initiate TRUVADA for a PrEP indication if signs or symptoms of acute HIV-1 infection are present
Please report adverse events to Gilead by calling 1-800-445-3235. Adverse events can also be reported to the FDA through www.fda.gov/medwatch or by calling 1-800-FDA-1088.