Prescription Drug Information: Emtricitabine and Tenofovir Disoproxil Fumarate

EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE — emtricitabine and tenofovir disoproxil fumarate tablet, film coated
Laurus Labs Limited

WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B and RISK OF DRUG RESISTANCE WITH USE OF EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE TABLETS FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED EARLY HIV-1 INFECTION

Severe acute exacerbations of hepatitis B virus (HBV) have been reported in HBV-infected patients who have discontinued emtricitabine and tenofovir disoproxil fumarate. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in HBV-infected patients who discontinue emtricitabine and tenofovir disoproxil fumarate. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1)].

Emtricitabine and tenofovir disoproxil fumarate used for HIV-1 PrEP must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initiating and periodically (at least every 3 months) during use. Drug-resistant HIV-1 variants have been identified with use of emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP if signs or symptoms of acute HIV-1 infection are present unless negative infection status is confirmed [see Warnings and Precautions (5.2)].

1 INDICATIONS AND USAGE

1.1 Treatment of HIV-1 Infection

Emtricitabine and tenofovir disoproxil fumarate tablets are 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 tablets are indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in at-risk adults and adolescents weighing at least 35 kg. 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)].

When considering emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP, factors that help to identify individuals at risk may include:

  • has partner(s) 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

2 DOSAGE AND ADMINISTRATION

2.1 Testing Prior to Initiation of Emtricitabine and Tenofovir Disoproxil Fumarate Tablets for Treatment of HIV-1 Infection or for HIV-1 PrEP

Prior to or when initiating emtricitabine and tenofovir disoproxil fumarate tablets, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1)].

Prior to initiation and during use of emtricitabine and tenofovir disoproxil fumarate tablets, 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 [see Warnings and Precautions (5.3)].

2.2 HIV-1 Screening for Individuals Receiving Emtricitabine and Tenofovir Disoproxil Fumarate Tablets for HIV-1 PrEP

Screen all patients for HIV-1 infection before initiating emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP and at least once every 3 months while taking emtricitabine and tenofovir disoproxil fumarate tablets [see Indications and Usage (1.2), Contraindications (4) and Warnings and Precautions (5.2)].

2.3 Recommended Dosage for Treatment of HIV-1 Infection in Adults and Pediatric Patients Weighing at Least 35 kg

Emtricitabine and tenofovir disoproxil fumarate tablets is a two-drug fixed dose combination product containing emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). The recommended dosage of emtricitabine and tenofovir disoproxil fumarate tablets in adults and in pediatric patients weighing at least 35 kg is one tablet (containing 200 mg of FTC and 300 mg of TDF) once daily taken orally with or without food [see Clinical Pharmacology (12.3)].

2.4 Recommended Dosage for Treatment of HIV-1 Infection in Pediatric Patients Weighing at Least 17 kg and Able to Swallow a Tablet

The recommended oral dosage of emtricitabine and tenofovir disoproxil fumarate tablets for pediatric patients weighing at least 17 kg and who can swallow a tablet is presented in Table 1. Tablets should be taken once daily with or without food. Weight should be monitored periodically and the emtricitabine and tenofovir disoproxil fumarate tablets dose adjusted accordingly.

Table 1 Dosing for Treatment of HIV-1 Infection in Pediatric Patients Weighing 17 kg to less than 35 kg
Body Weight (kg) Dosing of Emtricitabine and Tenofovir Disoproxil Fumarate Tablets (FTC/TDF)
17 to less than 22 one 100 mg /150 mg tablet once daily
22 to less than 28 one 133 mg /200 mg tablet once daily
28 to less than 35 one 167 mg /250 mg tablet once daily

2.5 Recommended Dosage for HIV-1 PrEP

The dosage of emtricitabine and tenofovir disoproxil fumarate tablets in HIV-1 uninfected adults and adolescents weighing at least 35 kg is one tablet (containing 200 mg of FTC and 300 mg of TDF) once daily taken orally with or without food [see Clinical Pharmacology (12.3)].

2.6 Dosage Adjustment in Patients with Renal Impairment

Treatment of HIV-1 Infection

Table 2 provides dosage interval adjustment for patients with renal impairment. No dosage adjustment is necessary for HIV-1 infected patients with mild renal impairment (creatinine clearance 50 to 80 mL/min). The safety and effectiveness of the dosing interval adjustment recommendations in patients with moderate renal impairment (creatinine clearance 30 to 49 mL/min) have not been clinically evaluated; therefore, clinical response to treatment and renal function should be closely monitored in these patients [see Warnings and Precautions (5.3)].

No data are available to make dosage recommendations in pediatric patients with renal impairment.

Table 2 Dosage Interval Adjustment for HIV-1 Infected Adult Patients with Altered Creatinine Clearance
Creatinine Clearance (mL/min)a
≥50 30 to 49 <30 (Including Patients Requiring Hemodialysis)
Recommended Dosing Interval Every 24 hours Every 48 hours Emtricitabine and tenofovir disoproxil fumarate is not recommended.

a. Calculated using ideal (lean) body weight

HIV-1 PrEP

Emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP is not recommended in HIV-1 uninfected individuals with estimated creatinine clearance below 60 mL/min [see Warnings and Precautions (5.3)].

If a decrease in estimated creatinine clearance is observed in uninfected individuals while using emtricitabine and tenofovir disoproxil fumarate tablets for HIV-1 PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use [see Warnings and Precautions (5.3)].

3 DOSAGE FORMS AND STRENGTHS

Emtricitabine and Tenofovir Disoproxil Fumarate Tablets are available in one dose strength:

  • 200 mg/300 mg Tablets: 200 mg of FTC and 300 mg of TDF (equivalent to 245 mg of tenofovir disoproxil): blue colored, capsule shaped, film-coated biconvex tablets, debossed with ‘LA49’ on one side and plain on the other side.

4 CONTRAINDICATIONS

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)].

5 WARNINGS AND PRECAUTIONS

5.1 Severe Acute Exacerbation of Hepatitis B in Patients with HBV Infection

All patients 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 patients who have discontinued emtricitabine and tenofovir disoproxil fumarate. Patients 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, initiation of anti-hepatitis B therapy may be warranted, especially in patients 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 Acquiring 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 only as part of a comprehensive prevention strategy that includes other prevention measures, such as safer sex practices, because emtricitabine and tenofovir disoproxil fumarate is not always effective in preventing acquisition of HIV-1 [see Clinical Studies (14.3 and 14.4)].

  • 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.

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 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 and 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.

While using emtricitabine and 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 [see Use in Specific Populations (8.4)].

  • If a screening 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 HIV-1, including acute or primary HIV-1 infection.

Counsel uninfected individuals to strictly adhere to the recommended 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 [see Use in Specific Populations (8.4), Microbiology (12.4),and Clinical Studies (14.3 and 14.4)].

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Medication Sections

Medication Information by RSS

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2020. All Rights Reserved.