EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

EMTRICITABINE (UNII: G70B4ETF4S) (EMTRICITABINE - UNII:G70B4ETF4S), TENOFOVIR DISOPROXIL FUMARATE (UNII: OTT9J7900I) (TENOFOVIR ANHYDROUS - UNII:W4HFE001U5)

Available from:

Zydus Pharmaceuticals USA Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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)] . Emtricitabine and tenofovir disoproxil fumarate tablets are 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 tablets for HIV-1 PrEP [see Dosage and Administration (2.2), 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 [see Warnings and Precautions (5.2)] . Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to emtricitabine and tenofovir disoproxil fumarate during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Data on the use of emtricitabine and tenofovir disoproxil fumarate during pregnancy from observational studies have shown no increased risk of major birth defects. Available data from the APR show no significant difference in the overall risk of major birth defects with first trimester exposure for emtricitabine (FTC) (2.3%) or tenofovir disoproxil fumarate (TDF) (2.1%) compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data) . The rate of miscarriage for individual drugs is not reported in the APR. In the U.S. general population, the estimated background risk of miscarriage in clinically recognized pregnancies is 15% to 20%. In animal reproduction studies, no adverse developmental effects were observed when the components of emtricitabine and tenofovir disoproxil fumarate were administered separately at doses/exposures ≥ 60 (FTC), ≥ 14 (TDF) and 2.7 (tenofovir) times those of the recommended daily dose of emtricitabine and tenofovir disoproxil fumarate (see Data ). Clinical Considerations Disease-associated maternal and/or embryo/fetal risk HIV-1 PrEP: 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 and tenofovir disoproxil fumarate for HIV-1 PrEP, during pregnancy. Data Human Data Emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP: In an observational study based on prospective reports to the APR, 78 HIV-seronegative women exposed to emtricitabine and tenofovir disoproxil fumarate during pregnancy delivered live-born infants with no major malformations. All but one were first trimester exposures, and the median duration of exposure was 10.5 weeks. There were no new safety findings in the women receiving emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP compared with HIV-1 infected women treated with other antiretroviral medications. Emtricitabine: Based on prospective reports to the APR of exposures to FTC-containing regimens during pregnancy resulting in live births (including over 3,300 exposed in the first trimester and over 1,300 exposed in the second/third trimester), the prevalence of major birth defects in live births was 2.6% (95% CI: 2.1% to 3.2%) and 2.3% (95% CI: 1.6% to 3.3%) following first and second/third trimester exposure, respectively, to FTC-containing regimens. Tenofovir Disoproxil Fumarate: Based on prospective reports to the APR of exposures to TDF-containing regimens during pregnancy resulting in live births (including over 4,000 exposed in the first trimester and over 1,700 exposed in the second/third trimester), the prevalence of major birth defects in live births was 2.4% (95% CI: 2.0% to 2.9%) and 2.4% (95% CI: 1.7% to 3.2%) following first and second/third trimester exposure, respectively, to TDF-containing regimens. Methodologic limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at < 20 weeks gestation. Additionally, published observational studies on emtricitabine and tenofovir exposure in pregnancy have not shown an increased risk for major malformations. Animal Data Emtricitabine: FTC was administered orally to pregnant mice (at 0 mg/kg/day, 250 mg/kg/day, 500 mg/kg/day or 1,000 mg/kg/day), and rabbits (at 0 mg/kg/day, 100 mg/kg/day, 300 mg/kg/day or 1,000 mg/kg/day) through organogenesis (on gestation days 6 through 15, and 7 through 19, respectively). No significant toxicological effects were observed in embryo-fetal toxicity studies performed with FTC in mice at exposures (AUC) approximately 60 times higher and in rabbits at approximately 120 times higher than human exposures at the recommended daily dose. In a pre/postnatal development study in mice, FTC was administered orally at doses up to 1,000 mg/kg/day; no significant adverse effects directly related to drug were observed in the offspring exposed daily from before birth (in utero ) through sexual maturity at daily exposures (AUC) of approximately 60 times higher than human exposures at the recommended daily dose. Tenofovir Disoproxil Fumarate: TDF was administered orally to pregnant rats (at 0 mg/kg/day, 50 mg/kg/day, 150 mg/kg/day or 450 mg/kg/day) and rabbits (at 0 mg/kg/day, 30 mg/kg/day, 100 mg/kg/day or 300 mg/kg/day) through organogenesis (on gestation days 7 through 17, and 6 through 18, respectively). No significant toxicological effects were observed in embryo-fetal toxicity studies performed with TDF in rats at doses up to 14 times the human dose based on body surface area comparisons and in rabbits at doses up to 19 times the human dose based on body surface area comparisons. In a pre/postnatal development study in rats, TDF was administered orally through lactation at doses up to 600 mg/kg/day; no adverse effects were observed in the offspring at tenofovir exposures of approximately 2.7 times higher than human exposures at the recommended daily dose of emtricitabine and tenofovir disoproxil fumarate. Risk Summary Based on published data, FTC and tenofovir have been shown to be present in human breast milk (see Data). It is not known if the components of emtricitabine and tenofovir disoproxil fumarate affect milk production or have effects on the breastfed child. Treatment of HIV-1 Infection: The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1. Because of the potential for: (1) HIV transmission (in HIV-negative infants); (2) developing viral resistance (in HIV-positive infants); and (3) adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are taking emtricitabine and tenofovir disoproxil fumarate for the treatment of HIV-1. HIV-1 PrEP: In HIV-uninfected women, the developmental and health benefits of breastfeeding and the mother's clinical need for emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP should be considered along with any potential adverse effects on the breastfed child from emtricitabine and 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. Data HIV-1 PrEP: In a study of 50 breastfeeding women who received emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP between 1 and 24 weeks postpartum (median 13 weeks), after 7 days of treatment, tenofovir was undetectable but FTC was detectable in the plasma of most infants. In these infants, the average FTC plasma concentration was less than 1% of the FTC Cmax observed in HIV-infected infants (up to 3 months of age) receiving the therapeutic dose of FTC (3 mg/kg/day). There were no serious adverse events. Two infants (4%) had an adverse event of mild diarrhea which resolved. Treatment of HIV-1 Infection No pediatric clinical trial was conducted to evaluate the safety and efficacy of emtricitabine and tenofovir disoproxil fumarate in patients with HIV-1 infection. Data from previously conducted trials with the individual drug products, FTC and TDF, were relied upon to support dosage recommendations for emtricitabine and tenofovir disoproxil fumarate. For additional information, consult the prescribing information for EMTRIVA and VIREAD. Emtricitabine and tenofovir disoproxil fumarate should only be administered to HIV-1 infected pediatric patients with body weight greater than or equal to 17 kg and who are able to swallow a tablet. Because it is a fixed-dose combination tablet, emtricitabine and tenofovir disoproxil fumarate cannot be adjusted for patients of lower weight [see Warnings and Precautions (5.5), Adverse Reactions (6.1) and Clinical Pharmacology (12.3)] . Emtricitabine and tenofovir disoproxil fumarate is not approved for use in pediatric patients weighing less than 17 kg. HIV-1 PrEP The safety and effectiveness of emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP in at-risk adolescents weighing at least 35 kg is supported by data from adequate and well-controlled studies of emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP in adults with additional data from safety and pharmacokinetic studies in previously conducted trials with the individual drug products, FTC and TDF, in HIV-1 infected adults and pediatric subjects [see Dosage and Administration (2.5), Adverse Reactions (6.1), Clinical Pharmacology (12.3 and 12.4), and Clinical Studies (14.3 and 14.4)]. Safety, adherence, and resistance were evaluated in a single-arm, open-label clinical trial (ATN113) in which 67 HIV-1 uninfected at-risk adolescent men who have sex with men received emtricitabine and tenofovir disoproxil fumarate once daily for HIV-1 PrEP. The mean age of subjects was 17 years (range 15 years to 18 years); 46% were Hispanic, 52% Black, and 37% White. The safety profile of emtricitabine and tenofovir disoproxil fumarate in ATN113 was similar to that observed in the adult HIV-1 PrEP trials [see Adverse Reactions (6.1)] . In the ATN113 trial, HIV-1 seroconversion occurred in 3 subjects. Tenofovir diphosphate levels in dried blood spot assays indicate that these subjects had poor adherence. No tenofovir- or FTC-associated HIV-1 resistance substitutions were detected in virus isolated from the 3 subjects who seroconverted [see Microbiology (12.4)]. Adherence to study drug, as demonstrated by tenofovir diphosphate 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 [see Warnings and Precautions (5.2)] . Safety and effectiveness of emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP in pediatric patients weighing less than 35 kg have not been established. Clinical trials of FTC, TDF, or emtricitabine and tenofovir disoproxil fumarate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Treatment of HIV-1 Infection The dosing interval for emtricitabine and tenofovir disoproxil fumarate should be modified in HIV-infected adult individuals with estimated creatinine clearance of 30 mL/min to 49 mL/min. Emtricitabine and tenofovir disoproxil fumarate is not recommended in individuals with estimated creatinine clearance below 30 mL/min and in individuals with end-stage renal disease requiring dialysis [see Dosage and Administration (2.6)] . HIV-1 PrEP Emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP is not recommended in HIV-1 uninfected individuals with estimated creatinine clearance below 60 mL/min. If a decrease in estimated creatinine clearance is observed in uninfected individuals while using emtricitabine and tenofovir disoproxil fumarate for HIV-1 PrEP, evaluate potential causes and re-assess potential risks and benefits of continued use [see Dosage and Administration (2.6)] .

Product summary:

Emtricitabine and tenofovir disoproxil fumarate tablets, 100 mg of FTC and 150 mg of TDF (equivalent to 123 mg of tenofovir disoproxil) are white to off-white-colored, oval-shaped, film-coated tablets, debossed with "1364" on one side and plain on other side and are supplied as follows: NDC 70710-1364-3 in bottles of 30 tablets with child-resistant closure NDC 70710-1364-9 in bottles of 90 tablets with child-resistant closure NDC 70710-1364-4 in unit-dose blister cartons of 100 tablets (10 x 10 unit-dose) Emtricitabine and tenofovir disoproxil fumarate tablets, 133 mg of FTC and 200 mg of TDF (equivalent to 163 mg of tenofovir disoproxil) are white to off-white-colored, rectangular-shaped, film-coated tablets, debossed with "1365" on one side and plain on other side and are supplied as follows: NDC 70710-1365-3 in bottles of 30 tablets with child-resistant closure NDC 70710-1365-9 in bottles of 90 tablets with child-resistant closure NDC 70710-1365-4 in unit-dose blister cartons of 100 tablets (10 x 10 unit-dose) Emtricitabine and tenofovir disoproxil fumarate tablets, 167 mg of FTC and 250 mg of TDF (equivalent to 204 mg of tenofovir disoproxil) are white to off-white-colored, modified capsule-shaped, film-coated tablets, debossed with "1366" on one side and plain on other side and are supplied as follows: NDC 70710-1366-3 in bottles of 30 tablets with child-resistant closure NDC 70710-1366-9 in bottles of 90 tablets with child-resistant closure NDC 70710-1366-4 in unit-dose blister cartons of 100 tablets (10 x 10 unit-dose) Emtricitabine and tenofovir disoproxil fumarate tablets, 200 mg of FTC and 300 mg of TDF (equivalent to 245 mg of tenofovir disoproxil) are white to off-white-colored, capsule-shaped, film-coated tablets, debossed with "1367" on one side and plain on other side and are supplied as follows: NDC 70710-1367-3 in bottles of 30 tablets with child-resistant closure NDC 70710-1367-9 in bottles of 90 tablets with child-resistant closure NDC 70710-1367-4 in unit-dose blister cartons of 100 tablets (10 x 10 unit-dose) Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

FUMARATE TABLET, FILM COATED
Zydus Pharmaceuticals USA Inc.
----------
Medication Guide
Emtricitabine (em" trye sye' ta been) and Tenofovir Disoproxil
Fumarate (ten of' oh vir dye"
soe prox' il fue' ma rate) Tablets
Read this Medication Guide before you start taking emtricitabine and
tenofovir disoproxil
fumarate tablets and each time you get a refill. There may be new
information. This
information does not take the place of talking to your healthcare
provider about your medical
condition or your treatment.
This Medication Guide provides information about two different ways
that emtricitabine and
tenofovir disoproxil fumarate tablets may be used. See the section
"What are emtricitabine
and tenofovir disoproxil fumarate tablets?" for detailed information
about how emtricitabine
and tenofovir disoproxil fumarate tablets may be used.
What is the most important information I should know about
emtricitabine and tenofovir
disoproxil fumarate tablets?
Emtricitabine and tenofovir disoproxil fumarate tablets can cause
serious side effects,
including:
•
Worsening of hepatitis B virus infection (HBV). Your healthcare
provider will test
you for HBV before start or when you start treatment with
emtricitabine and
tenofovir disoproxil fumarate tablets. If you have HBV infection and
take
emtricitabine and tenofovir disoproxil fumarate tablets, your HBV may
get worse
(flare-up) if you stop taking emtricitabine and tenofovir disoproxil
fumarate tablets.
A "flare-up" is when your HBV infection suddenly returns in a worse
way than
before.
•
Do not run out of emtricitabine and tenofovir disoproxil fumarate
tablets. Refill your
prescription or talk to your healthcare provider before your
emtricitabine and
tenofovir disoproxil fumarate tablets are all gone.
•
Do not stop taking emtricitabine and tenofovir disoproxil fumarate
tablets without
first talking to your healthcare provider.
•
If you stop taking emtricitabine and tenofovir disoproxil fumarate
tablets, your
healthcare provider will need to check your health often and do

Summary of Product characteristics

EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE- EMTRICITABINE AND
TENOFOVIR DISOPROXIL FUMARATE TABLET, FILM COATED
ZYDUS PHARMACEUTICALS USA INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
EMTRICITABINE AND
TENOFOVIR DISOPROXIL FUMARATE TABLETS SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING
INFORMATION FOR EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
TABLETS.
EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2004
WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B AND RISK OF
DRUG
RESISTANCE WITH USE OF EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
FOR
HIV-1 PRE-EXPOSURE PROPHYLAXIS (PREP) IN UNDIAGNOSED EARLY HIV-1
INFECTION
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
SEVERE ACUTE EXACERBATIONS OF HEPATITIS B (HBV) HAVE BEEN REPORTED IN
HBV-INFECTED
INDIVIDUALS WHO HAVE DISCONTINUED EMTRICITABINE AND TENOFOVIR
DISOPROXIL FUMARATE.
HEPATIC FUNCTION SHOULD BE MONITORED CLOSELY IN THESE INDIVIDUALS WHO
DISCONTINUE
EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE. IF APPROPRIATE
ANTI-HEPATITIS B
THERAPY MAY BE WARRANTED. (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 AT LEAST EVERY 3 MONTHS DURING USE. DRUG-RESISTANT
HIV-1 VARIANTS HAVE
BEEN IDENTIFIED WITH THE 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
INFECTION ARE PRESENT UNLESS NEGATIVE INFECTION STATUS IS CONFIRMED.
(5.2)
INDICATIONS AND USAGE
HIV-1 Treatment (1.1)
Emtricitabine and tenofovir disoproxil fumarate tablets are 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