Emtricitabine

FDA Drug Information • Also known as: Emtricitabine, Emtriva

Brand Names: Emtricitabine, Emtriva
Dosage Form: POWDER
Product Type: BULK INGREDIENT

⚠ Boxed Warning (Black Box)

WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued EMTRIVA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue EMTRIVA. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.1) ]. WARNING: POSTTREATMENT ACUTE EXACERBATION OF HEPATITIS B See full prescribing information for complete boxed warning . Severe acute exacerbations of Hepatitis B (HBV) have been reported in patients coinfected with HIV-1 and HBV who have discontinued EMTRIVA. Hepatic function should be monitored closely in patients coinfected with HIV-1 and HBV who discontinue EMTRIVA. If appropriate, initiation of anti-hepatitis B therapy may be warranted. ( 5.1 )

Description

11 DESCRIPTION EMTRIVA is the brand name of emtricitabine (FTC), a synthetic nucleoside analog with activity against human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. The chemical name of FTC is 5-fluoro-1-(2 R ,5 S )-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Emtricitabine is the (-) enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position. It has a molecular formula of C 8 H 10 FN 3 O 3 S and a molecular weight of 247.24. It has the following structural formula: Emtricitabine is a white to off-white powder with a solubility of approximately 112 mg/mL in water at 25 °C. The partition coefficient (log P) for FTC is −0.43 and the pKa is 2.65. EMTRIVA is available as capsules or as an oral solution. EMTRIVA capsules are for oral administration. Each capsule contains 200 mg of FTC and the inactive ingredients crospovidone, magnesium stearate, microcrystalline cellulose, povidone, titanium dioxide, gelatin, and FD&C blue No. 2. EMTRIVA oral solution is for oral administration. One milliliter (1 mL) of EMTRIVA oral solution contains 10 mg of FTC in an aqueous solution with the following inactive ingredients: cotton candy flavor, FD&C yellow No. 6, edetate disodium, methylparaben and propylparaben (added as preservatives), sodium phosphate (monobasic), propylene glycol, water, and xylitol (added as a sweetener). Sodium hydroxide and hydrochloric acid may be used to adjust pH. Chemical Structure

What Is Emtricitabine Used For?

1 INDICATIONS AND USAGE EMTRIVA ® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. EMTRIVA, a nucleoside analog HIV-1 reverse transcriptase inhibitor, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Testing: Prior to or when initiating EMTRIVA test for hepatitis B virus infection. ( 2.1 ) EMTRIVA may be taken without regard to food. ( 2.2 ) Adult Patients (18 years of age and older) ( 2.3 ): EMTRIVA capsules: One 200 mg capsule administered once daily orally. EMTRIVA oral solution: 240 mg (24 mL) administered once daily orally. Pediatric Patients (0–3 months of age) ( 2.4 ): EMTRIVA oral solution: 3 mg/kg administered once daily orally. Pediatric Patients (3 months through 17 years of age) ( 2.5 ): EMTRIVA capsules: For children weighing more than 33 kg who can swallow an intact capsule, one 200 mg capsule administered once daily orally. EMTRIVA oral solution: 6 mg/kg up to a maximum of 240 mg (24 mL) administered once daily orally. Dose interval adjustment in adult patients with renal impairment ( 2.6 ): Creatinine Clearance (mL/min) Formulation ≥50 mL/min 30–49 mL/min 15–29 mL/min <15 mL/min or on hemodialysis Hemodialysis Patients: If dosing on day of dialysis, give dose after dialysis. Capsule (200 mg) 200 mg every 24 hours 200 mg every 48 hours 200 mg every 72 hours 200 mg every 96 hours Oral Solution (10 mg/mL) 240 mg every 24 hours (24 mL) 120 mg every 24 hours (12 mL) 80 mg every 24 hours (8 mL) 60 mg every 24 hours (6 mL) 2.1 Testing Prior to Initiation of Treatment with EMTRIVA Prior to or when initiating EMTRIVA, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1) ]. 2.2 Recommended Dosage EMTRIVA is taken by mouth once daily and may be taken without regard to food [see Clinical Pharmacology (12.3) ] . 2.3 Recommended Dosage in Adult Patients (18 years of age and older) EMTRIVA capsules: One 200 mg capsule administered once daily orally. EMTRIVA oral solution: 240 mg (24 mL) administered once daily orally. 2.4 Recommended Dosage in Pediatric Patients (0–3 months of age) EMTRIVA oral solution: 3 mg per kg administered once daily orally. 2.5 Recommended Dosage in Pediatric Patients (3 months through 17 years of age) EMTRIVA oral solution: 6 mg per kg up to a maximum of 240 mg (24 mL) administered once daily orally. EMTRIVA capsules: For pediatric patients weighing more than 33 kg who can swallow an intact capsule, one 200 mg capsule administered once daily orally. 2.6 Dosage Adjustment in Patients with Renal Impairment Table 1 provides dosage interval adjustment for patients with renal impairment. No dosage adjustment is necessary for patients with mild renal impairment (creatinine clearance 50–80 mL/min). The safety and effectiveness of dose adjustment recommendations in patients with moderate to severe renal impairment (creatinine clearance below 50 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 (5.4) , Use in Specific Populations (8.6) ] . Table 1 Dose Interval Adjustment for Adult Patients with Altered Creatinine Clearance Creatinine...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV-1 and HBV [see Warnings and Precautions (5.1) ]. Immune Reconstitution Syndrome [see Warnings and Precautions (5.2) ]. Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.3) ]. Most common adverse reactions (incidence ≥10%) are headache, diarrhea, nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis. Skin hyperpigmentation was very common (≥10%) in pediatric patients. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions from Clinical Trials Experience in Adults More than 2,000 adult subjects with HIV-1 infection have been treated with EMTRIVA alone or in combination with other antiretroviral agents for periods of 10 days to 200 weeks in clinical trials. The most common adverse reactions (incidence greater than or equal to 10%, any severity) identified from any of the three large, controlled clinical trials include headache, diarrhea, nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis. In Trials 301A and 303, the most common adverse reactions that occurred in subjects receiving EMTRIVA with other antiretroviral agents were headache, diarrhea, nausea, and rash, which were generally mild to moderate. Approximately 1% of subjects discontinued participation in the clinical trials due to these events. All adverse reactions were reported with similar frequency in EMTRIVA and control treatment groups except for skin discoloration, which was reported with higher frequency in the EMTRIVA-treated group. Skin discoloration, manifested by hyperpigmentation on the palms or soles, was generally mild and asymptomatic. The mechanism and clinical significance are unknown. A summary of EMTRIVA treatment-emergent clinical adverse reactions in Trials 301A and 303 is provided in Table 2. Table 2 Selected Treatment-Emergent Adverse Reactions (All Grades, Regardless of Causality) Reported in ≥3% of EMTRIVA-Treated Subjects in Either Trial 301A or 303 (0–48 Weeks) 303 301A EMTRIVA + AZT/d4T + NNRTI/PI (N=294) 3TC + AZT/d4T + NNRTI/PI (N=146) EMTRIVA + didanosine + EFV (N=286) d4T + didanosine + EFV (N=285) AZT=zidovudine; d4T=stavudine; NNRTI/PI=non-nucleoside reverse transcriptase inhibitor/protease inhibitor; 3TC=lamivudine; EFV=efavirenz. Body as a Whole Asthenia 16% 10% 12% 17% Headache 13% 6% 22% 25% Abdominal pain 8% 11% 14% 17% Digestive System Diarrhea 23% 18% 23% 32% Nausea 18% 12% 13% 23% Vomiting 9% 7% 9% 12% Dyspepsia 4% 5% 8% 12% Musculoskeletal Myalgia 4% 4% 6% 3% Arthralgia 3% 4% 5% 6% Nervous System Insomnia 7% 3% 16% 21% Depressive disorders 6% 10% 9% 13% Paresthesia 5% 7% 6% 12% Dizziness 4% 5% 25% 26% Neuropathy/peripheral neuritis 4% 3% 4% 13% Abnormal dreams 2% <1% 11% 19% Respiratory Rhinitis 18% 12% 12% 10% Increased cough 14% 11% 14% 8% Skin Rash event Rash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash, and allergic reaction. 17% 14% 30% 33% Laboratory Abnormalities : Laboratory abnormalities in these trials occurred with similar frequency in the EMTRIVA and comparator groups. A summary of Grades 3−4 laboratory abnormalities is provided in Table 3. Table 3 Treatment-Emergent Grades 3–4 Laboratory Abnormalities Reported in ≥1% of EMTRIVA-Treated Subjects in Either Trial 301A or 303 303 301A EMTRIVA + AZT/d4T + NNRTI/PI (N=294)...

Drug Interactions

7 DRUG INTERACTIONS The potential for drug interactions with EMTRIVA has been studied in combination with AZT, indinavir, d4T, famciclovir, and tenofovir DF (TDF). There were no clinically significant drug interactions for any of these drugs. Drug interactions trials are described elsewhere in the labeling [see Clinical Pharmacology (12.3) ].

Contraindications

4 CONTRAINDICATIONS EMTRIVA is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the products. EMTRIVA is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the products. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to EMTRIVA during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no increase in the overall risk of major birth defects with first trimester exposure for emtricitabine (FTC) (2.3%) 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 15–20%. In animal reproduction studies, no adverse developmental effects were observed when FTC was administered at exposures ≥60 times that of the recommended daily dose of EMTRIVA (see Data ) . Data Human Data Based on prospective reports to the APR of exposures to FTC-containing regimens during pregnancy resulting in live births (including over 2,700 exposed in the first trimester and over 1,200 exposed in the second/third trimester), there was no increase between FTC and overall birth defects compared with the background birth defect rate of 2.7% in a U.S. reference population of the MACDP. The prevalence of birth defects in live births was 2.4% (95% CI: 1.9% to 3.1%) with first trimester exposure to FTC-containing regimens and 2.3% (95% CI: 1.5% to 3.3%) with the second/third trimester exposure to FTC-containing regimens. Prospective reports from the APR of overall major birth defects in pregnancies exposed to FTC are compared with a U.S. background major birth defect rate. Methodologic limitations of the APR include the use of MACDP as the external comparator group. Limitations of using an external comparator include differences in methodology and...

Overdosage

10 OVERDOSAGE If overdose occurs, the patient should be monitored for evidence of toxicity, and standard supportive treatment applied as necessary. Hemodialysis treatment removes approximately 30% of the FTC dose over a 3-hour dialysis period starting within 1.5 hours of FTC dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether FTC can be removed by peritoneal dialysis.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING EMTRIVA capsules are available in bottles containing 30 capsules with child-resistant closure as follows: 200 mg of FTC capsules are size 1 hard gelatin capsules with a blue cap and white body and printed with "200 mg" in black on the cap and with "GILEAD" and the corporate logo in black on the body (NDC 61958–0601–1). Store EMTRIVA capsules at 25 °C (77 °F); excursions permitted to 15–30 °C (59–86 °F). Dispense only in original container. Keep container tightly closed. EMTRIVA oral solution is a clear, orange to dark orange liquid containing 10 mg/mL of FTC and is available in unit of use plastic, amber bottles containing 170 mL of oral solution closed with a child resistant closure, and packaged with a marked dosing cup (NDC 61958–0602–1). Store EMTRIVA oral solution refrigerated at 2–8 °C (36–46 °F). EMTRIVA oral solution should be used within 3 months if stored by the patient at 25 °C (77 °F); excursions permitted to 15–30 °C (59–86 °F). Keep container tightly closed.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.