Emtriva Drug Information

EMTRIVA ® is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Testing Prior to Initiation of Treatment with EMTRIVA Prior to or when initiating EMTRIVA, test patients for hepatitis B virus infection.

Recommended Dosage EMTRIVA is taken by mouth once daily and may be taken without regard to food.

• Recommended Dosage in Adult Patients (18 years of age and older) EMTRIVA capsules: One 200 mg capsule 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.

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.

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 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. The most common adverse reactions (incidence greater than or equal to 10%, all grades) included diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.

Table 4 provides the treatment-emergent adverse reactions (Grades 2−4) occurring in greater than or equal to 5% of subjects treated in any treatment group. The adverse reaction profile in pediatric subjects was generally comparable to that observed in clinical trials of EMTRIVA in adult subjects. Hyperpigmentation was more frequent in children.

Additional adverse reactions identified from this trial include anemia. Selected treatment-emergent adverse events, regardless of causality, reported in subjects during 48 weeks of treatment were the following: infection (4 ).

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.

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. 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 populations, as well as confounding due to the underlying disease. Additionally, published observational studies on FTC exposure in pregnancy have not shown an increased risk for major malformations. 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.

Pediatric Use The safety and efficacy of FTC in patients between 3 months and 21 years of age is supported by data from three open-label, nonrandomized clinical trials in which FTC was administered to 169 HIV-1 infected treatment-naïve and experienced (defined as virologically suppressed on a 3TC containing regimen for which FTC was substituted for 3TC) subjects. The pharmacokinetics of FTC were studied in 20 neonates born to HIV-1 positive mothers. All neonates were HIV-1 negative at the end of the trial; the efficacy of FTC in preventing or treating HIV-1 could not be determined.

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

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.