Emtricitabine + Tenofovir alafenamide

Indications

Emtricitabine + Tenofovir alafenamide is used for: HIV Infection

Adult Dose

HIV Infection Indicated in combination with other antiretroviral agents (ARTs) 1 tablet PO qDay Hepatic impairment Mild-to-moderate (Child Pugh class A or B): No dosage adjustment required Severe (Child Pugh class C): Not studied

Child Dose

HIV Infection Indications Indicated in combination with other antiretroviral agents (ARTs), for pediatric patients >12 yr and >35 kg In combination with other ARTs other than protease inhibitors requiring a CYP3A inhibitor in adolescents and children weighing 25-35 kg Dosing <12 years: Safety and efficacy not established >12 years and weight >35 kg: 1 tablet PO qDay

Renal Dose

Renal impairment Mild-to-moderate (CrCl ?30 mL/min): No dosage adjustment required Severe (CrCl <30 mL/min): Not recommended

Administration

Oral Administration For oral use only Swallow 1 capsule once daily with or without food

Contra Indications

Precautions

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with the use of nucleoside analogs in combination with other ARTs; suspended treatment with clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity Patients with HIV-1 should be tested for the presence of chronic HBV infection before initiating ART therapy; emtricitabine/tenofovir AF is not approved for treatment of chronic HBV infection, and safety and efficacy not established in patients coinfected with HIV-1 and HBV (see Black Box Warnings) Immune reconstitution syndrome reported with combination ART therapy, including emtricitabine; during initial phase of combination ART treatment, patients whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment; autoimmune disorders (eg, Grave disease, polymyositis, Guillain-Barré syndrome) may also emerge New-onset or worsening renal impairment reported with tenofovir, including cases of acute renal failure and Fanconi syndrome Not for administration with other drugs containing emtricitabine or tenofovir disoproxil fumarate, or containing tenofovir alafenamide, including Atripla, Complera, Emtriva, Genvoya, Odefsey, Stribild, or Viread; due to similarities between emtricitabine and lamivudine, do not coadminister with other drugs containing lamivudine, including Combivir (lamivudine/zidovudine), Dutrebis (lamivudine/raltegravir)

Pregnancy-Lactation

Pregnancy Pregnancy exposure registry monitors pregnancy outcomes in women exposed to drug during pregnancy; healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263 There are insufficient human data on use during pregnancy to inform a drug-associated risk of birth defects and miscarriage; tenofovir alafenamide (TAF) use in women during pregnancy has not been evaluated; however, emtricitabine (FTC) use during pregnancy has been evaluated in a limited number of women reported to the APR Available data from APR show no difference in risk of overall major birth defects for FTC (2.4%) compared with background rate for major birth defects of 2.7% in a U.S. reference population of Metropolitan Atlanta Congenital Defects Program (MACDP); the rate of miscarriage is not reported in the APR Lactation The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed infants, to avoid risking postnatal transmission of HIV FTC has been shown to be present in human breast milk; not known if TAF is present in human breast milk; tenofovir has been shown to be present in milk of lactating rats and rhesus monkeys after administration of TDF; not known if TAF is present in animal milk Not known if drug combination affects milk production or has effects on breastfed child; because of potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed if they are receiving therapy

Interactions

Side Effects

Side effects of Emtricitabine + Tenofovir alafenamide : 1-10% Nausea (10%) Bone mineral density (BMD) decline >5% (10%) Diarrhea (7%) Creatine kinase >10 x ULN (7%) Headache (6%) Fatigue (5%) LDL-C >190 mg/dL (5%) Total cholesterol >300 mg/dL (2%)

Mode of Action

Emtricitabine: Nucleoside reverse transcriptase inhibitor (NRTI); following phosphorylation, interferes with HIV viral DNA polymerase and inhibits viral replication; cytosine analogue Tenofovir AF: NRTI prodrug of tenofovir; compared with tenofovir disoproxil fumarate (tenofovir DF, Viread), tenofovir alafenamide (AF) is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than tenofovir DF, as well as an improved renal and bone safety profile; inhibits HIV-1 RT by competing with the natural substrate deoxyadenosine 5′-triphosphate and, after incorporation into DNA, by DNA chain termination