Dosing and uses of Atripla (emtricitabine/tenofovir DF/efavirenz)
Adult dosage forms and strengths
emtricitabine/tenofovir DF/efavirenz
Note: tenofovir disoproxil fumarate (ie, tenofovir DF)
tablet
- 200mg/300mg/600mg
HIV Infection
1 tablet PO qDay on empty stomach (preferably qHS)
Dosage modification
- Rifampin coadministration in patient ≥50 kg: An additional 200 mg/day of efavirenz is recommended
- Rifampin decreases level or effect of efavirenz by CYP3A4 induction
Renal & Hepatic Impairment
Moderate-to-severe (CrCl <50 mL/min): Not recommended
Hepatic Impairment
Mild hepatic impairment (Child-Pugh class A): Caution advised; no dosage adjustment required
Moderate or severe hepatic impairment (Child-Pugh Class B, C): Not recommended
Administration
Dosing at bedtime may increase tolerability to nausea/vomiting
Pediatric dosage forms and strengths
emtricitabine/tenofovir DF/efavirenz
Note: tenofovir disoproxil fumarate (ie, tenofovir DF)
tablet
- 200mg/300mg/600mg
HIV Infection
<12 years: Safety and efficacy not established
≥12 years and <40 kg: Not recommended
≥12 years and ≥40 kg: 1 tab PO qDay on empty stomach
Dosage modification
- Rifampin coadministration in patient ≥50 kg: An additional 200 mg/day of efavirenz is recommended
- Rifampin decreases level or effect of efavirenz by CYP3A4 induction
Renal & Hepatic Impairment
Moderate-to-severe (CrCl <50 mL/min): Not recommended
Hepatic Impairment
Mild hepatic impairment (Child-Pugh class A): Caution advised; no dosage adjustment required
Moderate or severe hepatic impairment (Child-Pugh Class B, C): Not recommended
Administration
Dosing at bedtime may increase tolerability to nausea/vomiting
Atripla (emtricitabine/tenofovir DF/efavirenz) adverse (side) effects
>10%
Hypercholesterolemia (22%)
1-10%
Depression (9%)
Dizziness (8%)
Fatigue (9%)
Insomnia (5%)
Somnolence (4%)
Abnormal dreams (4%)
Rash (7%)
Increased triglycerides (4%)
Hyperglycemia (2%)
Nausea (9%)
Vomiting (2%)
Incrased serum amylase (8%)
Neutropenia (3%)
Increased ALT (2%)
Increased alkaline phosphatase (1%)
Increased creatinine (9%)
Hematuria (3%)
Sinusitis (8%)
Upper respiratory infection (8%)
Nasopharyngitis (5%)
<1%
Gycosuria
Warnings
Black box warnings
emtricitabine
- Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals
- Not FDA approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of this drug have not been established in patients coinfected with HBV and HIV
tenofovir
- Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued antihepatitis B therapy
- Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue therapy
- Resumption of antihepatitis B therapy may be warranted
- Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) reported with nucleoside analogues alone or in combination
Contraindications
Hypersensitivity
Concurrent administration with voriconazole
Cautions
(All NRTIs): Risk of potentially fatal lactic acidosis and severe hepatomegaly with steatosis
Do not coadminister with drugs containing emtricitabine, tenofovir, lamivudine, or efavirenz
Rash may occur; for patients with history of life-threatening rash (eg, Stevens-Johnson syndrome), discontinue therapy if severe rash develops
Increased risk of renal impairment; estimate CrCl in all patients before initiating and avoid concurrent or recent use of nephrotoxic drugs
History of hepatitis B or C
May cause CNS depression (avoid hazardous tasks)
May cause redistribution of fat (cushingoid appearance)
Immune resonstitution syndrome may occur
Use caution in patients with a history of seizures
Redistribution/accumulation of body fat observed in patients receiving antiretroviral therapy
Caution in patients with predisposition to pshychological reactions
Hepatic impairment
- Not recommended with moderate-to-severe hepatic impairment because there are insufficient data
- Patients with mild hepatic impairment may be treated with Atripla at the approved dose
- Efavirenz extensively metabolized by CYP450; limited clinical experience in patients with hepatic impairment
- Monitor liver enzymes in patients treated with other medications associated with liver toxicity
Bone effects of tenofovir
- Bone mineral density may decrease
- Osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported
See also individual drugs
- Emtricitabine
- Tenofovir
- Efavirenz
Pregnancy and lactation
Pregnancy category: d
Lactation: excretion in milk unknown/contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Atripla (emtricitabine/tenofovir DF/efavirenz)
Mechanism of action
Emtricitabine: Nucleoside Reverse Transcriptase Inhibitor (NRTI); following phosphorylation, interferes with HIV viral DNA polymerase and inhibits viral replication; cytosine analogue
Tenofovir: Nucleoside Reverse Transcriptase Inhibitor (NRTI); following hydrolysis and phosphorylation, inhibits HIV-1 reverse transcriptase by competing with AMP as substrate
Efavirenz: Non-nucleoside reverse transcriptase inhibitor (NNRTI); binds to reverse transcriptase and blocks DNA polymerase activity; does not require phosphorylation for activity
