ATRIPLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATRIPLA (ATRIPLA).
ATRIPLA is a fixed-dose combination of efavirenz (non-nucleoside reverse transcriptase inhibitor), emtricitabine (nucleoside reverse transcriptase inhibitor), and tenofovir disoproxil fumarate (nucleotide reverse transcriptase inhibitor). Efavirenz binds directly to reverse transcriptase and inhibits RNA-dependent and DNA-dependent DNA polymerase activity. Emtricitabine and tenofovir are phosphorylated to active metabolites that compete with natural substrates and incorporate into viral DNA, causing chain termination.
| Metabolism | Efavirenz is primarily metabolized by CYP2B6 and to a lesser extent by CYP3A4 and CYP2A6. Emtricitabine is minimally metabolized via oxidation and glucuronidation. Tenofovir disoproxil fumarate is a prodrug that undergoes diester hydrolysis to tenofovir, which is then phosphorylated; tenofovir is eliminated renally by glomerular filtration and active tubular secretion. |
| Excretion | Renal: 70% (emtricitabine as unchanged drug and metabolites), 61% (tenofovir as unchanged drug by glomerular filtration and active tubular secretion); Fecal: 16% (efavirenz as unchanged drug and metabolites). |
| Half-life | Efavirenz: 52-76 h (single dose), 40-55 h (multiple doses); Emtricitabine: 10 h; Tenofovir: 17 h. Clinical context: Once-daily dosing due to long half-life of efavirenz; accumulation occurs over 6-10 days to steady state. |
| Protein binding | Efavirenz: 99.5-99.75% bound to albumin; Emtricitabine: <4% bound; Tenofovir: <0.7% bound (plasma proteins). |
| Volume of Distribution | Efavirenz: 252 L (approx. 3.6 L/kg); Emtricitabine: 1.6-1.7 L/kg; Tenofovir: 1.2-1.3 L/kg. Clinical meaning: Large Vd indicates extensive tissue penetration (e.g., CNS, lymphoid tissue). |
| Bioavailability | Oral: Efavirenz 40-45% (with high-fat meal increases 39%; should be taken on empty stomach); Emtricitabine 93%; Tenofovir disoproxil fumarate 25% (increased to 39% with high-fat meal). |
| Onset of Action | Oral: Antiviral effect within days; full virologic suppression typically by 4-12 weeks. |
| Duration of Action | Oral: 24 h (once-daily dosing); continued suppression requires daily adherence; suboptimal adherence leads to rapid viral rebound within days to weeks. |
One tablet (tenofovir disoproxil fumarate 300 mg, emtricitabine 200 mg, efavirenz 600 mg) orally once daily on an empty stomach, preferably at bedtime to minimize CNS side effects.
| Dosage form | TABLET |
| Renal impairment | Not recommended in patients with creatinine clearance <50 mL/min. No dose adjustment required for CrCl ≥50 mL/min. Discontinue if CrCl declines below 50 mL/min. |
| Liver impairment | Not recommended in patients with moderate to severe hepatic impairment (Child-Pugh class B or C). Use with caution in mild hepatic impairment (Child-Pugh class A); no specific dose adjustment available. |
| Pediatric use | Approved for pediatric patients weighing at least 40 kg; dose is one tablet orally once daily. Not approved for patients <40 kg. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function closely due to age-related decline in creatinine clearance. Consider risk of CNS effects (dizziness, impaired concentration) and falls. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ATRIPLA (ATRIPLA).
| Breastfeeding | Not recommended due to potential adverse effects in infant; no M/P ratio available; advise alternative feeding methods. |
| Teratogenic Risk | First trimester: Based on human data, there is a risk of neural tube defects with efavirenz component. Second/third trimester: No specific structural anomalies identified; limited data. |
| Fetal Monitoring | Monitor liver function tests, renal function, CBC, viral load, and CD4 count periodically; consider fetal ultrasound for neural tube defects if exposed in first trimester. |
■ FDA Black Box Warning
WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs. ATRIPLA is not approved for treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued ATRIPLA. Hepatic function should be monitored closely in these patients.
| Serious Effects |
["Hypersensitivity to efavirenz, emtricitabine, tenofovir, or any component of formulation","Coadministration with elbasvir/grazoprevir due to risk of ALT elevations","Coadministration with voriconazole (significantly decreases voriconazole exposure)"]
| Precautions | ["Lactic acidosis/severe hepatomegaly with steatosis","Post-treatment acute exacerbation of hepatitis B","Hepatotoxicity","QT interval prolongation","Nervous system symptoms (e.g., dizziness, insomnia)","Psychiatric symptoms","Convulsions","Renal impairment","Bone effects (decreased bone mineral density)","Immune reconstitution syndrome","Lipid redistribution/accumulation","Risk of adverse reactions due to interactions with other drugs"] |
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| Fertility Effects | No significant impact on fertility reported in clinical studies; efavirenz may cause false-positive urine cannabinoid tests. |
| Food/Dietary | Avoid high-fat meals (e.g., >30g fat) as they increase efavirenz absorption and risk of CNS side effects. Take on an empty stomach or with a light, low-fat meal. No specific food restrictions beyond fat content. |
| Clinical Pearls | Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) is a complete single-tablet regimen for HIV-1. Avoid co-administration with ritonavir-boosted atazanavir due to potential for subtherapeutic atazanavir. Efavirenz may cause neuropsychiatric effects (dizziness, insomnia, vivid dreams) especially in first weeks; dosing at bedtime minimizes CNS symptoms. Screen for renal function and hepatitis B before initiation; tenofovir DF is nephrotoxic and can exacerbate HBV if discontinued abruptly. Contraindicated with drugs that are CYP3A4 substrates with narrow therapeutic index (e.g., midazolam, triazolam, ergotamine). |
| Patient Advice | Take Atripla exactly as prescribed, once daily on an empty stomach or with a light meal; avoid high-fat meals as they increase efavirenz levels and side effects. · Common side effects include dizziness, trouble sleeping, drowsiness, trouble concentrating, and unusual dreams; these often improve after 2-4 weeks. Take at bedtime to reduce impact. · This medication does not cure HIV or prevent transmission; practice safer sex and avoid sharing needles. Regular viral load and CD4 monitoring is essential. · Inform your doctor immediately if you experience symptoms of liver problems (yellowing skin/eyes, dark urine, light stools) or kidney problems (decreased urination, swelling in legs/ankles). · Avoid alcohol and recreational drugs while taking Atripla. Do not take St. John's wort as it reduces drug effectiveness. · Tell all healthcare providers you are taking Atripla, especially before starting new medications, including over-the-counter drugs and supplements. |