EFAVIRENZ; LAMIVUDINE; TENOFOVIR DISOPROXIL FUMARATE
Clinical safety rating: safe
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds to reverse transcriptase and blocks RNA-dependent and DNA-dependent DNA polymerase activities. Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits HIV reverse transcriptase via DNA chain termination. Tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor (NtRTI) that competes with natural substrates and causes DNA chain termination after phosphorylation to tenofovir diphosphate.
| Metabolism | Efavirenz is primarily metabolized by CYP2B6 and to a lesser extent by CYP3A4. Lamivudine is not significantly metabolized and is eliminated renally as unchanged drug. Tenofovir disoproxil fumarate is hydrolyzed to tenofovir, which is then phosphorylated to tenofovir diphosphate; tenofovir is eliminated renally by glomerular filtration and active tubular secretion. |
| Excretion | Efavirenz: 14-34% unchanged in urine, 16-61% as metabolites in feces; Lamivudine: ~70% unchanged in urine via glomerular filtration and active tubular secretion; Tenofovir disoproxil fumarate: 70-80% unchanged in urine via glomerular filtration and active tubular secretion. |
| Half-life | Efavirenz: 40-55 hours (single dose), 52-76 hours (multiple doses); Lamivudine: 5-7 hours; Tenofovir: 12-18 hours (prolonged to 24-30 hours when co-administered with efavirenz). |
| Protein binding | Efavirenz: 99.5-99.75% bound to albumin; Lamivudine: <36% bound to serum proteins; Tenofovir: <7% bound to proteins. |
| Volume of Distribution | Efavirenz: 2.5-4 L/kg; Lamivudine: 1.3 L/kg; Tenofovir: 0.8-1.2 L/kg. High Vd indicates extensive tissue penetration. |
| Bioavailability | Efavirenz: 40-45% (oral); Lamivudine: 86% (oral) in adults, higher in children; Tenofovir disoproxil fumarate: 25-40% under fasting conditions (increased with high-fat meal). |
| Onset of Action | Oral: Efavirenz reaches peak plasma concentration in 3-5 hours; Lamivudine: 0.5-1 hour; Tenofovir: 1-2 hours. Antiviral effect begins within days, maximal suppression by 4-6 weeks. |
| Duration of Action | Efavirenz: 24-48 hours due to long half-life; Lamivudine: ~8-12 hours; Tenofovir: >24 hours. Dosing interval for fixed-dose combination is once daily. |
| Molecular Weight | Efavirenz: 315.68 Da; Lamivudine: 229.26 Da; Tenofovir disoproxil fumarate: 635.52 Da |
One tablet (efavirenz 600 mg, lamivudine 300 mg, tenofovir disoproxil fumarate 300 mg) orally once daily on an empty stomach (preferably at bedtime to reduce CNS side effects).
| Dosage form | TABLET |
| Renal impairment | Not recommended for CrCl <50 mL/min. For CrCl 30-49 mL/min: use individual components with dose adjustment (e.g., lamivudine 150 mg daily, tenofovir 300 mg every 48 hours, efavirenz 600 mg daily). For CrCl <30 mL/min: contraindicated (tenofovir and lamivudine require significant reduction). |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class A or B: limited data; efavirenz may be used with caution (consider lower dose if intolerant), but lamivudine and tenofovir dose adjustment not typically required unless severe hepatic impairment. Monitor LFTs. |
| Pediatric use | Approved for patients weighing ≥40 kg: one tablet (efavirenz 600 mg, lamivudine 300 mg, tenofovir disoproxil fumarate 300 mg) orally once daily on empty stomach. For weight 25-40 kg: use individual components (efavirenz 400-600 mg once daily, lamivudine 150-300 mg once daily, tenofovir 150-300 mg once daily based on weight). Not recommended for <25 kg. |
| Geriatric use | No specific dose adjustment; monitor renal function (CrCl) and bone mineral density. Increased risk of renal toxicity and bone loss with tenofovir, and CNS effects with efavirenz. Use with caution if multiple comorbidities or polypharmacy. |
| 1st trimester | Use only if clearly needed. May cause teratogenicity (neural tube defects) if used in first trimester; avoid if possible. |
| 2nd trimester | Use with caution; monitor for mitochondrial toxicity and lactic acidosis. |
| 3rd trimester | Use if benefit outweighs risk; optimal dosing and monitoring required. |
Clinical note
Other nephrotoxic drugs increase risk of renal impairment Can cause renal impairment and decreased bone mineral density.
| FDA category | Animal |
| Placental transfer | All three components cross the placenta; lamivudine and tenofovir reach fetal concentrations similar to maternal; efavirenz crosses less efficiently. |
| Breastfeeding |
■ FDA Black Box Warning
WARNING: HEPATOTOXICITY, POST-TREATMENT ACUTE EXACERBATION OF HEPATITIS B, and TERATOGENICITY. Severe acute exacerbation of hepatitis B has been reported in patients who are co-infected with hepatitis B virus (HBV) and discontinue lamivudine or tenofovir disoproxil fumarate. Efavirenz can cause teratogenic effects; avoid use during first trimester of pregnancy.
| Common Effects | Hepatitis B |
| Serious Effects |
Known hypersensitivity to any componentConcomitant use with voriconazole (efavirenz reduces voriconazole levels)Severe hepatic impairment (Child-Pugh Class C)Combination with elbasvir/grazoprevir (efavirenz reduces efficacy)
| Precautions | Hepatotoxicity: Monitor hepatic function; discontinue if evidence of hepatotoxicity., Exacerbation of hepatitis B: Monitor HBV-infected patients for several months after discontinuation., Teratogenicity: Avoid use in pregnancy, especially first trimester., Lactic acidosis and severe hepatomegaly with steatosis: Reported with NRTIs., Renal impairment: Monitor renal function; adjust dose or avoid with creatinine clearance <30 mL/min., Bone effects: Decreased bone mineral density reported with tenofovir; monitor in patients with risk factors., Immune reconstitution syndrome: May occur during initial treatment., CNS effects: Efavirenz may cause dizziness, impaired concentration, and abnormal dreams; avoid driving., Lipid increases: Monitor lipid levels., QT prolongation: Caution with drugs that prolong QT interval., Seizures: Use caution in patients with history of seizures. |
Loading safety data…
| Efavirenz and tenofovir are excreted in breast milk in low concentrations; lamivudine is also present. Potential for HIV transmission via breastfeeding contraindicates use in HIV+ mothers in developed countries; in resource-limited settings, WHO recommends exclusive breastfeeding with maternal ART. |
| Lactation Rating | L3 - Moderate Safety |
| Teratogenic Risk | Efavirenz is contraindicated in pregnancy (first trimester) due to neural tube defects; lamivudine and tenofovir disoproxil fumarate have low teratogenic risk. Risk summary: First trimester – efavirenz associated with CNS defects (risk ratio 2.3); second/third trimester – low risk for lamivudine and tenofovir; combination use requires careful risk-benefit assessment. |
| Fetal Monitoring | Maternal: HIV viral load, CD4 count, liver function tests, renal function (creatinine, BUN), complete blood count; fetal: ultrasound for neural tube defects if efavirenz used in first trimester (consider alternative ART). Monitor for anemia, neutropenia, hepatotoxicity. |
| Fertility Effects | No known significant impact on fertility. Efavirenz may cause dizziness, which could affect sexual activity; no direct effects on spermatogenesis or oocyte development reported. Lamivudine and tenofovir are not associated with fertility impairment. |
| Food/Dietary | Take on an empty stomach, preferably at least 1 hour before or 2 hours after a meal, as high-fat meals increase efavirenz absorption and may worsen CNS side effects. Avoid alcohol and recreational drugs as they may increase CNS side effects. No specific food restrictions beyond moderate fat intake. |
| Clinical Pearls | Single-tablet regimen for HIV-1; monitor renal function due to tenofovir; avoid in CrCl <50 mL/min; CNS effects (dizziness, abnormal dreams) common with efavirenz, often improve within 2-4 weeks; do not use with elvitegravir/cobicistat due to antagonism; screen for hepatitis B before initiation as lamivudine and tenofovir are active against HBV. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily on an empty stomach, preferably at bedtime to reduce CNS side effects. · Do not miss doses; if you miss a dose, take it as soon as you remember, but do not double the next dose. · This drug does not cure HIV, but it can reduce the risk of transmitting HIV to others; continue to practice safe sex and avoid sharing needles. · Report any signs of kidney problems (decreased urination, swelling in legs/ankles) or liver problems (yellowing skin/eyes, dark urine, abdominal pain) to your healthcare provider immediately. · Common side effects include dizziness, drowsiness, vivid dreams, and trouble sleeping, which often improve within the first few weeks; taking at bedtime may help. · Do not take with other medications containing efavirenz, lamivudine, tenofovir, or emtricitabine unless directed by your healthcare provider. · If you have hepatitis B, do not stop this medication without consulting your doctor, as it may cause a severe flare-up of hepatitis. |