Usage
- Efavirenz is prescribed in combination with other antiretroviral medications for the treatment of Human Immunodeficiency Virus-1 (HIV-1) infection in adults, adolescents, and children 3 months of age and older and weighing at least 3.5 kg. It is not a cure for HIV/AIDS, but it helps manage the disease by reducing the viral load and slowing the progression to AIDS.
- Pharmacological Classification: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
- Mechanism of Action: Efavirenz binds directly to HIV-1 reverse transcriptase, a viral enzyme essential for HIV replication. This binding inhibits the enzyme’s activity and blocks the conversion of viral RNA into DNA, preventing the virus from multiplying.
Alternate Names
- International Nonproprietary Name (INN): efavirenz
- Brand Name: Sustiva (most common), Stocrin (other regions)
How It Works
- Pharmacodynamics: Efavirenz inhibits HIV-1 reverse transcriptase, leading to a decrease in viral replication and an increase in CD4 cell counts.
- Pharmacokinetics:
- Absorption: Efavirenz is well-absorbed orally. Food increases its bioavailability, which can lead to an increase in side effects. Therefore, it is recommended to take it on an empty stomach.
- Metabolism: Primarily metabolized by the cytochrome P450 enzymes, mainly CYP2B6 and CYP3A4, in the liver. Genetic polymorphisms in CYP2B6 can significantly affect efavirenz metabolism, leading to variations in drug levels and side effects.
- Elimination: Excreted primarily via hepatic metabolism, with less than 1% excreted unchanged in the urine.
- Mode of Action: Efavirenz non-competitively inhibits HIV-1 reverse transcriptase by binding directly to the enzyme’s allosteric site. This binding alters the enzyme’s conformation, preventing it from functioning properly.
- Receptor Binding/Enzyme Inhibition: Efavirenz acts as a non-competitive inhibitor of HIV-1 reverse transcriptase. It doesn’t bind to the active site where nucleosides/nucleotides would bind but instead binds to a distinct allosteric site on the enzyme.
- Elimination Pathways: Hepatic metabolism with negligible renal excretion. CYP2B6 is the major enzyme involved.
Dosage
Standard Dosage
Adults:
- 600 mg orally once daily, preferably at bedtime on an empty stomach.
Children (3 months and older):
- Dosing is weight-based and should be determined by the child’s weight. Refer to pediatric guidelines or resources like the NIH guidelines for specific dosing recommendations for various weight bands.
Special Cases:
- Elderly Patients: No specific dose adjustments, but caution is advised due to potential age-related decline in hepatic and renal function. Monitor closely for side effects.
- Patients with Renal Impairment: No dose adjustment is necessary due to minimal renal excretion.
- Patients with Hepatic Dysfunction:
- Mild impairment: Use with caution, monitor for adverse events.
- Moderate to severe impairment: Not recommended.
- Patients with Comorbid Conditions: Careful consideration is needed, especially with concomitant medications. Consult drug interaction resources.
Clinical Use Cases
Efavirenz is not specifically indicated for use in intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. It is specifically for chronic HIV management.
Dosage Adjustments
- Concomitant Voriconazole: Reduce efavirenz dose to 300 mg daily (using capsule formulation). Increase voriconazole maintenance dose to 400 mg every 12 hours.
- Concomitant Rifampicin (in patients weighing 50 kg or more): Increase efavirenz dose to 800 mg daily.
- CYP2B6 polymorphisms: Patients with slow metabolism genotypes may require dose reductions due to increased risk of side effects.
Side Effects
Common Side Effects:
- Dizziness, insomnia, drowsiness, vivid dreams, difficulty concentrating, headache, nausea, vomiting, diarrhea, fatigue, rash. These often improve after the first few weeks of treatment.
Rare but Serious Side Effects:
- Severe skin reactions (Stevens-Johnson syndrome), liver damage, depression, suicidal thoughts, hallucinations, seizures, changes in body fat distribution.
Long-Term Effects:
- Dyslipidemia, hyperglycemia, changes in body fat distribution.
Adverse Drug Reactions (ADR):
- Severe skin reactions (Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions), hepatic failure, severe psychiatric symptoms.
Contraindications
- Hypersensitivity to efavirenz.
- Severe hepatic impairment.
- Coadministration with elbasvir/grazoprevir.
Drug Interactions
Efavirenz has many drug interactions. It is important to consult a comprehensive drug interaction resource before prescribing.
- CYP450 Interactions: Efavirenz is both an inducer and inhibitor of CYP450 enzymes, affecting the metabolism of many drugs, including warfarin, certain anticonvulsants, some statins, and hormonal contraceptives.
- Examples:
- St. John’s Wort (increased efavirenz metabolism).
- Rifampicin (decreased efavirenz levels).
- Voriconazole (increased efavirenz and voriconazole levels).
- Methadone (decreased methadone levels).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: D. Use is not recommended during pregnancy, especially the first trimester, due to risk of birth defects. If used, inform the patient of the potential risks.
- Breastfeeding: Not recommended due to potential exposure of the infant to efavirenz through breast milk. The risk of HIV transmission through breastfeeding outweighs any potential benefits of efavirenz.
Drug Profile Summary
- Mechanism of Action: NNRTI, inhibits HIV-1 reverse transcriptase.
- Side Effects: Dizziness, insomnia, rash, psychiatric effects, liver toxicity.
- Contraindications: Hypersensitivity, severe hepatic impairment, concomitant use with elbasvir/grazoprevir.
- Drug Interactions: Numerous; consult interaction checker.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 600 mg daily; pediatric: weight-based.
- Monitoring Parameters: Liver function tests, lipid profile, blood glucose, HIV viral load, CD4 count, mental health status.
Popular Combinations
Efavirenz is often combined with two nucleoside reverse transcriptase inhibitors (NRTIs), such as tenofovir disoproxil fumarate and emtricitabine or lamivudine. Fixed-dose combinations of these three drugs are also available.
Precautions
- General Precautions: Evaluate for underlying liver disease, psychiatric history, and other medical conditions. Monitor for side effects throughout treatment.
- Specific Populations: Pregnancy (avoid if possible), breastfeeding (avoid), children and elderly (monitor closely).
- Lifestyle Considerations: Avoid alcohol and other drugs that may exacerbate CNS side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Efavirenz?
A: Adults: 600 mg once daily, preferably at bedtime on an empty stomach. Pediatric dosing is weight-based; consult pediatric guidelines.
Q2: What are the most common side effects?
A: Dizziness, insomnia, drowsiness, vivid dreams, difficulty concentrating, headache, rash.
Q3: What are the serious side effects I should watch out for?
A: Severe skin reactions, liver damage, depression, suicidal thoughts, psychiatric symptoms.
Q4: Can Efavirenz be used during pregnancy?
A: Not generally recommended, especially during the first trimester, due to the risk of birth defects.
Q5: Can Efavirenz be used during breastfeeding?
A: Not recommended due to potential infant exposure. HIV can be transmitted through breast milk.
Q6: How does food affect Efavirenz absorption?
A: Food increases Efavirenz absorption, potentially increasing side effects. Take on an empty stomach.
Q7: What are the major drug interactions with Efavirenz?
A: Many interactions exist. Consult a drug interaction resource. Key interactions include those with rifampicin, voriconazole, St. John’s wort, certain anticonvulsants, some statins, and hormonal contraceptives.
Q8: How does CYP2B6 genotype affect Efavirenz dosing?
A: Patients with slow metabolizing CYP2B6 genotypes may require dose reductions due to increased drug levels and risk of side effects.
Q9: What should I monitor in patients taking Efavirenz?
A: Liver function tests, lipid profile, blood glucose, HIV viral load, CD4 count, mental health status.
Q10: What is the mechanism of action of Efavirenz?
A: It’s a non-nucleoside reverse transcriptase inhibitor (NNRTI). It binds to HIV reverse transcriptase, blocking viral replication.
