Comprehensive Guide to Etravirine: Uses, Dosage, Side Effects, and More
What is Etravirine?
Overview of Etravirine
Generic Name: Etravirine
Brand Name: Intelence, generics
Drug Group: Non-nucleoside reverse transcriptase inhibitor (NNRTI, antiretroviral)
Commonly Used For
- Treat HIV-1 infection in treatment-experienced patients.
- Manage multidrug-resistant HIV.
- Support viral suppression in ART regimens.
Key Characteristics
Form: Oral tablets (100 mg, 200 mg, 25 mg for pediatric use) (detailed in Dosage section).
Mechanism: Binds to reverse transcriptase, inhibiting HIV-1 replication with a high genetic barrier to resistance.
Approval: FDA-approved (2008 for Intelence) and EMA-approved for HIV-1 in treatment-experienced patients.
Indications and Uses of Etravirine
Etravirine is indicated for HIV-1 management, particularly in complex cases, leveraging its unique resistance profile:
HIV-1 Infection (Treatment-Experienced): Treats HIV-1 in adults and adolescents (6+ years) with resistance to other NNRTIs (e.g., efavirenz, nevirapine), used with other antiretrovirals, per WHO and CDC guidelines, improving CD4 counts and viral suppression.
Multidrug-Resistant HIV: Manages HIV strains resistant to multiple classes (e.g., NRTIs, PIs), enhancing salvage therapy outcomes, supported by clinical trials like DUET-1 and DUET-2.
Post-Exposure Prophylaxis (PEP): Used off-label as part of PEP regimens for occupational or non-occupational HIV exposure, initiated within 72 hours, under infectious disease supervision, with emerging data on efficacy.
HIV-Associated Neurocognitive Disorders: Investigated off-label to reduce cognitive decline in HIV patients with neurocognitive impairment, improving quality of life, supported by neurology and HIV research.
Prevention of Mother-to-Child Transmission (PMTCT): Employed off-label in pregnant women with multidrug-resistant HIV to reduce transmission risk, administered with other agents, per obstetric and infectious disease protocols.
HIV/Hepatitis C Co-Infection: Explored off-label to optimize ART in patients with HIV/HCV co-infection, improving liver function when combined with direct-acting antivirals, with hepatology evidence.
Pediatric HIV with Resistance: Treats resistant HIV in children (6–17 years) with specific dosing, enhancing adherence and viral control, supported by pediatric HIV studies.
Late-Stage AIDS: Used off-label in advanced AIDS cases with limited options, improving immune reconstitution, with data from infectious disease cohorts.
HIV-2 Infection: Investigated off-label for HIV-2, though less effective due to different reverse transcriptase structure, requiring further research, noted in global health studies.
Dosage of Etravirine
Dosage for Adults
HIV-1 (Treatment-Experienced):
- 200 mg twice daily, taken with food, with other antiretrovirals (e.g., darunavir/ritonavir).
With Ritonavir-Boosted Protease Inhibitors:
- 200 mg twice daily, adjusted if combined with specific PIs, ensuring food intake.
Dosage for Children
6–17 years (weight-based):
- 16–20 kg: 100 mg twice daily.
- 20–25 kg: 125 mg twice daily.
- 25–30 kg: 150 mg twice daily.
- 30 kg: 200 mg twice daily, under pediatric infectious disease supervision.
Not recommended under 6 years.
Dosage for Pregnant Women
Pregnancy Category B: Limited data; use only if benefits outweigh risks, with viral load monitoring. Consult an obstetrician, adjusting dose if needed.
Dosage Adjustments
Renal Impairment: No adjustment needed; monitor in severe cases (CrCl <30 mL/min).
Hepatic Impairment: Mild (Child-Pugh A): No adjustment; moderate (Child-Pugh B): Use caution; severe (Child-Pugh C): Avoid.
Elderly: Start with 100 mg twice daily; increase to 200 mg if tolerated.
Concomitant Medications: Adjust if combined with CYP3A4 inducers/inhibitors (e.g., rifampin, ketoconazole), altering levels.
Additional Considerations
- Take this active ingredient with food to enhance absorption (e.g., a meal or snack).
- Use a pill organizer for consistent twice-daily dosing.
How to Use Etravirine
Administration:
- Swallow tablets whole with a meal or snack, using water; avoid crushing or chewing due to bitter taste.
- Take with other antiretrovirals as part of a regimen, maintaining the same schedule.
Timing: Use twice daily (e.g., morning and evening) with meals, ensuring consistency.
Monitoring: Watch for rash, jaundice, or signs of liver issues (e.g., dark urine).
Additional Tips:
- Store at 20–25°C (68–77°F), protecting from moisture and heat.
- Keep out of reach of children due to toxicity risk.
- Report severe fatigue, abdominal pain, or signs of allergic reaction immediately.
Contraindications for Etravirine
Hypersensitivity: Patients with a known allergy to Etravirine or NNRTIs.
Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C due to toxicity risk.
Concurrent Use with Certain Drugs: Avoid with strong CYP3A4 inducers (e.g., rifampin) or contraindicated medications (e.g., St. John’s wort).
Warnings & Precautions for Etravirine
General Warnings
Hepatotoxicity: Risk of liver injury, especially in HBV/HCV co-infection; monitor liver enzymes regularly.
Severe Skin Reactions: Risk of Stevens-Johnson syndrome or toxic epidermal necrolysis; discontinue if rash worsens.
Immune Reconstitution Syndrome: Risk of inflammation in early therapy; monitor closely.
Fat Redistribution: Lipodystrophy or fat accumulation; assess body composition.
Drug Resistance: Risk with non-adherence; ensure compliance.
Additional Warnings
Cardiovascular Events: Rare risk of myocardial infarction; monitor in at-risk patients.
Neurological Effects: Rare peripheral neuropathy; report numbness or tingling.
Hyperlipidemia: May increase cholesterol/triglycerides; check lipid profiles.
Renal Impairment: Monitor in severe cases; adjust if necessary.
Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.
Use in Specific Populations
Pregnancy: Category B; use only if essential with viral monitoring.
Breastfeeding: Avoid due to HIV transmission risk; monitor infant.
Elderly: Higher risk of toxicity; start with lower doses.
Children: Limited to 6+ years; supervise closely.
Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.
Additional Precautions
- Inform your doctor about liver disease, heart conditions, or medication history before starting this medication.
- Adhere strictly to dosing; missing doses increases resistance risk.
Overdose and Management of Etravirine
Overdose Symptoms
- Nausea, diarrhea, or abdominal pain.
- Severe cases: Liver failure, rash, or neurological symptoms.
- Headache, dizziness, or fatigue as early signs.
- Seizures with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help.
Supportive Care: Administer activated charcoal if ingested recently, monitor vital signs, and provide IV fluids.
Specific Treatment: Manage liver function, electrolytes, and symptoms; no specific antidote.
Monitor: Check liver enzymes, kidney function, and heart rate for 24–48 hours.
Additional Notes
- Overdose risk is low; store securely.
- Report persistent symptoms (e.g., jaundice, confusion) promptly.
Side Effects of Etravirine
Common Side Effects
- Rash (10–20%, monitor for severity)
- Nausea (5–15%, manageable with food)
- Diarrhea (4–12%, transient)
- Headache (3–10%, relieved with rest)
- Fatigue (2–8%, decreases with tolerance)
These effects may subside with dose adjustment.
Serious Side Effects
Seek immediate medical attention for:
- Hepatic: Jaundice, hepatitis, or liver failure.
- Dermatologic: Stevens-Johnson syndrome or toxic epidermal necrolysis.
- Metabolic: Hyperlipidemia, hyperglycemia, or lactic acidosis.
- Cardiovascular: Myocardial infarction or prolonged QT interval.
- Allergic: Rash, angioedema, or anaphylaxis.
Additional Notes
- Regular monitoring for liver function, lipids, and immune status is advised.
- Report any unusual symptoms (e.g., yellow skin, severe weakness) immediately to a healthcare provider.
Drug Interactions with Etravirine
This active ingredient may interact with:
- CYP3A4 Inhibitors/Inducers: Alters levels (e.g., ketoconazole, rifampin); adjust dose.
- Protease Inhibitors: Enhances or reduces effects (e.g., darunavir/ritonavir); monitor.
- Antiarrhythmics: Increases toxicity (e.g., amiodarone); monitor ECG.
- Oral Contraceptives: Reduces efficacy; use backup methods.
- Anticonvulsants: Alters metabolism (e.g., carbamazepine); adjust dose.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Take this NNRTI as prescribed to manage HIV, following the exact schedule.
Monitoring: Report rash, jaundice, or fatigue immediately.
Lifestyle: Avoid alcohol; maintain a balanced diet.
Diet: Take with food to enhance absorption; avoid high-fat meals if possible.
Emergency Awareness: Know signs of liver failure or allergic reaction; seek care if present.
Follow-Up: Schedule regular check-ups every 3–6 months to monitor viral load, liver health, and lipid levels.
Pharmacokinetics of Etravirine
Absorption: Well-absorbed orally (peak at 2.5–4 hours); enhanced with food.
Distribution: Volume of distribution ~351 L; 99.9% protein-bound.
Metabolism: Hepatic via CYP3A4, CYP2C9, and CYP2C19 to inactive metabolites.
Excretion: Primarily fecal (81–86%) as metabolites; renal (1.2%); half-life 41 hours.
Half-Life: 41 hours, with prolonged antiviral effect.
Pharmacodynamics of Etravirine
This drug exerts its effects by:
Binding to a hydrophobic pocket in HIV-1 reverse transcriptase, inhibiting viral DNA synthesis.
Offering activity against NNRTI-resistant strains due to its flexible structure.
Reducing viral load and improving immune function in treatment-experienced patients.
Exhibiting dose-dependent liver and skin toxicity risks.
Storage of Etravirine
- Temperature: Store at 20–25°C (68–77°F); protect from moisture.
- Protection: Keep in original container, away from light.
- Safety: Store in a locked container out of reach of children due to toxicity risk.
- Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Etravirine treat?
A: This medication treats HIV-1 in treatment-experienced patients.
Q: Can this active ingredient cause rash?
A: Yes, rash may occur; report if severe.
Q: Is Etravirine safe for children?
A: Yes, for 6+ years with a doctor’s guidance.
Q: How is this drug taken?
A: Orally as tablets twice daily with food, as directed.
Q: How long is Etravirine treatment?
A: Lifelong for HIV management with monitoring.
Q: Can I use Etravirine if pregnant?
A: Yes, with caution; consult a doctor.
Regulatory Information for Etravirine
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 2008 (Intelence) for HIV-1 in treatment-experienced patients.
European Medicines Agency (EMA): Approved for HIV-1 management.
Other Agencies: Approved globally for HIV; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Intelence (Etravirine) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Etravirine Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Etravirine: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Guidelines on HIV Treatment: Etravirine.
- WHO’s recommendations for Etravirine in HIV therapy.
- AIDS. (2022). Etravirine in Multidrug-Resistant HIV.
- Peer-reviewed article on Etravirine efficacy (note: access may require a subscription).
