Makindo Medical Notes

⚠️ Key Point: Efavirenz is effective and widely used but notable for CNS and psychiatric side effects and significant drug–drug interactions due to hepatic enzyme induction. 💊 Often given at bedtime to minimise CNS symptoms and taken on an empty stomach to reduce absorption-related toxicity.

🧠 About

• Efavirenz is a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) used in the management of HIV-1 infection.
• It is a core component of many first-line antiretroviral regimens (e.g. the fixed-dose combination Atripla® with emtricitabine and tenofovir).
• Always check the BNF entry for the latest prescribing guidance and drug interaction details.

⚙️ Mode of Action

• Efavirenz binds directly to reverse transcriptase at an allosteric (non-competitive) site, distinct from where nucleoside analogues act.
• This binding induces a conformational change in the enzyme, blocking DNA polymerase activity and halting viral replication.
• Active against HIV-1 but not HIV-2 (which has a structurally different reverse transcriptase).

💊 Indications & Dosing

• HIV-1 infection: Efavirenz 600 mg once daily.
• Take on an empty stomach (high-fat meals increase absorption and toxicity).
• Usually administered at bedtime to reduce CNS side effects such as vivid dreams and dizziness.
• Always used in combination antiretroviral therapy (cART) — never as monotherapy.

⚠️ Interactions

• Induces CYP3A4 and CYP2B6 — accelerates metabolism of many drugs, including hormonal contraceptives, methadone, some antiepileptics, and antifungals.
• Can reduce the effectiveness of oral contraceptives — advise additional contraception (e.g. condoms).
• Avoid combining with other CYP inducers or hepatotoxic drugs without careful review.
• See BNF for a full list of interactions.

⚕️ Cautions

• Teratogenic potential: Animal data suggest neural tube defects — avoid in early pregnancy if possible; use contraception during and for 12 weeks after treatment.
• Psychiatric history: Efavirenz can cause or worsen depression, anxiety, vivid dreams, and suicidal ideation.
• Liver disease or hepatitis B/C co-infection: increased risk of hepatotoxicity; monitor LFTs regularly.
• Genetic polymorphisms (e.g. CYP2B6 slow metabolisers, common in some ethnic groups) can increase CNS toxicity.

🚫 Contraindications

• Severe hepatic impairment.
• Previous severe psychiatric reaction to efavirenz.
• Concurrent use with St John’s wort or other potent CYP3A4 inducers.
• See BNF for full list.

💥 Side Effects

• CNS effects: vivid dreams, dizziness, insomnia, poor concentration, depersonalisation — usually within first 2–4 weeks.
• Psychiatric effects: dysphoria, anxiety, or depression — may require dose adjustment or switch.
• Dermatological: rash (can progress to Stevens–Johnson syndrome, though rare).
• Hepatic: transaminitis or hepatitis, especially in co-infection with HBV/HCV.
• Metabolic: hyperlipidaemia and fat redistribution with long-term use.

📖 Educational Summary

Efavirenz exemplifies the non-nucleoside class of reverse transcriptase inhibitors, which act allosterically rather than by chain termination. Its hallmark side effects — vivid dreams and mood changes — reflect its lipophilicity and CNS penetration. From a teaching perspective, this makes it an excellent example of how pharmacokinetics (CNS entry, hepatic induction) shapes both efficacy and adverse profile. It’s often replaced in newer regimens by drugs with fewer neuropsychiatric effects (e.g. doravirine or rilpivirine), but understanding its mechanism remains key to grasping antiretroviral pharmacology.

📚 References

• Efavirenz – British National Formulary
• BHIVA Guidelines for the Treatment of HIV (2023)
• NICE NG93: HIV Testing and Management
• Harrison’s Principles of Internal Medicine, 21st Edition – HIV Pharmacology