Efavirenz, a synthetic antiretroviral agent, is a non- nucleoside reverse transcriptase inhibitor. While Efavirenz is pharmacologically related to other non nucleoside reverse transcriptase inhibitors, Efavirenz differs structurally from these drugs and also differs structurally from other currently available anti-retroviral agents.

Pharmacology

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against HIV-1. It blocks the RNA- and DNA-dependent polymerase activities including HIV-1 replication.

Efavirenz in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV- RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long term suppression of HIVRNA with Efavirenz.

Adults: The recommended dosage of Efavirenz is 600 mg orally, once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs).

Pediatric Patients: Following table describes the recommended dose of Efavirenz for pediatric patients 3 years of age or older and weighing between 10 and 40 kg. The recommended dosage of Efavirenz for pediatric patients weighing greater than 40 kg is 600 mg, once daily.

• 10 to <15 kg: 200 mg
• 15 to < 20 kg: 250 mg
• 20 to < 25 kg: 300 mg
• 25 to < 32.5 kg: 350 mg
• 32.5 to < 40 kg: 400 mg
• 40 kg: 600 mg

Administration

It is recommended that Efavirenz be taken on an empty stomach, preferably at bedtime.

Hypersensitivity. Severe hepatic impairment. Lactation. Concomitant admin with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, ergot alkaloids, St John’s wort.

Rashes, psychiatric or CNS disturbances, amnesia, agitation, confusion, dizziness, vertigo, headache, euphoria, insomnia or somnolence, impaired concentration, abnormal thinking or dreaming, depersonalisation, convulsions, hallucinations, nausea, vomiting, diarrhoea, pancreatitis, fatigue, hepatic failure, photoallergic dermatitis; autoimmune disorders (e.g. Graves’ disease, polymyositis, Guillain-Barre syndrome), osteonecrosis. Accumulation or redistribution of body fat (lipodystrophy) including central obesity, peripheral and facial wasting, buffalo hump, breast enlargement, cushingoid appearance. Metabolic abnormalities e.g. hypercholesterolaemia, hyperglycaemia, hypertriglyceridaemia, hyperlactataemia, insulin resistance.

Overdose Effects

Symptoms: Increased adverse CNS effects including involuntary muscle contractions.

Management: Supportive and symptomatic treatment. May administer activated charcoal.

Patient with history of seizures and psychiatric disorders; acute porphyria. Patients receiving voriconazole or rifampicin (weighing ≥50 kg). Discontinue if severe rash or fever develops. Moderate hepatic and severe renal impairment. Childn. Pregnancy.

Use in Special Populations

Paediatric use: Efavirenz has not been studied in pediatric patients below 3 years of age or who weigh less than 10 kg.

Women taking hormone-based birth control: Women should not rely only on hormone-based birth control, such as pills, injections, or implants, because Efavirenz may make these contraceptives ineffective.

Pregnancy & Lactation

Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Lactation: Efavirenz may pass through breast milk and cause serious harm to the baby. It should not be used during lactation.