Efavirenz

Uses

Efavirenz in combination with other antiretroviral agents is used 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.

Efavirenz is also used to associated treatment for these conditions: Human Immunodeficiency Virus Type 1 (HIV-1) Infection

How Efavirenz works

Similar to zidovudine, efavirenz inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase). Antiviral activity of efavirenz is dependent on intracellular conversion to the active triphosphorylated form. The rate of efavirenz phosphorylation varies, depending on cell type. It is believed that inhibition of reverse transcriptase interferes with the generation of DNA copies of viral RNA, which, in turn, are necessary for synthesis of new virions. Intracellular enzymes subsequently eliminate the HIV particle that previously had been uncoated, and left unprotected, during entry into the host cell. Thus, reverse transcriptase inhibitors are virustatic and do not eliminate HIV from the body. Even though human DNA polymerase is less susceptible to the pharmacologic effects of triphosphorylated efavirenz, this action may nevertheless account for some of the drug's toxicity.

Dosage

Efavirenz dosage

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

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

Side Effects

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.

Precaution

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.

Interaction

Additive CNS effects w/ psychoactive drugs. May alter plasma warfarin concentrations. May reduce plasma concentrations of HIV integrase inhibitors (e.g. dolutegravir), other HIV NNRTIs (e.g. etravirine), HMG-CoA reductase inhibitors (e.g. simvastatin). Plasma concentrations of efavirenz is increased and that of voriconazole is reduced when given concomitantly. Reduced plasma concentrations w/ rifampicin.

Food Interaction

• Avoid excessive or chronic alcohol consumption. Alcohol may contribute to additive adverse effects when taken with efavirenz.
• Take on an empty stomach. Taking efavirenz with food increases efavirenz concentrations and may increase the frequency of adverse reactions. In patients who cannot swallow capsules, the capsule contents can be administered with a small amount of food or infant formula using the capsule sprinkle method of administration.

[Moderate] ADJUST DOSING INTERVAL: Administration with food increases the plasma concentrations of efavirenz and may increase the frequency of adverse reactions.

According to the product labeling, administration of efavirenz capsules (600 mg single dose) with a high-fat

For efavirenz tablets, administration of a single 600 mg dose with a high-fat

MANAGEMENT: Efavirenz should be taken on an empty stomach, preferably at bedtime.

Dosing at bedtime may improve the tolerability of nervous system symptoms such as dizziness, insomnia, impaired concentration, somnolence, abnormal dreams and hallucinations, although they often resolve on their own after the first 2 to 4 weeks of therapy .

Patients should be advised of the potential for additive central nervous system effects when efavirenz is used concomitantly with alcohol or psychoactive drugs, and to avoid driving or operating hazardous machinery until they know how the medication affects them.

Efavirenz Cholesterol interaction

[Moderate] Increases in total cholesterol and triglycerides have resulted during treatment with efavirenz.

Lipid levels monitoring should be performed before starting treatment and at periodic intervals during therapy.

Efavirenz Drug Interaction

Moderate: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, acetaminophen, acetaminophen, emtricitabine / tenofovir, emtricitabine / tenofovir, valproic acid, valproic acidUnknown: aspirin, aspirin, multivitamin, multivitamin, cyanocobalamin, cyanocobalamin, pyridoxine, pyridoxine, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Efavirenz Disease Interaction

Moderate: cholesterol, liver disease, mental symptoms, QT prolongation, seizures

Half Life

40-55 hours

Elimination Route

Nearly all of the urinary excretion of the radiolabeled drug was in the form of metabolites.

Pregnancy & Breastfeeding use

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.

Contraindication

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

Special Warning

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.

Acute Overdose

Symptoms: Increased adverse CNS effects including involuntary muscle contractions.

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

Storage Condition

Store at 25°C.

Innovators Monograph

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