efavirenz
Sustiva

Available forms
Available by prescription only
Capsules: 50 mg, 100 mg, 200 mg
Tablets: 600 mg

Indications and dosages
 Treatment of HIV-1 infection. Adults: 600 mg P.O. once daily on an empty stomach, preferably at bedtime, with a protease inhibitor or with nucleoside analogue reverse transcriptase inhibitors.
Children age 3 and older who weigh 40 kg (88 lb) or more: 600 mg P.O. once daily with a protease inhibitor or with nucleoside analogue reverse transcriptase inhibitors.
Children age 3 and older who weigh 10 to 39 kg (22 to 87 lb): Give the following doses with a protease inhibitor or with nucleoside analogue reverse transcriptase inhibitors.
Children who weigh 33 to 39 kg (72 to 87 lb): 400 mg P.O. once daily.
Children who weigh 25 to 32 kg (55 to 71 lb): 350 mg P.O. once daily.
Children who weigh 20 to 24 kg (44 to 54 lb): 300 mg P.O. once daily.
Children who weigh 15 to 19 kg (33 to 43 lb): 250 mg P.O. once daily.
Children who weigh 10 to 14 kg (22 to 32 lb): 200 mg P.O. once daily.

Pharmacodynamics
Antiretroviral action: Efavirenz inhibits the transcription of HIV-1 RNA to DNA, a critical step in the viral replication process. Therefore, drug lowers the amount of HIV in the blood (the viral load) and increases CD4 lymphocytes.

Pharmacokinetics
Absorption: Relative bioavailability increased by about 50% when taken with a high-fat meal.
Distribution: About 99.5% to 99.75% bound to plasma proteins; also distributed into CSF.
Metabolism: Metabolized primarily by cytochrome P-450 3A4 and cytochrome P-450 2B6 to hydroxylated inactive metabolites.
Excretion: 14% to 34% is excreted in urine (less than 1% is excreted unchanged), and 16% to 61% is excreted in feces. Terminal elimination half-life is 52 to 76 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to efavirenz or its components. Use cautiously in patients with hepatic impairment and in those concurrently receiving hepatotoxic drugs.

Interactions
Drug-drug. Amprenavir,clarithromycin, indinavir, lopinavir and ritonavir: May decrease plasma levels. Consider alternative therapy or dosage adjustment.
Drugs that induce the cytochrome P-450 enzyme system (such as phenobarbital, rifabutin, rifampin): Increase efavirenz clearance and lower plasma levels. Avoid use together.
Ergot derivatives, midazolam, triazolam: Competition for cytochrome P-450 enzyme system may inhibit metabolism of these drugs and cause serious or life-threatening adverse events (such as arrhythmias, prolonged sedation, or respiratory depression). Avoid use together.
Hormonal contraceptives: Potential interaction hasn’t been determined. Advise use of barrier contraception in addition to hormonal contraceptive.
Psychoactive drugs: May cause additive CNS effects. Avoid use together.
Ritonavir: Increases risk of adverse effects. Monitor patient.
Saquinavir: Decreases levels of both drugs. Don’t use with saquinavir as sole protease inhibitor.
Warfarin: Alters warfarin levels and effects. Monitor INR.
Drug-herb. St. John’s wort: May increase efavirenz clearance and lower plasma levels. Discourage use together.
Drug-food. High-fat meals: May increase absorption of drug. Instruct patient to follow a low-fat diet.
Drug-lifestyle. Alcohol use: Enhanced CNS effects. Discourage alcohol use.

Adverse reactions
CNS: abnormal dreams or thinking, agitation, amnesia, confusion, depersonalization, depression, dizziness, euphoria, fatigue, hallucinations, delusions, headache, hypoesthesia, impaired concentration, insomnia, somnolence, nervousness, fever.
GI: abdominal pain, anorexia, diarrhea, dyspepsia, flatulence, nausea, vomiting, pancreatitis.
GU: hematuria, kidney stones.
Skin: increased sweating, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, rash, pruritus.

Effects on lab test results
• May increase ALT, AST, and cholesterol levels.

Overdose and treatment
Overdose may cause CNS symptoms and involuntary muscle contractions.
 Treatment should involve supportive care, including frequent monitoring of vital signs and observation of clinical status. Activated charcoal may be given to aid in the removal of unabsorbed drug. Efavirenz is unlikely to be removed by hemodialysis.

Special considerations
• Give drug with other antiretrovirals because resistant viruses emerge rapidly when drug is used alone. Don’t use drug as monotherapy or add it as a single agent to a failing regimen.
• Giving drug with ritonavir is more likely to cause adverse effects (such as dizziness, nausea, paresthesia) and laboratory abnormalities (elevated liver enzyme levels).
Pregnant patients
• Pregnancy must be ruled out before starting therapy in women of childbearing age.
Breast-feeding patients
• HIV-infected women shouldn’t breast-feed their infants to avoid risking transmitting the disease. The drug appears in breast milk of animals. Instruct affected women not to breast-feed their infants.
Pediatric patients
• Children may be more prone to adverse reactions, especially diarrhea, nausea, vomiting, and rash.
Geriatric patients
• Elderly patients may be more susceptible to CNS effects of drug.

Patient education
• Tell patient to take drug once daily on an empty stomach, preferably at bedtime.
• Inform patient that drug doesn’t cure HIV infection and that it won’t deter development of opportunistic infections and other complications of HIV disease or transmission of HIV to others through sexual contact or blood contamination.
• Instruct patient to take drug at the same time daily and always with other antiretrovirals.
• Tell patient to take drug exactly as prescribed and not to stop without medical approval.
• Instruct patient to report adverse reactions.
• Inform patient that rash is the most common adverse effect. If this occurs, tell patient to report it immediately because it may be serious in rare cases.
• Advise patient that dizziness, difficulty sleeping or concentrating, drowsiness, or unusual dreams may occur the first few days of therapy. Reassure him that these symptoms generally resolve after 2 to 4 weeks and may be less problematic if drug is taken at bedtime.
• Tell patient to avoid alcoholic beverages, driving, or operating machinery until the effects of the drug are known.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use