Sustiva Side Effects

Generic name: efavirenz

Note: This document contains side effect information about efavirenz. Some of the dosage forms listed on this page may not apply to the brand name Sustiva.

Some side effects of Sustiva may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to efavirenz: oral capsule, oral tablet

Get emergency medical help if you have any of these signs of an allergic reaction while taking efavirenz (the active ingredient contained in Sustiva) hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using efavirenz and call your doctor at once if you have a severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Efavirenz may cause serious psychiatric symptoms including confusion, severe depression, suicidal thoughts, aggression, extreme fear, hallucinations, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.

Call your doctor at once if you have a serious side effect such as:

• nausea, stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• fever, chills, body aches, flu symptoms; or

• any other signs of new infection.

Less serious side effects of efavirenz may include:

• mild nausea, vomiting, or stomach pain, diarrhea or constipation;

• cough;

• blurred vision;

• headache, tired feeling, dizziness, spinning sensation;

• trouble concentrating, problems with balance or coordination;

• muscle or joint pain;

• sleep problems (insomnia), unusual dreams; or

• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to efavirenz: oral capsule, oral tablet

General

The most significant side effects associated with efavirenz (the active ingredient contained in Sustiva) have included nervous system symptoms, psychiatric symptoms, and rash. The most common side effects of at least moderate severity have included rash, dizziness, nausea, headache, fatigue, insomnia, and vomiting in greater than 5% of patients treated with efavirenz in combination with lamivudine-zidovudine or indinavir.

Nervous system

Very common (10% or more): Dizziness (any severity: 28.1%), insomnia (any severity: 16.3%)
Common (1% to 10%): Dizziness (moderate or severe intensity: up to 9%), impaired concentration (any severity: 8.3%; moderate or severe intensity: up to 5%), headache (moderate or severe intensity: up to 8%), insomnia (moderate or severe intensity: up to 7%), somnolence (any severity: 7%; moderate or severe intensity: up to 2%), abnormal dreams (any severity: 6.2%, moderate or severe intensity: up to 3%), hallucinations (any severity: 1.2%)
Rare (less than 0.1%): Vacuolar axonopathy and hypersomnolence leading to coma and death (at least 1 patient)
Frequency not reported: Amnesia, agitation, euphoria, depersonalization, confusion, abnormal thinking, stupor, vivid dreams, nightmares, impaired attention span
Postmarketing reports: Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor, vertigo, tinnitus

Nervous system symptoms of any grade and regardless of causality (52.7%) included dizziness, insomnia, impaired concentration, somnolence, abnormal dreams, hallucinations, amnesia, agitation, euphoria, depersonalization, confusion, abnormal thinking, and stupor during clinical trials of efavirenz in combination with other antiretroviral agents. These symptoms were mild in 33.3%, moderate in 17.4%, and severe in 2% of patients. Therapy was discontinued in 2.1% of patients due to these side effects.

Nervous system symptoms generally begin the first or second day of therapy and often resolve after 2 to 4 weeks. Dosing at bedtime may improve the tolerability of these effects.

Vacuolar axonopathy and hypersomnolence leading to coma and death was reported in a patient with elevated efavirenz levels.

Dermatologic

Treatment was discontinued in 1.7% of patients due to rash.

The median time to onset of rash in adults was 11 days. In most patients, the rash resolved within one month despite continued use of the drug. Patients who discontinue efavirenz (the active ingredient contained in Sustiva) therapy because of rash may be reinstated with the use of appropriate antihistamines and/or corticosteroids. The drug should be withdrawn if severe rash develops, such as that associated with blistering, desquamation, mucosal involvement, or fever.

There is limited experience with the use of efavirenz in patients who have previously discontinued other nonnucleoside reverse transcriptase inhibitors (NNRTIs) due to rash. In 19 such patients formerly on nevirapine, approximately half developed a mild to moderate rash, and two of them discontinued efavirenz because of the rash.

Very common (10% or more): Skin rash of any grade (26.3%), rash (includes erythema multiforme, rash, erythematous rash, follicular rash, maculopapular rash, petechial rash, pustular rash, urticaria, macules, papules, erythema, redness, inflammation, allergic rash, welts, hives, itchy, pruritus; moderate or severe intensity: up to 16%), Grade 2 rash (diffuse maculopapular rash, dry desquamation; 14.7%), Grade 1 rash (erythema, pruritus; 10.7%)
Common (1% to 10%): Pruritus (moderate or severe intensity: up to 9%)
Uncommon (0.1% to 1%): Grade 3 rash (vesiculation, moist desquamation, ulceration; 0.8%), Grade 4 rash (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, necrosis requiring surgery, exfoliative dermatitis; 0.1%)
Frequency not reported: Nail disorders, skin discoloration, leukocytoclastic vasculitis
Postmarketing reports: Erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome

Psychiatric

Very common (10% or more): Depression (any severity: up to 19%), anxiety (any severity: up to 13%)
Common (1% to 10%): Nervousness (any severity: up to 7%; moderate or severe intensity: up to 2%), depression (moderate or severe intensity: up to 5%), anxiety (moderate or severe intensity: up to 4%), severe depression (2.4%)
Uncommon (0.1% to 1%): Suicidal ideation (0.7%), nonfatal suicide attempts (0.5%), aggressive behavior (0.4%), paranoid reactions (0.4%), manic reactions (0.2%)
Frequency not reported: Obsessive disorder, irritability, mood changes
Postmarketing reports: Aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide

Psychiatric symptoms generally begin the first or second day of therapy and often resolve after 2 to 4 weeks. Dosing at bedtime may improve the tolerability of these effects.

Psychiatric side effects classified as serious during controlled trials included severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions. One percent of patients discontinued or interrupted efavirenz treatment due to one or more of these side effects.

Gastrointestinal

A 42-year-old HIV-positive woman's saquinavir in her highly active antiretroviral therapy was replaced with efavirenz (the active ingredient contained in Sustiva) to increase compliance. Two weeks following efavirenz initiation, the patient reported severe and constant burning in her tongue, gums, and oral mucosa and was diagnosed with burning mouth syndrome (BMS). Efavirenz therapy was discontinued and the BMS resolved within a week.

Very common (10% or more): Diarrhea (moderate or severe intensity: up to 14%)
Common (1% to 10%): Nausea (moderate or severe intensity: up to 10%), vomiting (moderate or severe intensity: up to 6%), dyspepsia (moderate or severe intensity: up to 4%), abdominal pain (moderate or severe intensity: up to 3%), anorexia (moderate or severe intensity: up to 2%)
Frequency not reported: Pancreatitis, burning mouth syndrome
Postmarketing reports: Constipation, malabsorption

Other

Very common (10% or more): Pain (moderate or severe intensity: up to 13%)
Common (1% to 10%): Fatigue (moderate or severe intensity: up to 8%), elevated amylase (greater than 2 times ULN; up to 6%)
Frequency not reported: False positive urine drug screening test results for tetrahydrocannabinol and benzodiazepines, asymptomatic increases in serum amylase levels, vitamin D deficiency
Postmarketing reports: Flushing, contraceptive failure (with an implantable hormonal contraceptive), asthenia

False positive urine drug screening test results for tetrahydrocannabinol and benzodiazepines have been reported in HIV-infected patients receiving efavirenz. False positive cannabinoid test results have been observed with the CEDIA (Cloned Enzyme Donor ImmunoAssay) DAU Multilevel THC assay and the InstaCheck multidrug Screen Panel. The Triage 8 and the Drug Screen Multi 5 have shown false-positive results for benzodiazepines and tetrahydrocannabinol.

Hepatic

Common (1% to 10%): Increased ALT (greater than 5 times ULN; up to 8%), increased AST (greater than 5 times ULN; up to 8%), increased GGT (greater than 5 times ULN; up to 8%)
Postmarketing reports: Hepatic failure (a few reports were characterized by a fulminant course, with some cases progressing to transplantation or death), hepatic enzyme increase, hepatitis

Isolated elevations of GGT in patients receiving efavirenz may reflect the enzyme inducing effects of the drug not associated with liver toxicity.

During clinical trials, elevations in ALT and AST to greater than five times ULN occurred in 20% and 13%, respectively, of patients seropositive for hepatitis B and/or C treated with efavirenz. Treatment was discontinued in 3% of coinfected patients due to liver or biliary system disorders.

Some of the postmarketing reports of hepatic failure occurred in patients with no preexisting liver disease or other identifiable risk factors.

Hematologic

Common (1% to 10%): Neutropenia (less than 750/mm3; up to 10%)
Rare (less than 0.1%): Hemolytic anemia

Metabolic

Very common (10% or more): Increased nonfasting serum cholesterol (up to 54%), increased HDL (up to 35%), increased nonfasting triglycerides (greater than or equal to 751 mg/dL; up to 11%)
Common (1% to 10%): Increased glucose (greater than 250 mg/dL; up to 5%)
Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")
Postmarketing reports: Hypercholesterolemia, hypertriglyceridemia

Increased nonfasting serum cholesterol and HDL have been reported, although the clinical significance of these elevations is unknown.

Cardiovascular

Frequency not reported: QT interval prolongation, torsades de pointes
Postmarketing reports: Palpitations

Hypersensitivity

Frequency not reported: Skin rash, eosinophilia, and systemic involvement (lymphadenopathy, interstitial nephritis, pneumonia, pulmonary infiltration, hepatitis, fever, rigor, myalgia, arthralgias)
Postmarketing reports: Allergic reactions

Musculoskeletal

Frequency not reported: Osteomalacia (due to efavirenz-induced vitamin D deficiency)
Postmarketing reports: Arthralgia, myalgia, myopathy

Immunologic

Frequency not reported: Immune reconstitution syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Genitourinary

Rare (less than 0.1%): Renal colic, urolithiasis

Analysis of a 3 mm stone, eliminated by a 47-year-old HIV-1-infected male patient, showed a stone consisting of 60% efavirenz metabolites.

Respiratory

Postmarketing reports: Dyspnea

Endocrine

Postmarketing reports: Gynecomastia

Ocular

Postmarketing reports: Abnormal vision

Renal

Rare (less than 0.1%): Podocyte damage (at least 1 report)

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