Sustiva Information
Sustiva (Efavirenz) Indications And Usage
Sustiva (Efavirenz) in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This indication is based on two clinical trials of at least one year duration that demonstrated prolonged suppression of HIV RNA [see ].
Sustiva (Efavirenz) Dosage Forms And Strengths
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200-mg capsules are gold color, reverse printed with “Sustiva (Efavirenz) ” on the body and imprinted “200 mg” on the cap.
50-mg capsules are gold color and white, printed with “Sustiva (Efavirenz) ” on the gold color cap and reverse printed “50 mg” on the white body.
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600-mg tablets are yellow, capsular-shaped, film-coated tablets, with “Sustiva (Efavirenz) ” printed on both sides.
Sustiva (Efavirenz) Warnings And Precautions
Fifty-three percent (531/1008) of patients receiving Sustiva (Efavirenz) in controlled trials reported central nervous system symptoms (any grade, regardless of causality) compared to 25% (156/635) of patients receiving control regimens [see ]. These symptoms included, but were not limited to, dizziness (28.1% of the 1008 patients), insomnia (16.3%), impaired concentration (8.3%), somnolence (7.0%), abnormal dreams (6.2%), and hallucinations (1.2%). These symptoms were severe in 2.0% of patients, and 2.1% of patients discontinued therapy as a result. These symptoms usually begin during the first or second day of therapy and generally resolve after the first 2-4 weeks of therapy. After 4 weeks of therapy, the prevalence of nervous system symptoms of at least moderate severity ranged from 5% to 9% in patients treated with regimens containing Sustiva (Efavirenz) and from 3% to 5% in patients treated with a control regimen. Patients should be informed that these common symptoms were likely to improve with continued therapy and were not predictive of subsequent onset of the less frequent psychiatric symptoms [see ]. Dosing at bedtime may improve the tolerability of these nervous system symptoms [see ].
Analysis of long-term data from Study 006 (median follow-up 180 weeks, 102 weeks, and 76 weeks for patients treated with Sustiva (Efavirenz) + zidovudine + lamivudine, Sustiva (Efavirenz) + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among Sustiva (Efavirenz) -treated patients were generally similar to those in the indinavir-containing control arm.
Patients receiving Sustiva (Efavirenz) should be alerted to the potential for additive central nervous system effects when Sustiva (Efavirenz) is used concomitantly with alcohol or psychoactive drugs.
Patients who experience central nervous system symptoms such as dizziness, impaired concentration, and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.
Pregnancy Category D.
There are no adequate and well-controlled studies in pregnant women. Sustiva (Efavirenz) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options. [See .]
In controlled clinical trials, 26% (266/1008) of patients treated with 600 mg Sustiva (Efavirenz) experienced new-onset skin rash compared with 17% (111/635) of patients treated in control groups [see ]. Rash associated with blistering, moist desquamation, or ulceration occurred in 0.9% (9/1008) of patients treated with Sustiva (Efavirenz) . The incidence of Grade 4 rash (eg, erythema multiforme, Stevens-Johnson syndrome) in patients treated with Sustiva (Efavirenz) in all studies and expanded access was 0.1%. Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first 2 weeks of initiating therapy with efavirenz (median time to onset of rash in adults was 11 days) and, in most patients continuing therapy with efavirenz, rash resolves within 1 month (median duration, 16 days). The discontinuation rate for rash in clinical trials was 1.7% (17/1008). Sustiva (Efavirenz) can be reinitiated in patients interrupting therapy because of rash. Sustiva (Efavirenz) should be discontinued in patients developing severe rash associated with blistering, desquamation, mucosal involvement, or fever. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash.
Rash was reported in 26 of 57 pediatric patients (46%) treated with Sustiva (Efavirenz) capsules [see ]. One pediatric patient experienced Grade 3 rash (confluent rash with fever), and two patients had Grade 4 rash (erythema multiforme). The median time to onset of rash in pediatric patients was 8 days. Prophylaxis with appropriate antihistamines before initiating therapy with Sustiva (Efavirenz) in pediatric patients should be considered.
Sustiva (Efavirenz) Adverse Reactions
The most significant adverse reactions observed in patients treated with Sustiva (Efavirenz) are:
The most common (>5% in either efavirenz treatment group) adverse reactions of at least moderate severity among patients in Study 006 treated with Sustiva (Efavirenz) in combination with zidovudine/lamivudine or indinavir were rash, dizziness, nausea, headache, fatigue, insomnia, and vomiting.
Sustiva (Efavirenz) Drug Interactions
Efavirenz has been shown to induce CYP3A and CYP2B6. Other compounds that are substrates of CYP3A or CYP2B6 may have decreased plasma concentrations when coadministered with Sustiva (Efavirenz) . studies have demonstrated that efavirenz inhibits CYP2C9, 2C19, and 3A4 isozymes in the range of observed efavirenz plasma concentrations. Coadministration of efavirenz with drugs primarily metabolized by these isozymes may result in altered plasma concentrations of the coadministered drug. Therefore, appropriate dose adjustments may be necessary for these drugs.
Drugs that induce CYP3A activity (eg, phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of efavirenz resulting in lowered plasma concentrations. Drug interactions with Sustiva (Efavirenz) are summarized in and [for pharmacokinetics data see and]. The tables include potentially significant interactions, but are not all inclusive.
Efavirenz does not bind to cannabinoid receptors. False-positive urine cannabinoid test results have been observed in non-HIV-infected volunteers receiving Sustiva (Efavirenz) when the Microgenics CEDIA DAU Multi-Level THC assay was used for screening. Negative results were obtained when more specific confirmatory testing was performed with gas chromatography/mass spectrometry.
Of the three assays analyzed (Microgenics CEDIA DAU Multi-Level THC assay, Cannabinoid Enzyme Immunoassay [Diagnostic Reagents, Inc], and AxSYM Cannabinoid Assay), only the Microgenics CEDIA DAU Multi-Level THC assay showed false-positive results. The other two assays provided true-negative results. The effects of Sustiva (Efavirenz) on cannabinoid screening tests other than these three are unknown. The manufacturers of cannabinoid assays should be contacted for additional information regarding the use of their assays with patients receiving efavirenz.
Sustiva (Efavirenz) Use In Specific Populations
Pregnancy Category D: See .
Antiretroviral Pregnancy Registry:
As of July 2010, the Antiretroviral Pregnancy Registry has received prospective reports of 792 pregnancies exposed to efavirenz-containing regimens, nearly all of which were first-trimester exposures (718 pregnancies). Birth defects occurred in 17 of 604 live births (first-trimester exposure) and 2 of 69 live births (second/third-trimester exposure). One of these prospectively reported defects with first-trimester exposure was a neural tube defect. A single case of anophthalmia with first-trimester exposure to efavirenz has also been prospectively reported; however, this case included severe oblique facial clefts and amniotic banding, a known association with anophthalmia. There have been six retrospective reports of findings consistent with neural tube defects, including meningomyelocele. All mothers were exposed to efavirenz-containing regimens in the first trimester. Although a causal relationship of these events to the use of Sustiva (Efavirenz) has not been established, similar defects have been observed in preclinical studies of efavirenz.
ACTG 382 is an ongoing, open-label study in 57 NRTI-experienced pediatric patients to characterize the safety, pharmacokinetics, and antiviral activity of Sustiva (Efavirenz) in combination with nelfinavir (20-30 mg/kg three times daily) and NRTIs. Mean age was 8 years (range 3-16). Sustiva (Efavirenz) has not been studied in pediatric patients below 3 years of age or who weigh less than 13 kg. At 48 weeks, the type and frequency of adverse experiences was generally similar to that of adult patients with the exception of a higher incidence of rash, which was reported in 46% (26/57) of pediatric patients compared to 26% of adults, and a higher frequency of Grade 3 or 4 rash reported in 5% (3/57) of pediatric patients compared to 0.9% of adults [see and ].
The starting dose of Sustiva (Efavirenz) was 600 mg once daily adjusted to body size, based on weight, targeting AUC levels in the range of 190-380 µM•h [see ]. The pharmacokinetics of efavirenz in pediatric patients were similar to the pharmacokinetics in adults who received 600-mg daily doses of Sustiva (Efavirenz) . In 48 pediatric patients receiving the equivalent of a 600-mg dose of Sustiva (Efavirenz) , steady-state C was 14.2 ± 5.8 µM (mean ± SD), steady-state C was 5.6 ± 4.1 µM, and AUC was 218 ± 104 µM•h.
Sustiva (Efavirenz) Overdosage
Some patients accidentally taking 600 mg twice daily have reported increased nervous system symptoms. One patient experienced involuntary muscle contractions.
Treatment of overdose with Sustiva (Efavirenz) should consist of general supportive measures, including monitoring of vital signs and observation of the patient’s clinical status. Administration of activated charcoal may be used to aid removal of unabsorbed drug. There is no specific antidote for overdose with Sustiva (Efavirenz) . Since efavirenz is highly protein bound, dialysis is unlikely to significantly remove the drug from blood.
Sustiva (Efavirenz) Description
Sustiva (Efavirenz) (efavirenz) is an HIV-1 specific, non-nucleoside, reverse transcriptase inhibitor (NNRTI). Efavirenz is chemically described as (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. Its empirical formula is CHClFNO and its structural formula is:
Efavirenz is a white to slightly pink crystalline powder with a molecular mass of 315.68. It is practically insoluble in water (
Sustiva (Efavirenz) Clinical Studies
For patients treated with Sustiva (Efavirenz) + zidovudine + lamivudine, Sustiva (Efavirenz) + indinavir, or indinavir + zidovudine + lamivudine, the percentage of responders with HIV-1 RNA
A Kaplan-Meier analysis of time to treatment failure through 72 weeks demonstrates a longer duration of virologic suppression (HIV RNA
Sustiva (Efavirenz) How Supplied/storage And Handling
Sustiva (Efavirenz) (efavirenz) capsules are available as follows:
Capsules 200 mg
Bottles of 90 NDC 0056-0474-92
Capsules 50 mg
Bottles of 30 NDC 0056-0470-30
Sustiva (Efavirenz) tablets are available as follows:
Tablets 600 mg
Bottles of 30 NDC 0056-0510-30
Sustiva (Efavirenz) Patient Counseling Information
See .
A statement to patients and healthcare providers is included on the product’s bottle labels:
Sustiva (Efavirenz) may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, nonprescription medication, or herbal products, particularly St. John’s wort.
Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known [see ].
Sustiva (Efavirenz)
Sustiva (Efavirenz)
Sustiva (Efavirenz)
Sustiva (Efavirenz)
