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 Clinical Studies (14)].
Sustiva Dosage and Administration
Adults
The recommended dosage of Sustiva (efavirenz) is 600 mg orally, once daily, in combination with a protease inhibitor and/or nucleoside analogue reverse transcriptase inhibitors (NRTIs). It is recommended that Sustiva be taken on an empty stomach, preferably at bedtime. The increased efavirenz concentrations observed following administration of Sustiva with food may lead to an increase in frequency of adverse reactions [see Clinical Pharmacology (12.3)]. Dosing at bedtime may improve the tolerability of nervous system symptoms [see Warnings and Precautions (5.5), Adverse Reactions (6.1), and Patient Counseling Information (17.4)].
Concomitant Antiretroviral Therapy
Sustiva must be given in combination with other antiretroviral medications [see Indications and Usage (1), Warnings and Precautions (5.2), Drug Interactions (7.1), and Clinical Pharmacology (12.3)].
Dosage Adjustment
If Sustiva is coadministered with voriconazole, the voriconazole maintenance dose should be increased to 400 mg every 12 hours and the Sustiva dose should be decreased to 300 mg once daily using the capsule formulation (one 200-mg and two 50-mg capsules or six 50-mg capsules). Sustiva tablets should not be broken. See Drug Interactions (7.1, Table 7) and Clinical Pharmacology (12.3, Tables 8 and 9).
If Sustiva is coadministered with rifampin to patients weighing 50 kg or more, an increase in the dose of Sustiva to 800 mg once daily is recommended [see Drug Interactions (7.1, Table 7) and Clinical Pharmacology (12.3, Table 9)].
Pediatric Patients
It is recommended that Sustiva be taken on an empty stomach, preferably at bedtime. Table 1 describes the recommended dose of Sustiva for pediatric patients 3 years of age or older and weighing between 10 and 40 kg [see Use in Specific Populations (8.4)]. The recommended dosage of Sustiva for pediatric patients weighing greater than 40 kg is 600 mg once daily.
| Body Weight | Sustiva Dose (mg) | |
|---|---|---|
| kg | lbs | |
| 10 to less than 15 | 22 to less than 33 | 200 |
| 15 to less than 20 | 33 to less than 44 | 250 |
| 20 to less than 25 | 44 to less than 55 | 300 |
| 25 to less than 32.5 | 55 to less than 71.5 | 350 |
| 32.5 to less than 40 | 71.5 to less than 88 | 400 |
| at least 40 | at least 88 | 600 |
Dosage Forms and Strengths
• Capsules
200-mg capsules are gold color, reverse printed with “Sustiva” on the body and imprinted “200 mg” on the cap.
50-mg capsules are gold color and white, printed with “Sustiva” on the gold color cap and reverse printed “50 mg” on the white body.
• Tablets
600-mg tablets are yellow, capsular-shaped, film-coated tablets, with “Sustiva” printed on both sides.
Contraindications
Hypersensitivity
Sustiva is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product.
Contraindicated Drugs
For some drugs, competition for CYP3A by efavirenz could result in inhibition of their metabolism and create the potential for serious and/or life-threatening adverse reactions (eg, cardiac arrhythmias, prolonged sedation, or respiratory depression). Drugs that are contraindicated with Sustiva are listed in Table 2.
| Drug Class: Drug Name | Clinical Comment |
|---|---|
| Antimigraine: ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine) | Potential for serious and/or life-threatening reactions such as acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. |
| Benzodiazepines: midazolam, triazolam | Potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. |
| Calcium channel blocker: bepridil | Potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| GI motility agent: cisapride | Potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| Neuroleptic: pimozide | Potential for serious and/or life-threatening reactions such as cardiac arrhythmias. |
| St. John’s wort (Hypericum perforatum) | May lead to loss of virologic response and possible resistance to efavirenz or to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI). |
Warnings and Precautions
Drug Interactions
Efavirenz plasma concentrations may be altered by substrates, inhibitors, or inducers of CYP3A. Likewise, efavirenz may alter plasma concentrations of drugs metabolized by CYP3A or CYP2B6 [see Contraindications (4.2) and Drug Interactions (7.1)].
Resistance
Sustiva must not be used as a single agent to treat HIV-1 infection or added on as a sole agent to a failing regimen. Resistant virus emerges rapidly when efavirenz is administered as monotherapy. The choice of new antiretroviral agents to be used in combination with efavirenz should take into consideration the potential for viral cross-resistance.
Coadministration with Related Products
Coadministration of Sustiva with ATRIPLA (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) is not recommended, since efavirenz is one of its active ingredients.
Psychiatric Symptoms
Serious psychiatric adverse experiences have been reported in patients treated with Sustiva. In controlled trials of 1008 patients treated with regimens containing Sustiva for a mean of 2.1 years and 635 patients treated with control regimens for a mean of 1.5 years, the frequency (regardless of causality) of specific serious psychiatric events among patients who received Sustiva or control regimens, respectively, were severe depression (2.4%, 0.9%), suicidal ideation (0.7%, 0.3%), nonfatal suicide attempts (0.5%, 0), aggressive behavior (0.4%, 0.5%), paranoid reactions (0.4%, 0.3%), and manic reactions (0.2%, 0.3%). When psychiatric symptoms similar to those noted above were combined and evaluated as a group in a multifactorial analysis of data from Study 006, treatment with efavirenz was associated with an increase in the occurrence of these selected psychiatric symptoms. Other factors associated with an increase in the occurrence of these psychiatric symptoms were history of injection drug use, psychiatric history, and receipt of psychiatric medication at study entry; similar associations were observed in both the Sustiva and control treatment groups. In Study 006, onset of new serious psychiatric symptoms occurred throughout the study for both Sustiva-treated and control-treated patients. One percent of Sustiva-treated patients discontinued or interrupted treatment because of one or more of these selected psychiatric symptoms. There have also been occasional postmarketing reports of death by suicide, delusions, and psychosis-like behavior, although a causal relationship to the use of Sustiva cannot be determined from these reports. Patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of Sustiva, and if so, to determine whether the risks of continued therapy outweigh the benefits. See Adverse Reactions (6.1).
Nervous System Symptoms
Fifty-three percent (531/1008) of patients receiving Sustiva in controlled trials reported central nervous system symptoms (any grade, regardless of causality) compared to 25% (156/635) of patients receiving control regimens [see Adverse Reactions (6.1, Table 4)]. 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 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 Warnings and Precautions (5.4)]. Dosing at bedtime may improve the tolerability of these nervous system symptoms [see Dosage and Administration (2)].
Analysis of long-term data from Study 006 (median follow-up 180 weeks, 102 weeks, and 76 weeks for patients treated with Sustiva + zidovudine + lamivudine, Sustiva + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among Sustiva-treated patients were generally similar to those in the indinavir-containing control arm.
Patients receiving Sustiva should be alerted to the potential for additive central nervous system effects when Sustiva 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.
Reproductive Risk Potential
Pregnancy Category D. Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. Pregnancy should be avoided in women receiving Sustiva. Barrier contraception must always be used in combination with other methods of contraception (eg, oral or other hormonal contraceptives). Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of Sustiva is recommended. Women of childbearing potential should undergo pregnancy testing before initiation of Sustiva. If this drug is used during the first trimester of pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
There are no adequate and well-controlled studies in pregnant women. Sustiva 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 Use in Specific Populations (8.1).]
Rash
In controlled clinical trials, 26% (266/1008) of patients treated with 600 mg Sustiva experienced new-onset skin rash compared with 17% (111/635) of patients treated in control groups [see Adverse Reactions (6.1, Table 5)]. Rash associated with blistering, moist desquamation, or ulceration occurred in 0.9% (9/1008) of patients treated with Sustiva. The incidence of Grade 4 rash (eg, erythema multiforme, Stevens-Johnson syndrome) in patients treated with Sustiva 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 can be reinitiated in patients interrupting therapy because of rash. Sustiva 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 capsules [see Adverse Reactions (6.1, 6.2)]. 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 in pediatric patients should be considered.
Hepatotoxicity
Monitoring of liver enzymes before and during treatment is recommended for patients with underlying hepatic disease, including hepatitis B or C infection; patients with marked transaminase elevations; and patients treated with other medications associated with liver toxicity [see Adverse Reactions (6.1) and Use in Specific Populations (8.6)]. A few of the postmarketing reports of hepatic failure occurred in patients with no pre-existing hepatic disease or other identifiable risk factors [see Adverse Reactions (6.3)]. Liver enzyme monitoring should also be considered for patients without pre-existing hepatic dysfunction or other risk factors. In patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range, the benefit of continued therapy with Sustiva needs to be weighed against the unknown risks of significant liver toxicity.
Convulsions
Convulsions have been observed in patients receiving efavirenz, generally in the presence of known medical history of seizures [see Nonclinical Toxicology (13.2)]. Caution must be taken in any patient with a history of seizures. Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.1)].
Lipid Elevations
Treatment with Sustiva has resulted in increases in the concentration of total cholesterol and triglycerides [see Adverse Reactions (6.1)]. Cholesterol and triglyceride testing should be performed before initiating Sustiva therapy and at periodic intervals during therapy.
Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Sustiva. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.
Fat Redistribution
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
Adverse Reactions
The most significant adverse reactions observed in patients treated with Sustiva are:
- psychiatric symptoms [see Warnings and Precautions (5.4)],
- nervous system symptoms [see Warnings and Precautions (5.5)],
- rash [see Warnings and Precautions (5.7)].
The most common (>5% in either efavirenz treatment group) adverse reactions of at least moderate severity among patients in Study 006 treated with Sustiva in combination with zidovudine/lamivudine or indinavir were rash, dizziness, nausea, headache, fatigue, insomnia, and vomiting.
Clinical Trials Experience in Adults
Because clinical studies are conducted under widely varying conditions, the adverse reaction rates reported cannot be directly compared to rates in other clinical studies and may not reflect the rates observed in clinical practice.
Selected clinical adverse reactions of moderate or severe intensity observed in ≥2% of Sustiva-treated patients in two controlled clinical trials are presented in Table 3.
| Study 006 LAM-, NNRTI-, and Protease Inhibitor-Naive Patients | Study ACTG 364 NRTI-experienced, NNRTI-, and Protease Inhibitor-Naive Patients | |||||
| Adverse Reactions | Sustivab + ZDV/LAM (n=412) | Sustivab + Indinavir (n=415) | Indinavir + ZDV/LAM (n=401) | Sustivab + Nelfinavir + NRTIs (n=64) | Sustivab + NRTIs (n=65) | Nelfinavir + NRTIs (n=66) |
|---|---|---|---|---|---|---|
| 180 weeksc | 102 weeksc | 76 weeksc | 71.1 weeksc | 70.9 weeksc | 62.7 weeksc | |
| a Includes adverse events at least possibly related to study drug or of unknown relationship for Study 006. Includes all adverse events regardless of relationship to study drug for Study ACTG 364. | ||||||
| b Sustiva provided as 600 mg once daily. | ||||||
| c Median duration of treatment. | ||||||
| d Includes erythema multiforme, rash, rash erythematous, rash follicular, rash maculopapular, rash petechial, rash pustular, and urticaria for Study 006 and macules, papules, rash, erythema, redness, inflammation, allergic rash, urticaria, welts, hives, itchy, and pruritus for ACTG 364. | ||||||
| — = Not Specified. | ||||||
| ZDV = zidovudine, LAM = lamivudine. | ||||||
| Body as a Whole | ||||||
| Fatigue | 8% | 5% | 9% | 0 | 2% | 3% |
| Pain | 1% | 2% | 8% | 13% | 6% | 17% |
| Central and Peripheral Nervous System | ||||||
| Dizziness | 9% | 9% | 2% | 2% | 6% | 6% |
| Headache | 8% | 5% | 3% | 5% | 2% | 3% |
| Insomnia | 7% | 7% | 2% | 0 | 0 | 2% |
| Concentration impaired | 5% | 3% | <1% | 0 | 0 | 0 |
| Abnormal dreams | 3% | 1% | 0 | — | — | — |
| Somnolence | 2% | 2% | <1% | 0 | 0 | 0 |
| Anorexia | 1% | <1% | <1% | 0 | 2% | 2% |
| Gastrointestinal | ||||||
| Nausea | 10% | 6% | 24% | 3% | 2% | 2% |
| Vomiting | 6% | 3% | 14% | — | — | — |
| Diarrhea | 3% | 5% | 6% | 14% | 3% | 9% |
| Dyspepsia | 4% | 4% | 6% | 0 | 0 | 2% |
| Abdominal pain | 2% | 2% | 5% | 3% | 3% | 3% |
| Psychiatric | ||||||
| Anxiety | 2% | 4% | <1% | — | — | — |
| Depression | 5% | 4% | <1% | 3% | 0 | 5% |
| Nervousness | 2% | 2% | 0 | 2% | 0 | 2% |
| Skin & Appendages | ||||||
| Rashd | 11% | 16% | 5% | 9% | 5% | 9% |
| Pruritus | <1% | 1% | 1% | 9% | 5% | 9% |
Pancreatitis has been reported, although a causal relationship with efavirenz has not been established. Asymptomatic increases in serum amylase levels were observed in a significantly higher number of patients treated with efavirenz 600 mg than in control patients (see Laboratory Abnormalities).
Nervous System Symptoms
For 1008 patients treated with regimens containing Sustiva and 635 patients treated with a control regimen in controlled trials, Table 4 lists the frequency of symptoms of different degrees of severity and gives the discontinuation rates for one or more of the following nervous system symptoms: dizziness, insomnia, impaired concentration, somnolence, abnormal dreaming, euphoria, confusion, agitation, amnesia, hallucinations, stupor, abnormal thinking, and depersonalization [see Warnings and Precautions (5.5)]. The frequencies of specific central and peripheral nervous system symptoms are provided in Table 3.
| Percent of Patients with: | Sustiva 600 mg Once Daily (n=1008) | Control Groups (n=635) |
|---|---|---|
| % | % | |
| a Includes events reported regardless of causality. | ||
| b Data from Study 006 and three Phase 2/3 studies. | ||
| c “Mild” = Symptoms which do not interfere with patient’s daily activities. | ||
| d “Moderate” = Symptoms which may interfere with daily activities. | ||
| e “Severe” = Events which interrupt patient’s usual daily activities. | ||
| Symptoms of any severity | 52.7 | 24.6 |
| Mild symptomsc | 33.3 | 15.6 |
| Moderate symptomsd | 17.4 | 7.7 |
| Severe symptomse | 2.0 | 1.3 |
| Treatment discontinuation as a result of symptoms | 2.1 | 1.1 |
Serious psychiatric adverse experiences have been reported in patients treated with Sustiva. In controlled trials, psychiatric symptoms observed at a frequency of >2% among patients treated with Sustiva or control regimens, respectively, were depression (19%, 16%), anxiety (13%, 9%), and nervousness (7%, 2%).
Rash
For 1008 adults and 57 pediatric patients treated with regimens containing Sustiva and 635 patients treated with a control regimen in controlled trials, the frequency of rash by NCI grade and the discontinuation rates as a result of rash in clinical studies are provided in Table 5 [see Warnings and Precautions (5.7)].
| Percent of Patients with: | Description of Rash Gradec | Sustiva 600 mg Once Daily Adults (n=1008) | Sustiva Pediatric Patients (n=57) | Control Groups Adults (n=635) |
|---|---|---|---|---|
| % | % | % | ||
| a Includes events reported regardless of causality. | ||||
| b Data from Study 006 and three Phase 2/3 studies. | ||||
| c NCI Grading System. | ||||
| Rash of any grade | — | 26.3 | 45.6 | 17.5 |
| Grade 1 rash | Erythema, pruritus | 10.7 | 8.8 | 9.8 |
| Grade 2 rash | Diffuse maculopapular rash, dry desquamation | 14.7 | 31.6 | 7.4 |
| Grade 3 rash | Vesiculation, moist desquamation, ulceration | 0.8 | 1.8 | 0.3 |
| Grade 4 rash | Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, necrosis requiring surgery, exfoliative dermatitis | 0.1 | 3.5 | 0.0 |
| Treatment discontinuation as a result of rash | — | 1.7 | 8.8 | 0.3 |
As seen in Table 5, rash is more common in pediatric patients and more often of higher grade (ie, more severe) [see Warnings and Precautions (5.7)].
Experience with Sustiva in patients who discontinued other antiretroviral agents of the NNRTI class is limited. Nineteen patients who discontinued nevirapine because of rash have been treated with Sustiva. Nine of these patients developed mild-to-moderate rash while receiving therapy with Sustiva, and two of these patients discontinued because of rash.
Laboratory Abnormalities
Selected Grade 3-4 laboratory abnormalities reported in ≥2% of Sustiva-treated patients in two clinical trials are presented in Table 6.
| Study 006 LAM-, NNRTI-, and Protease Inhibitor-Naive Patients | Study ACTG 364 NRTI-experienced, NNRTI-, and Protease Inhibitor-Naive Patients | ||||||
|---|---|---|---|---|---|---|---|
| Variable | Limit | Sustivaa + ZDV/LAM (n=412) | Sustivaa + Indinavir (n=415) | Indinavir + ZDV/LAM (n=401) | Sustivaa + Nelfinavir + NRTIs (n=64) | Sustivaa + NRTIs (n=65) | Nelfinavir + NRTIs (n=66) |
| 180 weeksb | 102 weeksb | 76 weeksb | 71.1 weeksb | 70.9 weeksb | 62.7 weeksb | ||
| a Sustiva provided as 600 mg once daily. | |||||||
| b Median duration of treatment. | |||||||
| c Isolated elevations of GGT in patients receiving Sustiva may reflect enzyme induction not associated with liver toxicity. | |||||||
| d Nonfasting. | |||||||
| ZDV = zidovudine, LAM = lamivudine, ULN = Upper limit of normal, ALT = alanine aminotransferase, AST = aspartate aminotransferase, GGT = gamma-glutamyltransferase. | |||||||
| Chemistry | |||||||
| ALT | >5 x ULN | 5% | 8% | 5% | 2% | 6% | 3% |
| AST | >5 x ULN | 5% | 6% | 5% | 6% | 8% | 8% |
| GGTc | >5 x ULN | 8% | 7% | 3% | 5% | 0 | 5% |
| Amylase | >2 x ULN | 4% | 4% | 1% | 0 | 6% | 2% |
| Glucose | >250 mg/dL | 3% | 3% | 3% | 5% | 2% | 3% |
| Triglyceridesd | ≥751 mg/dL | 9% | 6% | 6% | 11% | 8% | 17% |
| Hematology | |||||||
| Neutrophils | <750/mm3 | 10% | 3% | 5% | 2% | 3% | 2% |
Patients Coinfected with Hepatitis B or C
Liver function tests should be monitored in patients with a history of hepatitis B and/or C. In the long-term data set from Study 006, 137 patients treated with Sustiva-containing regimens (median duration of therapy, 68 weeks) and 84 treated with a control regimen (median duration, 56 weeks) were seropositive at screening for hepatitis B (surface antigen positive) and/or C (hepatitis C antibody positive). Among these coinfected patients, elevations in AST to greater than five times ULN developed in 13% of patients in the Sustiva arms and 7% of those in the control arm, and elevations in ALT to greater than five times ULN developed in 20% of patients in the Sustiva arms and 7% of patients in the control arm. Among coinfected patients, 3% of those treated with Sustiva-containing regimens and 2% in the control arm discontinued from the study because of liver or biliary system disorders [see Warnings and Precautions (5.8)].
Lipids
Increases from baseline in total cholesterol of 10-20% have been observed in some uninfected volunteers receiving Sustiva. In patients treated with Sustiva + zidovudine + lamivudine, increases from baseline in nonfasting total cholesterol and HDL of approximately 20% and 25%, respectively, were observed. In patients treated with Sustiva + indinavir, increases from baseline in nonfasting cholesterol and HDL of approximately 40% and 35%, respectively, were observed. Nonfasting total cholesterol levels ≥240 mg/dL and ≥300 mg/dL were reported in 34% and 9%, respectively, of patients treated with Sustiva + zidovudine + lamivudine; 54% and 20%, respectively, of patients treated with Sustiva + indinavir; and 28% and 4%, respectively, of patients treated with indinavir + zidovudine + lamivudine. The effects of Sustiva on triglycerides and LDL in this study were not well characterized since samples were taken from nonfasting patients. The clinical significance of these findings is unknown [see Warnings and Precautions (5.10)].
Clinical Trial Experience in Pediatric Patients
Clinical adverse experiences observed in ≥10% of 57 pediatric patients aged 3 to 16 years who received Sustiva capsules, nelfinavir, and one or more NRTIs in Study ACTG 382 [see Use In Specific Populations (8.4)] were rash (46%), diarrhea/loose stools (39%), fever (21%), cough (16%), dizziness/lightheaded/fainting (16%), ache/pain/discomfort (14%), nausea/vomiting (12%), and headache (11%). The incidence of nervous system symptoms was 18% (10/57). One patient experienced Grade 3 rash, two patients had Grade 4 rash, and five patients (9%) discontinued because of rash [see Warnings and Precautions (5.7) and Adverse Reactions (6.1, Table 5)].
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of Sustiva. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Body as a Whole: allergic reactions, asthenia, redistribution/accumulation of body fat [see Warnings and Precautions (5.12)]
Central and Peripheral Nervous System: abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor, vertigo
Endocrine: gynecomastia
Gastrointestinal: constipation, malabsorption
Cardiovascular: flushing, palpitations
Liver and Biliary System: hepatic enzyme increase, hepatic failure, hepatitis. A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing in some cases to transplantation or death.
Metabolic and Nutritional: hypercholesterolemia, hypertriglyceridemia
Musculoskeletal: arthralgia, myalgia, myopathy
Psychiatric: aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide
Respiratory: dyspnea
Skin and Appendages: erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome
Special Senses: abnormal vision, tinnitus
Drug Interactions
Drug-Drug Interactions
Efavirenz has been shown in vivo to induce CYP3A and CYP2B6. Other compounds that are substrates of CYP3A or CYP2B6 may ha
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