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Efavirenz is a brand name for Efavirenz. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS & USAGE Efavirenz in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and in pediatric patients at least 3 months old and weighing at least 3.5 kg. Efavirenz is a non-nucleoside reverse transcriptase inhibitor…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE & ADMINISTRATION • Efavirenz should be taken orally once daily on an empty stomach, preferably at bedtime. ( 2 ) • Recommended adult dose: 600 mg. 2 ) • With rifampin, increase efavirenz dose to 800 mg once daily for patients weighing 50 kg or more.
2 ) • Pediatric dosing is based on weight. 9 ) ]. 6 ) ]. 2 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).
It is recommended that efavirenz be taken on an empty stomach, preferably at bedtime. 3 )]. 1 ), and Patient Counseling Information ( 17 )]. Efavirenz capsules or tablets should be swallowed intact with liquid. 3 )]. Dosage Adjustment If efavirenz is coadministered with voriconazole, the voriconazole maintenance dose should be increased to 400 mg every 12 hours and the efavirenz 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).
Efavirenz tablets must not be broken. 3 , Tables 7 and 8] . 3 , Table 8)]. 3 Pediatric Patients It is recommended that efavirenz be taken on an empty stomach, preferably at bedtime. 3 )] . The recommended dosage of efavirenz for pediatric patients weighing 40 kg or greater is 600 mg once daily.
For pediatric 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 . 4)]. b Tablets must not be crushed
8 )]. gov/medwatch . 1 Clinical Trials Experience 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.
Adverse Reactions in Adults. 7 weeks c Psychiatric 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% Anxiety 2% 4% <1% — — — Depression 5% 4% <1% 3% 0 5% Nervousness 2% 2% 0 2% 0 2% Skin & Appendages Rash d 11% 16% 5% 9% 5% 9% Pruritis <1% 1% 1% 9% 5% 9% 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 Efavirenz tablets 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. 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 ).
6 )]. 1 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.
5 WARNINGS AND PRECAUTIONS • QTc prolongation : Consider alternatives to efavirenz in patients taking other medications with a known risk of Torsade de Pointes or in patients at higher risk of Torsade de Pointes. 2 ) • Do not use as a single agent or add on as a sole agent to a failing regimen.
Consider potential for cross resistance when choosing other agents. 3 ) •Not recommended with ATRIPLA, which contains efavirenz, emtricitabine, and tenofovir disoproxil fumarate, unless needed for dose adjustment when coadministered with rifampin.
4 ) • Serious psychiatric symptoms : Immediate medical evaluation is recommended for serious psychiatric symptoms such as severe depression or suicidal ideation. 5 , 17 ) • Nervous system symptoms (NSS): NSS are frequent and usually begin 1-2 days after initiating therapy and resolve in 2-4 weeks.
Dosing at bedtime may improve tolerability. NSS are not predictive of onset of psychiatric symptoms. 1 , 17 ) • Embryo-Fetal Toxicity : Avoid administration in the first trimester of pregnancy as fetal harm may occur. 1 ) • Hepatotoxicity : Monitor liver function tests before and during treatment in patients with underlying hepatic disease, including hepatitis B or C coinfection, marked transaminase elevations, or who are taking medications associated with liver toxicity.
Among reported cases of hepatic failure, a few occurred in patients with no pre-existing hepatic disease. 6 ) • Rash : Rash usually begins within 1-2 weeks after initiating therapy and resolves within 4 weeks. Discontinue if severe rash develops.
1 , 17 ) • Convulsions : Use caution in patients with a history of seizures. 10 ) • Lipids : Total cholesterol and triglyceride elevations. Monitor before therapy and periodically thereafter. 11 ) • Immune reconstitution syndrome : May necessitate further evaluation and treatment.
12 ) • Redistribution/accumulation of body fat : Observed in patients receiving antiretroviral therapy. 1 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.
, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product. 1 ) ]. , Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions to any of the components of this product.
( 4 ) •Coadministration of efavirenz with elbasvir/grazoprevir
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e "Severe" = Events which interrupt patient’s usual daily activities. Psychiatric Symptoms Serious psychiatric adverse experiences have been reported in patients treated with efavirenz tablets. In controlled trials, psychiatric symptoms observed at a frequency of greater than 2% among patients treated with efavirenz or control regimens, respectively, were depression (19%, 16%), anxiety (13%, 9%), and nervousness (7%, 2%).
Rash In controlled clinical trials, the frequency of rash (all grades, regardless of causality) was 26% for 1008 adults treated with regimens containing efavirenz and 17% for 635 adults treated with a control regimen. Most reports of rash were mild or moderate in severity.
1% for efavirenz and 0 for control groups. 8 )]. Experience with efavirenz 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 efavirenz.
Nine of these patients developed mild-to-moderate rash while receiving therapy with efavirenz, and two of these patients discontinued because of rash. Laboratory Abnormalities Selected Grade 3-4 laboratory abnormalities reported in greater than 2% of efavirenz tablets-treated patients in two clinical trials are presented in Table 4.
7 weeks b Chemistry ALT >5 x ULN 5% 8% 5% 2% 6% 3% AST >5 x ULN 5% 6% 5% 6% 8% 8% GGT c >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% Triglyce rides d ≥751 mg/dL 9% 6% 6% 11% 8% 17% Hematology Neutrophils <750/mm 3 10% 3% 5% 2% 3% 2% a Efairenz tablets provided as 600 mg once daily.
b Median duration of treatment. c Isolated elevations of GGT in patients receiving efavirenz 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 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 efavirenz-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 efavirenz 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 efavirenz arms and 7% of patients in the control arm.
9 )]. Lipids Increases from baseline in total cholesterol of 10-20% have been observed in some uninfected volunteers receiving efavirenz. In patients treated with efavirenz + zidovudine + lamivudine, increases from baseline in nonfasting total cholesterol and HDL of approximately 20% and 25%, respectively, were observed.
In patients treated with efavirenz + 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 efavirenz + zidovudine + lamivudine; 54% and 20%, respectively, of patients treated with efavirenz + indinavir; and 28% and 4%, respectively, of patients treated with indinavir + zidovudine + lamivudine.
The effects of efavirenz on triglycerides and LDL in this study were not well characterized since samples were taken from nonfasting patients. 11 )]. Adverse Reactions in Pediatric Patients 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.
Assessment of adverse reactions is based on three clinical trials in 182 HIV-1 infected pediatric patients (3 months to 21 years of age) who received efavirenz in combination with other antiretroviral agents for a median of 123 weeks.
The adverse reactions observed in the three trials were similar to those observed in clinical trials in adults except that rash was more common in pediatric patients (32% for all grades regardless of causality) and more often of higher grade (ie, more severe).
2%) pediatric patients had Grade 4 rash (all erythema multiforme). 8 )]. 2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of efavirenz tablets. 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.
13 )] Central and Peripheral Nervous System: abnormal coordination, ataxia, encephalopathy, 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 Metabolic and Nutritional: hypercholesterolemia, hypertriglyceridemia Musculoskeletal: arthralgia, myalgia, myopathy Psychiatric: aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide, catatonia Respiratory : dyspnea Skin and Appendages: erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome Special Senses: abnormal vision, tinnitus
1 )]. 2 )]. Consider alternatives to efavirenz when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes. 3 Resistance Efavirenz 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.
, with rifampin), since efavirenz is one of its active ingredients. 5 Psychiatric Symptoms Serious psychiatric adverse experiences have been reported in patients treated with efavirenz. 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 efavirenz and control treatment groups.
In Study 006, onset of new serious psychiatric symptoms occurred throughout the study for both efavirenz-treated and control-treated patients. One percent of efavirenz -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 efavirenz cannot be determined from these reports. Postmarketing cases of catatonia have also been reported and may be associated with increased efavirenz exposure.
1 )]. 1 , Table 3)]. 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 efavirenz and from 3% to 5% in patients treated with a control regimen.
5 )]. 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 efavirenz + zidovudine + lamivudine, efavirenz + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among efavirenz-treated patients were generally similar to those in the indinavir-containing control arm.
Late-onset neurotoxicity, including ataxia and encephalopathy (impaired consciousness, confusion, psychomotor slowing, psychosis, delirium), may occur months to years after beginning efavirenz therapy. Some events of late-onset neurotoxicity have occurred in patients with CYP2B6 genetic polymorphisms which are associated with increased efavirenz levels despite standard dosing of efavirenz.
Patients presenting with signs and symptoms of serious neurologic adverse experiences should be evaluated promptly to assess the possibility that these events may be related to efavirenz use, and whether discontinuation of efavirenz is warranted.
Patients receiving efavirenz should be alerted to the potential for additive central nervous system effects when 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.
7 Embryo-Fetal Toxicity Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. 3 )]. 1 )]. 9% (9/1008) of patients treated with efavirenz. 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).
7% (17/1008). 2 )]. Two pediatric patients experienced Grade 3 rash (confluent rash with fever, generalized rash), and four patients had Grade 4 rash (erythema multiforme). The median time to onset of rash in pediatric patients was 28 days (range 3-1642 days).
Prophylaxis with appropriate antihistamines before initiating therapy with efavirenz in pediatric patients should be considered. Efavirenz can generally be reinitiated in patients interrupting therapy because of rash. 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. , Stevens-Johnson syndrome), alternative therapy should be considered [see Contraindications ( 4 )]. 9 Hepatotoxicity Postmarketing cases of hepatitis, including fulminant hepatitis progressing to liver failure requiring transplantation or resulting in death, have been reported in patients treated with efavirenz.
Reports have included patients with underlying hepatic disease, including coinfection with hepatitis B or C, and patients without pre-existing hepatic disease or other identifiable risk factors. Efavirenz is not recommended for patients with moderate or severe hepatic impairment.
Careful monitoring is recommended for patients with mild hepatic impairment receiving efavirenz. 6 ) ]. 1 )] . Consider discontinuing efavirenz in patients with persistent elevations of serum transaminases to greater than five times the upper limit of the normal range.
Discontinue efavirenz if elevation of serum transaminases is accompanied by clinical signs or symptoms of hepatitis or hepatic decompensation. 2 )]. Caution should be taken in any patient with a history of seizures. 1 )]. 1 )]. Cholesterol and triglyceride testing should be performed before initiating efavirenz therapy and at periodic intervals during therapy.
12 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including efavirenz. 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 jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
13 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.