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Efavirenz (Monograph)

Drug class: HIV Nonnucleoside Reverse Transcriptase Inhibitors


Efavirenz (Systemic) is also contained as an ingredient in the following combinations:
Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Antiretroviral; HIV nonnucleoside reverse transcriptase inhibitor (NNRTI).

Uses for Efavirenz

Treatment of HIV Infection

Treatment of HIV-1 infection in adult and pediatric patients ≥3 months of age weighing ≥3.5 kg.

Efavirenz is commercially available as a single entity and in various fixed-combination preparations that contain additional antiretrovirals. Fixed-dose preparations include efavirenz, emtricitabine, and tenofovir disoproxil fumarate (tenofovir DF; e.g., Atripla) and efavirenz, lamivudine, and tenofovir DF (e.g., Symfi and Symfi Lo). See the full prescribing information for use of each of these combination products.

Efavirenz is commonly added to a dual-nucleoside reverse transcriptase inhibitor (NRTI) “backbone” to form a fully suppressive 3-drug antiretroviral regimen; consult guidelines for the most current information on recommended regimens. Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Alternative for postexposure prophylaxis of HIV infection following occupational exposure [off-label] (PEP) in health-care personnel and other individuals (used in conjunction with 2 NRTIs); use only with expert consultation.

USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir DF as the preferred regimen for PEP following occupational exposures to HIV. Efavirenz and 2 NRTIs can be considered an alternative regimen, but use for PEP only with expert consultation. Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF (may be given as emtricitabine/tenofovir DF; Truvada); alternative dual NRTIs are tenofovir DF and lamivudine, lamivudine and zidovudine (may be given as lamivudine/zidovudine; Combivir), or zidovudine and emtricitabine.

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Alternative for postexposure prophylaxis of HIV infection following nonoccupational exposure [off-label] (nPEP) (in conjunction with other antiretrovirals); use only with expert consultation.

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada); recommended alternative in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF (Truvada).

CDC states efavirenz is an alternative antiretroviral that can be used in nPEP regimens, but use in such regimens only with expert consultation. Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. Do not delay initiation of nPEP while waiting for expert consultation.

Efavirenz Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Premedication and Prophylaxis

Dispensing and Administration Precautions

The Institute for Safe Medication Practices (ISMP) list of error-prone abbreviations, symbols, and dose designations states that the use of abbreviations for antiretroviral medications (e.g., DOR, TAF, TDF) during the medication use process should be avoided as their use has been associated with serious medication errors.

Administration

Oral Administration

Single-entity efavirenz commercially available as capsules or tablets.

Administer capsules or tablets orally once daily on an empty stomach, preferably at bedtime.

Administration at bedtime may make adverse CNS effects (dizziness, insomnia, impaired concentration, somnolence, abnormal dreams) more tolerable.

Use efavirenz in conjunction with other antiretrovirals.

Single-entity efavirenz should not be used concomitantly with efavirenz/emtricitabine/tenofovir disoproxil fumarate (tenofovir DF; e.g., Atripla), unless needed for adjustment of efavirenz dosage (e.g., when the fixed combination is used concomitantly with rifampin).

Capsules

Swallow capsules whole on an empty stomach.

For adults and pediatric patients ≥3 months of age not able to swallow capsules or tablets, administer capsule contents by mixing with small amount (1–2 teaspoonfuls) of soft food (capsule sprinkle method). Consider mixing with infant formula only if infant cannot consume solid foods. Administer efavirenz mixture within 30 minutes after preparation; do not consume any additional food or infant formula for 2 hours after the mixture.

Mixing capsule contents into food: Add 1–2 teaspoonfuls of age-appropriate soft food (e.g., applesauce, grape jelly, yogurt) to a small container. Hold appropriate number of capsules (see Table 1) horizontally over the small container, twist open, and empty onto the food. Gently mix with a spoon; feed entire mixture to patient. Then, add additional 2 teaspoonfuls of soft food to the small container, stir to disperse remaining efavirenz residue, and feed to patient.

Mixing capsule contents into infant formula: Add 10 mL (2 teaspoonfuls) of reconstituted room temperature infant formula to a 30-mL medicine cup. Hold appropriate number of capsules (see Table 1) horizontally over the medicine cup, twist open, and empty onto the formula. Gently mix with small spoon. Draw up infant formula mixture into 10-mL oral dosing syringe; administer into infant's right or left inner cheek. Then, add additional 2 teaspoonfuls of infant formula to the medicine cup, stir to disperse remaining efavirenz residue, draw up into oral dosing syringe, and administer to infant.

Tablets

Swallow tablets whole with liquid on an empty stomach; do not break or crush.

Fixed Combinations Containing Efavirenz

Efavirenz is commercially available in fixed-combination tablets containing efavirenz, emtricitabine, and tenofovir DF (e.g., Atripla) and efavirenz, lamivudine, and tenofovir DF (e.g., Symfi and Symfi Lo). See the full prescribing information of combination products for administration information.

Pharmacogenetic Testing

Poor CYP2B6 metabolizers may be at increased risk for increased efavirenz levels and adverse effects (e.g., CNS toxicity, QT prolongation) with efavirenz. The Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends efavirenz dosage reductions for intermediate and poor CYP2B6 metabolizers. For adults and pediatric patients weighing ≥40 kg who are intermediate CYP2B6 metabolizers, consider initiating efavirenz at 400 mg/day (moderate recommendation). For adults and pediatric patients weighing ≥40 kg who are poor CYP2B6 metabolizers, consider initiating efavirenz at 200–400 mg/day (moderate recommendation). Consult CPIC guideline for more details and definitions of CYP2B6 phenotypes based on genotype.

Dosage

Pediatric Patients

Treatment of HIV Infection
Oral

Dosage in children ≥3 months of age weighing 3.5 to <40 kg is based on weight. (See Table 1.) Adolescents and children weighing ≥40 kg may receive usual adult dosage.

Table 1. Efavirenz Dosage in Children ≥3 Months of Age Weighing ≥3.5 kg1360

Weight (kg)

Efavirenz Dosage

Number of Capsules or Tablets

3.5 to <5

100 mg once daily

Two 50-mg capsules

5 to <7.5

150 mg once daily

Three 50-mg capsules

7.5 to <15

200 mg once daily

One 200-mg capsule

15 to <20

250 mg once daily

One 200-mg and one 50-mg capsule

20 to <25

300 mg once daily

One 200-mg and two 50-mg capsules

25 to <32.5

350 mg once daily

One 200-mg and three 50-mg capsules

32.5 to <40

400 mg once daily

Two 200-mg capsules

≥40

600 mg once daily

One 600-mg tablet or three 200-mg capsules

Adults

Treatment of HIV Infection
Oral

600 mg once daily.

Postexposure Prophylaxis of HIV following Occupational Exposure† [off-label]
Oral

600 mg once daily. Use in conjunction with 2 NRTIs.

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Dosage Adjustment for Concomitant Use with Voriconazole

Reduce efavirenz dosage to 300 mg once daily using capsule formulation and increase voriconazole to 400 mg every 12 hours.

Dosage Adjustment for Concomitant Use with Rifampin

Patients weighing ≥50 kg: Increase efavirenz dosage to 800 mg once daily.

Special Populations

Hepatic Impairment

Dosage adjustments not needed in patients with mild hepatic impairment (Child-Pugh Class A); do not use in those with moderate or severe hepatic impairment (Child-Pugh Class B or C).

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time. Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Efavirenz

Contraindications

Warnings/Precautions

DrugI nteractions

Efavirenz plasma concentrations may be altered if CYP3A substrates, inhibitors, or inducers used concomitantly. In addition, efavirenz may alter plasma concentrations of drugs metabolized by CYP3A or 2B6.

QT Prolongation

Prolongation of QT interval corrected for rate (QTc) reported, including patients with poor metabolizer genotype. Consider alternative antiretroviral in patients at increased risk of torsades de pointes and in those receiving a drug known to increase risk of torsades de pointes.

Resistance

Must be used in conjunction with other antiretrovirals; do not add as a single-agent to a failing antiretroviral regimen. When given as monotherapy, resistance evolves rapidly.

When choosing antiretroviral agents to be used in conjunction with efavirenz, consider potential for viral cross-resistance.

Psychiatric Symptoms

Serious adverse psychiatric symptoms (severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, manic reactions) reported rarely in efavirenz clinical studies.

Factors associated with increased occurrence of psychiatric symptoms include history of injection drug use, history of psychiatric disorders, and treatment with antipsychotic drugs at study entry.

Advise patients to immediately seek medical evaluation if they experience severe psychiatric symptoms while receiving the drug.

If serious psychiatric events occur, evaluate to determine if symptoms are related to efavirenz; if so, determine whether risks of continued efavirenz outweigh benefits.

Nervous System Symptoms

Dizziness or insomnia reported frequently; abnormal dreams, somnolence, hallucinations, or impaired concentration also reported. These adverse effects generally begin during first 1–2 days of therapy and usually resolve after first 2–4 weeks.

Late-onset neurotoxicity, including ataxia and encephalopathy (impaired consciousness, confusion, psychomotor slowing, psychosis, delirium) reported months to years after beginning efavirenz therapy. Some late-onset neurotoxicity events occurred in patients with CYP2B6 genetic polymorphisms, which are associated with increased efavirenz levels.

Inform patients that adverse CNS effects may occur during first few weeks of efavirenz therapy and that the drug may impair ability to perform hazardous activities requiring mental alertness or physical coordination (e.g., operating machinery or driving a motor vehicle). Inform patients that there is a potential for additive CNS effects if they use efavirenz concomitantly with psychoactive drugs or alcohol. If patient presents with serious neurologic adverse experiences, evaluate promptly to assess whether the events are related to efavirenz and whether the drug should be discontinued.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm if administered during first trimester of pregnancy. Teratogenicity demonstrated in animals. Birth defects (including neural tube defects) reported in humans, usually with first-trimester exposure.

Perform pregnancy test in females of reproductive potential to rule out pregnancy before initiating efavirenz.

Advise females of reproductive potential to use effective contraception during efavirenz therapy and for 12 weeks after therapy is stopped. If pregnancy occurs during efavirenz therapy, apprise patient of the potential risk to a fetus.

Rash

Rash reported frequently (more common in pediatric patients). Median time to rash onset was 11 days in adults and 28 days in pediatric patients; median duration of rash in adults was 16 days. Rash generally resolves within 1 month with continued efavirenz.

May reinitiate efavirenz in patients who temporarily interrupted therapy with the drug because of development of a rash. Discontinue in patients with serious rash (i.e., rash associated with blistering, desquamation, mucosal involvement, or fever). Antihistamines and/or corticosteroids may improve tolerability and hasten resolution of rash. Consider prophylaxis with antihistamines prior to initiation of efavirenz in children. Discontinue in patients with life-threatening cutaneous reactions (e.g., Stevens-Johnson syndrome) and consider alternative therapy.

Hepatotoxicity

Hepatic failure and hepatitis reported, some with a fulminant course requiring transplantation or resulting in death. Hepatotoxicity reported in patients with or without pre-existing hepatic disease or identifiable risk factors.

Use with caution and careful monitoring in patients with mild hepatic impairment; use not recommended in those with moderate to severe hepatic impairment.

Assess serum liver enzyme concentrations prior to and during efavirenz treatment in all patients.

In patients with serum hepatic enzyme concentrations >5 times ULN, consider discontinuing efavirenz. Discontinue therapy if elevations in serum hepatic enzyme concentrations develop with clinical signs or symptoms of hepatitis or hepatic decompensation.

Convulsions

Convulsions reported, generally in those with a history of seizures. Use with caution in patients with history of seizures. Monitor anticonvulsant plasma concentrations periodically if used in patients receiving anticonvulsants that are metabolized principally by the liver (e.g., phenytoin, phenobarbital).

Lipid Elevations

Increased serum concentrations of total cholesterol and triglycerides reported. Assess serum cholesterol and triglyceride levels prior to and periodically during therapy.

Immune Reconstitution Syndrome

During initial treatment, HIV-infected patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) also reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Fat Redistribution

Redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, reported in patients receiving antiretroviral therapy.

Mechanism and long-term consequences of fat redistribution unknown; causal relationship not established.

Pharmacogenomics

Efavirenz primarily metabolized by CYP2B6. Poor CYP2B6 metabolizers may be at increased risk for adverse effects with efavirenz, including CNS toxicity, hepatic injury, and QT interval prolongation. The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides recommendations for efavirenz dosing guided by CYP2B6 phenotype. Dosage adjustments recommended for adults and pediatric patients weighing ≥40 kg who are poor or intermediate CYP2B6 metabolizers. (See Pharmacogenetic Testing under Dosage and Administration: Administration.) Consult CPIC guideline for more details and definitions of CYP2B6 phenotypes based on genotype.

Use of Fixed Combinations

When preparations containing efavirenz in fixed combination with other drugs (e.g., efavirenz, emtricitabine, and tenofovir disoproxil fumarate [tenofovir DF; e.g., Atripla]; efavirenz, lamivudine, and tenofovir DF [e.g., Symfi and Symfi Lo]) are used, the cautions, precautions, contraindications, and drug interactions associated with each drug in the fixed combination must be considered; consult the full prescribing information of each fixed combination preparation for specific information.

Specific Populations

Pregnancy

Efavirenz may cause fetal harm if administered during first trimester of pregnancy. There are retrospective case reports of neural tube defects in infants born to mothers with first trimester exposure to efavirenz. Although prospective data in humans are inadequate to assess risks and a causal relationship between efavirenz exposure in the first trimester and neural tube defects is not established, similar malformations have been observed in animal studies. Manufacturer states that efavirenz should not be used during first trimester of pregnancy.

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Advise females of reproductive potential about teratogenic potential of efavirenz. Perform pregnancy testing in such patients before initiation of therapy. If efavirenz is used during the first trimester, or if pregnancy occurs during therapy, apprise patient of the potential risk to the fetus.

Lactation

Per HHS perinatal HIV transmission guideline, inform patients that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates postnatal HIV transmission risk to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces risk of breastfeeding HIV transmission to <1%, but not does not completely eliminate risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.

Females and Males of Reproductive Potential

Verify pregnancy status in females of reproductive potential prior to initiating therapy.

Advise females of reproductive potential to use effective contraception during therapy and for 12 weeks after discontinuance of efavirenz. Hormonal contraceptives containing progesterone may be less effective with efavirenz; advise patients to use barrier contraception in combination with other methods.

Pediatric Use

Safety and efficacy not evaluated in neonates and infants <3 months of age or those weighing <3.5 kg; not recommended in these pediatric patients.

Adverse effects reported with efavirenz in pediatric patients 3 months to 21 years of age are similar to those reported in adults with the exception of rash. Rash reported more frequently in children than adults and the incidence of moderate to severe rash has been greater in children than adults. Consider antihistamines for prevention of rash when initiating efavirenz in children.

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Pharmacokinetics not affected by mild hepatic impairment (Child-Pugh class A); data insufficient to determine whether moderate or severe hepatic impairment (Child-Pugh class B or C) affects pharmacokinetics. Efavirenz not recommended in patients with moderate or severe hepatic impairment (Child-Pugh Class B or C). Use with caution and careful monitoring in patients with mild hepatic impairment.

Renal Impairment

Pharmacokinetics not specifically studied; clinically important decreases in clearance not anticipated.

Common Adverse Effects

Moderate to severe adverse effects occurring in >5% of patients: impaired concentration, abnormal dreams, rash, dizziness, nausea, headache, fatigue, insomnia, and vomiting.

Drug Interactions

Substrate of CYP3A and CYP2B6.

Inhibits CYP2C9 and CYP2C19. Does not inhibit CYP2E1, and does not inhibit CYP2D6 or CYP1A2 at clinically relevant concentrations.

Induces CYP3A and CYP2B6.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inducers of CYP3A and CYP2B6 expected to reduce efavirenz plasma concentrations. Efavirenz induces CYP3A and CYP2B6, and may alter plasma concentrations of drugs metabolized by these enzymes. Efavirenz induces its own metabolism.

Efavirenz inhibits CYP2C9 and CYP2C19 at clinically important concentrations, and may alter the pharmacokinetics of drugs metabolized by these isoenzymes.

Drugs Associated with QT Prolongation

QT prolongation observed with efavirenz. Consider alternatives to efavirenz in patients who require therapy with another drug that has a known risk of torsades de pointes.

Specific Drugs and Laboratory Tests

Drug

Interaction

Comments

Abacavir

Clinically important interactions not expected

In vitro evidence of additive antiretroviral effects

Dosage adjustments not needed

Alcohol

Potential for increased CNS effects

Antacids (aluminum hydroxide, magnesium hydroxide, simethicone)

Does not alter absorption of efavirenz

Dosage adjustments not needed

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Carbamazepine: Decreased concentrations and AUCs of efavirenz and carbamazepine

Phenobarbital, phenytoin: Possible decreased concentrations of phenobarbital and phenytoin and/or efavirenz

Carbamazepine: Data insufficient to make dosage recommendations for concomitant use with efavirenz; use alternative anticonvulsant

Phenobarbital, phenytoin: Use caution and monitor anticonvulsant concentrations if used with efavirenz;

Antifungals, azoles (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole)

Fluconazole: No clinically important pharmacokinetic interactions

Itraconazole: Decreased concentrations of itraconazole; no change in efavirenz concentrations

Ketoconazole: Possible decreased concentrations of the antifungal

Posaconazole: Decreased posaconazole concentrations and AUC

Voriconazole: Decreased voriconazole concentrations; increased efavirenz concentrations

Fluconazole: Dosage adjustments not needed

Itraconazole: Dosage recommendation for concomitant use not available; consider alternative antifungal

Ketoconazole: Dosage recommendations for concomitant use not available; consider alternative antifungal

Posaconazole: Avoid concomitant use unless potential benefits outweigh risks

Voriconazole: Increase voriconazole maintenance dosage to 400 mg every 12 hours and decrease efavirenz dosage to 300 mg once daily (use efavirenz capsules; do not divide tablet); do not use usual voriconazole dosage with usual efavirenz dosage

Antimalarials

Fixed combination of artemether and lumefantrine (artemether/lumefantrine): Decreased concentrations and AUC of artemether and active metabolite of artemether; decreased lumefantrine AUC; possible QT interval prolongation

Fixed combination of atovaquone and proguanil (atovaquone/proguanil): Decreased AUC of atovaquone and proguanil predicted

Artemether/lumefantrine: Consider alternative antimalarial agent

Atovaquone/proguanil: Concomitant use not recommended

Antimycobacterials (rifabutin, rifampin)

Rifabutin: Decreased rifabutin concentrations; no change in efavirenz AUC

Rifampin: Decreased efavirenz concentrations and AUC

Rifabutin: Manufacturer of efavirenz states increase daily rifabutin dosage by 50% and consider doubling rifabutin dosage when given 2 or 3 times weekly

Rifampin: Manufacturer states increase efavirenz dosage to 800 mg once daily in those weighing ≥50 kg

Atazanavir

Ritonavir-boosted atazanavir: Possible increased atazanavir concentrations and AUC depending on specific regimen

Unboosted atazanavir: Substantially decreased atazanavir concentrations and AUC

Ritonavir-boosted atazanavir in treatment-naive adults: Use atazanavir 400 mg and ritonavir 100 mg once daily (with food) and efavirenz 600 mg once daily (without food, preferably at bedtime)

Ritonavir-boosted atazanavir in antiretroviral-experienced adults: Concomitant use not recommended

Bupropion

Decreased bupropion concentrations and AUC; increased concentrations of hydroxybupropion (an active metabolite)

Titrate bupropion dosage based on clinical response; do not exceed maximum recommended bupropion dosage

Calcium-channel blocking agents

Diltiazem: Decreased diltiazem concentrations; slightly increased efavirenz concentrations

Other calcium-channel blocking agents (e.g., felodipine, nicardipine, nifedipine, verapamil): Possible decreased concentrations of the calcium-channel blocking agent

Diltiazem: Titrate diltiazem dosage based on clinical response; adjustment of efavirenz dosage not needed

Other calcium-channel blocking agents: Titrate dosage of calcium-channel blocking agent according to clinical response

Cetirizine

Decreased cetirizine concentrations; no change in efavirenz concentrations

When used with cetirizine, dosage adjustments not needed

Elbasvir and grazoprevir

Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): Substantially decreased elbasvir and grazoprevir concentrations; possible loss of virologic response to elbasvir/grazopevir

Elbasvir/grazoprevir: Concomitant use contraindicated

Emtricitabine

Clinically important interactions not expected

In vitro evidence of additive antiretroviral effects

Dosage adjustments not needed

Estrogens/Progestins

Oral hormonal contraceptive containing ethinyl estradiol and norgestimate: Substantially decreased concentrations and AUC of norelgestromin and levonorgestrel (metabolites of norgestimate)

Etonogestrel (subcutaneous implant): Not studied, but decreased etonogestrel concentrations expected; subcutaneous implant contraceptive failure reported in women receiving efavirenz

Hormonal contraceptives (oral or other hormonal contraceptives): Use a barrier contraceptive in addition to hormonal contraceptive in females of reproductive potential during and for 12 weeks after efavirenz therapy is discontinued

Fosamprenavir

Substantially decreased concentrations of amprenavir (active metabolite of fosamprenavir) if used with fosamprenavir (without low-dose ritonavir)

In vitro evidence of additive synergistic antiretroviral effects

Fosamprenavir (without low-dose ritonavir): Appropriate dosages for concomitant use with efavirenz with respect to safety and efficacy not established

Ritonavir-boosted fosamprenavir: Increased ritonavir dosage (300 mg total daily) recommended when efavirenz used with ritonavir-boosted fosamprenavir once daily regimen; no change in ritonavir dosage necessary if efavirenz is used with ritonavir-boosted fosamprenavir twice-daily regimen

Glecaprevir and pibrentasvir

Decreased glecaprevir and pibrentasvir concentrations and potential loss of virologic response to glecaprevir/pibrentasvir

Concomitant use not recommended

Histamine H2-receptor antagonists (famotidine)

Systemic avalability not affected by famotidine

When used with famotidine, dosage adjustments not needed

HMG-CoA reductase inhibitors (statins)

Atorvastatin, pravastatin, and simvastatin: Decreased concentrations of the antilipemic agent; no clinically important effect on efavirenz concentrations

Atorvastatin, pravastatin, simvastatin: Consult statin prescribing information for dosage recommendations for concomitant use

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Cyclosporine, sirolimus, tacrolimus: Possible decreased concentrations of the immunosuppressive agent; no effect on efavirenz concentrations

Cyclosporine, sirolimus, tacrolimus: Dosage of immunosuppressive agent may need to be adjusted if used with efavirenz; whenever efavirenz is initiated or discontinued, monitor immunosuppressive agent concentrations for at least 2 weeks until stable

Lamivudine

No effect on lamivudine peak concentrations or AUC

In vitro evidence of additive antiretroviral effects

Dosage adjustments not needed

Lopinavir/ritonavir

Decreased lopinavir concentrations and AUC

In vitro evidence of additive antiretroviral effects

Once-daily lopinavir/ritonavir regimen not recommended with efavirenz

Refer to the lopinavir/ritonavir prescribing information for dosage recommendations when used concomitantly

Lorazepam

Increased lorazepam concentrations, but no effect on lorazepam AUC

Dosage adjustments not needed

Macrolides (azithromycin, clarithromycin)

Risk of QT interval prolongation

Azithromycin: Pharmacokinetic interaction unlikely

Clarithromycin: Decreased clarithromycin concentrations and AUC and increased 14-hydroxyclarithromycin concentrations and AUC

Consider alternative to macrolide antibiotics

Azithromycin: Dosage adjustments not needed

Maraviroc

Decreased maraviroc concentrations and AUC

Refer to maraviroc prescribing information for recommendations

Methadone

Decreased methadone concentrations and AUC

Closely monitor for signs of opiate withdrawal; increased methadone maintenance dosage may be necessary

Nelfinavir

Increased nelfinavir concentrations and AUC; decreased efavirenz concentrations and AUC

In vitro evidence of additive antiretroviral effects

Dosage adjustments not needed

Nevirapine

In vitro evidence of additive antiretroviral effects

Concomitant use not recommended

Praziquantel

Increased metabolism and decreased plasma concentration of praziquantel; risk of treatment failure

Concomitant use not recommended

Psychotherapeutic agents

Potential for increased CNS effects

Raltegravir

Decreased raltegravir concentrations and AUC

Dosage adjustments not necessary

Ritonavir

Increased ritonavir AUC and increased efavirenz AUC

In vitro evidence of additive antiretroviral effects

Monitor hepatic enzymes and monitor patient for adverse effects (e.g., dizziness, nausea, paresthesia) if used with efavirenz

Selective serotonin-reuptake inhibitors (SSRIs)

Paroxetine: No clinically important interactions

Sertraline: Decreased sertraline concentrations and AUC

Paroxetine: Dosage adjustments not needed

Sertraline: Adjust sertraline dosage based on clinical response

Sofosbuvir and velpatasvir

Decreased velpatasvir concentrations and AUC and potential loss of therapeutic efficacy

Concomitant use not recommended

Sofosbuvir, velpatasvir, and voxilaprevir

Decreased velpatasvir and voxilaprevir concentrations and potential loss of therapeutic efficacy

Concomitant use not recommended

Tenofovir DF

Clinically important interactions not expected

In vitro evidence of additive antiretroviral effects

Dosage adjustments not needed

Tests for cannabinoids

False-positive urine cannabinoid test when screening test used

Confirm positive cannabinoid screening test with a more specific test

Warfarin

Warfarin concentrations likely to be affected

Use with caution; closely monitor INR

Zidovudine

No effect on zidovudine peak concentrations or AUC

In vitro evidence of additive antiretroviral effects

Dosage adjustments not necessary

Efavirenz Pharmacokinetics

Absorption

Bioavailability

Peak plasma efavirenz concentrations attained within 3–5 hours.

Food

Administration with food increases efavirenz bioavailability.

Compared with administration in the fasting state, AUC increased 22 or 17% when a single 600-mg efavirenz dose as capsules was administered with a high-fat, high-calorie meal (894 kcal, 54 g fat, 54% calories from fat) or a reduced-fat normal calorie meal (440 kcal, 2 g fat, 4% calories from fat), respectively.

Compared with administration in the fasting state, AUC increased 28% when a single 600-mg efavirenz dose as tablets was administered with a high-fat, high-calorie meal (1000 kcal, 500–600 kcal from fat).

In healthy adults, 600-mg efavirenz dose administered by opening 200-mg capsules and mixing contents of 3 capsules with 2 teaspoonfuls of soft food (e.g., applesauce, grape jelly, yogurt) or infant formula resulted in efavirenz AUC that met bioequivalency criteria compared with intact capsules administered in fasting state.

Distribution

Extent

Not fully characterized.

Plasma Protein Binding

99.5–99.75%.

Elimination

Metabolism

Metabolized by CYP3A and CYP2B6; undergoes subsequent glucuronidation. Induces CYP enzymes, resulting in induction of its own metabolism.

Elimination Route

16–61% excreted in feces (principally as unchanged drug) and 14–34% eliminated in urine (principally as metabolites).

Not removed by dialysis.

Half-life

52–76 hours after a single dose and 40–55 hours after multiple doses.

Special Populations

Hepatic impairment: Pharmacokinetics not affected by mild impairment (Child-Pugh class A); data insufficient to determine whether affected by moderate or severe impairment (Child-Pugh class B or C).

Pharmacokinetics not affected by gender or race.

Stability

Storage

Oral

Capsules

20-25°C (excursions permitted between 15–30°C).

Tablets

20-25°C (excursions permitted between 15–30°C).

Actions and Spectrum

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Efavirenz

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

50 mg*

Efavirenz Capsules

100 mg*

Efavirenz Capsules

200 mg*

Efavirenz Capsules

Tablets, film-coated

600 mg*

Efavirenz Tablets

AHFS DI Essentials™. © Copyright 2025, Selected Revisions October 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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Frequently asked questions