Efavirenz

Class: Nonnucleoside Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: (±) - 6 - Chloro - 4 - (cyclopropylethynyl) - 1,4 - dihydro - 4 - (trifluoromethyl) - 2H - 3,1 - benzoxazin - 2 - one
Molecular Formula: C₁₄H₉ClF₃NO₂
CAS Number: 154635-17-3
Brands: Atripla, Sustiva

Introduction

Antiretroviral; nonnucleoside reverse transcriptase inhibitor (NNRTI).^{1 2 3 12 14}

Uses for Efavirenz

Treatment of HIV Infection

Treatment of HIV-1 infection in conjunction with other antiretrovirals.¹

The preferred NNRTI for initial treatment regimens, except during first trimester of pregnancy or in women of childbearing age who may become pregnant.^{37 52 53} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Fixed-combination preparation containing efavirenz, emtricitabine, and tenofovir (Atripla) used alone or in conjunction with other antiretrovirals.⁷⁸ Used to decrease pill burden and improve compliance.⁷⁸

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection† in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.⁷² Used in conjunction with other antiretrovirals.⁷²

Postexposure prophylaxis of HIV infection† following nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when such exposure represents a substantial risk for HIV transmission.⁷⁴ Used in conjunction with other antiretrovirals.⁷⁴

Efavirenz Dosage and Administration

Administration

Oral Administration

Administer single-entity preparation (Sustiva) or fixed-combination preparation (Atripla) orally once daily on an empty stomach, preferably at bedtime.^{1 37 78}

Administration at bedtime may make adverse CNS effects (dizziness, insomnia, impaired concentration, somnolence, abnormal dreams) more tolerable.^{1 35 44}

If used in individuals who cannot swallow capsules or tablets, the capsules (Sustiva) may be opened and added to liquids or foods;⁴⁴ efavirenz has a peppery taste that may be disguised by administering with grape jelly.⁴⁴ Do not break the tablets.¹

Because the dosage of efavirenz, emtricitabine, and tenofovir cannot be adjusted individually, the fixed combination containing efavirenz, emtricitabine, and tenofovir (Atripla) should not be used in patients with moderate to severe renal impairment (Cl_cr <50 mL/minute).⁷⁸

Dosage

Administer single-entity preparation (Sustiva) in conjunction with other antiretrovirals.¹

The fixed-combination preparation containing efavirenz, emtricitabine, and tenofovir (Atripla) may be used alone or in conjunction with other antiretrovirals.⁷⁸

If used in conjunction with atazanavir, fosamprenavir, indinavir, or lopinavir, adjustment in the treatment regimen necessary. (See Specific Drugs under Interactions.)

If used concomitantly with voriconazole, dosage adjustment for both drugs is needed.¹

Dosage of Atripla expressed as number of tablets.⁷⁸

Pediatric Patients

Treatment of HIV Infection

Oral

Dosage in Children ≥3 Years of Age1

Weight in kg	Dosage
10 to <15	200 mg once daily
15 to <20	250 mg once daily
20 to <25	300 mg once daily
25 to <32.5	350 mg once daily
32.5 to <40	400 mg once daily
≥40	600 mg once daily

Adults

Treatment of HIV Infection

Oral

600 mg once daily.^{1 37}

If used with voriconazole: Efavirenz 300 mg once daily (as capsules; do not divide tablets) and voriconazole 400 mg every 12 hours.¹

Atripla: 1 tablet once daily.⁷⁸

Postexposure Prophylaxis of HIV†

Occupational Exposure†

Oral

600 mg once daily.⁷²

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.⁷²

Nonoccupational Exposure†

Oral

600 mg once daily.⁷⁴

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.⁷⁴

Special Populations

Renal Impairment

Dosage adjustments not necessary.³⁷

Atripla: Dosage adjustment not necessary in patients with Cl_cr ≥50 mL/minute.⁷⁸ Not recommended in patients with Cl_cr <50 mL/minute.⁷⁸

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Cautions for Efavirenz

Contraindications

• 
  

  History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruption) to efavirenz or any ingredient in the formulation.¹

  
  


• 
  

  Concomitant use with drugs for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., cisapride, ergot alkaloids, midazolam, pimozide, triazolam).¹ (See Specific Drugs under Interactions.)

  
  


• 
  

  Concomitant use with drugs when such use may result in decreased plasma concentrations of efavirenz, possible loss of virologic response, and development of resistance (e.g., St. John’s wort [Hypericum perforatum]).¹ (See Specific Drugs under Interactions.)

  
  

Warnings/Precautions

Warnings

Interactions

Serious and/or life-threatening drug interactions, clinically important drug interactions, or loss of virologic effect can occur with some drugs.¹ (See Specific Drugs under Interactions.)

Psychiatric Symptoms

Serious adverse psychiatric symptoms (severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions) reported rarely in clinical studies.¹ Factors associated with increased occurrence of psychiatric symptoms include history of drug use (injection), history of psychiatric disorders, and treatment with an antipsychotic drug at study entry.¹

Use with caution in patients with unstable psychiatric disease.³⁷

Patients experiencing serious psychiatric adverse events should be evaluated to determine if symptoms are related to efavirenz, and if so, a determination should be made whether the risks of continued therapy outweigh the benefits.¹

Nervous System Effects

Dizziness or insomnia reported frequently; abnormal dreams, hallucinations, or impaired concentration also reported.¹ These adverse effects generally begin during the first 1–2 days of therapy, improve with continued therapy, and usually resolve after the first 2–4 weeks.^{1 35}

Seizures reported rarely.¹ Generally has occurred in patients with a history of seizures; caution advised in these patients.¹ Patients receiving anticonvulsant therapy may require periodic monitoring.¹ (See Specific Drugs under Interactions.)

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm. Teratogenicity demonstrated in animals. Birth defects (including neural tube defects) reported in humans, usually after first-trimester exposure.¹

Pregnancy should be avoided.¹ Women of childbearing potential should undergo a pregnancy test prior to initiating therapy.¹ In addition, women of childbearing potential should use 2 forms of contraception (i.e., barrier contraceptive and hormonal contraceptive).¹

Sensitivity Reactions

Dermatologic Reactions

Rash (maculopapular skin eruptions) reported frequently; rash associated with blistering, moist desquamation, or ulceration, erythema multiforme, and Stevens-Johnson Syndrome also reported.^{1 2 35} Median time to onset 11 days; median duration 16 days.¹

Discontinue efavirenz in patients who develop severe rash associated with blistering, desquamation, mucosal involvement, or fever.¹ Efavirenz Can be reinitiated after interruption for rash.¹ Antihistamines and/or corticosteroids may improve tolerability and hasten resolution of rash.¹

General Precautions

Do not use multiple efavirenz-containing preparations concomitantly.¹

Use of Fixed Combinations

When used in fixed combination with tenofovir and emtricitabine (Atripla), consider the cautions, precautions, and contraindications associated with the concomitant agents.⁷⁸

Lipid Effects

Increases in total serum cholesterol have occurred.¹ Monitor serum triglycerides and cholesterol concentrations.¹

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.¹

Immune Reconstitution Syndrome

During initial treatment, 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 jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.¹

Specific Populations

Pregnancy

Category D.¹

Antiretroviral Pregnancy Registry at 800-258-4263.¹ Women of childbearing potential should use effective contraceptive measures while receiving efavirenz.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Avoid use during first trimester of pregnancy and in women of childbearing age who may become pregnant (e.g., those who desire to become pregnant or who do not use effective and consistent contraception).^{37 69} Some experts state use can be considered after the first trimester in special circumstances.⁶⁹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.^{1 69}

Pediatric Use

Sustiva: Safety and efficacy not evaluated in neonates and children <3 years of age or who weigh <13 kg.¹

Adverse effects in children 3–16 years of age are similar to those reported in adults with the exception of rash.¹ Rash reported more frequently in children than adults and the incidence of moderate to severe rash has been greater in children than adults.¹

Atripla: Safety and efficacy not established in pediatric patients <18 years of age.⁷⁸

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.¹

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Hepatic Impairment

Use with caution in patients with hepatic impairment.¹

Monitor hepatic enzyme concentrations in patients with known or suspected hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection and in patients receiving other drugs associated with hepatotoxicity.¹

The benefits of continued efavirenz therapy versus the risks of hepatotoxicity should be considered in patients with serum hepatic enzyme concentrations >5 times the ULN.¹

Common Adverse Effects

Rash, dizziness, nausea, headache, fatigue, insomnia, vomiting.¹

Interactions for Efavirenz

Metabolized by CYP3A and CYP2B6.¹

Inhibits CYP2C9, CYP2C19, and CYP3A4, and to a lesser extent, CYP2D6 and CYP1A2.¹ Does not inhibit CYP2E1.¹

Induces CYP3A.¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A, CYP29C, or CYP2C19 with possible alteration in metabolism of efavirenz and/or other drug.¹

Specific Drugs

Drug	Interaction	Comments
Abacavir	In vitro evidence of additive antiretroviral effects1
Alcohol	Potential for additive CNS effects1
Antacids (aluminum hydroxide, magnesium hydroxide, simethicone)	Pharmacokinetic interaction unlikely1	Dosage adjustment not needed1
Anticoagulants, oral	Warfarin concentrations likely to be affected1	Use with caution; monitor INR1 37
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Carbamazepine: Decreased concentration of efavirenz and carbamazepine1 Possible decreased concentrations of phenobarbital and phenytoin and/or efavirenz 1 37	Use with caution; monitor anticonvulsant concentrations;1 37 insufficient information to make dosage recommendation with carbamazepine;1 consider alternative anticonvulsant37
Antifungals, azoles (fluconazole, itraconazole, ketoconazole, voriconazole)	Fluconazole: No clinically important pharmacokinetic interactions1 37 55 Itraconazole: Decreased concentrations of itraconazole; no change in efavirenz concentrations1 Ketoconazole: Possible decreased concentrations of the antifungal1 Posaconazole: Decreased concentrations of posaconazole37 Voriconazole: Decreased voriconazole concentrations; increased efavirenz concentrations1 37	Fluconazole: Dosage adjustment not needed1 55 Itraconazole: Dosage recommendation for concomitant use not available; consider alternative antifungal;1 some experts suggest dosage adjustment for itraconazole. If used concomitantly, monitor plasma concentrations of itraconazole37 Posaconazole: Consider alternative antifungal or monitor plasma concentrations of the antifungal37 Voriconazole: Concomitant use of usual dosages of voriconazole and efavirenz contraindicated;1 37 if used with voriconazole, manufacturer of efavirenz recommends increasing voriconazole maintenance dosage to 400 mg every 12 hours and decreasing efavirenz dosage to 300 mg (use capsules; do not divide tablet) once daily1
Antihistamines	Decreased cetirizine concentrations; no change in efavirenz concentrations1	When used with cetirizine, dosage adjustment not needed1
Antimycobacterials (rifabutin, rifampin, rifapentine)	Rifabutin: Decreased rifabutin concentrations; no change in efavirenz AUC1 37 54 55 Rifampin: Decreased efavirenz concentrations1 37	Rifabutin: Efavirenz dosage adjustment not needed; increase rifabutin dosage to 450–600 mg once daily or 600 mg 3 times weekly provided regimen does not include an HIV protease inhibitor1 37 Rifampin: Efavirenz 600 mg once daily for patients weighing <60 kg or consider using efavirenz 800 mg once daily37 Rifapentine: Concomitant use not recommended37
Atazanavir	Decreased atazanavir concentrations and AUC;37 73 no change in efavirenz concentrations37	In treatment-naive adults, a regimen of atazanavir 400 mg, ritonavir 100 mg (with food), and efavirenz 600 mg given once daily (without food) is recommended37 73 Concomitant use not recommended in treatment-experienced adults37 73 Do not use atazanavir concomitantly with efavirenz unless low-dose ritonavir also is given73
Benzodiazepines	Pharmacokinetic interaction with midazolam or triazolam; potential for prolonged or increased sedation or respiratory depression1 Increased lorazepam concentrations and AUC1	Concomitant use with midazolam or triazolam contraindicated;1 some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation37 When used with lorazepam, dosage adjustment not needed1
Calcium-channel blocking agents	Diltiazem: Decrease diltiazem concentrations; slightly increased efavirenz concentrations1 Possible decreased concentrations of other calcium-channel blocking agents that are substrates of CYP 3A4 (e.g., felodipine, nicardipine, nifedipine, verapamil)1	Diltiazem: Adjust diltiazem dosage according to clinical response; no dosage adjustment needed for efavirenz1 Calcium-channel blocking agents that are substrates of CYP 3A4: Adjust dosage according to clinical response1
Cisapride	Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1	Concomitant use contraindicated1 37
Darunavir	Increased efavirenz concentrations; decreased darunavir concentrations37 80	Clinical importance unknown;37 80 caution advised;80 use standard dosages and consider monitoring plasma concentrations37
Delavirdine	Not studied1	Concomitant use of NNRTIs not recommended37
Didanosine	In vitro evidence of additive antiretroviral effects1
Emtricitabine	In vitro evidence of additive or synergistic antiretroviral effects1 84
Enfuvirtide	In vitro evidence of additive antiretroviral effects1
Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)	Possibility of pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)1	Concomitant use contraindicated1 37 If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving efavirenz, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible69
Estrogens/Progestins	Hormonal contraceptives: Increased AUC of ethinyl estradiol; no change in efavirenz concentrations with oral contraceptive preparations1 42 55	Hormonal contraceptives: Use a barrier contraceptive as an alternative to or in addition to a hormonal contraceptive1 37
Etravirine	Decreased etravirine concentrations37 86	Concomitant use of NNRTIs not recommended37 86
Fosamprenavir	Substantially decreased amprenavir concentrations if used with fosamprenavir; additional pharmacokinetic interactions if fosamprenavir used with both ritonavir and efavirenz37 82	If fosamprenavir used with efavirenz, boosting with ritonavir required 37 82 When efavirenz is used with ritonavir-boosted fosamprenavir, fosamprenavir 1.4 g once daily with ritonavir 300 mg once daily or fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily recommended; efavirenz dosage adjustment not needed37
Histamine H2-receptor antagonists (famotidine)	Pharmacokinetic interaction unlikely with famotidine1	When used with famotidine, dosage adjustment not needed1
HMG-CoA reductase inhibitors	Decreased AUC of atorvastatin, pravastatin, and simvastatin1 37	Individualize dosage of antilipemic agent;1 if used with atorvastatin, pravastatin, or simvastatin, adjust dosage of antilipemic agent according to lipid response (up to maximum dosage)37
Indinavir	Decreased peak plasma concentrations and AUC of indinavir; no change in pharmacokinetics of efavirenz1 33 37 In vitro evidence of additive antiretroviral effects1	Adjustment of efavirenz dosage not needed; increase indinavir dosage to 1 g every 8 hours or consider ritonavir-boosted indinavir1 37
Lamivudine	Pharmacokinetic interaction unlikely1 In vitro evidence of additive antiretroviral effects1	Dosage adjustment not needed1
Lopinavir	Lopinavir 600 mg and ritonavir 150 mg twice daily with efavirenz 600 mg once daily: Increased lopinavir concentrations relative to lopinavir 400 mg and ritonavir 100 mg twice daily (without efavirenz)1 70 In vitro evidence of additive antiretroviral effects1	Once-daily lopinavir regimen not recommended with efavirenz1 70 For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily70 Manufacturer of lopinavir recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily70 For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)70
Macrolides (azithromycin, clarithromycin, erythromycin)	Clarithromycin: Decreased clarithromycin concentrations and increased 14-hydroxyclarithromycin concentrations;1 rash reported with concomitant administration1 Azithromycin: Pharmacokinetic interaction unlikely1 Erythromycin: Not studied1	Clarithromycin: Monitor for efficacy of the macrolide or use an alternative anti-infective1 37 Azithromycin: Dosage adjustment not needed1
Maraviroc	Decreased maraviroc concentrations37 85	If used concomitantly, recommended dosage of maraviroc is 600 mg twice daily37 85
Nelfinavir	Increased peak plasma concentrations and AUC of nelfinavir; decreased peak plasma concentrations and AUC of nelfinavir metabolite (M8); no change in pharmacokinetics of efavirenz1 37 38 43 In vitro evidence of additive antiretroviral effects1	Dosage adjustments not needed1 33 37 38
Nevirapine	Decreased efavirenz AUC;23 37 no change in nevirapine concentrations37	Concomitant use of NNRTIs not recommended37
Psychotherapeutic agents	Potential for additive CNS effects1 1 Paroxetine: Pharmacokinetic interaction unlikely1 Sertraline: Decreased sertraline concentrations1 Pimozide: Potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1	Paroxetine: Dosage adjustment not needed1 Sertraline: Increases in sertraline dosage should be guided by clinical response1 Pimozide: Concomitant use contraindicated1
Ritonavir	Increased ritonavir AUC and increased efavirenz AUC1 37 40 Higher incidence of dizziness, nausea, paresthesia, and elevated hepatic enzyme values with regimens that include both drugs1 44 In vitro evidence of additive antiretroviral effects1	Monitor hepatic enzymes;1 44 use usual dosages37
Saquinavir	Decreased peak plasma concentrations and AUC of saquinavir;1 33 37 decreased efavirenz concentrations37 Concomitant use with ritonavir-boosted saquinavir not evaluated83 In vitro evidence of additive antiretroviral effects1	Some clinicians recommend using saquinavir 1 g twice daily and ritonavir 100 mg twice daily with usual dosage of efavirenz37
St. John’s wort (Hypericum perforatum)	Decreased efavirenz concentrations; possible loss of virologic response and increased risk of efavirenz resistance1 63 64	Concomitant use contraindicated1 37
Tenofovir	No evidence of pharmacokinetic interaction76 In vitro evidence of additive or synergistic antiretroviral effects1	Dosage adjustment not needed1
Tipranavir	Tipranavir 500 mg twice daily and ritonavir 100 mg twice daily and efavirenz 600 mg once daily: Decreased tipranavir concentrations and no change in efavirenz concentrations37 77 In vitro evidence of additive antiretroviral effects77	Some experts state that dosage adjustment not necessary37
Valproic acid	No evidence of pharmacokinetic interaction75
Zidovudine	Pharmacokinetic interaction unlikely1 In vitro evidence of additive antiretroviral effects1	Dosage adjustment not necessary1

Efavirenz Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained within 3–5 hours.¹

The fixed-combination tablet containing efavirenz 600 mg, tenofovir disoproxil fumarate 300 mg, and emtricitabine 200 mg (Atripla) is bioequivalent to a 600-mg efavirenz tablet, a 300-mg tenofovir disoproxil fumarate tablet, and a 200-mg emtricitabine capsule given simultaneously.⁷⁸

Food

Administration with food increases bioavailability.¹

Compared with administration in the fasting state, AUC increased 22 or 17% when a single 600-mg 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.¹

Compared with administration in the fasting state, AUC increased 28% when a single 600-mg dose as tablets was administered with a high-fat, high-calorie meal (1000 kcal, 500–600 kcal from fat).¹

Distribution

Extent

Not fully characterized.¹

Low concentrations distributed into CSF.¹

Not known whether efavirenz crosses the placenta. Distributed into milk in rats; not known whether distributed into human milk.¹

Plasma Protein Binding

99.5–99.75%.¹

Elimination

Metabolism

Metabolized by CYP3A and CYP2B6; undergoes subsequent glucuronidation.¹

Elimination Route

16–61% excreted in feces (principally as unchanged drug) and 14–34% eliminated in urine as unchanged drug (<1%) or metabolites.¹

Not removed by hemodialysis; probably not removed by peritoneal dialysis.^{1 67}

Half-life

52–76 hours after a single dose and 50–55 hours after multiple doses.¹

Stability

Storage

Oral

Capsules and Tablets

25°C (may be exposed to 15–30°C).^{1 78}

Actions and SpectrumActions

• 
  

  Pharmacologically related to other NNRTIs (e.g., delavirdine, etravirine, nevirapine); differs structurally from these drugs; also differs pharmacologically and structurally from other currently available antiretrovirals.^{1 2 3 6 12 14 21 23 52 53}

  
  


• 
  

  Active against HIV-1; inactive against HIV-2.^{1 3}

  
  


• 
  

  Inhibits replication of HIV-1 by interfering with viral RNA- and DNA-directed polymerase activities of reverse transcriptase.^{1 3}

  
  


• 
  

  HIV-1 with reduced susceptibility to efavirenz have been selected in vitro and have emerged during therapy with the drug.^{1 3 7 8 9 14 18}

  
  


• 
  

  Strains of HIV-1 resistant to efavirenz may be cross-resistant to some other NNRTIs (i.e., delavirdine, nevirapine).^{1 3 7 8 9 10 19 23 32 37 44 50}

  
  


• 
  

  Cross-resistance between efavirenz and NRTIs unlikely since the drugs bind at difference sites on reverse transcriptase and have difference mechanisms of action.^{1 3 7 8 9 10 32} Cross-resistance between efavirenz and PIs unlikely since the drugs have different target enzymes and mechanisms of action.^{1 32}

  
  

Advice to Patients

• 
  

  Critical nature of compliance with HIV therapy.¹ Importance of using efavirenz in conjunction with other antiretrovirals— not for monotherapy.¹

  
  


• 
  

  Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.¹ HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.¹

  
  


• 
  

  Importance of taking on a empty stomach.¹

  
  


• 
  

  Potential for adverse CNS effects during the first weeks of therapy.¹ Importance of taking efavirenz at bedtime.¹ Use caution when driving or operating machinery until effects on individual known.¹

  
  


• 
  

  Potential for serious psychiatric symptoms.¹ Importance of seeking immediate medical evaluation if psychiatric symptoms occur.¹

  
  


• 
  

  Risk of rash.¹ Importance of contacting clinician if rash develops.¹

  
  


• 
  

  Importance of reading patient package insert from manufacturer.¹

  
  


• 
  

  Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Importance of advising women to avoid pregnancy.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Efavirenz

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	50 mg	Sustiva	Bristol-Myers Squibb
		200 mg	Sustiva	Bristol-Myers Squibb
	Tablets, film-coated	600 mg	Sustiva	Bristol-Myers Squibb

Efavirenz Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	600 mg with Tenofovir Disoproxil Fumarate 300 mg and Emtricitabine 200 mg	Atripla	Bristol-Myers Squibb and Gilead

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Atripla 600-200-300MG Tablets (BRISTOL-MYERS SQUIBB/GILEAD): 30/$1795.72 or 90/$5154.14

Sustiva 200MG Capsules (B-M SQUIBB U.S. (PRIMARY CARE)): 90/$623.02 or 270/$1755.89

Sustiva 600MG Tablets (B-M SQUIBB U.S. (PRIMARY CARE)): 30/$623.02 or 90/$1757.88

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 01, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. Bristol-Myers Squibb Company. Sustiva (efavirenz) capsules and tablets prescribing information. Princeton, NJ; 2009 Mar.

2. Adkins JC, Noble S. Efavirenz. Drugs. 1998; 56:1055-64. [PubMed 9878993]

3. Young SD, Britcher SF, Tran LE et al. L-743,726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type I reverse transcriptase. Antimicrob Agents Chemother. 1995; 39:2602-5. [PubMed 8592986]

4. Rabel SR, Maurin MB, Rowe SM et al. Determination of the pK_a and pH-solubility behavior of an ionizable cyclic carbamate, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one (DMP 266). Pharm Dev Technol. 1996; 1:91-5. [PubMed 9552335]

5. Anon. Three new drugs for HIV infection. Med Lett. 1998; 40:114-6.

6. Spence RA, Kati WM, Anderson KS et al. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science. 1995; 267:988-93. [PubMed 7532321]

7. Bacheler L, George H, Hollis G et al. Resistance to efavirenz (Sustiva) in vivo. 5th Conf Retrovir Oppor Infect. 1998:210. Abstract No. 703.

8. Jeffrey S, Baker D, Tritch R et al. Resistance and cross resistance profile for Sustiva (efavirenz, DMP 266). 5th Conf Retrovir Oppor Infect. 1998:210. Abstract No. 702.

9. Bacheler L, Weislow O, Snyder S et al. Virologic resistance to efavirenz. Int Conf AIDS. 1998; 12:287.

10. Winslow DL, Garber S, Reid C et al. Selection conditions affect the evolution of specific mutations in the reverse transcriptase gene associated with resistance to DMP 266. AIDS. 1996; 10:1205-9. [PubMed 8883581]

11. Merluzzi VJ, Hargrave KD, Labadia M et al. Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor. Science. 1990; 250:1411-13. [PubMed 1701568]

12. De Clerq E. The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection. Antiviral Res. 1998; 38:153-79. [PubMed 9754886]

13. Tashima KT, Caliendo AM, Ahmad M et al. Cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) suppression