e-FAV-e-renz

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: non nucleoside reverse transcriptase inhibitors

• HIV infection (in combination with one or more other antiretroviral agents).

• Inhibits HIV reverse transcriptase, which results in disruption of DNA synthesis.

• Slowed progression of HIV infection and decreased occurrence of sequelae.
• Increases CD4 cell counts and decreases viral load.

Absorption: 50% absorbed when ingested following a high-fat meal.

Distribution: Enters CSF.

Protein Binding: >99%.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP3A4 and CYP2B6 isonezymes. Excreted in urine and feces, primarily as metabolites.

Half-life: Following single dose: 52–76 hr. Following multiple doses: 40–55 hr.

(plasma concentrations)

Contraindicated in:

• Hypersensitivity
• Moderate to severe hepatic impairment
• Concurrent use of elbasvir and grazoprevir.

Use Cautiously in:

• History of mental illness or substance abuse (↑ risk of psychiatric symptomatology)
• Mild hepatic impairment (including coinfection with hepatitis B/C)
• History of seizure disorders (↑ risk of seizures)
• OB: Use in pregnancy only if other options have been exhausted; birth defects have been reported especially when used during the 1st trimester
• Lactation: Safety not established in breastfeeding; breastfeeding should be supported in people with HIV who are taking antiretroviral therapy as prescribed and are maintaining an undetectable amount of virus in the body
• Pedi: Children <3 mo (safety and effectiveness not established); ↑ incidence of rash in children
• Geri: Use lower initial dose in older adults due to ↑ incidence of renal or cardiac dysfunction.

CV: QT interval prolongation.

Derm: rash, pruritus, sweating.

Endo: Graves' disease, hypercholesterolemia, hypertriglyceridemia.

GI: nausea, abdominal pain, anorexia, autoimmune hepatitis, diarrhea, dyspepsia, flatulence, HEPATOTOXICITY.

GU: hematuria, renal calculi.

Metab: fat redistribution.

MS: polymyositis.

Neuro: abnormal dreams, ataxia, catatonia, delusions, depression, dizziness, drowsiness, encephalopathy, fatigue, Guillain-Barré syndrome, headache, hypoesthesia, impaired concentration, insomnia, nervousness, psychoses, SUICIDAL THOUGHTS/BEHAVIORS.
Misc: immune reconstitution syndrome.

Drug-Drug:

• May lead to loss of virologic response to elbasvir/grazoprevir; concurrent use contraindicated.
• Induces (stimulates) the hepatic cytochrome P450 3A4 enzyme system and would be expected to influence the effects of other drugs that are metabolized by this system; efavirenz itself is also metabolized by this system.
• ↑risk of CNS depression with other CNS depressants, including alcohol, antidepressants, antihistamines, and opioid analgesics.
• May ↓ the effectiveness of progestin-containing hormonal contraceptives (e.g., etonogestrel, norelgestromin, levonorgestrel).
• Use with voriconazole significantly ↓ voriconazole levels and ↑ efavirenz levels; avoid concurrent use with standard doses of voriconazole; if used together, ↑ dose of voriconazole to 400 mg every 12 hr and ↓ dose of efavirenz to 300 mg daily.
• May ↓ posaconazole levels and effectiveness; avoid concurrent use.
• May ↓ itraconazole levels and effectiveness; use alternative antifungal agent.
• May ↓ ketoconazole levels and effectiveness
• May ↓ fosamprenavir levels and effectiveness; ↑ dose of ritonavir when given with fosamprenavir/ritonavir once daily.
• May ↓ atazanavir levels and effectiveness; dosage adjustments may be needed in treatment-naive patients; avoid concurrent use in treatment-experienced patients.
• May ↓ lopinavir levels and effectiveness; ↑ dose of lopinavir/ritonavir; avoid concurrent use of lopinavir/ritonavir once daily.
• May ↑ ritonavir levels and risk of toxicity; monitor liver function tests.
• May ↓ raltegravir levels and effectiveness.
• May ↓ maraviroc levels and effectiveness; ↑ maraviroc dose.
• May alter the effects of warfarin.
• May ↓ levels and effectiveness of cyclosporine, tacrolimus, and sirolimus.
• May ↓ levels and effectiveness of bupropion and sertraline.
• Rifampin may ↓ levels and effectiveness; ↑ dose of efavirenz.
• Concurrent use with other NNRTIs, including etravirine, nevirapine, and rilpivirine, may lead to ↓ effectiveness; avoid concurrent use.
• May ↓ levels and effectiveness of raltegravir.
• Concurrent use with carbamazepine may ↓ levels and effectiveness of carbamazepine and efavirenz; use alternative anticonvulsant agent.
• Concurrent use with phenytoin or phenobarbital may ↓ levels and effectiveness of phenytoin, carbamazepine, and efavirenz.
• May ↓ levels and effectiveness of clarithromycin; consider using azithromycin.
• May ↓ levels and effectiveness of rifabutin; ↑ daily dose of rifabutin by 50%.
• May ↓ levels and effectiveness of calcium channel blockers, atorvastatin, pravastatin, simvastatin, methadone, and artemether/lumefantrine.
• Concurrent use with other QT interval prolonging medications may ↑ risk of QT interval prolongation or torsades de pointes.
• May ↓ effectiveness of pibrentasvir/glecaprevir, velpatasvir/sofosbuvir, and velpatasivir/sofosbuvir/voxilaprevir; avoid concurrent use.
• Praziquantel may ↓ levels and effectiveness; concurrent use not recommended.

Drug-Food:

• Ingestion following a high-fat meal↑ absorption by 50%.

• PO (Adults and Children 40 kg): 600 mg once daily; Concurrent rifampin therapy (in patients >50 kg): 800 mg once daily.
• PO (Children 3 mo and 32.5–39.9 kg): 400 mg once daily.
• PO (Children 3 mo and 25–32.4 kg): 350 mg once daily.
• PO (Children 3 mo and 20–24.9 kg): 300 mg once daily.
• PO (Children 3 mo and 15–19.9 kg): 250 mg once daily.
• PO (Children 3 mo and 7.5–14.9 kg): 200 mg once daily.
• PO (Children 3 mo and 5–7.4 kg): 150 mg once daily.
• PO (Children 3 mo and 3.5–4.9 kg): 100 mg once daily.

(Generic available)

• Capsules: 50 mg; 200 mg;
• Tablets: 600 mg;
• In combination with: emtricitabine and tenofovir disoproxil fumarate (Atripla); lamivudine and tenofovir disoproxil fumarate (Symfi, Symfi Lo). (See Appendix [not included in this PDA edition]).

• Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
• Assess for rash, especially during 1st mo of therapy. Onset is usually within 2 wk and resolves with continued therapy within 1 mo. May range from mild maculopapular with erythema and pruritus to exfoliative dermatitis and Stevens-Johnson syndrome. Occurs more often and may be more severe in children. If rash is severe or accompanied by blistering, desquamation, mucosal involvement, or fever, therapy must be discontinued immediately. Efavirenz may be reinstated concurrently with antihistamines or corticosteroids in patients discontinuing due to rash.
• Assess patient for CNS and psychiatric symptoms (dizziness, impaired concentration, somnolence, abnormal dreams, insomnia, suicidal thoughts and behaviors) during therapy. Symptoms usually begin during 1st or 2nd day of therapy and resolve after 2–4 wk. Administration at bedtime may minimize symptoms. Concurrent use with alcohol or psychoactive agents may cause additive CNS symptoms.

• • Verify negative pregnancy test prior to starting therapy.
  Monitor viral load and CD4 cell count regularly during therapy.
  • Monitor liver function tests before and periodically during therapy in all patients. Discontinue therapy if persistent ↑ in serum transaminases >5 times upper limit of normal or if clinical signs and symptoms of hepatic dysfunction occur.
  • May cause ↑ in total cholesterol and serum triglyceride levels.
  • May cause false-positive urine cannabinoid results.

• PO: Administer on an empty stomach, preferably at bedtime to minimize nervous system side effects. Avoid taking with a high-fat meal. Do not break tablets.
  • Capsule may be opened and contents sprinkled on a small amount (1 to 2 teaspoons) of food for children 3 mo old and weighing 3.5 kg and adults who cannot swallow capsules or tablets. Open capsule carefully; avoid spillage or dispersion of contents into the air. For infants receiving capsule sprinkle infant formula mixture, gently mix entire capsule contents into 2 teaspoons (10 mL) of reconstituted room temperature infant formula in a medicine cup; then draw up mixture into a 10 mL oral dosing syringe for administration. Use of infant formula for mixing should only be considered for those young infants who cannot consume solid foods. For patients able to tolerate solid foods, mix entire capsule contents gently with soft food (applesauce, grape jelly, yogurt). After administration of mixture, add a small amount (2 teaspoons) of food or formula to empty mixing container, stir to disperse any remaining efavirenz residue, and administer to patient. Administer mixture within 30 min of mixing. Avoid food for 2 hr after administration.

• Emphasize the importance of taking efavirenz as directed. It must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount, and do not stop taking without consulting health care professional. Take missed doses as soon as remembered; do not double doses. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• Instruct patient that efavirenz should not be shared with others.
• May cause dizziness, impaired concentration, or drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Instruct patient to notify health care professional immediately if rash or suicidal thoughts or behaviors occur.
• Inform patient that efavirenz does not cure HIV or prevent associated or opportunistic infections. Efavirenz may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading HIV to others. Advise patient that the long-term effects of efavirenz are unknown at this time.
• Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Inform patient of risk of developing late-onset neurotoxicity (ataxia, encephalopathy); may occur mos to yrs after starting therapy.
• May cause fetal harm, especially when used during the 1st trimester of pregnancy. Advise females of reproductive potential taking oral contraceptives to use a nonhormonal method of birth control during efavirenz therapy and for 12 wk following discontinuation. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding is planned. Encourage patients who become pregnant during therapy to join the Antiretroviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to efavirenz during pregnancy. Enroll patient by calling 1-800-258-4263.
• Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

• Delayed progression of HIV and decreased opportunistic infections in patients with HIV.
• Decrease in viral load and increase in CD4 cell counts.

Sustiva