Efavirenz

Class and Category

Pharmacologic Class: Non-nucleoside reverse transcriptase inhibitor
Therapeutic ClassAntiretroviral

Indications and Dosages

As adjunct to treat human immunodeficiency virus type 1 (HIV-1) in combination with other antiretroviral agents
CAPSULES, TABLETS
Adults and children weighing 40 kg (88 lb) or more. 600 mg once daily at bedtime on an empty stomach.
Children age 3 months and older and weighing 32.5 kg (71.5 lb) to less than 40 kg (88 lb). 400 mg once daily at bedtime on an empty stomach.
Children age 3 months and older and weighing 25 kg (55 lb) to less than 32.5 kg (71.5 lb). 350 mg once daily at bedtime on an empty stomach.
Children age 3 months and older and weighing 20 kg (44 lb) to less than 25 kg (55 lb). 300 mg once daily at bedtime on an empty stomach.
Children age 3 months and older and weighing 15 kg (33 lb) to less than 20 kg (44 lb). 250 mg once daily at bedtime on an empty stomach.
Children age 3 months and older and weighing 7.5 kg (16.5 lb) to less than 15 kg (33 lb). 200 mg once daily at bedtime on an empty stomach.
Children age 3 months and older and weighing 5 kg (11 lb) to less than 7.5 kg (16.5 lb). 150 mg once daily at bedtime on an empty stomach.
Children age 3 months and older and weighing 3.5 kg (7.7 lb) to less than 5 kg (11 lb). 100 mg once daily at bedtime on an empty stomach.
DOSAGE ADJUSTMENT: For adult patients weighing 50 kg (110 lb) and also receiving rifampin, the dosage increased to 800 mg once daily. For adult patients receiving voriconazole concurrently, the dosage decreased to 300 mg once daily.

Mechanism of Action
Inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral DNA integration, which is needed for the HIV replication cycle.

Contraindications
Concurrent therapy with elbasvir and grazoprevir, hypersensitivity to efavirenz
or its components.

Interactions
DRUGS
  1. Artemether, atazanavir, atorvastatin, atovaquone, boceprevir, bupropion, clarithromycin, cyclosporine, dihydroatemisinin, diltiazem, ethinyl estradiol/norgestimate, etonogestrel implant, felodipine, fosamprenavir, hydroxyitraconazole, immunosuppressants, indinavir, ketoconazole, itraconazole, lopinavir, lumefantrine, maraviroc, methadone, nicardipine, nifedipine, posaconazole, pravastatin, proguanil, rifabutin, saquinavir, sertraline, simeprevir, simvastatin, sirolimus, tacrolimus, velpatasvir/sofosbuvir, velpatasvir / sofosbuvir / voxilaprevir, verapamil: Decreased effectiveness of these drugs
  2. Carbamazepine, phenobarbital, phenytoin: Decreased plasma levels of both drugs
  3. CYP3A inducers: Decreased plasma levels of efavirenz with decreased effectiveness
  4. Elbasvir/grazoprevir, pibrentasvir / glecaprevir: Possibly loss of virologic response and reduced therapeutic effect 
  5. Other nonnucleoside reverse transcriptase inhibitors: Decreased or increased plasma levels of both drugs without added efficacy psychoactive drugs: Possibly additive central nervous system effects
  6. QT prolongation drugs such as artemether/lumefantrine, clarithromycin: Increased risk of Torsade de Pointes
  7. Rifabutin: Decreased plasma levels of both drugs decreasing effectiveness
  8. Rifampin: Decreased plasma efavirenz levels with possible decrease in effectiveness
  9. Ritonavir: Increased plasma levels of both efavirenz and ritonavir, possibly leading to elevated liver enzymes and other adverse reactions
  10. Voriconazole: Decreased voriconazole level and increased plasma efavirenz 
  11. warfarin: Decreased or increased warfarin levels, requiring close monitoring of INR and adjustment of warfarin dosage as needed

ACTIVITIES
Alcohol use: Possibly increased additive central nervous system effects

Adverse Reactions
  1. CNS: Abnormal dreams, aggression, agitation, amnesia, anxiety, asthenia, ataxia, catatonia, cerebellar balance and coordination disturbances, confusion, delusions, depersonalization, depression (severe), dizziness, emotional lability, encephalopathy, euphoria, fatigue, fever, hallucinations, headache, hypoesthesia, impaired concentration, insomnia, paranoid behavior, manic reactions, nervousness, neuropathy, neurosis, paranoia, paresthesia, psychosis-like behavior, seizures, somnolence, stupor, suicidal ideation, tremor, vertigo
  2. CV: Elevated cholesterol and triglyceride levels, palpitations, QT prolongation
  3. EENT: Abnormal vision, tinnitus
  4. ENDO: Cushingoid appearance, fat redistribution, gynecomastia, hyperglycemia
  5. GI: Abdominal pain, anorexia, constipation, diarrhea, dyspepsia, elevated amylase or liver enzymes, hepatic failure, hepatitis, hepatotoxicity, malabsorption, nausea, pancreatitis, vomiting
  6. HEME: Neutropenia
  7. MS: Arthralgia, myalgia, myopathy
  8. RESP: Dyspnea
  9. SKIN: Blisters, erythema multiforme, flushing, moist desquamation, photoallergic dermatitis, pruritus, rash, Stevens-Johnson syndrome, ulcerations
  10. Other: Allergic reactions, nonspecific pain, immune reconstitution syndrome

Childbearing Considerations
PREGNANCY
  • Be aware pregnancy testing should be done in women of childbearing age prior to initiation of drug therapy.
  • It is not known if a drug causes fetal harm. However, there are retrospective reports of neural tube defects in infants whose mothers were exposed to an efavirenz-containing regimen in the first trimester of pregnancy.
  • Drug should not be given during the first trimester of pregnancy.
    LACTATION
    • It is not known if the drug is present in breast milk.
    • The Centers for Disease Control and Prevention recommends that HIV-1 infected mothers not
    • breastfeed to avoid risking postnatal transmission of HIV-1 infection to infants. They also do not
    • recommend breastfeeding because of potential drug-induced adverse reactions in the infant.
    REPRODUCTION
    • Effective contraceptive measures should be in place prior to beginning drug therapy as well as
    • throughout therapy and for 12 weeks after the drug is discontinued.
    • Barrier contraception should always be used in combination with other methods of contraception.
    • Know that hormonal methods of contraception that contain progesterone may not be as effective.

    Nursing Considerations
    • Be aware that efavirenz should not be used as a single agent in treating HIV infection, because resistant virus emerges quickly when drug is used alone.
    • Know that efavirenz therapy is not recommended with the combination drug Atripla, which contains efavirenz, unless needed for dose adjustment when coadministered with rifampin.
    • Know that drug should not be used in patients taking other medications with a known risk of torsades de pointes or in patients at higher risk of torsades de pointes, because efavirenz may cause QT prolongation.
    • Obtain liver enzymes before therapy begins, as ordered, in patients with marked transaminase elevations, patients treated with other medications associated with liver toxicity, and patients with underlying hepatic disease, including hepatitis B or C infections. Also monitor liver enzymes throughout therapy, as ordered, on all patients, because efavirenz may cause hepatotoxicity. Know that persistent elevation of serum transaminase levels greater than five times the upper limit of the normal range may require efavirenz therapy to be discontinued.
    • Obtain cholesterol and triglyceride levels before efavirenz is begun and periodically throughout therapy, because drug may cause an increase in total cholesterol and triglycerides.
    • Use efavirenz cautiously in patients with a history of seizures, as drug may increase risk of seizures. Know that if patient is also taking anticonvulsant medications metabolized by the liver, such as phenobarbital or phenytoin, periodic monitoring of plasma levels of these drugs may be required.
    WARNING Monitor patient for rash. While usually mild to moderate, occurring within the first 2 weeks of therapy and resolving within a month, a rash rarely may evolve into more serious skin conditions that could become life-threatening and should be reported. Know that it is recommended that children be given antihistamines and/or corticosteroids before initiating therapy, as a prophylactic measure.
    • Monitor patient for serious psychiatric adverse reactions such as aggressive behavior, manic reactions, paranoia, severe depression, or suicidal ideation. Patients at increased risk include patients with drug addiction (injected) or psychiatric history including use of psychiatric drugs.
    • Monitor patient for nervous system symptoms that commonly occur with efavirenz use. Be especially watchful for abnormal dreams, dizziness, hallucinations, impaired concentration, insomnia, and somnolence. Be aware that these symptoms usually occur within a day or two of starting therapy and usually resolve in the first 2 to 4 weeks. However, know that late-onset neurotoxicity, including ataxia and encephalopathy, may occur months to years after beginning efavirenz therapy.
    • Be aware that immune reconstitution syndrome has occurred in patients treated with combination antiretroviral therapy, including efavirenz. The inflammatory response predisposes susceptible patients to opportunistic infections such as cytomegalovirus, Mycobacterium avium infection, Pneumocystis jiroveci pneumonia, or tuberculosis. Autoimmune disorders such as Graves’ disease, Guillain–BarrĂ© syndrome, or polymyositis have also occurred. Report sudden or unusual adverse reactions to prescriber.

    PATIENT TEACHING
    • Inform patient that efavirenz is not to be taken alone and to follow administration instructions as ordered, noting that drug should be taken on an empty stomach at bedtime.
    • Instruct patient or parent that if patient is unable to swallow capsule form, it may be opened and sprinkled on 1 to 2 teaspoonfuls of food such as applesauce, grape jelly, or yogurt. The capsule should be opened carefully so as not to spill any of the contents or disperse drug into the air. To accomplish this, tell patient to hold capsule horizontally over a small container and carefully twist open. If child is unable to consume food, the entire capsule contents may be gently mixed into 2 teaspoons of reconstituted room-temperature infant formula, stirred gently with a small spoon, and then drawn up into a 10-ml oral dosing syringe for administration. After administration, an additional 2 teaspoons of formula should be added to the empty mixing container, stirred, and administered. Caution that the food or formula mixture should be administered within 30 minutes of mixing and no additional food should be consumed for 2 hours after the drug is given.
    • Inform patient that efavirenz therapy may cause changes in his body appearance because of fat redistribution. Prepare him for the possibility of developing breast enlargement, central obesity, dorsocervical fat enlargement (buffalo hump), facial wasting, and peripheral wasting.
    • Instruct patient to report a rash. Also alert patient that drug may cause nervous system symptoms or psychiatric symptoms. Review these symptoms with patient and urge patient to report to prescriber if present. Advise him also to report any persistent, severe, or unusual signs and symptoms.
    • Warn family or caregiver to watch patient closely for evidence of suicidal behavior or thinking.
    • Inform patient that neurological adverse reactions such as abnormal dreams, drowsiness, dizziness, impaired concentration, and insomnia may occur in the first weeks of efavirenz therapy but taking drug at bedtime will help and symptoms should diminish with continued therapy. Alert patient to the possibility of late-onset neurotoxicity that may occur months to years after beginning efavirenz therapy. Encourage patient to report any abnormal neurological signs and symptoms regardless of how long efavirenz therapy has been taken.
    • Advise patient to contact prescriber before taking any new drugs, including over-the-counter preparations and herbals.
    • Caution patient to avoid hazardous activities such as driving until nervous system effects are known and abated.
    • Warn women of childbearing age that efavirenz may cause fetal harm when administered during the first trimester of pregnancy. Stress importance of using reliable birth control and tell the patient to alert prescriber immediately if pregnancy occurs or is suspected.
    • Inform mothers that breastfeeding should not be done while taking efavirenz.

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