efavirenz (e-fav-e-renz) Sustiva

 Indications

HIV infection (in combination with one or more other

antiretroviral agents).

Action

Inhibits HIV reverse transcriptase, which results in disruption

of DNA synthesis. Therapeutic Effects:

Slowed progression of HIV infection and decreased occurrence

of sequelae. Increases CD4 cell counts and

decreases viral load.

Pharmacokinetics

Absorption: 50% absorbed when ingested following

a high-fat meal.

Distribution: 99.5–99.75% bound to plasma proteins;

enters CSF.

Metabolism and Excretion: Mostly metabolized

by the liver.

Half-life: Following single dose—52–76 hr. Following

multiple doses—40–55 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO rapid 3–5 hr 24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Moderate to

severe hepatic impairment.

Use Cautiously in: History of mental illness or substance

abuse (qrisk of psychiatric symptomatology);

Mild hepatic impairment; History of seizure disorders

(qrisk of seizures); OB: Use in pregnancy only if other options have been exhausted; birth defects have been

reported; Lactation: Breast feeding not recommended

for HIV-infected mothers; efavirenz passes into breast

milk; Pedi: Children 3 mo (safety not established);q

incidence of rash; Geri: Cautious initial dosing due toq

incidence of renal or cardiac dysfunction.

Adverse Reactions/Side Effects

CNS: SUICIDIAL THOUGHTS/BEHAVIORS, abnormal

dreams, catatonia, delusions, depression, dizziness,

drowsiness, fatigue, headache, impaired concentration,

insomnia, nervousness, psychoses. CV: QT INTERVAL

PROLONGATION. GI: HEPATOTOXICITY, nausea, abdominal

pain, anorexia, diarrhea, dyspepsia, flatulence. GU:

hematuria, renal calculi. Derm: rash, sweating, pruritus.

Endo: hypercholesterolemia, hypertriglyceridemia.

Neuro: hypoesthesia. Misc: fat redistribution,

immune reconstitution syndrome.

Interactions

Drug-Drug: 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.qrisk of CNS depression with

other CNS depressants, including alcohol, antidepressants,

antihistamines, and opioid analgesics.

Maypthe effectiveness of progestin-containing hormonal

contraceptives (e.g., etonogestrel, norelgestromin,

levonorgestrel). Use with voriconazole significantlypvoriconazole

levels andqefavirenz levels;

avoid concurrent use with standard doses of voriconazole;

if used together,qdose of voriconazole to 400 mg

every 12 hr andpdose of efavirenz to 300 mg daily.

Maypposaconazole levels; avoid concurrent use.

Maypitraconazole levels; use alternative antifungal

agent. Maypketoconazole levels. Maypindinavir

levels;qdose of indinavir dose. Maypfosamprenavir

levels;qdose of ritonavir when given with fosamprenavir/

ritonavir once daily. Maypatazanavir levels; dosage

adjustments may be needed in treatment-naı¨ve patients;

avoid concurrent use in treatment-experienced

patients. Mayplopinavir levels;qdose of lopinavir/ritonavir;

avoid concurrent use of lopinavir/ritonavir

once daily. Mayqritonavir levels; monitor liver function

tests. Maypsaquinavir and raltegravir levels.p

maraviroc levels;qmaraviroc dose. May alter the effects

of warfarin. Mayplevels of cyclosporine, tacrolimus,

and sirolimus. Mayplevels of bupropion

and sertraline. Rifampin mayplevels;qdose of efavirenz.

Concurrent use with other NNRTIs including

etravirine, nevirapine, rilpivirine, and delavirdinemay

lead topeffectiveness and should be

avoided. Mayplevels of raltegravir. Mayplevels of

simeprevir; avoid concurrent use. Concurrent use

with carbamazepine mayplevels of carbamazepine

and efavirenz; use alternative anticonvulsant agent. Concurrent

use with phenytoin or phenobarbital mayp

levels of phenytoin, carbamazepine, and efavirenz. May

plevels of clarithromycin; consider using azithromycin.

Mayplevels of rifabutin;qdaily dose of rifabutin

by 50%. Mayplevels of calcium channel blockers,

atorvastatin, pravastatin, simvastatin, methadone,

and artemether/lumefantrine. Mayplevels of

progestin-containing contraceptives and etonogestrel;

use reliable method of barrier contraception

in addition to hormonal contraceptive agent. Concurrent

use with other QT interval prolonging medications

mayqrisk of QT interval prolongation or torsade

de pointes.

Drug-Food: Ingestion following a high-fat mealq

absorption by 50%.

Route/Dosage

PO (Adults and Children 40 kg): 600 mg once

daily; Concurrent rifampin therapy (in patients50

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.

Availability (generic available)

Capsules: 50 mg, 200 mg. Tablets: 600 mg. In combination

with: emtricitabine and tenofovir (Atripla)

(See Appendix B).