amprenavir Pharmacologic classification: protease inhibitor
Therapeutic classification: antiretroviral
Pregnancy risk category C
Available by prescription only
Capsules: 50 mg, 150 mg
Oral solution: 15 mg/ml
Indications and dosages
Treatment of HIV-1 infection with other antiretrovirals. Adults and children ages 13 to 16 who weigh 110 lb (50 kg) or more: 1,200 mg P.O. (eight 150-mg capsules) b.i.d. with other antiretrovirals.
Children ages 4 to 12 or 13 to 16 who weigh less than 110 lb: For capsules, 20 mg/kg P.O. b.i.d. or 15 mg/kg P.O. t.i.d. (to a maximum daily dose of 2,400 mg) with other antiretrovirals.
For oral solution, 22.5 mg/kg P.O. (1.5 ml/kg) b.i.d. or 17 mg/kg P.O. (1.1 ml/kg) t.i.d. (to a maximum daily dose of 2,800
mg) with other antiretrovirals.
≡ Dosage adjustment. Patients with moderate or severe hepatic impairment should receive reduced dosage. Those with a Child-Pugh score of 5 to
8 should receive 450 mg (capsules) P.O. b.i.d. Those with a Child-Pugh score of 9 to 12 should receive 300 mg (capsules) P.O.
Antiretroviral action: Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature noninfectious viral particles.
Absorption: Rapidly absorbed.
Distribution: About 90% bound to plasma proteins.
Metabolism: Metabolized in the liver by the cytochrome P-450 CYP3A4 enzyme system.
Excretion: Excretion of unchanged amprenavir in urine and feces is minimal. The plasma elimination half-life ranges from 7.1 to 10.6
Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components. Contraindicated in infants, children younger than age
4, pregnant women, patients with liver or kidney failure, and patients treated with disulfiram (Antabuse) or metronidazole
(Flagyl). Use cautiously in patients with sulfonamide allergy, those with hepatic impairment, and those with hemophilia A
and B. Use cautiously in patients with diabetes mellitus.
Drug-drug. Antacids: May interfere with absorption. Separate administration times by at least 1 hour.
Antiarrhythmics such as amiodarone, lidocaine (systemic), quinidine; anticoagulants such as warfarin, and tricyclic antidepressants: May affect serum levels of these drugs when used together. Monitor patient closely.
Bepridil, dihydroergotamine, midazolam, rifampin, and triazolam: Serious and life-threatening interactions may occur. Avoid use together.
Efavirenz: Decreases adequate area under the curve (AUC) of amprenavir. Increase dosage accordingly.
HMG-CoA reductase inhibitors: Increases levels of these drugs, increasing risk of myopathy, including rhabdomyolysis. Avoid use together.
Hormonal contraceptives: Metabolic interactions are possible. Advise patient to use alternative or additional methods of birth control.
Indinavir, nelfinavir, ritonavir: Increase plasma amprenavir level. Monitor patient closely.
Ketoconazole: Increases plasma levels of both drugs. Monitor patient closely for adverse reactions.
Macrolides: Increase plasma amprenavir level. No dosage adjustment is needed.
Psychotherapeutic agents: May cause increased CNS effects. Monitor patient closely.
Rifabutin: Decreases AUC of amprenavir, increases rifabutin level by almost 200%. Decrease rifabutin dosage to 150 mg daily or 300 mg two to three times a week.
Saquinavir: Decreases AUC of amprenavir. Monitor patient closely.
Sildenafil: Substantially increases sildenafil levels, which may cause an increase in sildenafil-associated effects, including hypotension,
visual changes, and priapism. Don’t exceed 25 mg of sildenafil in a 48-hour period.
Drug-herb. St. John’s wort: Decreases amprenavir levels. Discourage use together.
Drug-food. Grapefruit juice: May affect blood levels of drug. Don’t take with grapefruit juice.
High-fat meals: Reduce drug absorption. Advise patient not to take drug with high-fat meal.
CNS: paresthesia, depressive or mood disorders, headache.
GI: nausea, vomiting, diarrhea or loose stools, taste disorders.
Metabolic: hyperglycemia, hypertriglyceridemia, hypercholesterolemia.
Skin: rash, Stevens-Johnson syndrome.
Effects on lab test results
May increase glucose, triglyceride, and cholesterol levels.
Overdose and treatment
It isn’t known whether amprenavir can be removed by peritoneal lavage or hemodialysis. If overdose occurs, monitor patient
for evidence of toxicity and give supportive treatment as needed. No known antidote. Overdose may alter pharmacokinetics of
Drug is a sulfonamide. Patients with a known sulfonamide allergy should be treated with caution.
Hyperglycemia and new onset diabetes mellitus have been reported during use.
Amprenavir oral solution should be used only when the capsules or other protease inhibitor formulations aren’t therapeutic
Capsules and oral solution aren’t interchangeable on milligram per milligram basis.
Store capsules and oral solution at room temperature.
Monitor patient for adverse reactions. Drug may cause redistribution or accumulation of body fat including central obesity,
dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, or cushingoid appearance. Severe and
life-threatening reactions, including Stevens-Johnson syndrome, have occurred.
Perform CBC weekly and as clinically indicated to detect neutropenia in patients also receiving rifabutin.
Monitor patient for signs and symptoms of hyperglycemia.
To monitor maternal-fetal outcomes of pregnant women exposed to drug, an Antiretroviral Pregnancy Registry has been established.
Prescribers may call 1-800-258-4263 to register patients who have been exposed to drug during pregnancy.
It isn’t known if drug appears in breast milk, so instruct breast-feeding women not to breast-feed if they’re receiving drug.
In addition, it’s recommended that HIV-infected women not breast-feed to avoid the risk of transmitting HIV to their infants.
An adverse event profile similar to that in adults is seen in children. Safety, efficacy, and pharmacokinetics of drug haven’t
been evaluated in children younger than age 4.
Dosing in elderly patients should be cautious because of the likelihood of decreased hepatic, renal, or cardiac function,
and of concomitant disease or other drug therapy.
Inform patient that drug isn’t a cure for HIV infection and opportunistic infections and that other complications of the disease
may continue to develop. The drug doesn’t reduce the risk of transmitting HIV to others through sexual contact.
Tell patient he may take drug without regard to meals but that he should avoid taking it with high-fat meals because absorption
may be decreased.
Advise patient to take drug each day as prescribed. It must always be taken with other antiretrovirals. Tell patient not to
alter or discontinue drug without medical approval.
Tell patient to take a missed dose as soon as possible and then return to the normal schedule. However, if a dose is skipped,
don’t double the next dose.
Instruct patients taking hormonal contraceptives to use alternate contraceptive measures during drug therapy.
Advise patients receiving sildenafil that there is an increased risk of sildenafil-associated adverse events including hypotension,
visual changes, and priapism, and should promptly report any symptoms to their doctors. Tell them not to exceed 25 mg of sildenafil
in a 48-hour period.
Advise patient to report signs and symptoms of hyperglycemia.
Reactions may be common, uncommon, life-threatening, or
COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use