Antiretroviral Agent, Protease Inhibitor

Treatment of HIV infections in combination with at least two other antiretroviral agents; oral solution should only be used when capsules or other protease inhibitors are not therapeutic options

Unknown

Hypersensitivity to amprenavir or any component; concurrent therapy with rifampin, astemizole, bepridil, cisapride, dihydroergotamine, ergotamine, midazolam, and triazolam; severe previous allergic reaction to sulfonamides; oral solution is contraindicated in infants or children <4 years of age, pregnant women, patients with renal or hepatic failure, and patients receiving concurrent metronidazole or disulfiram

Because of hepatic metabolism and effect on cytochrome P-450 enzymes, amprenavir should be used with caution in combination with other agents metabolized by this system (see Contraindications and Drug Interactions). Use with caution in patients with diabetes mellitus, sulfonamide allergy, hepatic impairment, or hemophilia. Redistribution of fat may occur (eg, buffalo hump, peripheral wasting, cushingoid appearance). Additional vitamin E supplements should be avoided. Concurrent use of sildenafil should be avoided. Certain ethnic populations (Asians, Eskimos, Native Americans) may be at increased risk of propylene glycol-associated adverse effects; use of of the oral solution of amprenavir should be avoided.

Protease inhibitors cause dyslipidemia which includes elevated cholesterol and triglycerides and a redistribution of body fat centrally to cause "protease paunch," buffalo hump, facial atrophy, and breast enlargement. These agents also cause hyperglycemia.

Dermatologic: Rash (28%)

Endocrine & metabolic: Hyperglycemia (37% to 41%), hypertriglyceridemia (36% - 47%)

Gastrointestinal: Nausea (38% to 73%), vomiting (20% to 29%), diarrhea (33% to 56%)

Miscellaneous: Perioral tingling/numbness

1% to 10%:

Central nervous system: Depression (4% to 15%), headache, paresthesia, fatigue

Endocrine & metabolic: Hypercholesterolemia (4% to 9%)

Dermatologic: Stevens-Johnson syndrome (1% of total, 4% of patients who develop a rash)

Gastrointestinal: Taste disorders (1% to 10%)

Monitor for signs and symptoms of propylene glycol toxicity if the oral solution is administered.

CYP3A4 inhibitor and substrate

Binds to the protease activity site and inhibits the activity of the enzyme. HIV protease is required for the cleavage of viral polyprotein precursors into individual functional proteins found in infectious HIV. Inhibition prevents cleavage of these polyproteins, resulting in the formation of immature, noninfectious viral particles.

Absorption: 1-2 hours

Distribution: 430 L

Protein binding: 90%

Metabolism: Hepatic, via cytochrome P-450 isoenzymes (primarily CYP3A4)

Half-life: 7.1-10.6 hours

Elimination: Biliary (75%) and urine (14%) as metabolites

Oral:

Children 4-12 years and older (<50 kg): 20 mg/kg twice daily or 15 mg/kg 3 times daily; maximum: 2400 mg/day

Children >13 years (>50 kg) and Adults: 1200 mg twice daily

Solution: Children 4-12 years or older (up to 18 years weighing <50 kg): 22.5 mg/kg twice daily or 17 mg/kg 3 times daily; maximum: 2800/day

Dosage adjustment in hepatic impairment:

Child-Pugh score between 5-8: 450 mg twice daily

Child-Pugh score between 9-12: 300 mg twice daily

No information available to require special precautions

Perioral tingling/numbness, taste disorders in up to 10% of patients

Amprenavir is not a cure for HIV, nor has it been found to reduce transmission of HIV. Take as directed, with or without food. Maintain adequate fluid intake (2-3 L/day of fluids unless instructed to restrict fluid intake) and adequate nutritional intake (small, frequent meals may help). You will be more susceptible to infection (avoid crowds or exposure to contagious diseases or infection). You may experience headache or confusion (use caution when driving or engaging in tasks requiring alertness until response to drug in known); headache (mild analgesic may help); nausea, vomiting, or increase flatulence (small frequent meals, may help); diarrhea (increased dietary fiber, exercise, or boiled milk may help). Inform prescriber if you experience muscle numbness or tingling; unresolved persistent vomiting, diarrhea, or abdominal pain; difficulty breathing or chest pain; unusual skin rash; or change in color of stool or urine. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant or breast-feed.

Capsules: 50 mg, 150 mg

Solution: 15 mg/mL

Propylene glycol is included in the oral solution. A dose of 22.5 mg/kg twice daily corresponds to an intake of 1650 mg/kg of propylene glycol.

Kaul DR, Cinti SK, Carver PL, et al, "HIV Protease Inhibitors: Advances in Therapy and Adverse Reactions, Including Metabolic Complications," Pharmacotherapy, 1999, 19(3):281-98.