amprenavir

amprenavir /am·pren·a·vir/ (am-pren´ah-vir) an HIV protease inhibitor used in the treatment of HIV-1 infection.

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amprenavir,

an antiviral (protease inhibitor).

indication It is used to treat HIV in combination with other antiretroviral agents.

contraindication Known hypersensitivity prohibits its use.

adverse effects Life-threatening side effects include Stevens-Johnson syndrome and acute hemolytic anemia. Other serious adverse effects include new-onset diabetes, hyperglycemia, and exacerbation of preexisting diabetes mellitus. Common side effects include diarrhea, abdominal pain, nausea, paresthesia, and rash.

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amprenavir

Agenerase

Pharmacologic class: Protease inhibitor

Therapeutic class: Antiretroviral

Pregnancy risk category C

FDA Boxed Warning

• Oral solution is contraindicated in children younger than age 4 and certain other patients because of potential toxicity risk from large amount of excipient (propylene glycol). Use with caution in other patient populations.

Action

Inhibits replication of human immunodeficiency virus-1 (HIV-1) by interfering with HIV-1 protease, thereby blocking viral maturation and causing formation of noninfectious virions

Availability

Capsules: 50 mg, 150 mg

Oral solution: 15 mg/ml

⊘Indications and dosages

➣ Treatment of HIV-1 infection

Adults and children ages 13 to 16 weighing more than 50 kg (110 lb): Capsules - 1,200 mg P.O. b.i.d. Oral solution - 1,400 mg P.O. b.i.d.

Children ages 4 to 12, and children ages 13 to 16 weighing less than 50 kg (110 lb): Capsules - 20 mg/kg P.O. b.i.d. or 15 mg/kg P.O. t.i.d., to a maximum dosage of 2,400 mg/day, given with other antiretrovirals. Oral solution - 22.5 mg/kg P.O. b.i.d. or 17 mg/kg P.O. t.i.d., to a maximum dosage of 2,800 mg/day, given with other antiretrovirals

Dosage adjustment

• Renal or hepatic impairment

Contraindications

• Hypersensitivity to drug
• Renal or hepatic failure
• Concomitant metronidazole or disulfiram use
• Pregnancy
• Children younger than age 4

Precautions

Use cautiously in:
• hepatic or renal impairment, diabetes mellitus, hemophilia
• patients receiving concurrent amiodarone, parenteral lidocaine, tricyclic antidepressants, or quinidine.

Administration

☞ Stop drug if patient develops signs or symptoms of Stevens-Johnson syndrome.
• Don't give with meals or grapefruit juice or within 1 hour of antacids.
• Be aware that capsules and oral solution aren't interchangeable on a milligram-to-milligram basis.

Route	Onset	Peak	Duration
P.O.	Rapid	1-2 hr	8-12 hr

Adverse reactions

CNS: depression, dizziness, mood disorders, headache, anxiety, peripheral paresthesia, oral and perioral paresthesia, mood disorders

GI: nausea, vomiting, diarrhea, abdominal pain

Hematologic: acute hemolytic anemia, spontaneous bleeding (in patients with hemophilia A or B)

Metabolic: hyperglycemia, hypertriglyceridemia, hypercholesterolemia, cushingoid appearance (moon face, buffalo hump)

Skin: rash, pruritus

Other: abnormal taste, abnormal fat redistribution, peripheral wasting, breast enlargement, Stevens-Johnson syndrome

Interactions

Drug-drug. Abacavir, cimetidine, pimozide, ritonavir: increased amprenavir blood level

Amiodarone, benzodiazepines, calcium channel blockers, cisapride, ergot alkaloids, lidocaine (systemic), quinidine, tricyclic antidepressants: competitive interference, resulting in life-threatening reactions

Antacids: interference with amprenavir absorption

Anticonvulsants: decreased amprenavir blood level; increased carbamazepine blood level (with carbamazepine)

Antihistamines, dapsone, lovastatin, simvastatin: increased levels of these drugs, possibly leading to toxicity

Azole antifungals (itraconazole, ketoconazole): changes in blood level of either drug

Clozapine, sildenafil: increased blood levels of these drugs

Erythromycin: increased blood levels of both drugs

Hormonal contraceptives: reduced contraceptive efficacy

Indinavir: increased amprenavir blood level, decreased indinavir blood level

Rifampin, saquinavir: decreased amprenavir blood level, increased rifampin or saquinavir blood level

Warfarin: inhibition of warfarin metabolism, possibly resulting in life-threatening effects

Zidovudine: increased levels of both drugs

Drug-diagnostic tests. Cholesterol, glucose, triglycerides: increased levels

Drug-food. Fatty foods, grapefruit juice: interference with drug absorption

Drug-herbs. St. John's wort: more than 50% reduction in amprenavir blood level

Patient monitoring

☞ Watch for signs and symptoms of depression; assess for suicidal ideation.
• Monitor blood glucose, triglyceride, and cholesterol levels.
• Monitor clotting functions in patients with hemophilia.
• Evaluate body fat distribution throughout course of therapy.
• Assess dental hygiene and monitor oral health in patients with oral or perioral paresthesia.

Patient teaching

☞ Tell patient to contact prescriber if rash or signs or symptoms of depression occur.
• Instruct patient not to take drug with fatty foods, grapefruit juice, or antacids, because they impede drug absorption.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Advise patient to minimize GI upset by eating small, frequent servings of foods and drinking plenty of fluids.
• Inform patient that drug may interfere with hormonal contraceptive use. Suggest she use alternative birth control measure.
• Advise patient that he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.

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amprenavir

AIDS A protease inhibitor in clinical trials for treating HIV, used in combination with other protease inhibitors–eg, nelfinavir, indinavir, or saquinavir Adverse effects N&V, diarrhea, headache, perioral paresthesias, stomach discomfort, rash; other effects include hyperglycemia, DM, acute hemolytic anemia, spontaneous bleeding in hemophiliacs, and fat redistribution. See AIDS, Combination therapy, HIV, Protease inhibitor.