amprenavir
(am-pren-a-veer)
Agenerase

Classification
Therapeutic: antiretrovirals
Pharmacologic: protease inhibitors

Pregnancy Category C


Copyright © 2007 by F.A. Davis Company

Indications
Management of HIV infection in combination with other antiretrovirals.

Action
Inhibits the action of HIV protease and prevents the cleavage of viral polyproteins. Therapeutic Effects: Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV and its sequelae.

Pharmacokinetics
Absorption: Rapidly absorbed after oral administration; absorption from liquid formulation is 14%; less than from capsules
Distribution: 90%; bound to plasma proteins
Metabolism and Excretion: Mostly metabolized by the liver; <3% excreted unchanged by the kidneys
Half-life: 7.1–10.6 hr

TIME/ACTION PROFILE (blood levels)

ROUTEONSETPEAKDURATION
POrapid 1–2 hr8–12 hr


Contraindications/Precautions
Contraindicated in: Hypersensitivity. Concurrent use of bepredil, dihydroergotamine, ergotamine, midazolam, and triazolam (may cause serious, potentially fatal toxicity). Concurrent use of rifampinor supplemental vitamin E. If amprenavir is used concurrently with ritonavir , flecainide and propafenone are contraindicated. Oral solution contains significant amounts of propylene glycol and is contraindicated in pregnancy, children <4 yrs, hepatic/renal impairment, concurrent disulfiram or metronidazole.
Use Cautiously in: Hypersensitivity to sulfonamides. Hepatic impairment (dosage reduction required). Hemophilia (may increase bleeding). Diabetes mellitus (may worsen hyperglycemia). Pregnancy or lactation (safety not established; breastfeeding not recommended in HIV-infected patients).
Exercise Extreme Caution in: Concurrent use of amiodarone, parenteral lidocaine, tricyclic antidepressants, or quinidine (may produce potentially life-threatening drug interactions).

Adverse Reactions/Side Effects*
*CAPITALS indicate life threatening; underlines indicate most frequent.

CNS: depression/mood disorder. GI: diarrhea, nausea, taste disorders, vomiting. Derm: rash. Endo: hyperglycemia. Metab: hyperlipidemia, redistribution/accumulation of body fat.

Interactions
Drug–Drug: Increases blood levels and the risk of toxicity from midazolam, triazolam, ergot derivatives and pimozide; concurrent use is contraindicated; may also increase blood levels and effects of other benzodiazepines. Increases blood levels and the risk of toxicity from amiodarone, lidocaine (parenteral), quinidine, tricyclic antidepressants, and warfarin; careful monitoring is required. If ritonavir is used concurrently, additional use of flecainide or propafenone is contraindicated (increased risk of arrhythmias). Significantly increases blood levels of rifabutin; decrease dose by 50% if used concurrently. May increase blood levels and toxicity of HMG CoA reductase inhibitors, erythromycin, dapsone, itraconazole, ketoconazole alprazolam, diazepam, flurazepam, calcium channel blockers, clozapine, carbamazepime, cyclosporine and tacrolimusand loratadine. Concurrent use with sildenafil increases the risk of priapism, hypotension, and visual changes. Rifampin significantly decreases blood levels and efficacy of amprenavir; concurrent use is contraindicated. Phenobarbital, phenytoin, carbamazepine, dexamethasone efavirenz, delavirdine nevirapineand hormonal contraceptives decrease amprenavir levels and may decrease antiretroviral activity. Cimetidine, indinavir, lopinavir, ritonavir, and nelfinavir may increase amprenavir levels (when used conconcurrently with ritonavir, amprenavir dosage should be decreased). Saquinavir may decrease levels. Antacids and didanosine (due to buffer content) may decrease absorption (separate administration by 1 hr). Methadone decreasese amprenavir levels and amprenavir decreases methadone levels; dosage adjustments may be necessary.
Drug–Natural: Use with St. John’s wort may cause decreased drug levels and effectiveness.
Drug–Food: Ingestion of a high-fat meal may decrease absorption.

Route/Dosage

PO (Adults >13 yr >50 kg): 1200 mg (eight 150-mg capsules) twice daily with other antiretrovirals.
PO (Children 4–13 yr or Adolescents 13–16 yr £50 kg): Capsules—20 mg/kg twice daily or 15 mg/kg 3 times daily with other antiretrovirals (not to exceed 2400 mg/day). Oral solution—22.5 mg/kg (1.5 ml/kg) twice daily or 17 mg/kg (1.1 ml/kg) three times daily (not to exceed 2800 mg/day).
Hepatic Impairment
PO (Adults): Child-Pugh score 5–8—450 mg twice daily with other antiretrovirals; Child-Pugh score 9–12—300 mg twice daily with other antiretrovirals.

Availability
Both capsules and oral solution contain amounts of vitamin E that exceed the Reference Daily Intake (RDI).
Capsules: 50 mg, 150 mg . Oral solution (grape–bubblegum–peppermint flavor): 15 mg/ml.

NURSING IMPLICATIONS


Assessment
Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections throughout therapy.
Assess patient for allergy to sulfonamides. May exhibit cross-sensitivity.
Assess patient for skin reactions throughout therapy Reactions may be severe and life threatening. Discontinue therapy if severe reactions or moderate rashes with systemic symptoms occur.
Lab Test Considerations: Monitor viral load and CD4 cell count regularly during therapy.
May cause increased serum glucose, cholesterol, and triglyceride levels.


Potential Nursing Diagnoses
Risk for infection (Indications).
Noncompliance (Patient/Family Teaching).


Implementation
Administer antacids or didanosine at least 1 hr before or after amprenavir.
PO: May be administered with or without food. Avoid high-fat meals, which may decrease absorption. Capsules and oral solution may be stored at room temperature; do not refrigerate or freeze Oral solution and capsules are not interchangeable on a mg-per-mg basis.
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Patient/Family Teaching
Emphasize the importance of taking amprenavir exactly as directed. It must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount and do not stop taking without consulting health care professional. If a dose is missed, take as soon as remembered within 4 hr, then return to regular schedule. If more than 4 hr from scheduled dose, omit dose and take next scheduled dose; do not double doses.
Instruct patient that amprenavir should not be shared with others.
Inform patient that amprenavir does not cure AIDS or prevent associated or opportunistic infections. Amprenavir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of amprenavir are unknown at this time.
Emphasize the importance of providing health care professional with accurate current drug history and notifying health care professional before taking any prescription or OTC medications because of potentially serious drug interactions. Vitamin E supplements should be avoided during amprenavir therapy.
Some hormonal contraceptives decrease amprenavir levels and effectiveness; advise patient to use a nonhormonal form of contraception during therapy.
Instruct patient to notify health care professional if nausea, vomiting, diarrhea, or rash occurs.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.


Evaluation/Desired Outcomes
Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
Decrease in viral load and increase in CD4 cell counts.

Copyright © 2007 by F.A. Davis Company