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Pharmacologic class: Human immunodeficiency virus (HIV) protease inhibitor
Therapeutic class: Antiretroviral
Pregnancy risk category C
Blocks HIV reverse transcriptase, an enzyme necessary for HIV replication. Blockade leads to reduced viral load and increased CD4+ cell count, helping to ward off other infections when drug is given with other antiretrovirals.
Oral suspension: 50 mg/ml
Tablets: 700 mg
Indications and dosages
➣ HIV-1 infection, given in combination with other antiretrovirals
Adults (therapy-naive): 1,400 mg P.O. b.i.d. or 1,400 mg P.O. daily given with rotonavir 200 mg daily; or 1,400 mg P.O. daily with ritonavir 100 mg daily; or 700 mg b.i.d. with ritonavir 100 mg b.i.d.
Adults (protease inhibitor-experienced): 700 mg P.O. b.i.d. with ritonavir 100 mg b.i.d.
Children ages 2 and older: Calculate dosage based on weight, but don't exceed adult dosage. When given in combination with ritonavir, fosamprenavir tablets may be used for children weighing at least 39 kg (86 lb); ritonavir capsules may be used for those weighing at least 33 kg (73 lb). See table below for more information.
• Mild, moderate and severe hepatic impairment
• Hypersensitivity to drug or amprenavir
• Concomitant use of drugs that depend highly on CYP3A4 for clearance and for which elevated blood levels may lead to serious or life-threatening events (such as some antiarrhythmics, antimycobacterials, ergot derivatives, GI motility agents, HMG co-reductase inhibitors, neuroleptics, nonnucleoside reverse transcriptase inhibitors, and sedative-hypnotics)
• Coadministration with ritonavir in patients receiving flecainide or propafenone
• Concomitant use of St. John's wort
Use cautiously in:
• sulfa allergy
• hepatic impairment
• diabetes mellitus
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 2 (safety and efficacy not established).
• Assess cholesterol and triglyceride levels and hepatic function tests before starting therapy.
• Give oral suspension to adults without food and to children with food.
• Administer tablets with or without food.
GI: nausea, vomiting, diarrhea, abdominal pain
Hematologic: spontaneous bleeding (in hemophiliacs), acute hemolytic anemia
Metabolic: diabetes mellitus, body fat redistribution or accumulation
Skin: pruritus, maculopapular rash, severe or life-threatening skin reactions
Other: immune reconstitution syndrome
Drug-drug. Alfuzosin: increased alfuzosin level, resulting in hypotension
Antimycobacterials (rifampin): decreased fosamprenavir blood level, possible loss of virologic response and possible resistance to fosamprenavir or to its protease inhibitor class (concomitant rifampin use contraindicated)
Amitriptyline, amlodipine, atorvastatin, benzodiazepines (alprazolam, clorazepate, diazepam, flurazepam), bepridil, cyclosporine, diltiazem, esomeprazole, felodipine, fluticasone, imipramine, isradipine, itraconazole, ketoconazole, lidocaine (systemic), nicardipine, nifedipine, nimodipine, nisoldipine, quinidine, rapamycin, rosuvastatin, tacrolimus, trazodone, verapamil: increased blood levels of these drugs
Carbamazepine, cimetidine, dexamethasone, efavirenz, famotidine, nizatidine, phenobarbital, phenytoin, ranitidine, saquinavir: decreased fosamprenavir blood levels
Cisapride, pimozide: possible serious or life-threatening reactions, such as arrhythmias (concomitant use with fosamprenavir contraindicated)
CYP3A4 inducers: significant decrease in fosamprenavir blood level and reduced therapeutic effect
CYP3A4 inhibitors: increased fosamprenavir blood level and increased incidence of adverse effects
Delavirdine: possible loss of virologic response and possible resistance to delavirdine
Ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine): serious or life-threatening reactions such as acute ergot toxicity (concomitant use with fosamprenavir contraindicated)
Flecainide, propafenone: increased risk of serious, life-threatening cardiac arrhythmias (concomitant use contraindicated)
HIV protease inhibitors (lopinavir/ritonavir): decreased blood levels of both drugs
Hormonal contraceptives: possible changes in hormone levels and liver enzyme elevations (if used in combination with fosamprenavir and ritonavir)
Indinavir, nelfinavir: increased fosamprenavir blood level
Lovastatin, simvastatin: increased risk of serious reactions such as myopathy, including rhabdomyolysis (concomitant use with fosamprenavir contraindicated)
Methadone: decreased methadone blood level
Midazolam, triazolam: serious or life-threatening reactions, such as prolonged or increased sedation or respiratory depression (concomitant use with fosamprenavir contraindicated)
Nevirapine: decreased fosamprenavir and increased nevirapine blood levels
Paroxetine (in combination with fosamprenavir and ritonavir): decreased paroxetine blood level
PDE5 inhibitors (such as sildenafil): increased risk of adverse reactions (such as hypotension, visual changes, priapism)
Phenytoin (in combination with fosamprenavir and ritonavir): increased fosamprenavir, decreased phenytoin blood level
Rifabutin: increased rifabutin and metabolite blood levels
Warfarin: altered blood levels
Drug-diagnostic tests. ALT, AST, glucose, lipase, triglycerides: increased levels
Drug-food. High-fat meal: reduced fosamprenavir effect
Drug-herbs. St. John's wort: significant decrease in fosamprenavir blood level with loss of therapeutic effect and possible resistance to fosamprenavir or its protease inhibitor class (concomitant use contraindicated)
☞ Monitor patient closely for rash; discontinue drug if severe rash or moderate rash plus systemic symptoms develops.
• Be aware that immune reconstitution syndrome has occurred in patients treated with combination antiretroviral therapy. During initial phase of such therapy, patients whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, and tuberculosis), which may necessitate further evaluation and treatment.
• Closely monitor International Normalized Ratio if patient is receiving warfarin concomitantly.
• Closely monitor hepatic function tests during therapy.
• Periodically monitor cholesterol and triglyceride levels.
• Watch for new-onset diabetes mellitus, exacerbation of preexisting diabetes, and hyperglycemia.
• Advise adult patient to take oral suspension without food.
• Tell caregivers to give oral suspension with food to child.
• Instruct patient to shake oral suspension bottle vigorously before each use; mention that refrigeration may improve taste.
• Instruct patient to take tablets with or without food.
☞ Advise patient to immediately report new infections or rash, which may become severe and potentially life-threatening.
• Inform patient that drug doesn't cure HIV infection or reduce risk of passing HIV to others through sexual contact, needle sharing, or blood exposure.
• Tell patient that drug may cause body fat redistribution or accumulation and that the cause and long-term health effects of this condition aren't known.
• Advise patient that drug may interact with many drugs and herbs (especially St. John's wort). Caution patient to discuss use of herbs and other drugs with prescriber.
• Advise male receiving PDE5 inhibitors (such as sildenafil, tadalafil, vardenafil) that he may be at increased risk for adverse events, including hypotension, visual changes, and priapism. Instruct him to promptly report symptoms.
• Advise patient taking hormonal contraceptives to use alternative contraception during therapy because hormone levels may be altered and liver enzyme levels may increase.
• Advise female to notify prescriber if she is pregnant or intends to become pregnant.
• Instruct women not to breastfeed while taking drug.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, food, and herbs mentioned above.