fos-am-PREN-a-veer

Therapeutic Classification: antiretrovirals

Pharmacologic Classification: protease inhibitors

• HIV infection (in combination with other antiretroviral agents).

• Inhibits the action of HIV protease and prevents the cleavage of viral polyproteins.

• Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV and its sequelae.

Absorption: Fosamprenavir is a prodrug. Following oral administration, it is rapidly converted to amprenavir by the gut lining during absorption.

Distribution: Penetration into RBCs is concentration dependent.

Metabolism/Excretion: Primarily metabolized by the liver by the CYP3A4 isoenzyme. Minimal renal excretion.

Half-life: 7.7 hr.

(blood levels)

Contraindicated in:

• Hypersensitivity, sulfonamide/sulfa hypersensitivity
• Severe hepatic impairment
• Concurrent use of flecainide, propafenone, rifampin, ergot derivatives, St. John's wort, lovastatin, simvastatin, lomitapide, pimozide, lurasidone, sildenafil (Revatio), alfuzosin, midazolam or triazolam
• Lactation: Avoid breastfeeding in mothers with HIV.

Use Cautiously in:

• Hepatic impairment
• OB: May be used during pregnancy if patient is already on a stable, twice-daily fosamprenavir/ritonavir regimen and if she is virologically suppressed (HIV-1 RNA <50 copies/mL)
• Pedi: Treatment-nave children <4 wk and protease inhibitor-experienced children <6 mo (safety and effectiveness not established).
• Geri: Consider age-related ↓ in body mass, cardiac/hepatic/renal impairment, concurrent illness and medications in older adults

CV: MI.

Derm: rash, STEVENS-JOHNSON SYNDROME.

Endo: glucose intolerance.

GI: diarrhea, nausea, vomiting, ↑ liver enzymes, abdominal pain.

GU: nephrolithiasis.

Hemat: neutropenia.

Metab: ↑body fat, hyperlipidemia, hypertriglyceridemia.

Neuro: headache, fatigue, mood disorders.
Misc: (INCLUDING ANGIOEDEMA)HYPERSENSITIVITY REACTIONS , immune reconstitution syndrome.

Drug-Drug:

• Amprenavir, the active moiety of fosamprenavir is metabolized by CYP3A4; it also inhibits and induces this enzyme system. The action of any other medication that is also handled by or affects this system may be altered by concurrent use.
• ↑blood levels and risk of toxicity from flecainide, propafenone, rifampin, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine), lomitapide, lovastatin, simvastatin, pimozide, lurasidone, sildenafil (Revatio), alfuzosin, midazolam, or triazolam; concurrent use contraindicated.
• Blood levels are ↓ by efavirenz (additional ritonavir may be required when used together), nevirapine, lopinavir/ritonavir, carbamazepine, phenobarbital, phenytoin, dexamethasone, histamine H₂-receptor antagonists, and proton-pump inhibitors; monitor for ↓ antiretroviral activity.
• Concurrent use with raltegravir may ↓ levels of amprenavir and raltegravir.
• May ↓ dolutegravir levels (↑ dose of dolutegravir to 50 mg twice daily).
• Levels are ↑ by nelfinavir.
• May ↓ methadone and paroxetine levels.
• May ↑ fentanyl levels; monitor for respiratory depression.
• May ↑ levels and risk of toxicity from amiodarone, disopyramide, lidocaine, quinidine ; monitor antiarrhythmic levels, when possible. ketoconazole, and itraconazole (dose of itraconazole or ketoconazole should not exceed 200 mg/day when fosamprenavir is used with ritonavir or 400 mg/day when used without), rifabutin (monitor for neutropenia, ↓ rifabutin dose by 50% when used with fosamprenavir or by 75% when used with fosamprenavir with ritonavir), cyclosporine or tacrolimus (monitor blood levels of immunosuppressants), calcium channel blockers (clinical monitoring recommended), some benzodiazepines (alprazolam, clorazepate, diazepam; dose ↓ of benzodiazepine may be needed), sildenafil, tadalafil, vardenafil (use cautiously; ↓ dose of sildenafil to 25 mg every 48 hr, for tadalafil single dose should not exceed 10 mg in any 72-hr period, dose of vardenafil should not exceed 2.5 mg every 24 hr if used without ritonavir or 2.5 mg every 72 hr with ritonavir with monitoring for toxicity) and tricyclic antidepressants (blood level monitoring recommended).
• ↑risk of myopathy with atorvastatin; do not exceed atorvastatin dose of 20 mg/day.
• May alter the effects of warfarin (monitor INR) or hormonal contraceptives (use alternative method of contraception).
• May ↑ fluticasone levels; concurrent use not recommended.
• May ↑ risk of adverse effects with salmeterol; concurrent use not recommended.
• May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day; if patient already receiving bosentan, discontinue bosentan at least 36 hr before initiation of fosamprenavir and then restart bosentan at least 10 days later at 62.5 mg once daily or every other day.
• May ↑ tadalafil (Adcirca) levels; initiate tadalafil (Adcirca) at 20 mg once daily; if patient already receiving tadalafil (Adcirca), discontinue tadalafil (Adcirca) at least 24 hr before initiation of fosamprenavir and then restart tadalafil (Adcirca) at least 7 days later at 20 mg once daily.
• May ↑ colchicine levels; ↓ dose of colchicine; do not administer colchicine if patients have renal or hepatic impairment.
• Concurrent use with paritaprevir may ↑ fosamprenavir and paritaprevir levels; adjust fosamprenavir dose to 1400 mg daily when used with paritaprevir/ritonavir/ombitasvir/dasabuvir; avoid concurrent use of fosamprenavir/ritonavir with paritaprevir/ritonavir/ombitasvir/dasabuvir.
• Concurrent use with maraviroc may ↓ fosamprenavir levels and ↑ maraviroc levels; adjust maraviroc dose to 150 mg twice daily.
• May ↑ quetiapine levels; ↓ quetiapine dose to 1/6 of current dose.
• May ↑ levels and risk of toxicity of dasatinib, everolimus, ibrutinib, nilotinib, and vinblastine.
• Antacids containing aluminum hydroxide and magnesium hydroxide may ↓ levels and effectiveness when taken at the same time; separate administration by several hours.

Drug-Natural Products:

• Concurrent use of St. John's wort is contraindicated; ↓ blood levels and may lead to ↓ virologic response.

• PO (Adults): Treatment-nave patients without ritonavir: 1400 mg twice daily; Treatment-nave patients with ritonavir: 1400 mg once daily with ritonavir 100 or 200 mg once daily, or 700 mg twice daily with ritonavir 100 mg twice daily. Protease inhibitor–experienced patients: 700 mg twice daily with ritonavir 100 mg twice daily. If efavirenz is added to a once daily regimen using both fosamprenavir and ritonavir, an additional 100 mg of ritonavir (total of 300 mg) should be given. Pregnancy: 700 mg twice daily with ritonavir 100 mg twice daily; if patient taking 800 mg once daily with ritonavir 100 mg once daily before pregnancy, may continue with this regimen if they are virologically suppressed (HIV-1 RNA <50 copies/mL), and if switch to twice daily regimen may compromise tolerability or compliance.
• PO (Children 4 wk [Treatment-nave] or 6 mo [Protease inhibitor-experienced]): 20 kg: 18 mg/kg twice daily (not to exceed 700 mg twice daily) with ritonavir 3 mg/kg twice daily (not to exceed 100 mg twice daily); 15–19.9 kg: 23 mg/kg twice daily (not to exceed 700 mg twice daily) with ritonavir 3 mg/kg twice daily (not to exceed 100 mg twice daily); 11–14.9 kg: 30 mg/kg twice daily (not to exceed 700 mg twice daily) with ritonavir 3 mg/kg twice daily (not to exceed 100 mg twice daily); <11 kg: 45 mg/kg twice daily (not to exceed 700 mg twice daily) with ritonavir 7 mg/kg twice daily (not to exceed 100 mg twice daily).

(Generic available)

• Tablets: 700 mg;

• Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
• Assess patient for allergy to sulfonamides. May exhibit cross-sensitivity.
• Assess patient for skin reactions during therapy. Reactions may be severe and life threatening. Discontinue therapy if severe reactions or moderate rashes with systemic symptoms occur.

• Monitor viral load and CD4 cell count regularly during therapy.
  • Monitor serum triglyceride and cholesterol levels prior to and periodically during therapy. May cause ↑ serum glucose cholesterol, and triglyceride levels.
  • May cause ↑ AST and ALT levels.
  • May cause neutropenia.

• PO: Tablets may be administered with or without food.

• Emphasize the importance of taking fosamprenavir as directed. Advise patient to read the Patient Informationbefore starting therapy and with each Rx refill in case of changes. Fosamprenavir 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. Take missed doses as soon as remembered if within 4 hr of scheduled dose. If more than 4 hr, skip dose, then return to regular schedule; do not double doses.
• Instruct patient that fosamprenavir should not be shared with others.
• Inform patient that fosamprenavir does not cure AIDS or prevent associated or opportunistic infections. Fosamprenavir may 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 fosamprenavir are unknown at this time.
• Advise patient of potential for hypersensitivity reactions that may result in death. Instruct patient to discontinue fosamprenavir and notify health care professional immediately if symptoms of hypersensitivity, rash, or signs of immune reconstitution syndrome (signs and symptoms of an infection) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's Wort, because of potentially serious drug interactions.
• Instruct patient to notify health care professional if nausea, vomiting, diarrhea, or rash occurs.
• Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
• Advise females of reproductive potential to use effective contraception during therapy and to avoid breastfeeding. May decrease effectiveness of hormonal contraceptives; advise patient to use a nonhormonal form of contraception during therapy. Advise patient to notify health care professional if pregnancy is planned or suspected. Encourage women who become pregnant to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263.
• Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

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

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