fosamprenavir


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Related to fosamprenavir: ritonavir

fosamprenavir

(fos-am-pren-a-veer) ,

Lexiva

(trade name),

Telzir

(trade name)

Classification

Therapeutic: antiretrovirals
Pharmacologic: protease inhibitors
Pregnancy Category: C

Indications

With other antiretrovirals in the management of HIV infection.

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: 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 and Excretion: Mostly metabolized the liver (CYP3A4 enzyme system). Minimal renal excretion.
Half-life: 7.7 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POrapid1.5–4 hr12–24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity, sulfonamide/sulfa hypersensitivity;Severe hepatic impairment;Concurrent use of flecainide, propafenone, rifampin, ergot derivatives, St. John's wort, lovastatin, simvastatin, pimozide, delavirdine, sildenafil (Revatio), alfuzosin, midazolam or triazolam.
Use Cautiously in: Geriatric: Consider age-related ↓ in body mass, cardiac/hepatic/renal impairment, concurrent illness and medications;Hepatic impairment;Concurrent use of medications handled by or affecting the CYP3A4 enzyme system (may require serum level monitoring, dose or dosing interval alterations); Obstetric / Lactation: Safety not established; breast feeding not recommended in HIV-infected patients Pediatric: Treatment-naïve children <4 wk and protease inhibitor experienced children <6 mo (safety not established)

Adverse Reactions/Side Effects

Reflects use with other antiretrovirals

Central nervous system

  • headache (most frequent)
  • fatigue
  • mood disorders

Cardiovascular

  • myocardial infarction (life-threatening)

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • abdominal pain
  • ↑ liver enzymes

Dermatologic

  • rash (most frequent)

Endocrinologic

  • glucose intolerance

Genitourinary

  • nephrolithiasis

Hematologic

  • neutropenia

Metabolic

  • ↑ cholesterol
  • fat redistribution
  • ↑ triglycerides

Miscellaneous

  • allergic reactions including stevens-johnson syndrome (life-threatening)
  • angioedema (life-threatening)
  • immune reconstitution syndrome

Interactions

Drug-Drug interaction

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, ergonovine, methylergonovine ), lovastatin, simvastatin, pimozide, delavirdine, 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, saquinavir, 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.Levels are ↑ by indinavir and nelfinavir.May ↓ methadone and paroxetine levels.↑ levels and risk of toxicity from amiodarone, lidocaine, quinidine (monitor blood levels), 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, flurazepam ; 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 telaprevir may ↓ levels of fosamprenavir and telaprevir; avoid concurrent useConcurrent use with boceprevir may ↓ levels of fosamprenavir and boceprevir; avoid concurrent useConcurrent use with maraviroc may ↓ fosamprenavir levels and ↑ maraviroc levels; adjust maraviroc dose to 150 mg twice dailyConcurrent use of St. John's wort is contraindicated; ↓ blood levels and may lead to ↓ virologic response.

Route/Dosage

Oral (Adults) Treatment-naive patients without ritonavir—1400 mg twice daily; Treatment-naive 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.
Oral (Children ≥4 wk [Treatment-naive] 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)

Hepatic Impairment

Oral (Adults) Mild hepatic impairment—700 mg twice daily without ritonavir (therapy-naive) or 700 mg twice daily with ritonavir 100 mg once daily (therapy-naive or protease inhibitor experienced); Moderate hepatic impairment—700 mg twice daily without ritonavir (therapy-naive) or 450 mg twice daily with ritonavir 100 mg once daily (therapy-naive or protease inhibitor experienced); Severe hepatic impairment—350 mg twice daily without ritonavir (therapy-naive) or 300 mg twice daily with ritonavir 100 mg once daily (therapy-naive or protease inhibitor experienced).

Availability

Tablets: 700 mg
Oral suspension: 50 mg/mL

Nursing implications

Nursing 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 ↑ serum glucose cholesterol, and triglyceride levels.
    • May cause ↑ AST and ALT levels.
    • May cause neutropenia.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Do not confuse Lexiva with Pexeva (paroxetine).
  • Oral: Tablets may be administered with or without food. Oral suspension should be taken without food in adults and with food in children. Shake suspension vigorously before administering. Refrigeration of suspension may improve taste. If emesis occurs within 30 minutes after dosing, redose.

Patient/Family Teaching

  • Emphasize the importance of taking fosamprenavir as directed. Advise patient to read the Patient Information that comes with the prescription prior to initiation of therapy and with each prescription 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. If a dose is skipped, do not double the next 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 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 fosamprenavir are unknown at this time.
  • 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 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.
  • May decrease effectiveness of hormonal contraceptives; advise patient to use a nonhormonal form of contraception during therapy.
  • 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.

fosamprenavir

an antiretroviral.
indications This drug is used in combination with other antiretrovirals to treat HIV-1 infection.
contraindications Known hypersensitivity to protease inhibitors prohibits the use of this drug.
adverse effects Adverse effects of this drug include rash, pruritus, headache, fatigue, depression, oral paresthesia, and redistribution or accumulation of body fat. Common side effects include nausea, diarrhea, vomiting, and abdominal pain.
References in periodicals archive ?
ART DRUGS Category I Stavudine (d4T) * NRTI--thymidine base Zidovudine (ZDV) * Category II Didanosine (ddI) * ([dagger]) NRTI--other Lamivudine (3TC) * Emtricitabine (FTC) Abacavir (ABC) * NtRTI Tenofovir (TDF) ([dagger]) Category III Nevirapine (NVP) * NNRTI Efavirenz (EFV) ([paragraph]) Etravirine (ETR) ([section]) Category IV Ritonavir (RTV) * PI Lopinavir/ritonavir (LPV/RTV) * Saquinavir (SQV) Indinavir (IDV) ([dagger]) Darunavir (DRV) ([section]) Atazanavir (ATV) ([dagger]) Fosamprenavir (FPV) Category V Raltegravir ([section]) Integrase inhibitors Category VI Maraviroc ([section]) CCR5 inhibitors * Available in paediatric formulations.
A randomized study comparing ritonavir-boosted fosamprenavir with Kaletra found that they have comparable virologic responses at 96 weeks.
Atazanavir is a once-daily drug and, while both fosamprenavir and saquinavir boosted by ritonavir have been shown to work in once-daily studies, they are not licensed for this indication.
Other common PI-based regimens use fosamprenavir or a lopinavir/ritonavir formulation, both of which are labeled category C.
The concomitant use of fentanyl transdermal system with all cytochrome P450 3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, amiodarone, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil) may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.
the university of lots 3 and 5 with the active substance fosamprenavir take into account the currently valid from 01/02/2015 packaging regulations.
5ml 4 ml annex E) 3 tablets BD of 100/25 may be substituted with 2 tablets am and 1 tablet pm of 200/50 Note: higher doses of Lop/rit may be required when co-administered with enzyme-inducing drugs such as NVP, EFV; fosamprenavir, rifampicin.
These include boosted atazanavir (the CASTLE study), boosted darunavir (the ARTEMIS study), boosted fosamprenavir (the KLEAN study), boosted saquinavir (the GEMINI study) and boosted tipranavir (BI1182.
Hoffman-LaRoche developed an "improved" version of saquinavir (Fortovase) and GlaxoSmithKline developed fosamprenavir (Lexiva) to replace amprenavir (Agenerase).
Fosamprenavir should be boosted and given twice daily, particularly in patients with multidrug-resistant virus.
Food and Drug Administration approved the protease inhibitor Lexiva (generic name fosamprenavir, also called 908).
tender subject of active ingredient / combination are efavirenz + emtricitabine + tenofovir, maraviroc, emtricitabine, etravirine, lopinavir + ritonavir, abacavir + lamivudine, darunavir, atazanavir, fosamprenavir, emtricitabine + tenofovir and tenofovir with different strengths is 25-800 mg.