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Fosamprenavir Calcium (Monograph)

Brand name: Lexiva
Drug class: HIV Protease Inhibitors

Medically reviewed by Drugs.com on Aug 10, 2024. Written by ASHP.

Introduction

Antiretroviral; HIV protease inhibitor (PI).

Uses for Fosamprenavir Calcium

Treatment of HIV Infection

Treatment of HIV-1 infection; used in conjunction with other antiretrovirals in adult and pediatric patients.

Used in conjunction with low-dose ritonavir (ritonavir-boosted fosamprenavir) or without low-dose ritonavir (unboosted fosamprenavir).

Not recommended as initial treatment of HIV due to the risk of treatment failure with unboosted regimens and less clinical data compared with other ritonavir-boosted regimens. Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Recommended as an alternative regimen in conjunction with other antiretrovirals for postexposure prophylaxis of HIV infection following occupational exposure† [off-label] (PEP) in health-care personnel and other individuals only after expert consultation.

USPHS recommends a 3-drug regimen of raltegravir and emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) as preferred regimen for PEP following occupational exposures to HIV. Fosamprenavir (with or without low-dose ritonavir) and 2 NRTIs can be considered an alternative regimen, but use for PEP only with expert consultation. Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF; alternatives are tenofovir DF and lamivudine, zidovudine and lamivudine, or zidovudine and emtricitabine.

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.

Fosamprenavir Calcium Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Dispensing and Administration Precautions

Administration

Administer orally with low-dose ritonavir (ritonavir-boosted fosamprenavir) or without low-dose ritonavir (unboosted fosamprenavir).

Administered as oral suspension or tablets.

Oral Suspension

Pediatric patients: Take with food.

Adults: Take without food.

If vomiting occurs soon after a dose of the oral suspension (within 30 minutes), repeat dose.

Taste of the suspension can be improved by refrigeration.

Shake vigorously prior to each dose.

Tablets

Take with or without food.

Dosage

Available as fosamprenavir calcium; dosage expressed in terms of fosamprenavir.

When used in combination with ritonavir, consult the full prescribing information for ritonavir.

Pediatric Patients

Children 4 weeks to 18 years of age: Dosage is based on weight. Do not exceed adult dosage.

Only use fosamprenavir in infants born at 38 weeks’ gestation or later who have attained a postnatal age of 28 days.

Do not use once-daily regimens (with or without low-dose ritonavir) in pediatric patients.

Do not use fosamprenavir (with or without low-dose ritonavir) in PI-experienced pediatric patients <6 months of age.

Do not use twice-daily regimens (without low-dose ritonavir) in PI-naïve or PI-experienced pediatric patients <2 years of age.

Treatment of HIV Infection
Oral

PI-naïve infants and children ≥4 weeks of age (oral suspension): Twice-daily regimen with low-dose ritonavir. See Table 1.

Table 1. Dosage of Ritonavir-boosted Fosamprenavir in PI-naïve Pediatric Patients ≥4 Weeks of Age1

Weight (kg)

Fosamprenavir Dosage (Oral Suspension)

Ritonavir Dosage

<11

45 mg/kg twice daily

7 mg/kg twice daily

11 to <15

30 mg/kg twice daily

3 mg/kg twice daily

15 to <20

23 mg/kg twice daily

3 mg/kg twice daily

≥20

18 mg/kg twice daily

3 mg/kg twice daily

Alternatively, PI-naïve pediatric patients ≥2 years of age (oral suspension): 30 mg/kg twice daily (without low-dose ritonavir).

PI-naïve pediatric patients weighing ≥47 kg (tablets): 1400 mg twice daily (without ritonavir).

PI-naïve pediatric patients weighing ≥39 kg can receive fosamprenavir tablets when used in combination with ritonavir.

Oral

PI-experienced pediatric patients ≥6 months of age (oral suspension): Twice-daily regimen with low-dose ritonavir. See Table 2.

Table 2. Dosage of Ritonavir-boosted Fosamprenavir in PI-experienced Pediatric Patients ≥6 Months of Age1

Weight (kg)

Fosamprenavir Dosage (Oral Suspension)

Ritonavir Dosage

<11

45 mg/kg twice daily

7 mg/kg twice daily

11 to <15

30 mg/kg twice daily

3 mg/kg twice daily

15 to <20

23 mg/kg twice daily

3 mg/kg twice daily

≥20

18 mg/kg twice daily

3 mg/kg twice daily

PI-experienced pediatric patients weighing ≥47 kg (tablets): 1400 mg twice daily (without ritonavir).

PI-experienced pediatric patients weighing ≥39 kg can receive fosamprenavir tablets when used in combination with ritonavir.

Adults

Treatment of HIV Infection
Oral

Antiretroviral-naïve: 1400 mg twice daily (without low-dose ritonavir).

1400 mg once daily with low-dose ritonavir (100 or 200 mg once daily).

Alternatively, 700 mg twice daily with low-dose ritonavir (100 mg twice daily).

Oral

Protease inhibitor (PI)-experienced: 700 mg twice daily with low-dose ritonavir (100 mg twice daily). Once-daily ritonavir-boosted fosamprenavir regimens not recommended.

Oral

Pregnant adults: 700 mg twice daily with low-dose ritonavir (100 mg twice daily). Consider this regimen only in pregnant patients already on a stable twice-daily regimen of fosamprenavir 700 mg and ritonavir 100 mg prior to pregnancy who are virologically suppressed (HIV-1 RNA <50 copies per mL).

Closely monitor viral load to ensure viral suppression is maintained.

Postexposure Prophylaxis following Occupational Exposure to HIV† [off-label] (PEP)
Oral

1400 mg once daily with low-dose ritonavir (100 mg once daily). Alternatively, 1400 mg twice daily (without low-dose ritonavir).

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Special Populations

Hepatic Impairment

Fosamprenavir (with or without low-dose ritonavir): Use with caution in patients with hepatic impairment. Dosage reductions necessary in adults; data not available to support dosage recommendations for pediatric patients with hepatic impairment.

Mild hepatic impairment (Child-Pugh score 5–6): In antiretroviral-naïve adults, fosamprenavir 700 mg twice daily with low-dose ritonavir (100 mg once daily) or fosamprenavir 700 mg twice daily (without ritonavir). In PI-experienced adults, fosamprenavir 700 mg twice daily with low-dose ritonavir (100 mg once daily).

Moderate hepatic impairment (Child-Pugh score 7–9): In antiretroviral-naïve adults, fosamprenavir 450 mg twice daily with low-dose ritonavir (100 mg once daily) or fosamprenavir 700 mg twice daily (without ritonavir). In PI-experienced adults, fosamprenavir 450 mg twice daily with low-dose ritonavir (100 mg once daily).

Severe hepatic impairment (Child-Pugh score 10–15): In antiretroviral-naïve adults, fosamprenavir 300 mg twice daily with low-dose ritonavir (100 mg once daily) or fosamprenavir 350 mg twice daily (without ritonavir). In PI-experienced adults, fosamprenavir 300 mg twice daily with low-dose ritonavir (100 mg once daily).

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time. Select dosage with caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Detailed Fosamprenavir dosage information

Cautions for Fosamprenavir Calcium

Contraindications

Warnings/Precautions

Skin Reactions

Rash (usually maculopapular and of mild to moderate intensity, with or without pruritus) reported. Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, reported rarely.

Discontinue fosamprenavir if severe or life-threatening rash or moderate rash accompanied by systemic symptoms occurs.

Sulfa Allergy

Because fosamprenavir contains a sulfonamide moiety, use with caution in patients with known sulfonamide allergy. Potential for cross-sensitivity between sulfonamide drugs and fosamprenavir unknown.

Drug Interactions

When ritonavir-boosted fosamprenavir is used, the usual cautions, precautions, and contraindications associated with ritonavir should be considered. Serious, life-threatening, or fatal drug interactions or loss of virologic effect and possible development of resistance can occur with drugs that inhibit or induce CYP3A.

Consider potential for drug interactions prior to and during ritonavir-boosted fosamprenavir therapy; review all drugs patient is receiving and monitor for adverse effects.

Hepatic Toxicity

Use of fosamprenavir with ritonavir at higher than recommended dosages may result in transaminase elevations and should not be used.

HIV-infected patients with HBV or HCV coinfection or marked elevations in transaminases prior to fosamprenavir therapy may be at increased risk for developing or worsening of transaminase elevations.

Perform appropriate laboratory tests to evaluate hepatic function prior to initiating fosamprenavir and monitor patients closely during treatment.

Diabetes and Hyperglycemia

Hyperglycemia (potentially persistent), new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of protease inhibitors (PIs); diabetic ketoacidosis also occurred in some cases.

Initiate or adjust dosage of insulin or oral hypoglycemic agents for treatment of these events as needed.

Causal relationships between therapy with PIs and these events not established.

Immune Reconstitution Syndrome

During initial treatment, patients who respond to combination antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex, M. tuberculosis, cytomegalovirus, Pneumocystis jirovecii); this is called immune reconstitution syndrome and may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; however, time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Increase in Body Fat

Increase in body fat reported. Mechanism and long-term consequences unknown; causal relationship not established.

Lipid Elevations

Increases in triglyceride and cholesterol concentrations have occurred with ritonavir-boosted fosamprenavir.

Determine serum triglyceride and cholesterol concentrations prior to initiating fosamprenavir and periodically monitor during therapy; manage lipid disorders as clinically appropriate.

Hemolytic Anemia

Acute hemolytic anemia reported in a patient who received amprenavir (no longer commercially available in the US).

Hemophilia A and B

Spontaneous bleeding reported in some patients with hemophilia A or B treated with PIs; causal relationship not established.

Increased hemostatic therapy (e.g., antihemophilic factor) may be needed. Treatment with PIs continued or restarted in many of the reported cases.

Nephrolithiasis

Nephrolithiasis reported during postmarketing experience. If signs or symptoms of nephrolithiasis occur, consider temporarily interrupting or discontinuing fosamprenavir.

Resistance and Cross-resistance

Possible amprenavir resistance in patients treated with fosamprenavir. The possible effect of fosamprenavir therapy on subsequent therapy with other PIs unknown.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry (APR) at 800-258-4263 or [Web].

Limited data on use of fosamprenavir in pregnancy. Data insufficient to adequately assess risk of birth defects and miscarriage. Based on prospective reports to the APR of 146 live births following exposures to fosamprenavir, 2 birth defects each were reported with first- and second/third- trimester exposures.

Consider use of ritonavir-boosted fosamprenavir only in pregnant patients already on a stable twice-daily regimen of fosamprenavir 700 mg and ritonavir 100 mg prior to pregnancy who are virologically suppressed (HIV-1 RNA <50 copies per mL). Closely monitor viral load to ensure viral suppression is maintained.

Safety, efficacy, and pharmacokinetics of fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily studied in a clinical trial of pregnant women infected with HIV type 1 (HIV-1).

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Unknown whether affects human milk production or breast-fed infant.

Per HHS perinatal HIV transmission guideline, inform patients that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates postnatal HIV transmission risk to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces risk of breastfeeding HIV transmission to <1%, but not does not completely eliminate risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.

Females and Males of Reproductive Potential

May reduce the efficacy of combined hormonal contraceptives. Advise patients to use an effective alternative contraceptive method or additional barrier method.

Pediatric Use

Studies have evaluated safety, efficacy, and pharmacokinetics of fosamprenavir (with and without ritonavir) in PI-naïve and PI-experienced HIV-1-infected pediatric patients 4 weeks to <18 years of age and weighing ≥3 kg.

Pharmacokinetics, safety, tolerability, and efficacy not established in PI-naïve pediatric patients <4 weeks of age. Treatment with fosamprenavir not recommended in PI-experienced pediatric patients <6 months of age.

Do notuse once-daily regimen (with or without low-dose ritonavir) in pediatric patients.

Do not use twice-daily regimen (without low-dose ritonavir) in pediatric patients <2 years of age.

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently from younger adults.

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Use with caution because amprenavir concentrations may be increased; assess hepatic function prior to and periodically during therapy.

Dosage reduction necessary in adults with hepatic impairment (Child-Pugh score of 5 or greater); data not available to support dosage recommendations for pediatric patients with hepatic impairment.

Increased risk for developing or worsening of transaminase elevations in HIV-infected patients with chronic HBV or HCV coinfection and those with marked increases in AST or ALT concentrations prior to fosamprenavir therapy.

Renal Impairment

Pharmacokinetics not studied in in renal impairment; renal impairment not expected to have a clinically important effect on pharmacokinetics.

Common Adverse Effects

Most common adverse effects (incidence ≥4%) in adults: Diarrhea, nausea, vomiting, headache, rash. Vomiting and neutropenia were reported more frequently in pediatric patients compared to adults.

Drug Interactions

Amprenavir (active metabolite of fosamprenavir) is metabolized by CYP3A4.

Amprenavir inhibits CYP3A4 and also may induce CYP3A4.

Amprenavir does not inhibit CYP2D6, 1A2, 2C9, 2C19, or 2E1, or uridine glucuronosyltransferase (UDPGT).

Some interaction studies have been performed using fosamprenavir. These studies may not predict magnitude of interaction with ritonavir-boosted fosamprenavir.

Since fosamprenavir is metabolized to amprenavir, interactions reported with amprenavir (no longer commercially available in the US) also apply to fosamprenavir.

When fosamprenavir is used with low-dose ritonavir, consider interactions reported with low-dose ritonavir. Refer to the full prescribing for ritonavir for specific information.

Ritonavir is a potent CYP2D6 inhibitor. Ritonavir also appears to induce CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2B6.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A4 with possible alteration in metabolism of amprenavir and/or the other drug.

Drugs Affecting or Affected by P-glycoprotein Transport

Amprenavir is a substrate of and an inducer of P-glycoprotein (P-gp) transport system.

Specific Drugs

Drug

Interaction

Comments

Abacavir

Studies using amprenavir indicate pharmacokinetic interaction unlikely

No in vitro evidence of antagonistic antiretroviral effects

Alfuzosin

Potential for increased alfuzosin concentrations that could result in hypotension

Concomitant use with fosamprenavir contraindicated

Antacids containing aluminum hydroxide/ magnesium hydroxide

Decreased amprenavir concentrations

Use with caution when administered at the same time; staggered coadministration not evaluated

Antiarrhythmic agents (amiodarone, disopyramide, flecainide, systemic lidocaine, propafenone, quinidine)

Possible increased antiarrhythmic agent concentrations

Potential for serious or life-threatening effects (e.g., cardiac arrhythmias) if ritonavir-boosted fosamprenavir used in patients receiving flecainide or propafenone

In patients receiving ritonavir-boostedfosamprenavir, concomitant use with flecainide or propafenone contraindicated

Caution if fosamprenavir used concomitantly with amiodarone, disopyramide, systemic lidocaine, or quinidine; antiarrhythmic concentration monitoring recommended, if available

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Carbamazepine, phenobarbital, phenytoin: Possible decreased amprenavir concentrations with unboosted fosamprenavir; potential for decreased fosamprenavir efficacy

Phenytoin: Increased amprenavir concentrations and decreased phenytoin concentrations when used with ritonavir-boosted fosamprenavir

Carbamazepine, phenobarbital, phenytoin: Use concomitantly with caution

Phenytoin: Usual dosages of ritonavir-boosted fosamprenavir may be used, but monitor phenytoin concentrations and increase phenytoin dosage as needed

Antifungals, azoles (itraconazole, ketoconazole)

Itraconazole, ketoconazole: Possible increased antifungal concentrations

Itraconazole, ketoconazole: Increase monitoring for adverse effects

In patients receiving fosamprenavir (without low-dose ritonavir), may need to reduce antifungal dosage in those receiving >400 mg of itraconazole or ketoconazole daily; in those receiving ritonavir-boosted fosamprenavir, high doses of itraconazole or ketoconazole (>200 mg daily) not recommended

Antimycobacterials (rifabutin, rifampin)

Rifabutin: 150 mg every other day with ritonavir-boosted fosamprenavir results in increased amprenavir concentrations and increased rifabutin metabolite concentrations compared with rifabutin 300 mg daily alone

Rifampin: Studies using amprenavir indicate decreased amprenavir concentrations; possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance

Rifabutin: If fosamprenavir (without low-dose ritonavir) used with rifabutin, reduce rifabutin dosage by at least 50% of the recommended dose; if ritonavir-boostedfosamprenavir used with rifabutin, reduce rifabutin dosage by at least 75% of the usual dosage of 300 mg daily (maximum dosage of 150 mg once every other day or 3 times weekly); monitor for neutropenia by performing CBCs weekly and as clinically indicated

Rifampin: Concomitant use contraindicated (because of potential loss of virologic response and possible resistance to fosamprenavir or to other protease inhibitors [PIs])

Antineoplastic agents (dasatinib, nilotinib, ibrutinib, vinblastine, everolimus)

Dasatinib, nilotinib, ibrutinib, vinblastine, everolimus: Increased concentrations of the antineoplastic agent and potentially increased risk of adverse events

If coadministration necessary, consult prescribing information for the antineoplastic drug

Antipsychotics (lurasidone, pimozide, quetiapine)

Lurasidone: Possible increased lurasidone concentrations; potential for serious and/or life-threatening adverse effects if used concomitantly with ritonavir-boosted fosamprenavir

Pimozide: Possible increased pimozide concentrations; potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)

Quetiapine: Increased quetiapine concentrations expected

Lurasidone: Concomitant use with ritonavir-boosted fosamprenavir contraindicated; if concomitant use with unboosted fosamprenavir necessary, reduce lurasidone dosage

Pimozide: Concomitant use contraindicated

Quetiapine: If possible, consider alternative antiretroviral therapy to avoid increases in quetiapine exposures; if initiating fosamprenavir (with ritonavir) in patient receiving quetiapine, reduce quetiapine to one-sixth of original dosage; monitor for adverse effects of quetiapine; if quetiapine is initiated in a patient taking fosamprenavir (with ritonavir), refer to the quetiapine prescribing information for initial dosage and titration

Atazanavir

Ritonavir-boosted fosamprenavir: Decreased atazanavir concentrations; no change in amprenavir concentrations

Fosamprenavir (without low-dose ritonavir): No data

In vitro evidence of synergistic antiretroviral effects

Fosamprenavir (with or without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established

Benzodiazepines (alprazolam, clorazepate, diazepam, flurazepam, midazolam, triazolam)

Midazolam or triazolam: Possible increased concentrations of midazolam or triazolam; potential for serious and/or life-threatening adverse reactions (e.g., prolonged or increased sedation or respiratory depression)

Alprazolam, clorazepate, diazepam, flurazepam: Possible increased benzodiazepine concentrations

Midazolam or triazolam: Concomitant use contraindicated

Alprazolam, clorazepate, diazepam, flurazepam: Clinical importance of pharmacokinetic interaction unknown; a decrease in benzodiazepine dosage may be needed

Bosentan

Increased bosentan concentrations

In patients already receiving fosamprenavir for ≥10 days, initiate bosentan using a dosage of 62.5 mg once daily or every other day based on individual tolerability

In patients already receiving bosentan, discontinue bosentan for ≥36 hours prior to initiating fosamprenavir; after ≥10 days of fosamprenavir, resume bosentan at a dosage of 62.5 mg once daily or every other day based on individual tolerability

Calcium-channel blocking agents (diltiazem, felodipine, nifedipine, nicardipine, nimodipine, verapamil, amlodipine, nisoldipine, isradipine)

Possible increased concentrations of calcium-channel blocking agent

Use concomitantly with caution; clinical monitoring recommended

Cisapride

Possible increased cisapride concentrations; potential for serious and/or life-threatening adverse reactions (e.g., cardiac arrhythmias)

Concomitant use contraindicated

Clarithromycin

Studies using amprenavir indicate increased amprenavir concentrations and slightly decreased clarithromycin concentrations

Colchicine

Increased colchicine concentrations

Patients with renal or hepatic impairment: Concomitant use of colchicine and ritonavir-boosted fosamprenavir not recommended

Colchicine for treatment of gout flares: In those receiving ritonavir-boosted fosamprenavir, use initial colchicine dose of 0.6 mg followed by 0.3 mg 1 hour later and repeat dose no earlier than 3 days later; in those receiving fosamprenavir (without low-dose ritonavir), use initial colchicine dose of 1.2 mg and repeat dose no earlier than 3 days later

Colchicine for prophylaxis of gout flares: In those receiving ritonavir-boostedfosamprenavir, decrease colchicine dosage to 0.3 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once every other day in those originally receiving 0.6 once daily; in those receiving fosamprenavir (without low-dose ritonavir), decrease colchicine dosage to 0.3 mg twice daily or 0.6 mg once daily in those originally receiving 0.6 mg twice daily or decrease dosage to 0.3 mg once daily in those originally receiving 0.6 mg once daily

Colchicine for treatment of familial Mediterranean fever (FMF): In those receiving ritonavir-boosted fosamprenavir, use maximum colchicine dosage of 0.6 mg daily (may be given as 0.3 mg twice daily); in those receiving fosamprenavir (without low-dose ritonavir), use maximum colchicine dosage of 1.2 mg daily (may be given as 0.6 mg twice daily)

Corticosteroids (dexamethasone, fluticasone)

Fluticasone (orally inhaled, intranasal): Increased fluticasone concentrations

Dexamethasone: Possible decreased amprenavir concentrations and decreased antiretroviral efficacy

Fluticasone (orally inhaled, intranasal): May significantly reduce serum cortisol concentrations; adrenal insufficiency and Cushing's syndrome reported; do not use concomitantly unless potential benefits of inhaled corticosteroid outweigh risks of systemic corticosteroid adverse effects; consider alternative, especially when long-term corticosteroid use anticipated

Dexamethasone (systemic): Use concomitantly with caution

Delavirdine

Increased amprenavir concentrations and decreased delavirdine concentrations; possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance

No in vitro evidence of antagonistic antiretroviral effects

Concomitant use contraindicated

Didanosine

No in vitro evidence of antagonistic antiretroviral effects

Drug

Interaction

Comments

Dolutegravir

Decreased dolutegravir concentrations

Ritonavir-boosted fosamprenavir: Use dolutegravir 50 mg twice daily; in patients with documented or suspected integrase inhibitor (INSTI) resistance, consider alternative whenever possible

Efavirenz

Decreased amprenavir concentrations if used with fosamprenavir (with or without low-dose ritonavir)

No in vitro evidence of antagonistic antiretroviral effects

Fosamprenavir (without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established

Ritonavir-boosted fosamprenavir once daily: An additional 100 mg per day of ritonavir (300 mg total) recommended with coadministration of efavirenz

Ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine)

Possible increased concentrations of ergot derivatives and potential for serious and/or life-threatening adverse reactions such as acute ergot toxicity (peripheral vasospasm and ischemia of the extremities and other tissues)

Concomitant use contraindicated

Estrogens/progestins

Hormonal contraceptive containing ethinyl estradiol with norethindrone: Decreased ethinyl estradiol concentrations (with or without ritonavir); decreased amprenavir concentrations (with ritonavir-boosted fosamprenavir)

Possible loss of virologic response; increased risk of transaminase elevations

Hormonal contraceptives: Consider alternative methods of nonhormonal contraception

Fentanyl

Increased fentanyl concentrations

Carefully monitor therapeutic effects and adverse effects of fentanyl (e.g., potentially fatal respiratory depression)

Histamine H2-receptor antagonists (cimetidine, famotidine, nizatidine)

Decreased amprenavir plasma concentrations when used concomitantly with unboosted fosamprenavir; possible decreased antiretroviral efficacy

Use concomitantly with caution

HMG-CoA reductase inhibitors (statins)

Atorvastatin, lovastatin, simvastatin: Increased concentrations of the statin; increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis

Atorvastatin: Do not exceed atorvastatin dosage of 20 mg daily; carefully titrate atorvastatin dosage; use lowest necessary dosage

Lovastatin: Concomitant use with fosamprenavir contraindicated

Simvastatin: Concomitant use with fosamprenavir contraindicated

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Increased concentrations of immunosuppressive agent

Monitor immunosuppressive agent concentrations

Lamivudine

Studies using amprenavir indicate no evidence of pharmacokinetic interaction

No in vitro evidence of antagonistic antiretroviral effects

Lomitapide

Increased lomitapide concentrations

Concomitant use contraindicated (potential for significantly increased transaminases)

Lopinavir/ritonavir

Decreased amprenavir and lopinavir concentrations; increased incidence of adverse effects reported

In vitro evidence of additive antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

Maraviroc

Increased maraviroc concentrations; decreased amprenavir concentrations

Recommended maraviroc dosage during concurrent use is 150 mg twice daily with usual dosage of ritonavir-boosted fosamprenavir; do not use unboosted fosamprenavir

Methadone

Decreased methadone concentrations

Data indicate interaction not clinically important; monitor for opiate withdrawal symptoms

Nelfinavir

Increased plasma amprenavir concentrations with concomitant use of fosamprenavir (without ritonavir) and nelfinavir; concomitant use of ritonavir-boostedfosamprenavir and nelfinavir not evaluated

No in vitro evidence of antagonistic antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

Nevirapine

Decreased amprenavir concentrations and increased nevirapine concentrations

Ritonavir-boosted fosamprenavir (once-daily regimen): Concomitant use with nevirapine not studied

No in vitro evidence of antagonistic antiretroviral effects

Fosamprenavir (without low-dose ritonavir): Concomitant use not recommended

No dosage adjustment required when nevirapine is administered with fosamprenavir plus ritonavir twice daily

Paroxetine

Decreased paroxetine concentrations

Adjust paroxetine dosage based on clinical response and tolerability

Drug

Interaction

Comments

Proton-pump inhibitors (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)

Esomeprazole: When used with fosamprenavir (without low-dose ritonavir), no change in amprenavir concentrations, and increased esomeprazole concentration; when used with ritonavir-boosted fosamprenavir, clinically important pharmacokinetic interaction unlikely

Proton-pump inhibitors can be administered at the same time as fosamprenavir with no change in plasma amprenavir concentrations

Raltegravir

Fosamprenavir (with or without low-dose ritonavir): Decreased concentrations of raltegravir and amprenavir

Fosamprenavir (with or without low-dose ritonavir): Appropriate dosage for concomitant use with respect to safety and efficacy not established

St. John’s wort (Hypericum perforatum)

Possible decreased amprenavir concentrations; possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance

Concomitant use contraindicated

Salmeterol

Possible increased salmeterol concentrations and increased risk of salmeterol-associated adverse cardiovascular effects, including QT-interval prolongation, palpitations, and sinus tachycardia

Concomitant use not recommended

Saquinavir

Decreased amprenavir concentrations with concomitant use of fosamprenavir (without ritonavir) and saquinavir; concomitant use of ritonavir-boosted fosamprenavir and saquinavir not evaluated

No in vitro evidence of antagonistic antiretroviral effects

Appropriate dosages for concomitant use with respect to safety and efficacy not established

Sildenafil

Possible increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, priapism)

Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with fosamprenavir (with or without low-dose ritonavir) is contraindicated; safe and effective dosages for concomitant use not established

Sildenafil for treatment of erectile dysfunction: If used concomitantly with fosamprenavir (with or without low-dose ritonavir), a sildenafil dosage of 25 mg once every 48 hours is recommended; closely monitor for sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, priapism)

Tadalafil

Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, priapism)

If tadalafil (Adcirca) is initiated for treatment of PAH in patients who have been receiving fosamprenavir (with or without low-dose ritonavir) for ≥1 week, use initial tadalafil dosage of 20 mg once daily and, if tolerated, may increase dosage to 40 mg once daily

If fosamprenavir (with or without low-dose ritonavir) is indicated in patient already receiving tadalafil (Adcirca) for treatment of PAH, discontinue tadalafil for ≥24 hours prior to initiating fosamprenavir; after ≥1 week of the antiretroviral agent, resume tadalafil at dosage of 20 mg once daily and, if tolerated, may increase dosage to 40 mg once daily

If tadalafil is used for treatment of erectile dysfunction in patients already receiving fosamprenavir (with or without low-dose ritonavir), do not exceed tadalafil dosage of 10 mg once every 72 hours and closely monitor for tadalafil-related adverse effects (e.g., hypotension, syncope, visual disturbances, priapism, syncope)

Tenofovir

No change in amprenavir concentrations with ritonavir-boosted fosamprenavir

No in vitro evidence of antagonistic antiretroviral effects

Trazodone

Possible increased trazodone concentrations

Increased risk of trazodone-associated adverse effects

Use concomitantly with caution; consider reduced trazodone dosage

Tricyclic antidepressants (amitriptyline, imipramine)

Amitriptyline, imipramine: Possible increased concentrations of the tricyclic antidepressant

Monitor plasma concentrations of the tricyclic antidepressant during concurrent use

Vardenafil

Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, priapism)

If ritonavir-boosted fosamprenavir is used in patients receiving vardenafil for treatment of erectile dysfunction, do not exceed vardenafil dosage of 2.5 mg once every 72 hours; if unboosted fosamprenavir is used in patients receiving vardenafil for treatment of erectile dysfunction, do not exceed vardenafil dosage of 2.5 mg once every 24 hours; closely monitor for vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, priapism)

Warfarin

Possible altered warfarin concentrations

Monitor INR

Zidovudine

Studies using amprenavir indicate possible increased amprenavir AUC; possible increased zidovudine plasma concentrations and AUC

No in vitro evidence of antagonistic antiretroviral effects
Fosamprenavir drug interactions (more detail)

Fosamprenavir Calcium Pharmacokinetics

Absorption

Bioavailability

Fosamprenavir calcium is a prodrug of amprenavir (no longer commercially available in the US).

Absolute oral bioavailability of amprenavir after administration of fosamprenavir calcium has not been established; peak amprenavir concentrations attained 1.5–4 hours after administration of the prodrug.

When a single 1.4-g dose is administered on an empty stomach as tablets or the oral suspension, amprenavir exposure (AUC) is similar, but peak amprenavir concentrations are 14.5% higher with the suspension compared with the tablet.

Food

Fosamprenavir tablets: Administration of with food has no effect on bioavailability of amprenavir.

Fosamprenavir suspension: Administration with food (i.e., standardized high-fat meal) reduces peak plasma concentrations of amprenavir by 46%, delays time to peak plasma concentration by 0.72 hours, and reduces AUC by 28% compared with administration in the fasting state.

Distribution

Extent

Amprenavir is distributed into milk in animals. Not known whether drug is distributed into human milk.

Plasma Protein Binding

90% bound to plasma proteins, primarily to α1-acid glycoprotein.

Elimination

Metabolism

Following oral administration, fosamprenavir calcium is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate in the intestinal epithelium during absorption.

Amprenavir is metabolized in liver principally by CYP3A4.

Elimination Route

About 14% of a single oral dose excreted in urine and 75% eliminated in feces as metabolites. Only minimal amounts of unchanged amprenavir are eliminated in urine or feces.

Half-life

Amprenavir elimination half-life is approximately 7.7 hours.

Special Populations

Following administration of ritonavir-boosted fosamprenavir, AUC of amprenavir increased by approximately 22, 70, or 80% in those with mild, moderate, or severe hepatic impairment, respectively. Plasma protein binding decreased in these individuals.

Pharmacokinetics not studied to date in adults with impaired renal function, but renal impairment not expected to have a clinically important effect on pharmacokinetics.

Pharmacokinetics of fosamprenavir 700 mg twice daily in combination with ritonavir 100 mg twice daily studied in pregnant women; total amprenavir exposures (AUC) were lower during pregnancy compared with postpartum period.

Pharmacokinetics of fosamprenavir (with and without ritonavir) studied in PI-naïve and PI-experienced pediatric patients 4 weeks to <18 years of age and weighing ≥3 kg.

Stability

Storage

Oral

Suspension

5–30°C; avoid freezing.

Tablets

Tightly closed container at 25°C (excursions permitted to 15–30°C).

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Fosamprenavir Calcium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

50 mg (of fosamprenavir) per mL

Lexiva

Viiv

Tablets, film-coated

700 mg (of fosamprenavir)*

Fosamprenavir Calcium Tablets

Lexiva

AHFS DI Essentials™. © Copyright 2024, Selected Revisions August 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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