Lexiva

Generic Name: Fosamprenavir Calcium
Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: C-[(3S)-tetrahydro-3-furanyl] ester [(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-1-(phenylmethyl)-2-(phosphonooxy)propyl] carbamic acid disodium salt
Molecular Formula: C25H34N3Na2O9PS
CAS Number: 226700-80-7

Introduction

Antiretroviral; HIV protease inhibitor (PI).1

Uses for Lexiva

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and certain pediatric patients ≥4 weeks of age; used in conjunction with other antiretrovirals.1

Used in conjunction with low-dose ritonavir (ritonavir-boosted fosamprenavir) or without low-dose ritonavir (unboosted fosamprenavir);1 usually used in PI-based regimens that include a PI and 2 nucleoside reverse transcriptase inhibitors (NRTIs).1 201

For initial treatment in antiretroviral-naive adults or adolescents, experts state fosamprenavir (with or without low-dose ritonavir) not recommended.200 Regimens that include unboosted fosamprenavir may be associated with virologic failure and may result in emergence of resistance, and clinical trial data for ritonavir-boosted fosamprenavir more limited compared with data available for other ritonavir-boosted PIs.200

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For initial treatment in antiretroviral-naive pediatric patients, experts state ritonavir-boosted fosamprenavir in conjunction with 2 NRTIs can be considered in pediatric patients ≥6 months of age, but only in special circumstances when preferred or alternative regimens cannot be used.201 Fosamprenavir (without low-dose ritonavir) not recommended for pediatric patients of any age because of decreased fosamprenavir exposure and increased medication burden.201

Consider the following factors when initiating ritonavir-boosted fosamprenavir: Data insufficient to determine whether a regimen that includes ritonavir-boosted fosamprenavir is as effective as a regimen that includes the fixed-combination of lopinavir and ritonavir (lopinavir/ritonavir) in adults who previously received PIs (PI-experienced).1 Once-daily ritonavir-boosted fosamprenavir not recommended in PI-experienced adults or in any pediatric patient.1

Postexposure Prophylaxis following Occupational Exposure to HIV

Postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.199

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.199 Fosamprenavir (with or without low-dose ritonavir) and 2 NRTIs can be considered an alternative regimen, but use for PEP only with expert consultation.199 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.199

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.199 Do not delay initiation of PEP while waiting for expert consultation.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV

Postexposure prophylaxis of HIV infection following nonoccupational exposure (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

Lexiva Dosage and Administration

Administration

Oral Administration

Administer orally with low-dose ritonavir (ritonavir-boosted fosamprenavir) or without low-dose ritonavir (unboosted fosamprenavir).1 (See Dosage under Dosage and Administration.)

Oral Suspension

Pediatric patients: Take with food.1

Adults: Take without food.1

If vomiting occurs soon after a dose (within 30 minutes), repeat dose.1

Taste of the suspension can be improved by refrigeration.1

Shake vigorously prior to each dose.1

Tablets

Take with or without food.1

Dosage

Available as fosamprenavir calcium; dosage expressed in terms of fosamprenavir.1

Pediatric Patients

Children 4 weeks to 18 years of age: Dosage is based on weight.1 Do not exceed adult dosage.1

Do not use once-daily regimen (with or without low-dose ritonavir) in pediatric patients.1 201

Do not use twice-daily regimen (with low-dose ritonavir) in PI-experienced children <6 months of age.1

Do not use twice-daily regimen (without low-dose ritonavir) in PI-naive or PI-experienced children <2 years of age.1

Treatment of HIV Infection
Antiretroviral-naive Pediatric Patients
Oral

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

Table 1. Dosage of Ritonavir-boosted Fosamprenavir in PI-naive Pediatric Patients 4 Week of Age or Older1

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-naive children ≥2 years of age (oral suspension): 30 mg/kg twice daily (without low-dose ritonavir).1

PI-naive children weighing ≥39 kg (tablets): 700 mg twice daily with low-dose ritonavir (100 mg twice daily).1 201

PI-naive children ≥2 years of age weighing ≥47 kg (tablets): 1.4 g twice daily (without low-dose ritonavir).1

Antiretroviral-experienced Pediatric Patients
Oral

PI-experienced children ≥6 months of age (oral suspension): Twice-daily regimen with low-dose ritonavir.1 (See Table 2.)

Table 2. Dosage of Ritonavir-boosted Fosamprenavir in PI-experienced Pediatric Patients 6 months of Age or Older1

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 children ≥6 months of age weighing ≥39 kg (tablets): 700 mg twice daily with low-dose ritonavir (100 mg twice daily).1

PI-experienced children ≥2 years of age or older weighing ≥47 kg (tablets): 1.4 g twice daily (without low-dose ritonavir).1

Adults

Treatment of HIV Infection
Antiretroviral-naive Adults
Oral

1.4 g twice daily (without low-dose ritonavir).1

1.4 g once daily with low-dose ritonavir (100 or 200 mg once daily).1 Alternatively, 700 mg twice daily with low-dose ritonavir (100 mg twice daily).1

Antiretroviral-experienced Adults
Oral

PI-experienced adults: 700 mg twice daily with low-dose ritonavir (100 mg twice daily).1 Once-daily regimen not recommended.1

Postexposure Prophylaxis following Occupational Exposure to HIV
Oral

1.4 g once daily with low-dose ritonavir (100 mg once daily).199 Alternatively, 1.4 g twice daily (without low-dose ritonavir).199 Use in conjunction with 2 NRTIs (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).199

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.199

Postexposure Prophylaxis following Nonoccupational Exposure to HIV
Oral

1.4 g twice daily (without low-dose ritonavir).198 Use in conjunction with other antiretrovirals.198

Initiate nPEP as soon as possible following nonoccupational exposure to HIV (preferably ≤72 hours after exposure); continue for 28 days.198

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection
Oral

Maximum 1.4 g twice daily (without low-dose ritonavir) or 700 mg twice daily with low-dose ritonavir (100 mg twice daily).1 Do not exceed adult dosage.1

Adults

Treatment of HIV Infection
Antiretroviral-naive Adults
Oral

Maximum 1.4 g once daily with low-dose ritonavir (200 mg once daily) or 700 mg twice daily with low-dose ritonavir (100 mg twice daily).1 Higher than recommended dosages of fosamprenavir and/or ritonavir associated with increased serum transaminase concentrations; higher dosages not recommended.1

Antiretroviral-experienced Adults
Oral

Maximum 700 mg twice daily with low-dose ritonavir (100 mg twice daily).1 Higher than recommended dosages of fosamprenavir and/or ritonavir associated with increased serum transaminase concentrations; higher dosages not recommended.1

Special Populations

Hepatic Impairment

Fosamprenavir (with or without low-dose ritonavir): Use with caution in patients with hepatic impairment.1 Dosage reductions necessary in adults; data not available to support dosage recommendations for pediatric patients.1

Mild hepatic impairment (Child-Pugh score 5–6): In antiretroviral-naive adults, fosamprenavir 700 mg twice daily with low-dose ritonavir (100 mg once daily) or fosamprenavir 700 mg twice daily (without low-dose ritonavir).1 In PI-experienced adults, fosamprenavir 700 mg twice daily with low-dose ritonavir (100 mg once daily).1

Moderate hepatic impairment (Child-Pugh score 7–9): In antiretroviral-naive adults, fosamprenavir 450 mg twice daily with low-dose ritonavir (100 mg once daily) or fosamprenavir 700 mg twice daily (without low-dose ritonavir).1 In PI-experienced adults, fosamprenavir 450 mg twice daily with low-dose ritonavir (100 mg once daily).1

Severe hepatic impairment (Child-Pugh score 10–15): In antiretroviral-naive adults, fosamprenavir 300 mg twice daily with low-dose ritonavir (100 mg once daily) or fosamprenavir 350 mg twice daily (without low-dose ritonavir).1 In PI-experienced adults, fosamprenavir 300 mg twice daily with low-dose ritonavir (100 mg once daily).1

Renal Impairment

Dosage adjustments not necessary.200

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Cautions for Lexiva

Contraindications

  • Known hypersensitivity to fosamprenavir, amprenavir (no longer commercially available in the US), or any ingredient in the formulation.1

  • Concomitant use with drugs highly dependent on CYP3A4 for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, cisapride, ergot alkaloids, pimozide, sildenafil used for treatment of pulmonary arterial hypertension [PAH], lovastatin, simvastatin, midazolam, triazolam).1 (See Specific Drugs under Interactions.)

  • Concomitant use with drugs that may lead to loss of virologic response (e.g., rifampin, St. John's wort [Hypericum perforatum]).1 (See Specific Drugs under Interactions.)

  • Concomitant use of a ritonavir-boosted fosamprenavir regimen and flecainide or propafenone.1 (See Antiarrhythmic Agents under Interactions.)

Warnings/Precautions

Sensitivity Reactions

Dermatologic and Hypersensitivity Reactions

Rash (usually maculopapular and of mild to moderate intensity, with or without pruritus) reported.1 Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, reported rarely.1

Discontinue if severe or life-threatening rash or moderate rash accompanied by systemic symptoms occurs.1

Sulfonamide Sensitivity

Because fosamprenavir contains a sulfonamide moiety, use with caution in patients with known sulfonamide allergy.1

Potential for cross-sensitivity between sulfonamide drugs and fosamprenavir unknown.1

Interactions

When a ritonavir-boosted fosamprenavir regimen is used, the usual cautions, precautions, and contraindications associated with ritonavir should be considered.1

Serious and/or life-threatening drug interactions or loss of virologic effect can occur with some drugs.1 (See Contraindications under Cautions and Specific Drugs under Interactions.)

Hepatic Effects

HIV-infected patients with HBV or HCV coinfection or marked elevations in transaminase concentrations prior to fosamprenavir therapy may be at increased risk for developing transaminase elevations.1

Perform appropriate laboratory tests to evaluate hepatic function prior to initiating fosamprenavir and monitor patients closely during treatment.1 (See Hepatic Impairment under Cautions.)

Use of fosamprenavir with ritonavir at higher than recommended dosages may result in elevated transaminase concentrations.1

Hyperglycemic and Diabetogenic Effects

Hyperglycemia (potentially persistent), new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of PIs; diabetic ketoacidosis has occurred.1

Monitor blood glucose and initiate or adjust dosage of insulin or oral hypoglycemic agents as needed.1

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]);1 this may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and general cushingoid appearance.1 Mechanism and long-term consequences of fat redistribution unknown; causal relationship not established.1

Evaluate patients for physical signs of fat redistribution.19

Lipid Effects

Increases in triglyceride and cholesterol concentrations have occurred with ritonavir-boosted fosamprenavir.1 19 21 HIV infection itself is associated with lipid disorders.19

Determine serum triglyceride and cholesterol concentrations prior to initiating fosamprenavir and periodically monitor during therapy; manage lipid disorders as clinically appropriate.1 19 (See HMG-CoA Reductase Inhibitors under Interactions.)

Hematologic Effects

Neutropenia has been reported with fosamprenavir;1 acute hemolytic anemia has been reported in at least one patient who received amprenavir (no longer commercially available in the US).1

Hemophilia A and B

Spontaneous bleeding reported with PIs;1 causal relationship not established.1

Increased hemostatic therapy (e.g., antihemophilic factor) may be needed.1

Nephrolithiasis

Nephrolithiasis reported during postmarketing experience.1 19 If signs or symptoms of nephrolithiasis occur, consider temporarily interrupting or discontinuing fosamprenavir.1 19

HIV Resistance

Possible amprenavir resistance in patients treated with fosamprenavir.1 The possible effect of fosamprenavir therapy on subsequent therapy with other PIs unknown.1

Cardiovascular Effects

Postmarketing reports of myocardial infarction in patients receiving fosamprenavir.1 Possible association between cumulative exposure to fosamprenavir/amprenavir and increased risk of myocardial infarction.19 Higher relative risk of myocardial infarction reported with PIs compared with other antiretroviral drug classes, possibly due to ability of PIs to elevate serum lipid concentrations.19 20 HIV infection itself is associated with ischemic heart disease.19

Monitor modifiable risk factors for cardiovascular disease (e.g., hypertension, diabetes, smoking) and manage as clinically appropriate.19 Individualize treatment, carefully considering risks and benefits of continued treatment.19

Specific Populations

Pregnancy

Category C.1

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 202

Some experts state data insufficient to recommend routine use of fosamprenavir for initial treatment in antiretroviral-naive pregnant women;202 if the drug is used in pregnant women, these experts state ritonavir-boosted fosamprenavir must be used.202

Lactation

Distributed into milk in rats;1 not known whether distributed into human milk.1

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1 202

Pediatric Use

Safety and efficacy not established in PI-naive children <4 weeks of age or in PI-experienced children <6 months of age.1

In PI-naive infants, use only in those born at ≥38 weeks gestation who have attained postnatal age of ≥28 days.1

Do not use once-daily regimen (with or without low-dose ritonavir) in pediatric patients.1

Do not use twice-daily regimen (without low-dose ritonavir) in pediatric patients <2 years of age.1

Experts state consider use of ritonavir-boosted fosamprenavir for initial treatment only in pediatric patients ≥6 months of age and only in special circumstances; experts also state do not use fosamprenavir (without low-dose ritonavir) in pediatric patients of any age.201 (See Treatment of HIV Infection under Uses.)

Adverse effects in pediatric patients similar to those reported in adults; vomiting and neutropenia reported more frequently than in adults.1

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently from younger adults.1

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Hepatic Impairment

Use with caution because concentrations may be increased; assess hepatic function prior to and periodically during therapy.1

Dosage adjustments necessary in adults with hepatic impairment (Child-Pugh score 5 or greater);1 data not available to support dosage recommendations for pediatric patients.1 (See Hepatic Impairment under Dosage and Administration.)

Increased risk for further elevations in hepatic enzyme concentrations in HIV-infected patients with chronic HBV or HCV coinfection and those with marked increases in AST or ALT concentrations prior to fosamprenavir therapy.1

Common Adverse Effects

Diarrhea, nausea, vomiting, headache, rash.1

Interactions for Lexiva

Amprenavir (active metabolite of fosamprenavir) is metabolized by CYP3A4.1

Amprenavir inhibits CYP3A4 and also may induce CYP3A4.1

Amprenavir does not inhibit CYP2D6, 1A2, 2C9, 2C19, or P2E11 or uridine glucuronosyltransferase (UDPGT).1

Some interaction studies have been performed using fosamprenavir.1 These studies may not predict magnitude of interaction with ritonavir-boosted fosamprenavir.1

Since fosamprenavir is metabolized to amprenavir, interactions reported with amprenavir (no longer commercially available in the US) also apply to fosamprenavir.1

When fosamprenavir is used with low-dose ritonavir, consider interactions reported with low-dose ritonavir.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors or substrates of CYP3A4 with possible alteration in metabolism of amprenavir and/or the other drug.1

Drugs Affecting or Affected by P-glycoprotein Transport

Amprenavir is a substrate of and an inducer of P-glycoprotein (P-gp) transport system.1

Specific Drugs

Drug

Interaction

Comments

Abacavir

Studies using amprenavir indicate pharmacokinetic interaction unlikely1

In vitro evidence of synergistic antiretroviral effects1

Alfuzosin

Potential for increased alfuzosin concentrations that could result in hypotension1

Concomitant use with fosamprenavir (with or without low-dose ritonavir) is contraindicated1

Antacids

Decreased amprenavir concentrations and AUC1

Manufacturer of fosamprenavir states interaction not considered clinically important and makes no restrictions for concomitant use with antacids2

Some experts recommend fosamprenavir be given simultaneously with or at least 2 hours before or 1 hour after antacids200

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

Possible increased antiarrhythmic agent concentrations1

Potential for serious or life-threatening effects (e.g., cardiac arrhythmias) if ritonavir-boosted fosamprenavir used in patients receiving flecainide or propafenone1

Potential for serious or life-threatening effects (e.g., cardiac arrhythmias) if fosamprenavir used in conjunction with amiodarone, systemic lidocaine, or quinidine1

In patients receiving ritonavir-boosted fosamprenavir, concomitant use with flecainide or propafenone contraindicated1

Caution if fosamprenavir used concomitantly with amiodarone, systemic lidocaine, or quinidine; antiarrhythmic concentration monitoring recommended1

Amiodarone or dronedarone: Some experts state do not use concomitantly with fosamprenavir (with or without low-dose ritonavir)200

Anticoagulants, oral

Rivaroxaban: Possible increased rivaroxaban concentrations; may increase bleeding risk200

Warfarin: Possible altered warfarin concentrations1

Rivaroxaban: Avoid concomitant use200

Warfarin: Monitor INR,1 especially when initiating or discontinuing fosamprenavir;200 adjust warfarin dosage as needed200

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Carbamazepine, phenobarbital, phenytoin: Possible decreased amprenavir concentrations and decreased virologic response when used with unboosted fosamprenavir1 200

Carbamazepine, phenobarbital: Possible increased carbamazepine concentrations and decreased amprenavir concentrations when used with ritonavir-boosted fosamprenavir200

Phenytoin: Increased amprenavir concentrations and decreased phenytoin concentrations when used with ritonavir-boosted fosamprenavir1 200

Carbamazepine, phenobarbital, phenytoin: Use concomitantly with unboosted fosamprenavir with caution;1 some experts state do not use concomitantly with unboosted fosamprenavir200

Carbamazepine, phenobarbital: If using ritonavir-boosted fosamprenavir, consider alternative anticonvulsant or monitor concentrations of the anticonvulsant and amprenavir and assess antiretroviral response200

Phenytoin: Usual dosages of ritonavir-boosted fosamprenavir may be used, but monitor phenytoin concentrations and increase phenytoin dosage as needed1 200

Antifungals, azoles (itraconazole, ketoconazole, posaconazole, voriconazole)

Itraconazole: Possible increased antifungal and amprenavir concentrations1 200

Ketoconazole: Possible increased ketoconazole concentrations with fosamprenavir (with or without low-dose ritonavir)1

Posaconazole: Decreased amprenavir and posaconazole AUCs when used concomitantly with fosamprenavir (without low-dose ritonavir) compared with AUCs reported when used concomitantly with ritonavir-boosted fosamprenavir200

Voriconazole: Although specific data not available on interaction with ritonavir-boosted fosamprenavir, studies using low-dose ritonavir and voriconazole indicate decreased voriconazole concentrations;9 200 in addition, fosamprenavir (without low-dose ritonavir) possibly may result in increased concentrations of both drugs200

Itraconazole: In patients receiving fosamprenavir (with or without low-dose ritonavir), consider monitoring itraconazole concentrations to guide dosage adjustments; in those receiving fosamprenavir (without low-dose ritonavir), may need to reduce antifungal dosage in those receiving >400 mg of itraconazole daily;1 200 in those receiving ritonavir-boosted fosamprenavir, itraconazole dosage >200 mg daily not recommended unless plasma concentrations are monitored1 200

Ketoconazole: In patients receiving fosamprenavir (without low-dose ritonavir), may need to reduce antifungal dosage in those receiving >400 mg of ketoconazole daily;1 in those receiving ritonavir-boosted fosamprenavir, use caution and ketoconazole dosage >200 mg daily not recommended1

Posaconazole: Do not use concomitantly with fosamprenavir (without low-dose ritonavir)200

Voriconazole: Monitor for toxicities if used with fosamprenavir (without low-dose ritonavir);9 200 do not use with ritonavir-boosted fosamprenavir unless potential benefits outweigh risks;9 200 if used with ritonavir-boosted fosamprenavir, consider monitoring voriconazole concentrations and adjusting voriconazole dosage accordingly9 200

Antimycobacterials (bedaquiline, rifabutin, rifampin, rifapentine)

Bedaquiline: Possible increased bedaquiline concentrations;200 clinical importance unknown200

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 alone1

Rifampin: Studies using amprenavir indicate decreased amprenavir concentrations;1 possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance1

Rifapentine: Possible decreased fosamprenavir concentrations200

Bedaquiline: Use concomitantly with ritonavir-boosted fosamprenavir with caution and only if potential benefits outweigh risks;200 monitor for QTc interval prolongation and liver dysfunction200

Rifabutin: If fosamprenavir (without low-dose ritonavir) used with rifabutin, reduce rifabutin dosage by at least 50%1 (150 mg once daily or 300 mg 3 times weekly has been suggested);200 if ritonavir-boosted fosamprenavir used with rifabutin, reduce rifabutin dosage by at least 75% (maximum dosage of 150 mg once every other day or 3 times weekly);1 200 monitor for neutropenia by performing CBCs weekly and as clinically indicated;1 monitor for antimycobacterial response and consider therapeutic drug monitoring200

Rifampin: Concomitant use contraindicated1

Rifapentine: Concomitant use not recommended200

Antipsychotics (pimozide, quetiapine)

Pimozide: Possible increased pimozide concentrations;1 potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1

Quetiapine: Increased quetiapine concentrations expected200

Pimozide: Concomitant use contraindicated1

Quetiapine: Initiate quetiapine at lowest dosage and titrate as needed; if initiating fosamprenavir (with or without low-dose ritonavir) in patient receiving quetiapine, reduce quetiapine to one-sixth of original dosage; monitor for efficacy and adverse effects of quetiapine200

Atazanavir

Ritonavir-boosted fosamprenavir: Decreased atazanavir concentrations and AUC; no change in amprenavir concentrations and AUC 1

Fosamprenavir (without low-dose ritonavir): No data1

In vitro evidence of synergistic antiretroviral effects1

Fosamprenavir (with or without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established1 200

Avanafil

Possible increased avanafil concentrations and AUC if used concomitantly with fosamprenavir (with or without low-dose ritonavir)188 200

If avanafil used for treatment of erectile dysfunction, do not exceed avanafil dosage of 50 mg once every 24 hours;188 200 concomitant use with ritonavir-boosted fosamprenavir not recommended200

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

Midazolam or triazolam: Possible increased concentrations of midazolam or triazolam; potential for serious and/or life-threatening effects (e.g., prolonged or increased sedation or respiratory depression)1

Other benzodiazepines: Possible increased concentrations of alprazolam, clorazepate, diazepam, flurazepam1

Midazolam or triazolam: Manufacturer of fosamprenavir states that concomitant use is contraindicated;1 some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation;200 consider an alternative benzodiazepine metabolized by non-CYP pathways (e.g., lorazepam, oxazepam, temazepam)200

Other benzodiazepines: Clinical importance of pharmacokinetic interaction unknown; a decrease in benzodiazepine dosage may be needed1

Boceprevir

Concomitant use with ritonavir-boosted fosamprenavir not studied; concomitant use with other ritonavir-boosted PIs (ritonavir-boosted atazanavir, ritonavir-boosted darunavir, lopinavir/ritonavir) decreases concentrations and AUCs of boceprevir and the PIs 1 17 185 and may reduce efficacy of HCV and HIV treatment17 18

Concomitant use with low-dose ritonavir alone results in decreased boceprevir concentrations and AUC185

Concomitant use with ritonavir-boosted PIs not recommended1 12

If boceprevir was initiated for treatment of chronic HCV in a patient coinfected with HIV receiving a suppressive antiretroviral regimen containing a ritonavir-boosted PI, inform patient of possible drug interaction and closely monitor for HCV treatment response and potential HCV and HIV virologic rebound12 17 18 200

Bosentan

Increased bosentan concentrations1

In patients already receiving fosamprenavir (with or without low-dose ritonavir) for ≥10 days, initiate bosentan using a dosage of 62.5 mg once daily or every other day based on individual tolerability1 200

In patients already receiving bosentan, discontinue bosentan for at least 36 hours prior to initiating fosamprenavir (with or without low-dose ritonavir); after ≥10 days of fosamprenavir, resume bosentan using a dosage of 62.5 mg once daily or every other day based on individual tolerability1 200

Buprenorphine

No clinically important pharmacokinetic interactions200

Ritonavir-boosted fosamprenavir: Dosage adjustments not necessary; clinical monitoring recommended200

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

Possible increased concentrations of calcium-channel blocking agent1

Use concomitantly with caution; clinical monitoring recommended1

Cisapride

Possible increased cisapride concentrations; potential for serious and/or life-threatening effects (e.g., cardiac arrhythmias)1

Concomitant use contraindicated1

Clarithromycin

Ritonavir-boosted fosamprenavir: Possible increased clarithromycin concentrations200

Studies using amprenavir indicate increased amprenavir concentrations and AUC and slightly decreased clarithromycin concentrations1

Fosamprenavir (without low-dose ritonavir): Dosage adjustment not needed200

Ritonavir-boosted fosamprenavir: Consider alternative macrolide (e.g., azithromycin);200 if used concomitantly, monitor for clarithromycin-related toxicities200

Ritonavir-boosted fosamprenavir: Some experts recommend reduce clarithromycin dosage by 50% if Clcr 30–60 mL/minute and reduce by 75% if Clcr <30 mL/minute 1

Colchicine

Increased colchicine concentrations1

Patients with renal or hepatic impairment: Concomitant use of colchicine and ritonavir-boosted fosamprenavir not recommended1

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 later1

Colchicine for prophylaxis of gout flares: In those receiving ritonavir-boosted fosamprenavir, 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;1 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 daily1

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);1 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)1

Corticosteroids (beclomethasone, budesonide, dexamethasone, fluticasone, methylprednisolone, prednisolone, prednisone, triamcinolone)

Beclomethasone (orally inhaled, intranasal): Clinically important pharmacokinetic interactions not expected200

Budesonide or fluticasone (orally inhaled, intranasal): Increased corticosteroid concentrations;1 200 may result in adrenal insufficiency, including Cushing's syndrome200

Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations;200 may result in adrenal insufficiency, including Cushing's syndrome200

Budesonide or prednisone (systemic): Increased corticosteroid concentrations;200 may result in adrenal insufficiency, including Cushing's syndrome200

Dexamethasone (systemic): Possible decreased amprenavir concentrations and decreased antiretroviral efficacy1 200

Budesonide or fluticasone (orally inhaled, intranasal): Do not use concomitantly unless potential benefits of inhaled corticosteroid outweigh risks of systemic corticosteroid adverse effects;200 consider alternative (e.g., beclomethasone),1 200 especially when long-term corticosteroid use anticipated1

Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Do not use concomitantly; consider alternative nonsteroidal therapies; if intra-articular corticosteroid required, use alternative antiretroviral that does not alter CYP3A4 activity (e.g., dolutegravir, raltegravir)200

Budesonide or prednisone (systemic): Do not use concomitantly unless potential benefits outweigh risks of systemic corticosteroid adverse effects200

Dexamethasone (systemic): Use concomitantly with caution;1 200 consider alternative corticosteroid for long-term use200

Darunavir

Data not available regarding concomitant use of darunavir and fosamprenavir (with or without low-dose ritonavir)200

Delavirdine

Studies using amprenavir indicate possible increased amprenavir concentrations and AUC and possible decreased delavirdine plasma concentrations and AUC;1 possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance1

In vitro evidence of synergistic antiretroviral effects1

Concomitant use contraindicated1

Didanosine

In vitro evidence of synergistic antiretroviral effects1

Dolutegravir

Ritonavir-boosted fosamprenavir: Decreased dolutegravir concentrations and AUC;200 236 effect on fosamprenavir pharmacokinetics unlikely236

No in vitro evidence of antagonistic antiretroviral effects with amprenavir236

Ritonavir-boosted fosamprenavir: In integrase strand transfer inhibitor-naive (INSTI-naive) patients, use dolutegravir 50 mg twice daily;200 236 in INSTI-experienced patients with documented or suspected INSTI resistance, consider alternative to ritonavir-boosted fosamprenavir whenever possible200 236

Efavirenz

Substantially decreased amprenavir concentrations if used with fosamprenavir (without low-dose ritonavir);1 additional pharmacokinetic interactions if used with ritonavir-boosted fosamprenavir1

In vitro evidence of synergistic antiretroviral effects1

Fosamprenavir (without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established1

Ritonavir-boosted fosamprenavir: Use usual efavirenz dosage with fosamprenavir 1.4 g once daily and ritonavir 300 mg once daily or, alternatively, fosamprenavir 700 mg twice daily and ritonavir 100 mg twice daily1 200

Elvitegravir and cobicistat

Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir DF (EVG/COBI/TDF/FTC): Possible altered concentrations of elvitegravir, cobicistat, and/or fosamprenavir200

EVG/COBI/TDF/FTC: Do not use concomitantly200

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Possible increased concentrations of ergot alkaloids and potential for serious and/or life-threatening effects such as ergot toxicity (peripheral vasospasm and ischemia of the extremities and other tissues)1

Concomitant use contraindicated1

If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving fosamprenavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible202

Estrogens/ Progestins

Hormonal contraceptive containing ethinyl estradiol 35 mcg with norethindrone 0.5 mg per tablet: Decreased ethinyl estradiol and norethindrone concentrations with ritonavir-boosted fosamprenavir; clinically important increase in serum transaminase concentrations1

Hormonal contraceptives: Possible loss of virologic response if used with fosamprenavir (without low-dose ritonavir)1

Hormone replacement therapy: Possible increase in serum transaminase concentrations with ritonavir-boosted fosamprenavir1

Hormonal contraceptives: Concomitant use not recommended;200 use alternative nonhormonal (e.g., barrier) contraceptives1 200

Etravirine

Fosamprenavir (with or without low-dose ritonavir): Substantially increased amprenavir concentrations214

Fosamprenavir (with or without low-dose ritonavir): Do not administer concomitantly200

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

Decreased amprenavir plasma concentrations and AUC;1 possible decreased antiretroviral efficacy1

Use concomitantly with caution;1 administer fosamprenavir (without low-dose ritonavir) at least 2 hours before the H2-receptor antagonist;200 consider using ritonavir-boosted fosamprenavir200

HMG-CoA reductase inhibitors (statins)

Atorvastatin, lovastatin, rosuvastatin, simvastatin: Increased concentrations and AUCs of the statin; increased risk of statin-associated adverse effects, including myopathy and rhabdomyolysis1 186 200

Atorvastatin: Do not exceed atorvastatin dosage of 20 mg daily in patients receiving fosamprenavir (with or without low-dose ritonavir);1 186 200 carefully titrate atorvastatin dosage; use lowest necessary dosage with close monitoring for adverse effects1 200

Lovastatin: Concomitant use with fosamprenavir (with or without low-dose ritonavir) contraindicated1 186 200

Pitavastatin: Dosage adjustments not necessary200

Rosuvastatin: Dosage adjustments not necessary200

Simvastatin: Concomitant use with fosamprenavir (with or without low-dose ritonavir) contraindicated1 186 200

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus1

Monitor concentrations of the immunosuppressive agent1

Indinavir

Fosamprenavir: Possible increased amprenavir concentrations and AUC; effect on indinavir concentrations not well established1

Ritonavir-boosted fosamprenavir: Concomitant use not evaluated1

In vitro evidence of additive antiretroviral effects1

Fosamprenavir (with or without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established1

Lamivudine

Studies using amprenavir indicate no evidence of pharmacokinetic interaction1

In vitro evidence of synergistic antiretroviral effects1

Lopinavir/ritonavir

Fosamprenavir: Decreased amprenavir concentrations and AUC; no change in lopinavir concentrations or AUC1

Ritonavir-boosted fosamprenavir: Decreased amprenavir concentrations and AUC; altered lopinavir concentrations and AUC (decreased or increased)1

Increased incidence of adverse effects reported1

In vitro evidence of additive antiretroviral effects1

Fosamprenavir (with or without low-dose ritonavir): Concomitant use not recommended;200 appropriate dosages for concomitant use with respect to safety and efficacy not established1 200

Maraviroc

Increased maraviroc concentrations and AUC; decreased amprenavir concentrations and AUC1 200 224

No in vitro evidence of antagonistic antiretroviral effects224

Recommended maraviroc dosage is 150 mg twice daily with usual dosage of ritonavir-boosted fosamprenavir;1 200 224 do not use unboosted fosamprenavir1 224

Methadone

Decreased methadone concentrations;1 opiate withdrawal unlikely but may occur200

Methadone dosage may need to be adjusted;1 monitor for opiate withdrawal and increase methadone dosage as clinically indicated1 200

Nelfinavir

Studies using amprenavir indicate concomitant use may affect pharmacokinetics of both drugs;1 concomitant use of ritonavir-boosted fosamprenavir and nelfinavir not evaluated1

In vitro evidence of additive antiretroviral effects1

Appropriate dosages for concomitant use with respect to safety and efficacy not established1

Nevirapine

Fosamprenavir (without low-dose ritonavir): Decreased amprenavir AUC and increased nevirapine AUC1

Ritonavir-boosted fosamprenavir (twice-daily regimen): Decreased amprenavir AUC and increased nevirapine AUC1

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

In vitro evidence of additive antiretroviral effects1

Fosamprenavir (without low-dose ritonavir): Concomitant use not recommended1

RItonavir-boosted fosamprenavir (twice-daily regimen): Use usual nevirapine dosage with fosamprenavir 700 mg twice daily and ritonavir 100 mg twice daily1

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

Esomeprazole: When used with fosamprenavir (without low-dose ritonavir), no change in amprenavir concentrations or AUC, and increased esomeprazole AUC;1 when used with ritonavir-boosted fosamprenavir, clinically important pharmacokinetic interaction unlikely1

Can be administered at the same time as proton-pump inhibitors with no change in plasma amprenavir concentrations1

Dosage adjustments of fosamprenavir (with or without low-dose ritonavir) not needed200

Raltegravir

Fosamprenavir (with or without low-dose ritonavir): Decreased concentrations and AUCs of raltegravir and amprenavir1

Fosamprenavir (with or without low-dose ritonavir): Appropriate dosage for concomitant use with respect to safety and efficacy not established;1 some experts state dosage adjustments not necessary200

Rilpivirine

Possible increased rilpivirine concentrations; not expected to affect amprenavir concentrations226

Some experts state dosage adjustments not necessary200

Ritonavir

Increased plasma concentrations and AUC of amprenavir1 200

Concomitant low-dose ritonavir used for therapeutic advantage (ritonavir-boosted fosamprenavir);1 increased potential for drug interactions since ritonavir is a potent inhibitor of CYP3A4 and also inhibits CYP2D61

In vitro evidence of additive antiretroviral effects1

When ritonavir-boosted fosamprenavir is used in a once-daily regimen, recommended dosage is fosamprenavir 1.4 g once daily with ritonavir 100 or 200 mg once daily; when used in a twice-daily regimen, recommended dosage is fosamprenavir 700 mg twice with ritonavir 100 mg twice daily1 200

Once-daily regimen of ritonavir-boosted fosamprenavir not recommended in PI-experienced patients1

St. John’s wort (Hypericum perforatum)

Possible decreased amprenavir concentrations;1 possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance1

Concomitant use contraindicated1

Salmeterol

Possible increased salmeterol concentrations and increased risk of salmeterol-associated adverse cardiovascular effects, including QT interval prolongation, palpitations, and sinus tachycardia1

Concomitant use not recommended1

Saquinavir

Decreased amprenavir concentrations1

In vitro evidence of synergistic antiretroviral effects1

Appropriate dosages for concomitant use with respect to safety and efficacy not established1 200

Selective serotonin-reuptake inhibitors (SSRIs)

Paroxetine: Decreased SSRI concentrations with ritonavir-boosted fosamprenavir1

Paroxetine: Titrate dosage of the SSRI based on clinical response and tolerability1 200

Sildenafil

Possible increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)1

Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with fosamprenavir (with or without low-dose ritonavir) is contraindicated;1 200 fosamprenavir manufacturer states that a safe and effective dose for concomitant use not established1

Sildenafil for treatment of erectile dysfunction: If used concomitantly with fosamprenavir (with or without low-dose ritonavir), do not exceed sildenafil dosage of 25 mg once every 48 hours and closely monitor for sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)1 200

Simeprevir

Possible altered simeprevir concentrations187

Concomitant use with fosamprenavir (with or without low-dose ritonavir) not recommended187 200

Stavudine

In vitro evidence of synergistic antiretroviral effects1

Tadalafil

Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)1 200

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, increase dosage to 40 mg once daily1

If fosamprenavir (with or without low-dose ritonavir) is indicated in patient already receiving tadalafil (Adcirca) for treatment of PAH, discontinue tadalafil for at least 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, increase dosage to 40 mg once daily1

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, prolonged erection, syncope)1

If tadalafil is used for treatment of benign prostatic hyperplasia, do not exceed tadalafil dosage of 2.5 mg once daily200

Telaprevir

Ritonavir-boosted fosamprenavir: Decreased concentrations and AUCs of telaprevir and amprenavir1 184 200

Ritonavir-boosted fosamprenavir: Concomitant use not recommended1 184 200

Tenofovir

No change in amprenavir concentrations with ritonavir-boosted fosamprenavir1

In vitro evidence of synergistic antiretroviral effects1

Tipranavir

Possible decreased amprenavir concentrations if used concomitantly with ritonavir-boosted tipranavir211

Concomitant use with ritonavir-boosted tipranavir not recommended211

Trazodone

Possible increased trazodone concentrations with fosamprenavir (with or without low-dose ritonavir)1

Increased risk of trazodone-associated adverse effects1

Use concomitantly with caution; consider reduced trazodone dosage;1 use lowest possible trazodone dosage and monitor for adverse CNS and cardiovascular effects200

Tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline)

Amitriptyline, desipramine, imipramine, nortriptyline: Possible increased concentrations of the tricyclic antidepressant1 200

Amitriptyline, desipramine, imipramine, nortriptyline: Use lowest possible antidepressant dosage; titrate antidepressant dosage based on clinical assessment and/or antidepressant concentrations200

Vardenafil

Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection)1 200

If fosamprenavir (with or without low-dose ritonavir) is used in patients receiving vardenafil for treatment of erectile dysfunction, do not exceed vardenafil dosage of 2.5 mg once every 72 hours and closely monitor for vardenafil-related adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1

Zidovudine

Studies using amprenavir indicate possible increased amprenavir AUC;1 possible increased zidovudine plasma concentrations and AUC1

In vitro evidence of synergistic antiretroviral effects1

Lexiva Pharmacokinetics

Absorption

Bioavailability

Fosamprenavir calcium is a prodrug of amprenavir (no longer commercially available in the US).1

Absolute oral bioavailability of amprenavir after administration of fosamprenavir calcium has not been established;1 peak amprenavir concentrations attained 1.5–4 hours after administration of the prodrug.1

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.1

Food

Tablets: Administration of fosamprenavir calcium tablets with food has no effect on bioavailability of amprenavir.1

Suspension: Administration of fosamprenavir calcium suspension 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.1

Distribution

Extent

Amprenavir crosses the placenta and is distributed into milk in animals.1 Not known whether drug crosses human placenta or is distributed into human milk.1

Plasma Protein Binding

90% bound to plasma proteins, primarily to α1-acid glycoprotein.1

Elimination

Metabolism

Following oral administration, fosamprenavir calcium is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate in the intestinal epithelium during absorption.1

Amprenavir is metabolized in liver principally by CYP3A4.1

Elimination Route

About 14% of an oral dose excreted in urine and 75% eliminated in feces as metabolites.1 Only minimal amounts eliminated unchanged in urine or feces.1

Half-life

Amprenavir elimination half-life approximately 7.7 hours.1

Special Populations

Following administration of ritonavir-boosted fosamprenavir, AUC of amprenavir increased 22, 70, or 80% in those with mild, moderate, or severe hepatic impairment, respectively.1 Plasma protein binding decreased in these individuals.1

Pharmacokinetics not studied to date in patients with impaired renal function,1 but renal impairment not expected to have a clinically important effect on pharmacokinetics.1

Pharmacokinetics studied in pediatric patients 2–5 years of age receiving fosamprenavir 30 mg/kg twice daily, patients 6–11 years of age receiving fosamprenavir 18 mg/kg and ritonavir 3 mg/kg twice daily, and in those 12–18 years of age receiving fosamprenavir 700 mg and ritonavir 100 mg twice daily.1

Stability

Storage

Oral

Oral Suspension

5–30°C; avoid freezing.1

Tablets

Tight container at 25°C (may be exposed to 15–30°C).1

Actions and Spectrum

  • Fosamprenavir calcium is a prodrug of amprenavir (no longer commercially available in the US) and has little or no antiretroviral activity until hydrolyzed in vivo to amprenavir.1

  • Amprenavir, a PI, inhibits replication of HIV-1 by interfering with HIV protease.1

  • HIV-1 with reduced susceptibility to amprenavir were selected in vitro and have emerged during therapy with fosamprenavir.1

  • Varying degrees of cross-resistance occur among PIs; only limited data available to date regarding cross-resistance between amprenavir and other PIs.1

Advice to Patients

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.1 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1

  • Importance of using in conjunction with other antiretrovirals–not for monotherapy.1

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.1 Sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.1

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.1 200

  • Importance of reading patient information provided by the manufacturer.1

  • If a dose is missed, take the dose as soon as it is remembered and take next dose at regularly scheduled time.1 If a dose is skipped, do not take a double dose to make up for the missed dose.1

  • When the oral suspension is used, advise adults to take the preparation on an empty stomach.1 Advise children to take the oral suspension with food.1 Refrigeration of the suspension may improve the taste.1

  • When the oral suspension is used, repeat dose if vomiting occurs within 30 minutes of ingestion.1

  • Importance of patients informing their clinician if they are allergic to sulfonamides.1

  • Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products (e.g., St. John’s wort), as well as any concomitant illnesses.1

  • Advise patients receiving selective phosphodiesterase type 5 (PDE5) inhibitors (e.g., avanafil, sildenafil, tadalafil, vardenafil) that they may be at increased risk of PDE5 inhibitor-associated adverse effects (e.g., hypotension, syncope, visual disturbances, priapism) and that any symptoms should be promptly reported to their clinician.1 Fosamprenavir should not be used concomitantly with sildenafil used for treatment of pulmonary arterial hypertension (PAH).1

  • Importance of women using a reliable nonhormonal (e.g., barrier) method of contraception because of the potential interaction with hormonal contraceptives.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise HIV-infected women not to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

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

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)

Lexiva

ViiV

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lexiva 700MG Tablets (VIIV HEALTHCARE): 30/$439.98 or 90/$1,240.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions October 24, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2013 Apr.

2. GlaxoSmithKline, Research Triangle Park, NC: personal communication.

5. Rodriguez-French A, Boghossian J, Gray GE et al. The NEAT study: a 48-week open-label study to compare the antiviral efficacy and safety of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1-infected patients. J Acquir Immune Defic Syndr. 2004; 35: 22-32. [IDIS 510085] [PubMed 14707788]

6. Gathe JC, I’ve P, Wood R et al. SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir/ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients. AIDS. 2004; 18:1529-37. [PubMed 15238771]

8. Wire MB, Ballow C, Preston SL et al. Pharmacokinetics and safety of GW433908 and ritonavir, with and without efavirenz, in healthy volunteers. AIDS. 2004; 18:897-907. [PubMed 15060437]

9. Pfizer. Vfend IV (voriconazole for injection) and Vfend (voriconazole) tablets prescribing information. New York, NY; 2010 Jun.

12. Reddy SS. Dear healthcare professional letter. Results of pharmacokinetic study in healthy volunteers given Victrelis (boceprevir) and ritonavir-boosted HIV protease inhibitors may indicate clinically significant drug interactions for patients coinfected with chronic hepatitis C and HIV. West Point, PA: Merck; 2012 Feb 6.

16. Corbett AH, Patterson KB, Tien H-C et al. Dose separation does not overcome the pharmacokinetic interaction between fosamprenavir and lopinavir/ritonavir. Antimicrob Agents Chemother. 2006; 50:2756-61. [PubMed 16870769]

17. Food and Drug Administration. FDA drug safety communication: Important drug interactions between Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs. 2012 Feb 8. From FDA website. Accessed 2012 Apr 23.

18. Food and Drug Administration. FDA drug safety communication: Updated information on drug interactions between Victrelis (boceprevir) and certain boosted HIV protease inhibitor drugs. 2012 Apr 26. From FDA website. Accessed 2012 Jul 9.

19. GlaxoSmithKline. Dear Healthcare Professional letter: Lexiva (fosamprenavir calcium) tablets and oral suspension: myocardial infarction and dyslipidemia. Research Triangle Park, NC; 2009 Nov.

20. DAD Study Group, Friis-Møller N, Reiss P et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007; 356:1723-35. [PubMed 17460226]

21. Bergersen BM. Cardiovascular risk in patients with HIV Infection: impact of antiretroviral therapy. Drugs. 2006; 66:1971-87. [PubMed 17100407]

184. Vertex Pharmaceuticals Incorporated. Incivek (telaprevir) film-coated tablets prescribing information. Cambridge, MA; 2012 Jun.

185. Merck & Co. Victrelis (boceprevir) capsules prescribing information. Whitehouse Station, NJ; 2012 Apr.

186. Food and Drug Administration. FDA drug safety communication: Interactions between certain HIV or hepatitis C drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury. 2012 Mar 1. From FDA website. Accessed 2012 Apr 23.

187. Janssen Products LP. Olysio (simeprevir) capsules prescribing information. Titusville, NJ; 2013 Nov.

188. Vivus. Stendra (avanafil) tablets prescribing information. Mountain View, CA; 2012 Apr.

198. Center for Disease Control and Prevention. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: Recommendations from the U.S. Department of Health and Human Services. MMWR Morb Mortal Wkly Rep. 2005; 54(No. RR-2):1-19. [PubMed 15647722]

199. Kuhar DT, Henderson DK, Struble KA et al. Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis. Infect Control Hosp Epidemiol. 2013; 34:875-92. [PubMed 23917901]

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 1, 2014). Updates may be available at HHS AIDS Information (AIDSinfo) website.

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (February 12, 2014). Updates may be available at HHS AIDS Information (AIDSinfo) website.

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (March 28, 2014). Updates may be available at HHS AIDS Information (AIDSinfo) website.

211. Boehringer Ingelheim. Aptivus (tipranavir) capsules and oral solution prescribing information. Ridgefield, CT; 2014 Apr.

214. Janssen. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2014 Mar.

224. ViiV Healthcare. Senzentry (maraviroc) tablets prescribing information. Research Triangle Park, NJ; 2014 Mar.

226. Janssen Therapeutics. Edurant (rilpivirine) tablets prescribing information. Titusville, NJ; 2014 May.

236. ViiV Healthcare. Tivicay (dolutegravir) tablets prescribing information. Research Triangle Park, NC; 2013 Aug.

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