Fosamprenavir (Monograph)
Brand name: Lexiva
Drug 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).
Uses for Fosamprenavir
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.
Used in conjunction with low-dose ritonavir (ritonavir-boosted fosamprenavir) or without low-dose ritonavir (unboosted fosamprenavir); usually used in PI-based regimens that include a PI and 2 nucleoside reverse transcriptase inhibitors (NRTIs).
For initial treatment in antiretroviral-naive adults or adolescents, experts state fosamprenavir (with or without low-dose ritonavir) not recommended. Regimens that include unboosted fosamprenavir may be associated with virologic failure and may result in selection of mutations that confer resistance to fosamprenavir and darunavir; clinical trial data for ritonavir-boosted fosamprenavir more limited compared with data available for other ritonavir-boosted PIs.
For initial treatment in antiretroviral-naive pediatric patients, experts state ritonavir-boosted fosamprenavir not recommended in any age group because other more advantageous ritonavir-boosted PIs are available. Fosamprenavir (without low-dose ritonavir) also not recommended for pediatric patients of any age because of concerns related to inconvenient dosing and possibility of selection of resistance mutations.
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). Once-daily ritonavir-boosted fosamprenavir not recommended in PI-experienced adults or in any pediatric patient.
Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)
Postexposure prophylaxis of HIV infection following occupational exposure† [off-label] (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.
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.
Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)
Postexposure prophylaxis of HIV infection following nonoccupational exposure† [off-label] (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when the exposure represents a substantial risk for HIV transmission. Used in conjunction with other antiretrovirals.
When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF; Truvada); recommended alternative in these patients is ritonavir-boosted darunavir used in conjunction with emtricitabine/tenofovir DF.
CDC states that fosamprenavir is an alternative antiretroviral that can be used in nPEP regimens, but use in such regimens only with expert consultation.
Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. Do not delay initiation of nPEP while waiting for expert consultation.
Fosamprenavir Dosage and Administration
Administration
Oral Administration
Administer orally with low-dose ritonavir (ritonavir-boosted fosamprenavir) or without low-dose ritonavir (unboosted fosamprenavir). (See Dosage under Dosage and Administration.)
Oral Suspension
Pediatric patients: Take with food.
Adults: Take without food.
If vomiting occurs soon after a dose (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.
Pediatric Patients
Children 4 weeks to 18 years of age: Dosage is based on weight. Do not exceed adult dosage.
Do not use once-daily regimen (with or without low-dose ritonavir) in pediatric patients.
Do not use twice-daily regimen (with low-dose ritonavir) in PI-experienced children <6 months of age.
Do not use twice-daily regimen (without low-dose ritonavir) in PI-naive or PI-experienced children <2 years of age.
Treatment of HIV Infection
Antiretroviral-naive Pediatric Patients
OralPI-naive children ≥4 weeks of age (oral suspension): Twice-daily regimen with low-dose ritonavir. (See Table 1.)
|
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).
PI-naive children weighing ≥39 kg (tablets): 700 mg twice daily with low-dose ritonavir (100 mg twice daily).
PI-naive children ≥2 years of age weighing ≥47 kg (tablets): 1.4 g twice daily (without low-dose ritonavir).
Antiretroviral-experienced Pediatric Patients
OralPI-experienced children ≥6 months of age (oral suspension): Twice-daily regimen with low-dose ritonavir. (See Table 2.)
|
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).
PI-experienced children ≥2 years of age or older weighing ≥47 kg (tablets): 1.4 g twice daily (without low-dose ritonavir).
Adults
Treatment of HIV Infection
Antiretroviral-naive Adults
Oral1.4 g twice daily (without low-dose ritonavir).
1.4 g 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).
Antiretroviral-experienced Adults
OralPI-experienced adults: 700 mg twice daily with low-dose ritonavir (100 mg twice daily). Once-daily regimen not recommended.
Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)† [off-label]
Oral
1.4 g once daily with low-dose ritonavir (100 mg once daily). Alternatively, 1.4 g twice daily (without low-dose ritonavir). Use in conjunction with 2 NRTIs (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).
Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.
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). Do not exceed adult dosage.
Adults
Treatment of HIV Infection
Antiretroviral-naive Adults
OralMaximum 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). Higher than recommended dosages of fosamprenavir and/or ritonavir associated with increased serum transaminase concentrations; higher dosages not recommended.
Antiretroviral-experienced Adults
OralMaximum 700 mg twice daily with low-dose ritonavir (100 mg twice daily). Higher than recommended dosages of fosamprenavir and/or ritonavir associated with increased serum transaminase concentrations; higher dosages not recommended.
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.
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). 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-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). 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-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). In PI-experienced adults, fosamprenavir 300 mg twice daily with low-dose ritonavir (100 mg once daily).
Renal Impairment
Dosage adjustments not necessary.
Geriatric Patients
Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
Cautions for Fosamprenavir
Contraindications
-
Known hypersensitivity to fosamprenavir, amprenavir (no longer commercially available in the US), or any ingredient in the formulation.
-
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). (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]). (See Specific Drugs under Interactions.)
-
Concomitant use of a ritonavir-boosted fosamprenavir regimen and flecainide or propafenone. (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. Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, reported rarely.
Discontinue if severe or life-threatening rash or moderate rash accompanied by systemic symptoms occurs.
Sulfonamide Sensitivity
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.
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 can occur with some drugs. (See Contraindications under Cautions and Specific Drugs under Interactions.)
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 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.
Perform appropriate laboratory tests to evaluate hepatic function prior to initiating fosamprenavir and monitor patients closely during treatment. (See Hepatic Impairment under Cautions.)
Use of fosamprenavir with ritonavir at higher than recommended dosages may result in elevated transaminase concentrations.
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.
Monitor blood glucose and initiate or adjust dosage of insulin or oral hypoglycemic agents as needed.
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]); this may necessitate further evaluation and treatment.
Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.
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. Mechanism and long-term consequences of fat redistribution unknown; causal relationship not established.
Evaluate patients for physical signs of fat redistribution.
Lipid Effects
Increases in triglyceride and cholesterol concentrations have occurred with ritonavir-boosted fosamprenavir. HIV infection itself is associated with lipid disorders.
Determine serum triglyceride and cholesterol concentrations prior to initiating fosamprenavir and periodically monitor during therapy; manage lipid disorders as clinically appropriate. (See HMG-CoA Reductase Inhibitors under Interactions.)
Hematologic Effects
Neutropenia has been reported with fosamprenavir; acute hemolytic anemia has been reported in at least one patient who received amprenavir (no longer commercially available in the US).
Hemophilia A and B
Spontaneous bleeding reported with PIs; causal relationship not established.
Increased hemostatic therapy (e.g., antihemophilic factor) may be needed.
Nephrolithiasis
Nephrolithiasis reported during postmarketing experience. If signs or symptoms of nephrolithiasis occur, consider temporarily interrupting or discontinuing fosamprenavir.
HIV Resistance
Possible amprenavir resistance in patients treated with fosamprenavir. The possible effect of fosamprenavir therapy on subsequent therapy with other PIs unknown.
Cardiovascular Effects
Postmarketing reports of myocardial infarction in patients receiving fosamprenavir. Possible association between cumulative exposure to fosamprenavir/amprenavir and increased risk of myocardial infarction. 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. HIV infection itself is associated with ischemic heart disease.
Monitor modifiable risk factors for cardiovascular disease (e.g., hypertension, diabetes, smoking) and manage as clinically appropriate. Individualize treatment, carefully considering risks and benefits of continued treatment.
Specific Populations
Pregnancy
Category C.
Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].
Some experts state data insufficient to recommend routine use of fosamprenavir for initial treatment in antiretroviral-naive pregnant women; if the drug is used in pregnant women, these experts state ritonavir-boosted fosamprenavir must be used.
Lactation
Distributed into milk in rats; not known whether distributed into human milk.
Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.
Pediatric Use
Safety and efficacy not established in PI-naive children <4 weeks of age or in PI-experienced children <6 months of age.
In PI-naive infants, use only in those born at ≥38 weeks gestation who have attained postnatal age of ≥28 days.
Do not use 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.
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. (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.
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 concentrations may be increased; assess hepatic function prior to and periodically during therapy.
Dosage adjustments necessary in adults with hepatic impairment (Child-Pugh score 5 or greater); data not available to support dosage recommendations for pediatric patients. (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.
Common Adverse Effects
Diarrhea, nausea, vomiting, headache, rash.
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 P2E1 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.
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.
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 In vitro evidence of synergistic antiretroviral effects |
|
|
Alfuzosin |
Potential for increased alfuzosin concentrations that could result in hypotension |
Concomitant use with fosamprenavir (with or without low-dose ritonavir) is contraindicated |
|
Antacids |
Decreased amprenavir concentrations and AUC |
Manufacturer of fosamprenavir states interaction not considered clinically important and makes no restrictions for concomitant use with antacids Some experts recommend fosamprenavir be given simultaneously with or at least 2 hours before or 1 hour after antacids |
|
Antiarrhythmic agents (amiodarone, dronedarone, 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 Potential for serious or life-threatening effects (e.g., cardiac arrhythmias) if fosamprenavir used in conjunction with amiodarone, systemic lidocaine, or quinidine |
In patients receiving ritonavir-boosted fosamprenavir, concomitant use with flecainide or propafenone contraindicated Caution if fosamprenavir used concomitantly with amiodarone, systemic lidocaine, or quinidine; antiarrhythmic concentration monitoring recommended Amiodarone or dronedarone: Some experts state do not use concomitantly with fosamprenavir (with or without low-dose ritonavir) |
|
Anticoagulants, oral |
Apixaban, edoxaban, rivaroxaban: Increased anticoagulant concentrations Dabigatran: Possible increased dabigatran concentrations Warfarin: Possible altered warfarin concentrations |
Apixaban, edoxaban, rivaroxaban: Avoid concomitant use Dabigatran: Dosage adjustments not needed in patients with Clcr >50 mL/minute; avoid concomitant use in those with Clcr <50 mL/minute Warfarin: Monitor INR, especially when initiating or discontinuing fosamprenavir; adjust warfarin dosage as needed |
|
Anticonvulsants (carbamazepine, ethosuximide, lamotrigine, phenobarbital, phenytoin) |
Carbamazepine, phenobarbital, phenytoin: Possible decreased amprenavir concentrations and decreased virologic response when used with unboosted fosamprenavir Carbamazepine, phenobarbital: Possible increased carbamazepine concentrations and decreased amprenavir concentrations when used with ritonavir-boosted fosamprenavir Ethosuximide: Possible increased ethosuximide concentrations Lamotrigine: Possible decreased lamotrigine concentrations if used concomitantly with ritonavir-boosted fosamprenavir Phenytoin: Increased amprenavir concentrations and decreased phenytoin concentrations when used with ritonavir-boosted fosamprenavir |
Carbamazepine, phenobarbital, phenytoin: Use concomitantly with unboosted fosamprenavir with caution; some experts state do not use concomitantly with unboosted fosamprenavir Carbamazepine, phenobarbital: If using ritonavir-boosted fosamprenavir, consider alternative anticonvulsant or monitor concentrations of the anticonvulsant and amprenavir and assess antiretroviral response Ethosuximide: Monitor for ethosuximide toxicity Lamotrigine: If used with ritonavir-boosted fosamprenavir, consider increasing lamotrigine dosage and monitoring lamotrigine concentrations; alternatively, consider alternative anticonvulsant Phenytoin: Usual dosages of ritonavir-boosted fosamprenavir may be used, but monitor phenytoin concentrations and increase phenytoin dosage as needed |
|
Antifungals, azoles (itraconazole, isavuconazonium, ketoconazole, posaconazole, voriconazole) |
Itraconazole: Possible increased antifungal and amprenavir concentrations Isavuconazonium (prodrug of isavuconazole): Possible increased isavuconazole concentrations and altered fosamprenavir concentrations if used concomitantly with fosamprenavir (without low-dose ritonavir) Ketoconazole: Possible increased ketoconazole concentrations with fosamprenavir (with or without low-dose ritonavir) Posaconazole: Decreased posaconazole AUC and increased amprenavir concentrations when used concomitantly with fosamprenavir (without low-dose ritonavir); increased posaconazole and amprenavir concentrations when used with ritonavir-boosted fosamprenavir Voriconazole: Although specific data not available on interaction with ritonavir-boosted fosamprenavir, studies using low-dose ritonavir and voriconazole indicate decreased voriconazole concentrations; in addition, fosamprenavir (without low-dose ritonavir) possibly may result in increased concentrations of both drugs |
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; in those receiving ritonavir-boosted fosamprenavir, itraconazole dosage >200 mg daily not recommended unless plasma concentrations are monitored Isavuconazonium: If used with fosamprenavir (with or without low-dose ritonavir), consider monitoring isavuconazole concentrations and monitor for fosamprenavir-associated adverse effects and virologic response Ketoconazole: In patients receiving fosamprenavir (without low-dose ritonavir), may need to reduce antifungal dosage in those receiving >400 mg of ketoconazole daily; in those receiving ritonavir-boosted fosamprenavir, use caution and ketoconazole dosage >200 mg daily not recommended Posaconazole: If used with fosamprenavir (without low-dose ritonavir), monitor posaconazole concentrations; if used with ritonavir-boosted fosamprenavir, consider monitoring posaconazole concentrations and monitor for fosamprenavir-associated adverse effects Voriconazole: Monitor for toxicities if used with fosamprenavir (without low-dose ritonavir); do not use with ritonavir-boosted fosamprenavir unless potential benefits outweigh risks; if used with ritonavir-boosted fosamprenavir, consider monitoring voriconazole concentrations and adjusting voriconazole dosage accordingly |
|
Antimycobacterials (bedaquiline, rifabutin, rifampin, rifapentine) |
Bedaquiline: Possible increased bedaquiline concentrations; clinical importance unknown 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 Rifapentine: Possible decreased fosamprenavir concentrations |
Bedaquiline: Use concomitantly with ritonavir-boosted fosamprenavir with caution and only if potential benefits outweigh risks; monitor for QTc interval prolongation and liver dysfunction Rifabutin: If fosamprenavir (without low-dose ritonavir) used with rifabutin, reduce rifabutin dosage by at least 50% (150 mg once daily or 300 mg 3 times weekly has been suggested); 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); monitor for neutropenia by performing CBCs weekly and as clinically indicated; monitor for antimycobacterial response and consider therapeutic drug monitoring Rifampin: Concomitant use contraindicated Rifapentine: Concomitant use not recommended |
|
Antiplatelet agents (ticagrelor, vorapaxar) |
Ticagrelor, vorapaxar: Increased antiplatelet agent concentrations expected |
Ticagrelor, vorapaxar: Avoid concomitant use |
|
Antipsychotics (lurasidone, perphenazine, pimozide, quetiapine, risperidone, thioridazine) |
Lurasidone: Potential for serious and/or life-threatening adverse effects if used concomitantly with ritonavir-boosted fosamprenavir Perphenazine, risperidone, thioridazine: Possible increased antipsychotic concentrations 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 Perphenazine, risperidone, thioridazine: If used with ritonavir-boosted fosamprenavir, initiate antipsychotic at lowest dosage and adjust maintenance dosage; monitor for toxicities associated with the antipsychotic Pimozide: Concomitant use contraindicated 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 quetiapine |
|
Atazanavir |
Ritonavir-boosted fosamprenavir: Decreased atazanavir concentrations and AUC; no change in amprenavir concentrations and AUC 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 |
|
Avanafil |
Possible increased avanafil concentrations and AUC if used concomitantly with fosamprenavir (with or without low-dose ritonavir) |
If avanafil used for treatment of erectile dysfunction, do not exceed avanafil dosage of 50 mg once every 24 hours; concomitant use with ritonavir-boosted fosamprenavir not recommended |
|
β-adrenergic blocking agents (atenolol, labetalol, metoprolol, nadolol, sotalol, timolol) |
Metoprolol, timolol: Possible increased concentrations of the β-blocker |
Metoprolol, timolol: Decrease in β-blocker dosage may be needed based on clinical response; consider using certain β-blockers not metabolized by CYP isoenzymes (e.g., atenolol, labetalol, nadolol, sotalol) |
|
Benzodiazepines (alprazolam, clonazepam, 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) Other benzodiazepines: Possible increased concentrations of alprazolam, clonazepam, clorazepate, diazepam, flurazepam |
Midazolam or triazolam: Manufacturer of fosamprenavir states that concomitant use is contraindicated; some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation; consider an alternative benzodiazepine metabolized by non-CYP pathways (e.g., lorazepam, oxazepam, temazepam) Other benzodiazepines: Clinical importance of pharmacokinetic interaction unknown; a decrease in benzodiazepine dosage may be needed |
|
Bosentan |
Increased bosentan concentrations |
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 tolerability 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 tolerability |
|
Buprenorphine |
No clinically important pharmacokinetic interactions |
Ritonavir-boosted fosamprenavir: Dosage adjustments not necessary; clinical monitoring recommended; if route of buprenorphine administration changed from transmucosal to subdermal implantation, monitor patient to ensure effect of buprenorphine is adequate and not excessive |
|
Buspirone |
Increased buspirone concentrations expected |
Use low dosage of buspirone with caution and titrate based on clinical response |
|
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 effects (e.g., cardiac arrhythmias) |
Concomitant use contraindicated |
|
Clarithromycin |
Ritonavir-boosted fosamprenavir: Possible increased clarithromycin concentrations Studies using amprenavir indicate increased amprenavir concentrations and AUC and slightly decreased clarithromycin concentrations |
Fosamprenavir (without low-dose ritonavir): Dosage adjustment not needed Ritonavir-boosted fosamprenavir: Consider alternative macrolide (e.g., azithromycin); if used concomitantly, monitor for clarithromycin-related toxicities 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 |
|
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-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; 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 (beclomethasone, budesonide, dexamethasone, fluticasone, methylprednisolone, prednisolone, prednisone, triamcinolone) |
Beclomethasone (orally inhaled, intranasal): Clinically important pharmacokinetic interactions not expected Budesonide or fluticasone (orally inhaled, intranasal): Increased corticosteroid concentrations; may result in adrenal insufficiency, including Cushing's syndrome Methylprednisolone, prednisolone, triamcinolone (intra-articular or other local injections): Increased corticosteroid concentrations; may result in adrenal insufficiency, including Cushing's syndrome Budesonide or prednisone (systemic): Increased corticosteroid concentrations; may result in adrenal insufficiency, including Cushing's syndrome Dexamethasone (systemic): Possible decreased amprenavir concentrations and decreased antiretroviral efficacy |
Budesonide or fluticasone (orally inhaled, intranasal): Do not use concomitantly unless potential benefits of inhaled corticosteroid outweigh risks of systemic corticosteroid adverse effects; consider alternative (e.g., beclomethasone), especially when long-term corticosteroid use anticipated 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) Budesonide or prednisone (systemic): Do not use concomitantly unless potential benefits outweigh risks of systemic corticosteroid adverse effects Dexamethasone (systemic): Use concomitantly with caution; consider alternative corticosteroid for long-term use |
|
Daclatasvir |
No effect on daclatasvir concentrations if used concomitantly with fosamprenavir (with or without low-dose ritonavir) |
Dosage adjustments not needed |
|
Darunavir |
Data not available regarding concomitant use of darunavir and fosamprenavir (with or without low-dose ritonavir) |
|
|
Delavirdine |
Studies using amprenavir indicate possible increased amprenavir concentrations and AUC and possible decreased delavirdine plasma concentrations and AUC; possible decreased antiretroviral efficacy and increased risk of antiretroviral resistance In vitro evidence of synergistic antiretroviral effects |
Concomitant use contraindicated |
|
Didanosine |
In vitro evidence of synergistic antiretroviral effects |
|
|
Dolutegravir |
Ritonavir-boosted fosamprenavir: Decreased dolutegravir concentrations and AUC; effect on fosamprenavir pharmacokinetics unlikely No in vitro evidence of antagonistic antiretroviral effects with amprenavir |
Ritonavir-boosted fosamprenavir: In integrase strand transfer inhibitor-naive (INSTI-naive) patients, use dolutegravir 50 mg twice daily; in INSTI-experienced patients with documented or suspected INSTI resistance, consider alternative to ritonavir-boosted fosamprenavir whenever possible |
|
Efavirenz |
Substantially decreased amprenavir concentrations if used with fosamprenavir (without low-dose ritonavir); additional pharmacokinetic interactions if used with ritonavir-boosted fosamprenavir In vitro evidence of synergistic antiretroviral effects |
Fosamprenavir (without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established 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 daily |
|
Elbasvir and grazoprevir |
Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): No data |
|
|
Elvitegravir |
Cobicistat-boosted elvitegravir: Altered concentrations of elvitegravir, cobicistat, and/or fosamprenavir if used with fosamprenavir (with or without low-dose ritonavir) |
Cobicistat-boosted elvitegravir: Do not used concomitantly with fosamprenavir (with or without low-dose ritonavir) |
|
Eplerenone |
Increased eplerenone concentrations expected |
Experts state concomitant use contraindicated |
|
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) |
Concomitant use contraindicated 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 possible |
|
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 concentrations Hormonal contraceptives: Possible loss of virologic response if used with fosamprenavir (without low-dose ritonavir) Subdermal implants containing etonogestrel, transdermal systems containing ethinyl estradiol and norelgestromin: No data |
Hormonal contraceptives: Consider alternative or additional contraception methods or consider alternative antiretroviral regimen Subdermal implants containing etonogestrel, transdermal systems containing ethinyl estradiol and norelgestromin: Consider alternative or additional methods of contraception or consider alternative antiretroviral regimen |
|
Etravirine |
Fosamprenavir (with or without low-dose ritonavir): Substantially increased amprenavir concentrations |
Fosamprenavir (with or without low-dose ritonavir): Do not administer concomitantly |
|
Flibanserin |
Increased flibanserin concentrations expected |
Experts state concomitant use contraindicated |
|
Fluvoxamine |
Possible altered fosamprenavir concentrations |
Consider alternative antidepressant or alternative antiretroviral therapy |
|
Histamine H2-receptor antagonists (cimetidine, famotidine, nizatidine, ranitidine) |
Decreased amprenavir plasma concentrations and AUC; possible decreased antiretroviral efficacy |
Use concomitantly with caution; administer fosamprenavir (without low-dose ritonavir) at least 2 hours before the H2-receptor antagonist; consider using ritonavir-boosted fosamprenavir |
|
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 rhabdomyolysis |
Atorvastatin: Do not exceed atorvastatin dosage of 20 mg daily in patients receiving fosamprenavir (with or without low-dose ritonavir); carefully titrate atorvastatin dosage; use lowest necessary dosage with close monitoring for adverse effects Lovastatin: Concomitant use with fosamprenavir (with or without low-dose ritonavir) contraindicated Pitavastatin: Dosage adjustments not necessary Rosuvastatin: Dosage adjustments not necessary Simvastatin: Concomitant use with fosamprenavir (with or without low-dose ritonavir) contraindicated |
|
Immunosuppressive agents (cyclosporine, everolimus, sirolimus, tacrolimus) |
Increased concentrations of immunosuppressive agent expected |
Monitor immunosuppressive agent concentrations; some experts state initiate immunosuppressive agent with adjusted dosage to account for potential increased concentrations, monitor for toxicities, consult a specialist if needed |
|
Indinavir |
Fosamprenavir: Possible increased amprenavir concentrations and AUC; effect on indinavir concentrations not well established Ritonavir-boosted fosamprenavir: Concomitant use not evaluated In vitro evidence of additive antiretroviral effects |
Fosamprenavir (with or without low-dose ritonavir): Appropriate dosages for concomitant use with respect to safety and efficacy not established |
|
Ivabradine |
Increased ivabradine concentrations expected |
Experts state concomitant use contraindicated |
|
Lamivudine |
Studies using amprenavir indicate no evidence of pharmacokinetic interaction In vitro evidence of synergistic antiretroviral effects |
|
|
Ledipasvir and sofosbuvir |
Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): Pharmacokinetic interactions not expected if used concomitantly with fosamprenavir (with or without low-dose ritonavir) Concomitant use of ledipasvir/sofosbuvir and HIV antiretroviral regimen that includes ritonavir-boosted fosamprenavir and tenofovir DF: Possible increased tenofovir concentrations; safety of increased tenofovir concentrations not established |
Ledipasvir/sofosbuvir: Dosage adjustments not needed if used concomitantly with fosamprenavir (with or without low-dose ritonavir) Concomitant use of ledipasvir/sofosbuvir and HIV antiretroviral regimen that includes ritonavir-boosted fosamprenavir and tenofovir DF: Consider alternative HCV treatment or an alternative antiretroviral regimen; if concomitant use necessary, monitor patient for tenofovir-associated adverse effects |
|
Lopinavir/ritonavir |
Fosamprenavir: Decreased amprenavir concentrations and AUC; no change in lopinavir concentrations or AUC Ritonavir-boosted fosamprenavir: Decreased amprenavir concentrations and AUC; altered lopinavir concentrations and AUC (decreased or increased) Increased incidence of adverse effects reported In vitro evidence of additive antiretroviral effects |
Fosamprenavir (with or without low-dose ritonavir): Concomitant use not recommended; appropriate dosages for concomitant use with respect to safety and efficacy not established |
|
Maraviroc |
Increased maraviroc concentrations and AUC; decreased amprenavir concentrations and AUC No in vitro evidence of antagonistic antiretroviral effects |
Recommended maraviroc dosage is 150 mg twice daily with usual dosage of ritonavir-boosted fosamprenavir; do not use unboosted fosamprenavir |
|
Methadone |
Decreased methadone concentrations; opiate withdrawal unlikely but may occur |
Methadone dosage may need to be adjusted; monitor for opiate withdrawal and increase methadone dosage as clinically indicated |
|
Nelfinavir |
Studies using amprenavir indicate concomitant use may affect pharmacokinetics of both drugs; concomitant use of ritonavir-boosted fosamprenavir and nelfinavir not evaluated In vitro evidence of additive antiretroviral effects |
Appropriate dosages for concomitant use with respect to safety and efficacy not established |
|
Nevirapine |
Fosamprenavir (without low-dose ritonavir): Decreased amprenavir AUC and increased nevirapine AUC Ritonavir-boosted fosamprenavir (twice-daily regimen): Decreased amprenavir AUC and increased nevirapine AUC Ritonavir-boosted fosamprenavir (once-daily regimen): Concomitant use with nevirapine not studied In vitro evidence of additive antiretroviral effects |
Fosamprenavir (without low-dose ritonavir): Concomitant use not recommended RItonavir-boosted fosamprenavir (twice-daily regimen): Use usual nevirapine dosage with fosamprenavir 700 mg twice daily and ritonavir 100 mg twice daily |
|
Ombitasvir, paritaprevir, ritonavir, and dasabuvir |
Fosamprenavir (without low-dose ritonavir): Concomitant use with fixed combination of ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/ritonavir) with dasabuvir may result in increased paritaprevir and amprenavir concentrations Ritonavir-boosted fosamprenavir: Increased paritaprevir concentrations expected if used concomitantly with ombitasvir/paritaprevir/ritonavir with dasabuvir; possible increased amprenavir concentrations |
Fosamprenavir (without low-dose ritonavir): If used concomitantly with ombitasvir/paritaprevir/ritonavir with dasabuvir, dosage adjustments not established but fosamprenavir manufacturer states consider fosamprenavir 1.4 g once daily Ritonavir-boosted fosamprenavir: Concomitant use with ombitasvir/paritaprevir/ritonavir with dasabuvir not recommended |
|
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; when used with ritonavir-boosted fosamprenavir, clinically important pharmacokinetic interaction unlikely |
Can be administered at the same time as proton-pump inhibitors with no change in plasma amprenavir concentrations Dosage adjustments of fosamprenavir (with or without low-dose ritonavir) not needed |
|
Raltegravir |
Fosamprenavir (with or without low-dose ritonavir): Decreased concentrations and AUCs of raltegravir and amprenavir |
Fosamprenavir (with or without low-dose ritonavir): Appropriate dosage for concomitant use with respect to safety and efficacy not established; some experts state dosage adjustments not necessary |
|
Rilpivirine |
Possible increased rilpivirine concentrations; not expected to affect amprenavir concentrations |
Some experts state dosage adjustments not necessary |
|
Ritonavir |
Increased plasma concentrations and AUC of amprenavir Concomitant low-dose ritonavir used for therapeutic advantage (ritonavir-boosted fosamprenavir); increased potential for drug interactions since ritonavir is a potent inhibitor of CYP3A4 and also inhibits CYP2D6 In vitro evidence of additive antiretroviral effects |
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 daily Once-daily regimen of ritonavir-boosted fosamprenavir not recommended in PI-experienced patients |
|
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 In vitro evidence of synergistic antiretroviral effects |
Appropriate dosages for concomitant use with respect to safety and efficacy not established |
|
Selective serotonin-reuptake inhibitors (SSRIs) |
Paroxetine: Decreased SSRI concentrations with ritonavir-boosted fosamprenavir |
Paroxetine: Titrate dosage of the SSRI based on clinical response and tolerability |
|
Sildenafil |
Possible increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection) |
Sildenafil (Revatio) for treatment of pulmonary arterial hypertension (PAH): Concomitant use with fosamprenavir (with or without low-dose ritonavir) is contraindicated; fosamprenavir manufacturer states that a safe and effective dose for concomitant use not established 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) |
|
Simeprevir |
Fosamprenavir (without low-dose ritonavir): Possible altered simeprevir concentrations; altered amprenavir concentrations not expected Ritonavir-boosted fosamprenavir: Increased simeprevir concentrations expected; altered amprenavir concentrations not expected |
Concomitant use with fosamprenavir (with or without low-dose ritonavir) not recommended |
|
Stavudine |
In vitro evidence of synergistic antiretroviral effects |
|
|
Suvorexant |
Increased suvorexant concentrations expected |
Experts state concomitant use not recommended |
|
Tadalafil |
Possible increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection) |
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 daily 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 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, prolonged erection, syncope) If tadalafil is used for treatment of benign prostatic hyperplasia, do not exceed tadalafil dosage of 2.5 mg once daily |
|
Tenofovir |
No change in amprenavir concentrations with ritonavir-boosted fosamprenavir In vitro evidence of synergistic antiretroviral effects |
|
|
Tipranavir |
Possible decreased amprenavir concentrations if used concomitantly with ritonavir-boosted tipranavir |
Concomitant use with ritonavir-boosted tipranavir not recommended |
|
Trazodone |
Possible increased trazodone concentrations with fosamprenavir (with or without low-dose ritonavir) Increased risk of trazodone-associated adverse effects |
Use concomitantly with caution; consider reduced trazodone dosage; use lowest possible trazodone dosage and monitor for adverse CNS and cardiovascular effects |
|
Tricyclic antidepressants (amitriptyline, desipramine, imipramine, nortriptyline) |
Amitriptyline, desipramine, imipramine, nortriptyline: Possible increased concentrations of the tricyclic antidepressant |
Amitriptyline, desipramine, imipramine, nortriptyline: Use lowest possible antidepressant dosage; titrate antidepressant dosage based on clinical assessment and/or antidepressant concentrations |
|
Vardenafil |
Possible increased vardenafil concentrations and increased risk of vardenafil-associated adverse effects (e.g., hypotension, syncope, visual disturbances, prolonged erection) |
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) |
|
Zidovudine |
Studies using amprenavir indicate possible increased amprenavir AUC; possible increased zidovudine plasma concentrations and AUC In vitro evidence of synergistic antiretroviral effects |
|
|
Zolpidem |
Ritonavir-boosted fosamprenavir: Possible increased zolpidem concentrations |
Ritonavir-boosted fosamprenavir: Experts state initiate using low dosage of zolpidem; dosage reduction may be needed |
Fosamprenavir 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
Tablets: Administration of fosamprenavir calcium tablets with food has no effect on bioavailability of amprenavir.
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.
Distribution
Extent
Amprenavir crosses the placenta and is distributed into milk in animals. Not known whether drug crosses human placenta or 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 an oral dose excreted in urine and 75% eliminated in feces as metabolites. Only minimal amounts eliminated unchanged in urine or feces.
Half-life
Amprenavir elimination half-life approximately 7.7 hours.
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. Plasma protein binding decreased in these individuals.
Pharmacokinetics not studied to date in patients with impaired renal function, but renal impairment not expected to have a clinically important effect on pharmacokinetics.
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.
Stability
Storage
Oral
Oral Suspension
5–30°C; avoid freezing.
Tablets
Tight container at 25°C (may be exposed to 15–30°C).
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.
-
Amprenavir, a PI, inhibits replication of HIV-1 by interfering with HIV protease.
-
HIV-1 with reduced susceptibility to amprenavir were selected in vitro and have emerged during therapy with fosamprenavir.
-
Varying degrees of cross-resistance occur among PIs; only limited data available to date regarding cross-resistance between amprenavir and other PIs.
Advice to Patients
-
Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.
-
Importance of using in conjunction with other antiretrovirals–not for monotherapy.
-
Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur. Sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.
-
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. 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.
-
Importance of reading patient information provided by the manufacturer.
-
If a dose is missed, take the dose as soon as it is remembered and take next dose at regularly scheduled time. If a dose is skipped, do not take a double dose to make up for the missed dose.
-
When the oral suspension is used, advise adults to take the preparation on an empty stomach. Advise children to take the oral suspension with food. Refrigeration of the suspension may improve the taste.
-
When the oral suspension is used, repeat dose if vomiting occurs within 30 minutes of ingestion.
-
Importance of patients informing their clinician if they are allergic to sulfonamides.
-
Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.
-
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.
-
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. Fosamprenavir should not be used concomitantly with sildenafil used for treatment of pulmonary arterial hypertension (PAH).
-
Importance of women using a reliable nonhormonal (e.g., barrier) method of contraception because of the potential interaction with hormonal contraceptives.
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.
-
Importance of advising patients of other important precautionary information. (See Cautions.)
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.
|
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 |
ViiV |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions May 15, 2017. 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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