Fosamprenavir
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Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Dosing in liver impairment
Patients with Hepatic Impairment See Clinical Pharmacology . Mild Hepatic Impairment (Child-Pugh Score Ranging from 5 to 6) Fosamprenavir calcium tablets should be used with caution at a reduced dosage of 700 mg twice daily without ritonavir (therapy-naive) or 700 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced).
Moderate Hepatic Impairment (Child-Pugh Score Ranging from 7 to 9) Fosamprenavir calcium tablets should be used with caution at a reduced dosage of 700 mg twice daily without ritonavir (therapy-naive) or 450 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced). Severe Hepatic Impairment (Child-Pugh Score Ranging from 10 to 15) Fosamprenavir calcium tablets should be used with caution at a reduced dosage of 350 mg twice daily without ritonavir (therapy-naive) or 300 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced).
There are no data to support dosing recommendations for pediatric patients with hepatic impairment.
Drug interactions
Check fosamprenavir against a medication listLabel text (16 paragraphs)
Coadministration of fosamprenavir calcium with drugs that induce CYP3A4 may decrease amprenavir (active metabolite) concentrations leading to potential loss of virologic activity. (7, 12.3) Coadministration with drugs that inhibit CYP3A4 may increase amprenavir concentrations. (7, 12.3) Coadministration of fosamprenavir calcium or fosamprenavir calcium and ritonavir may result in clinically significant interactions with drugs metabolized by CYP3A4. (7) Coadministration of fosamprenavir calcium and ritonavir may result in clinically significant interactions with drugs metabolized by CYP2D6. (7)
7.1 Cytochrome P450 Inhibitors and Inducers Amprenavir, the active metabolite of fosamprenavir, is an inhibitor of CYP3A4 metabolism and therefore should not be administered concurrently with medications with narrow therapeutic windows that are substrates of CYP3A4. Data also suggest that amprenavir induces CYP3A4. Amprenavir is metabolized by CYP3A4. Coadministration of fosamprenavir calcium and drugs that induce CYP3A4, such as rifampin, may decrease amprenavir concentrations and reduce its therapeutic effect. Coadministration of fosamprenavir calcium and drugs that inhibit CYP3A4 may increase amprenavir concentrations and increase the incidence of adverse effects.
The potential for drug interactions with fosamprenavir calcium changes when fosamprenavir calcium is coadministered with the potent CYP3A4 inhibitor ritonavir. The magnitude of CYP3A4-mediated drug interactions (effect on amprenavir or effect on coadministered drug) may change when fosamprenavir calcium is coadministered with ritonavir. Because ritonavir is a CYP2D6 inhibitor, clinically significant interactions with drugs metabolized by CYP2D6 are possible when coadministered with fosamprenavir calcium plus ritonavir. Ritonavir also appears to induce CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2B6, as well as other enzymes, including glucuronosyl transferase.
There are other agents that may result in serious and/or life-threatening drug interactions [see Contraindications (4)] .
7.2 Established and Other Potentially Significant Drug Interactions If fosamprenavir calcium is used in combination with ritonavir, see full prescribing information for ritonavir for additional information on drug interactions [see Contraindications (4), Clinical Pharmacology (12.3)] . Table 6 provides a listing of established or potentially clinically significant drug interactions. Information in the table applies to fosamprenavir calcium with or without ritonavir, unless otherwise indicated. Table 6.
Established and Other Potentially Significant Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration of Amprenavir or Concomitant Drug Clinical Comment HCV/HIV-Antiviral Agents HCV protease inhibitor: Boceprevir Fosamprenavir calcium: ↓ Amprenavir (predicted) ↔ or ↓ Boceprevir (predicted) Fosamprenavir calcium /ritonavir: ↓Amprenavir (predicted) ↓Boceprevir (predicted) Coadministration of fosamprenavir calcium or fosamprenavir calcium/ ritonavir and boceprevir is not recommended.
HCV protease inhibitor: Simeprevir Fosamprenavir calcium: ↔ Amprenavir (predicted) ↑ or ↓ Simeprevir (predicted) Fosamprenavir calcium /ritonavir: ↔Amprenavir (predicted) ↑Simeprevir (predicted) Coadministration of fosamprenavir calcium or fosamprenavir calcium/ritonavir and simeprevir is not recommended. HCV protease inhibitor: Paritaprevir (coformulated with ritonavir and ombitasvir and coadministered with dasabuvir) Fosamprenavir calcium: ↑Amprenavir (predicted) ↑ or ↔Paritaprevir (predicted) Fosamprenavir calcium /ritonavir: ↑ or ↔Amprenavir (predicted) ↑Paritaprevir (predicted) Appropriate doses of the combinations with respect to safety and efficacy have not been established.
Fosamprenavircalcium 1,400 mg once daily may be considered when coadministered with paritaprevir/ritonavir/ombitasvir/ dasabuvir. Coadministration of Fosamprenavircalcium /ritonavir and paritaprevir/ritonavir/ombitasvir/ dasabuvir is not recommended. Non-nucleoside reverse transcriptase inhibitor: Delavirdine a Fosamprenavir calcium: ↑ Amprenavir ↓ Delavirdine Coadministration is contraindicated as it may lead to loss of virologic response and possible resistance to delavirdine [see Contraindications (4)] .
Fosamprenavir calcium/ritonavir: ↑ Amprenavir ↓Delavirdine Non-nucleoside reverse transcriptase inhibitor: Efavirenz a Fosamprenavir calcium: ↓ Amprenavir Fosamprenavir calcium/ritonavir: ↓ Amprenavir Appropriate doses of the combinations with respect to safety and efficacy have not been established. An additional 100 mg/day (300 mg total) of ritonavir is recommended when efavirenz is administered with fosamprenavir calcium /ritonavir once daily. No change in the ritonavir dose is required when efavirenz is administered with Fosamprenavir calcium plus ritonavir twice daily.
Non-nucleoside reverse transcriptase inhibitor: Nevirapine a Fosamprenavir calcium: ↓ Amprenavir ↑ Nevirapine Coadministration of nevirapine and fosamprenavir calcium without ritonavir is not recommended. Fosamprenavir calcium/ritonavir: ↓ Amprenavir ↑ Nevirapine No dosage adjustment required when nevirapine is administered with fosamprenavir calcium/ritonavir twice daily. The combination of nevirapine administered with fosamprenavir calcium/ritonavir once-daily regimen has not been studied. HIV protease inhibitor: Atazanavir a Fosamprenavir calcium: Interaction has not been evaluated. Appropriate doses of the combinations with respect to safety and efficacy have not been established.
Fosamprenavir calcium/ritonavir: ↓ Atazanavir ↔ Amprenavir HIV protease inhibitors: Indinavir a , nelfinavir a Fosamprenavir calcium: ↑ Amprenavir Effect on indinavir and nelfinavir is not well established. Fosamprenavir calcium/ritonavir: Interaction has not been evaluated. Appropriate doses of the combinations with respect to safety and efficacy have not been established. HIV protease inhibitors: Lopinavir/ritonavir a ↓ Amprenavir ↓ Lopinavir An increased rate of adverse events has been observed. Appropriate doses of the combinations with respect to safety and efficacy have not been established.
HIV protease inhibitor: Saquinavir a Fosamprenavir calcium: ↓ Amprenavir Effect on saquinavir is not well established. Fosamprenavir calcium/ritonavir: Interaction has not been evaluated. Appropriate doses of the combination with respect to safety and efficacy have not been established. HIV integrase inhibitor: Raltegravir a Fosamprenavir calcium: ↓ Amprenavir ↓ Raltegravir Fosamprenavir calcium/ritonavir: ↓ Amprenavir ↓ Raltegravir Appropriate doses of the combination with respect to safety and efficacy have not been established.
HIV integrase inhibitor: Dolutegravir a Fosamprenavir calcium /ritonavir: ↓Dolutegravir The recommended dose of dolutegravir is 50 mg twice daily when coadministered with Fosamprenavircalcium /ritonavir. Use an alternative combination where possible in patients with known or suspected integrase inhibitor resistance. HIV CCR5 co-receptor antagonist: Maraviroc a Fosamprenavir calcium/ritonavir: ↓ Amprenavir ↑ Maraviroc No dosage adjustment required for fosamprenavir calcium /ritonavir. The recommended dose of maraviroc is 150 mg twice daily when coadministered with fosamprenavir calcium/ritonavir. Fosamprenavir calcium should be given with ritonavir when coadministered with maraviroc.
Other Agents Alpha 1-adrenoreceptor antagonist: Alfuzosin ↑Alfuzosin Coadministration is contraindicated due to potential hypotension [see Contraindications (4)] . Antacid: MAALOX TC ↓Amprenavir Use with caution when administered at the same time. Fosamprenavir calcium may be less effective due to decreased amprenavir plasma concentrations. Staggered coadministration of antacids and fosamprenavir calcium has not been evaluated. Antiarrhythmics: Amiodarone, disopyramide, lidocaine (systemic), and quinidine Flecainide, propafenone ↑ Antiarrhythmics ↑Antiarrhythmics Therapeutic concentration monitoring, if available, is recommended for antiarrhythmics.
Coadministration is contraindicated due to potential for serious and/or life-threatening reactions such as cardiac arrhythmias if fosamprenavir calcium is co-prescribed with ritonavir [see Contraindications (4)] . Anticoagulant: Warfarin Concentrations of warfarin may be affected. It is recommended that INR (international normalized ratio) be monitored. Anticonvulsants: Carbamazepine, phenobarbital, phenytoin Fosamprenavir calcium: ↓ Amprenavir Use with caution. Fosamprenavir calcium may be less effective due to decreased amprenavir plasma concentrations in patients taking these agents concomitantly.
Phenytoin a Fosamprenavir calcium/ritonavir: ↑ Amprenavir ↓ Phenytoin Plasma phenytoin concentrations should be monitored and phenytoin dose should be increased as appropriate. No change in fosamprenavir calcium/ritonavir dose is recommended. Antidepressant: Paroxetine, trazodone ↓ Paroxetine Any paroxetine dose adjustment should be guided…
Contraindications
Fosamprenavir calcium is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome) to any of the components of this product or to amprenavir. Fosamprenavir calcium is contraindicated when coadministered with drugs that are highly dependent on cytochrome P450 (CYP)3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. These drugs and other contraindicated drugs (which may lead to reduced efficacy of fosamprenavir calcium and possible resistance) are listed below [see Drug Interactions (7), Clinical Pharmacology (12.3)] .
The list of contraindicated drugs applies to the use of fosamprenavir calcium with or without ritonavir, unless otherwise indicated. If fosamprenavir calcium is coadministered with ritonavir, reference should be made to the full prescribing information for ritonavir for additional contraindications.
Fosamprenavir calcium is contraindicated when coadministered with the following drugs: Alpha 1-adrenoreceptor antagonist: Alfuzosin Antiarrhythmics: Flecainide (with ritonavir ), propafenone (with ritonavir ) Antimycobacterial: Rifampin Antipsychotic: Lurasidone (with ritonavir ), pimozide Ergot derivatives: Dihydroergotamine, ergonovine, ergotamine, methylergonovine GI motility agent: Cisapride Herbal product: St.
John’s wort ( Hypericum perforatum ) Lipid modifying agents: Lomitapide, lovastatin, simvastatin Non-nucleoside reverse transcriptase inhibitor: Delavirdine PDE5 inhibitor: Sildenafil (Revatio) (for treatment of pulmonary arterial hypertension) Sedative/hypnotics: Midazolam, triazolam Hypersensitivity to fosamprenavir calcium or amprenavir (e.g., Stevens-Johnson syndrome). (4) Drugs highly dependent on cytochrome P450 (CYP)3A4 for clearance and for which elevated plasma levels may result in serious and/or life-threatening events. (4) Review ritonavir contraindications when used in combination. (4)
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
DLikelihood score D: Possible rare cause of clinically apparent liver injury.
Amprenavir is an antiretroviral protease inhibitor used in the therapy and prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Fosamprenavir is a prodrug of amprenavir that has better oral bioavailability and that has largely replaced amprenavir in clinical use. Both amprenavir and fosamprenavir can cause transient and usually asymptomatic elevations in serum aminotransferase levels and are rare causes of clinically apparent, acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to fosamprenavir calcium during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Limited data are available for use of fosamprenavir calcium in pregnancy.
fosamprenavir calcium 700 mg twice daily taken with ritonavir 100 mg twice daily should only be considered in pregnant patients who are already on a stable twice-daily regimen of fosamprenavir calcium/ritonavir 700 mg/100 mg prior to pregnancy, and who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) (see Clinical Considerations and Data). There are insufficient human data on the use of fosamprenavir during pregnancy to adequately assess a drug-associated risk for birth defects and miscarriage. Given the limited number of pregnancies exposed to fosamprenavir-based regimens, no conclusions can be drawn on the safety of fosamprenavir in pregnancy.
The background risk for major birth defects and miscarriage for the indicated population is unknown. The background rate for major birth defects in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) is 2.7% (see Data) . The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. In animal reproduction studies, no evidence of major adverse developmental outcomes was observed following oral administration of fosamprenavir.
Systemic exposure to amprenavir (the active ingredient) was less than (rabbits) or up to 2 times (rats) those in humans at the maximum recommended human dose (MRHD) with or without ritonavir. In contrast, oral administration of amprenavir was associated with abortions in pregnant rabbits at doses that produced approximately one-twentieth the human exposure at the MRHD.
In the rat pre- and postnatal development study, toxicities to the offspring, including reduced survival and reproductive performance, were observed at maternal systemic exposures (AUC) to amprenavir that were approximately 2 times the exposure in humans at the MRHD of fosamprenavir alone or approximately the same as those seen in humans following administration of the MRHD of fosamprenavir in combination with ritonavir (see Data). Clinical Considerations Virologic Monitoring During Pregnancy and the Postpartum Period: Based on limited data on the use of fosamprenavir calcium during pregnancy, no dosage adjustments are…
Breastfeeding (LactMed)
No published information is available on the use of fosamprenavir during breastfeeding. Fosamprenavir is not recommended during breastfeeding. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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