Lexiva (fosamprenavir calcium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Fosamprenavir calcium, an antiretroviral agent, is a human immunodeficiency virus (HIV) protease inhibitor (PI).
Fosamprenavir calcium is a prodrug of amprenavir (no longer commercially available in the US) and has little or no antiviral activity until it is hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium. Amprenavir is an inhibitor of human immunodeficiency virus type 1 (HIV-1) protease. During HIV replication, HIV protease cleaves viral polypeptide products of the gag and gag-pol genes to form structural proteins of the virion core and essential viral enzymes.
By interfering with the formation of these essential proteins and enzymes, amprenavir blocks maturation of the virus and causes formation of nonfunctional, immature, noninfectious virions.
HIV-1 strains with reduced susceptibility to amprenavir can be produced in vitro and strains with reduced susceptibility have emerged during fosamprenavir therapy. Varying degrees of cross-resistance among HIV protease inhibitors observed.
The absolute oral bioavailability of amprenavir after administration of fosamprenavir calcium has not been established. Peak amprenavir concentrations are attained 1.5-4 hours after administration of the prodrug. When a single 1.4-g dose of fosamprenavir 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.
Administration of fosamprenavir calcium tablets with food has no effect on bioavailability of amprenavir. 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 the AUC by 28% compared with administration in the fasting state.
In vitro studies indicate amprenavir is 90% bound to plasma proteins, primarily to alpha1-acid glycoprotein. 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 the liver principally by cytochrome P-450 (CYP) isoenzyme 3A4.
Approximately 14% of an oral dose of fosamprenavir is excreted in urine and 75% is eliminated in feces as metabolites; only minimal amounts are eliminated unchanged in urine or feces. The plasma elimination half-life of amprenavir is approximately 7.7 hours.
USES: This drug is used with other HIV medications to help control HIV infection. It helps to decrease the amount of HIV in your body so your immune system can work better. This lowers your chance of getting HIV complications (such as new infections, cancer) and improves your quality of life.
Fosamprenavir belongs to a class of drugs known as protease inhibitors. It may be given with ritonavir, another protease inhibitor, to increase ("boost") the levels of fosamprenavir. This helps fosamprenavir work better.
Fosamprenavir is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, continue to take all HIV medications exactly as prescribed by your doctor. Use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity as directed by your doctor.
Do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.
Generic name: fosamprenavir calcium
Pronunciation: (fos-am-PREN-uh-veer)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Lexiva
Indications
The following indications are listed for Lexiva:
- Hiv Infection
Also known as: Human Immunodeficiency Virus Disease, Human Immunodeficiency Virus Infection.
Dosing
Dosage of fosamprenavir calcium is expressed in terms of fosamprenavir.
When fosamprenavir is used in combination with ritonavir, consult the full prescribing information for ritonavir.
Fosamprenavir calcium is administered orally as oral suspension or tablets.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Concomitant use of fosamprenavir (with or without low-dose ritonavir) with certain drugs is contraindicated or requires particular caution.
When a ritonavir-boosted fosamprenavir regimen is used, consider the usual cautions, precautions, and contraindications associated with ritonavir.
Initiation of ritonavir-boosted fosamprenavir in patients receiving cytochrome P-450 (CYP) isoenzyme 3A substrates or initiation of CYP3A substrates in patients already receiving ritonavir-boosted fosamprenavir may increase plasma concentrations of such substrate drugs. Initiation of CYP3A inhibitors or inducers may increase or decrease plasma concentrations of ritonavir-boosted fosamprenavir, respectively. Depending on the specific drug interaction, adverse effects related to increased exposures of the concomitant drug that could be serious, life-threatening, or fatal may occur or clinically important ritonavir-boosted fosamprenavir-associated adverse effects or loss of virologic effect of fosamprenavir and possible development of resistance could occur.
Consider potential drug interactions prior to and during ritonavir-boosted fosamprenavir therapy. Review all drugs that the patient is receiving and monitor for adverse effects associated with other drugs used concomitantly with ritonavir-boosted fosamprenavir.
Because fosamprenavir is metabolized to amprenavir (the active metabolite) in vivo, interactions reported with amprenavir (no longer commercially available in the US) are expected to occur in patients receiving fosamprenavir. Results of studies using fosamprenavir may not be predictive of the magnitude of interaction with ritonavir-boosted fosamprenavir.
If fosamprenavir is used in combination with ritonavir, also consider drug interactions reported with ritonavir; refer to the full prescribing for ritonavir for specific information.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome) to fosamprenavir, amprenavir (active metabolite of fosamprenavir; no longer commercially available in the US), or any ingredient in the formulation.
*Concomitant use with drugs highly dependent on cytochrome P-450 (CYP) isoenzyme 3A4 for metabolism 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 and possible resistance) include: alfuzosin, cisapride, delavirdine, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), pimozide, sildenafil used for treatment of pulmonary arterial hypertension, lomitapide, lovastatin, simvastatin, midazolam, triazolam, rifampin, St. John's wort (Hypericum perforatum), flecainide (when used with fosamprenavir plus ritonavir), propafenone (when used with fosamprenavir plus ritonavir), and lurasidone (when used with fosamprenavir plus ritonavir). Unless otherwise noted, these contraindications apply to the use of fosamprenavir with or without ritonavir. When fosamprenavir is used in combination with ritonavir, consult the full prescribing information for ritonavir for additional considerations.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects (incidence >=4%) in adults receiving fosamprenavir are diarrhea, nausea, vomiting, headache, and rash. Vomiting and neutropenia were reported more frequently in pediatric patients compared to adults.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Three open-label studies have evaluated the safety, efficacy, and pharmacokinetics of fosamprenavir (with and without ritonavir) in PI-naive and PI-experienced HIV-1-infected pediatric patients 4 weeks to <18 years of age and weighing >=3 kg.
Pharmacokinetics, safety, tolerability, and efficacy of fosamprenavir have not been established in pediatric patients younger than 4 weeks of age. Treatment with fosamprenavir is not recommended in PI-experienced pediatric patients younger than 6 months of age.
Do not use once-daily regimens of fosamprenavir (with or without low-dose ritonavir) in pediatric patients. Do not use twice-daily regimens of fosamprenavir (without low-dose ritonavir) in pediatric patients <2 years of age.
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to fosamprenavir during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com.
In animal reproduction studies, no major adverse developmental outcomes were observed following oral administration of fosamprenavir. Systemic exposure to amprenavir (fosamprenavir's active metabolite) in rabbits or rats was less than or up to 2 times, respectively, the exposures in humans at the maximum recommended human dose (MRHD) with or without ritonavir. However, abortions were observed following oral administration of amprenavir in pregnant rabbits at doses that produced approximately one-twentieth the human exposure at the MRHD.
In the pre- and postnatal development study in rats, toxicities to the offspring were observed at maternal systemic exposures 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 at the MRHD of fosamprenavir in combination with ritonavir.
There are limited data on use of fosamprenavir in pregnancy. Data are insufficient to date to adequately assess the risk of birth defects and miscarriage in pregnant women receiving fosamprenavir. Based on prospective reports to the APR of 146 live births following exposures to fosamprenavir, 2 birth defects each were reported with first- and second/third- trimester exposures.
The safety, efficacy, and pharmacokinetics of fosamprenavir 700 mg twice daily in combination with ritonavir 100 mg twice daily were studied in a clinical trial of HIV-1-infected pregnant women during the second and third trimesters and postpartum. The use of this regimen should only be considered in pregnant patients who are already on a stable twice-daily regimen of fosamprenavir 700 mg twice daily plus ritonavir 100 mg prior to pregnancy, and who are virologically suppressed (HIV-1 RNA <50 copies per mL). Total amprenavir exposures (AUC) were lower during pregnancy compared with the postpartum period; thus, closely monitor viral load to ensure viral suppression is maintained.
Amprenavir is distributed into milk in rats. It is not known whether amprenavir is distributed into human milk, affects human milk production, or affects the breast-fed infant.
The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding. The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The manufacturer makes no specific dosage recommendations for geriatric patients. Dosage should be selected with caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.
Experience in patients >=65 years of age is insufficient 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 potential for concomitant disease and drug therapy.
The pharmacokinetics of fosamprenavir have not been studied in patients >65 years of age.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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