Fosamprenavir

Contraindications

Hypersensitivity (eg, Stevens-Johnson syndrome) to fosamprenavir, amprenavir, or other component

Concomitant use of drugs that depend heavily on CYP3A4 for clearance; metabolite amprenavir is a strong CYP3A4 inhibitor; use w/ ritonavir another strong CYP3A4 inhibitor may have additive inhibitory effects; check Drug Interactions

Drugs that are contraindicated with fosamprenavir (with or without ritonavir) include alpha1-adrenoreptor agonists (eg, alfuzosin), antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, quinidine), rifampin, voriconazole, ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), cisapride, St. John’s wort, lovastatin, simvastatin, lurasidone, pimozide, sildenafil (when used for PAH), midazolam, and triazolam

Cautions

New onset DM, exacerbation of pre-existing DM & hyperglycemia reported with unknown frequency/unknown causal relationship

Sulfonamide allergy

Monitor labs prior to and during treatment with Hepatitis B or C, or elevated transaminases

Few reports of spontaneous bleeding in patients. with Hemophilia A and B

During initial treatment, inflammatory response to indolent or residual opportunistic infections may occur and require treatment

Fat redistribution with "cushingoid appearance" and "buffalo hump" may occur

Increased risk for myocardial infarction (thought to be caused by protease inhibitors increasing risk of hyperlipidemia)

Monitor triglycerides and cholesterol levels before initiating, then periodically; initiate clinical management of lipid disorders as required

Combination treatment with ritonavir may lead to increased triglyceride level

Unknown effect on activity of subsequently administered protease inhibitors

Risk of immune reconstitution syndrome if used in combination with other antiretroviral drugs; autoimmune disorders (eg Graves disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment

Vomiting more common in children

Cases of nephrolithiasis reported with fosamprenavir

Acute hemolytic anemia reported with amprenavir

Discontinue therapy if severe skin reactions including Stevens-Johnson syndrome occur

Taking this medication will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Many drugs can interact with fosamprenavir, and some drugs should not be used together. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

• other drugs to treat HIV or AIDS;
• an antibiotic or antifungal medicine;
• an antidepressant or anti-psychotic medicine;
• antiviral medicine to treat hepatitis C;
• a blood thinner (warfarin, Coumadin, Jantoven);
• cholesterol-lowering medicine;
• heart or blood pressure medicine;
• medicine to prevent organ transplant rejection;
• medicine to prevent or treat nausea and vomiting;
• medicine to treat a breathing disorder;
• narcotic medicine;
• a sedative;
• seizure medicine;
• steroid medicine;
• stomach acid reducers; or
• Viagra and other erectile dysfunction medicines.

This list is not complete and many other drugs can interact with fosamprenavir. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Tell your healthcare provider if you are breastfeeding. You should not breastfeed if you are HIV-positive because of the chance of passing the HIV virus to your baby through your milk. Also, it is not known if fosamprenavir can pass into your breast milk and if it can harm your baby. If you are a woman who has or will have a baby, talk with your healthcare provider about the best way to feed your baby.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Severe skin rash

• Abdominal or stomach pain
• blurred vision
• depression
• dry mouth
• flushed, dry skin
• fruit-like breath odor
• increased hunger
• increased thirst
• increased urination
• mood or mental changes
• nausea
• sweating
• troubled breathing
• unexplained weight loss
• unusual tiredness or weakness
• vomiting

• Back, leg, or stomach pains
• bleeding gums
• blistering, peeling, or loosening of the skin
• chills
• cough
• dark urine
• diarrhea
• difficulty with breathing
• fever
• general body swelling
• itching
• joint or muscle pain
• loss of appetite
• nosebleeds
• pale skin
• red skin lesions often with a purple center
• red, irritated eyes
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• yellowing of the eyes or skin

• Large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Mild or moderate rash

• Burning or prickling sensation around the mouth
• headache

• Breast enlargement
• buffalo hump
• increased fat deposits on the face, neck, and trunk
• obesity

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Fosamprenavir Calcium
• GW433908G

• Antiretroviral, Protease Inhibitor (Anti-HIV)

Fosamprenavir is rapidly and almost completely converted to amprenavir by cellular phosphatases in vivo. Amprenavir binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. This results in the formation of immature, noninfectious viral particles.

Absorption

63%

Metabolism

Fosamprenavir is rapidly and almost completely converted to amprenavir by cellular phosphatases in gut epithelium; amprenavir is hepatically metabolized via CYP isoenzymes (primarily CYP3A4); glucuronide conjugation of oxidized metabolites also occurs

Excretion

Minimal excretion of unchanged drug in urine (1%) and feces; 75% of dose excreted as metabolites via biliary tract into feces and 14% excreted as metabolites in urine

Time to Peak

1.5 to 4 hours (median: 2.5 hours)

Half-Life Elimination

~7.7 hours (amprenavir)

Protein Binding

~90% (to alpha1-acid glycoprotein); decreased in hepatic impairment

Refer to adult dosing.

Commonly reported side effects of fosamprenavir include: skin rash. See below for a comprehensive list of adverse effects.

Adult patients:
Mild dysfunction (Child-Pugh score ranging from 5 to 6):
Therapy-naive: 700 mg orally twice a day (without ritonavir) or fosamprenavir 700 mg orally twice a day plus ritonavir 100 mg once a day

PI-experienced: Fosamprenavir 700 mg orally twice a day plus ritonavir 100 mg once a day

Moderate dysfunction (Child-Pugh score ranging from 7 to 9):
Therapy-naive: 700 mg orally twice a day (without ritonavir) or fosamprenavir 450 mg orally twice a day plus ritonavir 100 mg once a day

PI-experienced: Fosamprenavir 450 mg orally twice a day plus ritonavir 100 mg once a day

Severe dysfunction (Child-Pugh score ranging from 10 to 15):
Therapy-naive: 350 mg orally twice a day (without ritonavir) or fosamprenavir 300 mg orally twice a day plus ritonavir 100 mg once a day

PI-experienced: Fosamprenavir 300 mg orally twice a day plus ritonavir 100 mg once a day

Pediatric patients: Data not available

Data not available

LactMed Record Number

661

Last Revision Date

20170110

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Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.