Fosamprenavir

What is Fosamprenavir?

• Fosamprenavir (Lexiva) is an HIV protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Fosamprenavir

Fosamprenavir structure

Fosamprenavir ball-and-stick

What are the uses of this medicine?

• Fosamprenavir (Lexiva) in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection.

• HIV is the virus that causes AIDS (acquired immune deficiency syndrome).
• Lexiva belongs to a class of anti-HIV medicines called protease inhibitors.
• Lexiva is always used with other anti-HIV medicines.
• When used in combination therapy, Lexiva may help lower the amount of HIV found in your blood, raise CD4+ (T) cell counts, and keep your immune system as healthy as possible, so it can help fight infection.
• However, Lexiva does not work in all patients with HIV.

How does this medicine work?

• Fosamprenavir is an antiviral agent.
• Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed.
• Amprenavir is an inhibitor of HIV-1 protease.
• Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who: are taking certain other medicines:

• HALCION® (triazolam; used for insomnia)
• Ergot medicines: dihydroergotamine, ergonovine, ergotamine, and methylergonovine such as CAFERGOT®, MIGRANAL®, D.H.E. 45®, ergotrate maleate, METHERGINE®, and others (used for migraine headaches)
• PROPULSID® (cisapride), used for certain stomach problems
• VERSED® (midazolam), used for sedation
• ORAP® (pimozide), used for Tourette’s disorder

are allergic to Lexiva or any of its ingredients.

• are allergic to AGENERASE (amprenavir).
• You should not take AGENERASE (amprenavir) and Lexiva at the same time.

What drug interactions can this medicine cause?

Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking. Be sure to mention any of the following:

• alfuzosin (Uroxatral)
• cisapride (Propulsid) (not available in the US)
• delavirdine (Rescriptor); ergot medications such as dihydroergotamine
• (D.H.E. 45, Migranal), ergoloid mesylates (Hydergine), ergonovine, ergotamine (Ergomar, in Cafergot, in Migergot), and methylergonovine (Methergine)
• lomitapide (Juxtapid)
• lovastatin (Altoprev)
• midazolam (Versed)
• pimozide (Orap)
• rifampin (Rifadin, Rimactane, in Rifater, in Rifamate)
• sildenafil (only Revatio brand used for lung disease)
• simvastatin (Zocor, in Vytorin)
• St. John's wort
• triazolam (Halcion)
• anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); antidepressants such as amitriptyline, imipramine (Surmontil),
• paroxetine (Brisdelle, Paxil, Pexeva), and trazodone
• atorvastatin (Lipitor, in Caduet)
• antacids containing aluminum and magnesium (Maalox, others)
• benzodiazepines such as alprazolam (Xanax), clorazepate (Gen-Xene, Tranxene), diazepam (Diastat, Valium), and flurazepam
• bosentan (Tracleer)
• calcium channel blockers such as amlodipine (Norvasc, in Exforge, others), diltiazem (Cardizem, Cartia, Tiazac, others), felodipine, isradipine, nicardipine (Cardene), nifedipine (Adalat, Afeditab CR, Procardia), nimodipine (Nymalize), nisoldipine (Sular), and verapamil (Calan, Covera, Verelan, in Tarka)
• colchicine (Colcrys, Mitigare)
• dasatinib (Sprycel)
• dexamethasone
• everolimus (Afinitor)
• fentanyl (Duragesic)
• fluticasone (Flonase, Flovent, in Advair)
• histamine H2-receptor blockers such as cimetidine, famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac); ibrutinib (Imbruvica)
• itraconazole (Onmel, Sporanox)
• medications for irregular heartbeat such as amiodarone (Nexterone, Pacerone), disopyramide (Norpace), lidocaine (Lidoderm; in Xylocaine with Epinephrine), and quinidine (in Nuedexta)
• ketoconazole (Nizoral)
• nilotinib (Tasigna)
• medications for seizures such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, others), phenobarbital, and phenytoin (Dilantin, Phenytek); medications that suppress the immune system such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune), or tacrolimus (Astagraf XL, Prograf)
• methadone (Dolophine, Methadose)
• other medications to treat HIV including dolutegravir (Tivicay), efavirenz (Sustiva, in Atripla), indinavir (Crixivan), lopinavir (Kaletra), maraviroc (Selzentry), nelfinavir (Viracept), nevirapine (Viramune), raltegravir (Isentress), ritonavir (Norvir, in Kaletra, in Viekira Pak), and saquinavir (Invirase)
• certain medications to treat hepatitis C virus including boceprevir (no longer available in U.S.; Victrelis), paritaprevir (in Viekira XR), and simeprevir (no longer available in U.S.; Olysio)
• certain phosphodiesterase inhibitors (PDE-5 inhibitors) used for erectile dysfunction such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra)
• quetiapine (Seroquel)
• rifabutin (Mycobutin)
• salmeterol (Serevent, in Advair)
• tadalafil (Adcirca)vinblastine

Is this medicine FDA approved?

• The US Food and Drug Administration (FDA) approved it on 20 October 2003, while the European Medicines Agency (EMA) approved it on 12 July 2004.

How should this medicine be used?

Recommended dosage: Therapy-Naive Adults:

• Lexiva 1,400 mg twice daily
• Lexiva 1,400 mg once daily plus ritonavir 200 mg once daily
• Lexiva 1,400 mg once daily plus ritonavir 100 mg once daily
• Lexiva 700 mg twice daily plus ritonavir 100 mg twice daily

Protease Inhibitor-Experienced Adults:

• Lexiva 700 mg twice daily plus ritonavir 100 mg twice daily.

Pediatric Patients (2 to 18 years of age):

• Dosage should be calculated based on body weight (kg) and should not exceed adult dose.

Hepatic Impairment:

• Recommended adjustments for patients with mild, moderate, or severe hepatic impairment.

Administration:

• Fosamprenavir comes as a tablet and a suspension (liquid) to take by mouth.
• It is usually taken once or twice a day.
• The tablets can be taken with or without food. In patients at least 18 years old, the suspension should be taken without food.
• In patients younger than 18 years old, the suspension should be taken with food.
• If you are taking the suspension, shake it well before each use to mix the medication evenly.
• If you vomit less than 30 minutes after you take fosamprenavir, you should take another full dose of fosamprenavir.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As 700 mg tablets and 50 mg/mL oral suspension

This medicine is available in fallowing brand namesː

• Lexiva

What side effects can this medication cause?

The most common side effects of this medicine include:

• skin rash
• diabetes and high blood sugar (hyperglycemia)
• increased bleeding problems in some patients with hemophilia
• worse liver disease
• changes in blood tests
• changes in body fat
• kidney stones
• nausea
• vomiting
• diarrhea

What special precautions should I follow?

• Certain drugs should not be coadministered with Lexiva due to risk of serious or life-threatening adverse reactions.
• Lexiva should be discontinued for severe skin reactions including Stevens-Johnson syndrome. Lexiva should be used with caution in patients with a known sulfonamide allergy.
• Use of higher than approved doses may lead to transaminase elevations. Patients with hepatitis B or C are at increased risk of transaminase elevations.
• Patients receiving Lexiva may develop new onset or exacerbations of diabetes mellitus, hyperglycemia , immune reconstitution syndrome, redistribution/accumulation of body fat, and elevated triglyceride and cholesterol concentrations. Monitor cholesterol and triglycerides prior to therapy and periodically thereafter.
• Acute hemolytic anemia has been reported with amprenavir.
• Spontaneous bleeding may occur, and additional factor VIII may be required.
• Cases of nephrolithiasis have been reported with fosamprenavir. If signs or symptoms of nephrolithiasis occur, temporary interruption or discontinuation of therapy may be considered.
• Lexiva should be used with caution in patients with a known sulfonamide allergy. Fosamprenavir contains a sulfonamide moiety.
• Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Lexiva.
• Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance,” have been observed in patients receiving antiretroviral therapy, including Lexiva.
• Treatment with Lexiva plus ritonavir has resulted in increases in the concentration of triglycerides and cholesterol. Triglyceride and cholesterol testing should be performed prior to initiating therapy with Lexiva and at periodic intervals during therapy.
• Patients should be instructed to shake the bottle vigorously before each use and that refrigeration of the oral suspension may improve the taste for some patients.
• Patients should be informed that Lexiva is not a cure for HIV infection and that they may continue to develop opportunistic infections and other complications associated with HIV disease.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• transaminase elevations

Management of overdosage:

• There is no known antidote for Lexiva.
• It is not known whether amprenavir can be removed by peritoneal dialysis or hemodialysis.
• If overdosage occurs, the patient should be monitored for evidence of toxicity and standard supportive treatment applied as necessary.

Can this medicine be used in pregnancy?

• Pregnancy Category C.
• There are no adequate and well-controlled studies in pregnant women.
• Lexiva should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Can this medicine be used in children?

• No data are available for pediatric patients <2 years of age.
• The safety, pharmacokinetic profile, and virologic response of Lexiva Oral Suspension and Tablets were evaluated in pediatric patients 2 to 18 years of age.

What are the active and inactive ingredients in this medicine?

Active Ingredient:

• fosamprenavir calcium.

Inactive Ingredients:

• colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and povidone K30. The tablet film-coating contains the inactive ingredients hypromellose, iron oxide red, titanium dioxide, and triacetin.

Who manufactures and distributes this medicine?

• Lexiva and AGENERASE are registered trademarks of GlaxoSmithKline.
• GlaxoSmithKline Vertex Pharmaceuticals Incorporated
• Research Triangle Park, NC 27709 Cambridge, MA

What should I know about storage and disposal of this medication?

• Lexiva Tablets should be stored at room temperature between 59° and 86°F (15° to 30°C).
• Keep the container of Lexiva Tablets tightly closed.
• Lexiva Oral Suspension may be stored at room temperature or refrigerated.
• Refrigeration of Lexiva Oral Suspension may improve taste for some patients.
• Do not freeze.
• Keep Lexiva and all medicines out of the reach of children.
• Do not keep medicine that is out of date or that you no longer need.
• Be sure that if you throw any medicine away, it is out of the reach of children.

• Dailymed label info on Fosamprenavir
• FDA Fosamprenavir