Lexiva


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Related to Lexiva: Telzir

fosamprenavir calcium

Lexiva, Telzir (CA) (UK)

Pharmacologic class: Human immunodeficiency virus (HIV) protease inhibitor

Therapeutic class: Antiretroviral

Pregnancy risk category C

Action

Blocks HIV reverse transcriptase, an enzyme necessary for HIV replication. Blockade leads to reduced viral load and increased CD4+ cell count, helping to ward off other infections when drug is given with other antiretrovirals.

Availability

Oral suspension: 50 mg/ml

Tablets: 700 mg

Indications and dosages

HIV-1 infection, given in combination with other antiretrovirals

Adults (therapy-naive): 1,400 mg P.O. b.i.d. or 1,400 mg P.O. daily given with rotonavir 200 mg daily; or 1,400 mg P.O. daily with ritonavir 100 mg daily; or 700 mg b.i.d. with ritonavir 100 mg b.i.d.

Adults (protease inhibitor-experienced): 700 mg P.O. b.i.d. with ritonavir 100 mg b.i.d.

Children ages 2 and older: Calculate dosage based on weight, but don't exceed adult dosage. When given in combination with ritonavir, fosamprenavir tablets may be used for children weighing at least 39 kg (86 lb); ritonavir capsules may be used for those weighing at least 33 kg (73 lb). See table below for more information.

Dosage adjustment

• Mild, moderate and severe hepatic impairment

Contraindications

• Hypersensitivity to drug or amprenavir
• Concomitant use of drugs that depend highly on CYP3A4 for clearance and for which elevated blood levels may lead to serious or life-threatening events (such as some antiarrhythmics, antimycobacterials, ergot derivatives, GI motility agents, HMG co-reductase inhibitors, neuroleptics, nonnucleoside reverse transcriptase inhibitors, and sedative-hypnotics)
• Coadministration with ritonavir in patients receiving flecainide or propafenone
• Concomitant use of St. John's wort

Precautions

Use cautiously in:
• sulfa allergy
• hepatic impairment
• diabetes mellitus
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 2 (safety and efficacy not established).

Administration

• Assess cholesterol and triglyceride levels and hepatic function tests before starting therapy.
• Give oral suspension to adults without food and to children with food.
• Administer tablets with or without food.

Adverse reactions

CNS: headache

GI: nausea, vomiting, diarrhea, abdominal pain

GU: nephrolithiasis

Hematologic: spontaneous bleeding (in hemophiliacs), acute hemolytic anemia

Metabolic: diabetes mellitus, body fat redistribution or accumulation

Skin: pruritus, maculopapular rash, severe or life-threatening skin reactions

Other: immune reconstitution syndrome

Interactions

Drug-drug.Alfuzosin: increased alfuzosin level, resulting in hypotension

Antimycobacterials (rifampin): decreased fosamprenavir blood level, possible loss of virologic response and possible resistance to fosamprenavir or to its protease inhibitor class (concomitant rifampin use contraindicated)

Amitriptyline, amlodipine, atorvastatin, benzodiazepines (alprazolam, clorazepate, diazepam, flurazepam), bepridil, cyclosporine, diltiazem, esomeprazole, felodipine, fluticasone, imipramine, isradipine, itraconazole, ketoconazole, lidocaine (systemic), nicardipine, nifedipine, nimodipine, nisoldipine, quinidine, rapamycin, rosuvastatin, tacrolimus, trazodone, verapamil: increased blood levels of these drugs

Carbamazepine, cimetidine, dexamethasone, efavirenz, famotidine, nizatidine, phenobarbital, phenytoin, ranitidine, saquinavir: decreased fosamprenavir blood levels

Cisapride, pimozide: possible serious or life-threatening reactions, such as arrhythmias (concomitant use with fosamprenavir contraindicated)

CYP3A4 inducers: significant decrease in fosamprenavir blood level and reduced therapeutic effect

CYP3A4 inhibitors: increased fosamprenavir blood level and increased incidence of adverse effects

Delavirdine: possible loss of virologic response and possible resistance to delavirdine

Ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine): serious or life-threatening reactions such as acute ergot toxicity (concomitant use with fosamprenavir contraindicated)

Flecainide, propafenone: increased risk of serious, life-threatening cardiac arrhythmias (concomitant use contraindicated)

HIV protease inhibitors (lopinavir/ritonavir): decreased blood levels of both drugs

Hormonal contraceptives: possible changes in hormone levels and liver enzyme elevations (if used in combination with fosamprenavir and ritonavir)

Indinavir, nelfinavir: increased fosamprenavir blood level

Lovastatin, simvastatin: increased risk of serious reactions such as myopathy, including rhabdomyolysis (concomitant use with fosamprenavir contraindicated)

Methadone: decreased methadone blood level

Midazolam, triazolam: serious or life-threatening reactions, such as prolonged or increased sedation or respiratory depression (concomitant use with fosamprenavir contraindicated)

Nevirapine: decreased fosamprenavir and increased nevirapine blood levels

Paroxetine (in combination with fosamprenavir and ritonavir): decreased paroxetine blood level

PDE5 inhibitors (such as sildenafil): increased risk of adverse reactions (such as hypotension, visual changes, priapism)

Phenytoin (in combination with fosamprenavir and ritonavir): increased fosamprenavir, decreased phenytoin blood level

Rifabutin: increased rifabutin and metabolite blood levels

Warfarin: altered blood levels

Drug-diagnostic tests.ALT, AST, glucose, lipase, triglycerides: increased levels

Drug-food. High-fat meal: reduced fosamprenavir effect

Drug-herbs.St. John's wort: significant decrease in fosamprenavir blood level with loss of therapeutic effect and possible resistance to fosamprenavir or its protease inhibitor class (concomitant use contraindicated)

Patient monitoring

Monitor patient closely for rash; discontinue drug if severe rash or moderate rash plus systemic symptoms develops.
• Be aware that immune reconstitution syndrome has occurred in patients treated with combination antiretroviral therapy. During initial phase of such therapy, patients whose immune system responds may develop inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium complex, cytomegalovirus, Pneumocystis jiroveci pneumonia, and tuberculosis), which may necessitate further evaluation and treatment.
• Closely monitor International Normalized Ratio if patient is receiving warfarin concomitantly.
• Closely monitor hepatic function tests during therapy.
• Periodically monitor cholesterol and triglyceride levels.
• Watch for new-onset diabetes mellitus, exacerbation of preexisting diabetes, and hyperglycemia.

Patient teaching

• Advise adult patient to take oral suspension without food.
• Tell caregivers to give oral suspension with food to child.
• Instruct patient to shake oral suspension bottle vigorously before each use; mention that refrigeration may improve taste.
• Instruct patient to take tablets with or without food.

Advise patient to immediately report new infections or rash, which may become severe and potentially life-threatening.
• Inform patient that drug doesn't cure HIV infection or reduce risk of passing HIV to others through sexual contact, needle sharing, or blood exposure.
• Tell patient that drug may cause body fat redistribution or accumulation and that the cause and long-term health effects of this condition aren't known.
• Advise patient that drug may interact with many drugs and herbs (especially St. John's wort). Caution patient to discuss use of herbs and other drugs with prescriber.
• Advise male receiving PDE5 inhibitors (such as sildenafil, tadalafil, vardenafil) that he may be at increased risk for adverse events, including hypotension, visual changes, and priapism. Instruct him to promptly report symptoms.
• Advise patient taking hormonal contraceptives to use alternative contraception during therapy because hormone levels may be altered and liver enzyme levels may increase.
• Advise female to notify prescriber if she is pregnant or intends to become pregnant.
• Instruct women not to breastfeed while taking drug.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, food, and herbs mentioned above.

fosamprenavir

(fos-am-pren-a-veer) ,

Lexiva

(trade name),

Telzir

(trade name)

Classification

Therapeutic: antiretrovirals
Pharmacologic: protease inhibitors
Pregnancy Category: C

Indications

With other antiretrovirals in the management of HIV infection.

Action

Inhibits the action of HIV protease and prevents the cleavage of viral polyproteins.

Therapeutic effects

Increased CD4 cell counts and decreased viral load with subsequent slowed progression of HIV and its sequelae.

Pharmacokinetics

Absorption: Fosamprenavir is a prodrug. Following oral administration, it is rapidly converted to amprenavir by the gut lining during absorption.
Distribution: Penetration into RBCs is concentration dependent.
Metabolism and Excretion: Mostly metabolized the liver (CYP3A4 enzyme system). Minimal renal excretion.
Half-life: 7.7 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POrapid1.5–4 hr12–24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity, sulfonamide/sulfa hypersensitivity;Severe hepatic impairment;Concurrent use of flecainide, propafenone, rifampin, ergot derivatives, St. John's wort, lovastatin, simvastatin, pimozide, delavirdine, sildenafil (Revatio), alfuzosin, midazolam or triazolam.
Use Cautiously in: Geriatric: Consider age-related ↓ in body mass, cardiac/hepatic/renal impairment, concurrent illness and medications;Hepatic impairment;Concurrent use of medications handled by or affecting the CYP3A4 enzyme system (may require serum level monitoring, dose or dosing interval alterations); Obstetric / Lactation: Safety not established; breast feeding not recommended in HIV-infected patients Pediatric: Treatment-naïve children <4 wk and protease inhibitor experienced children <6 mo (safety not established)

Adverse Reactions/Side Effects

Reflects use with other antiretrovirals

Central nervous system

  • headache (most frequent)
  • fatigue
  • mood disorders

Cardiovascular

  • myocardial infarction (life-threatening)

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • abdominal pain
  • ↑ liver enzymes

Dermatologic

  • rash (most frequent)

Endocrinologic

  • glucose intolerance

Genitourinary

  • nephrolithiasis

Hematologic

  • neutropenia

Metabolic

  • ↑ cholesterol
  • fat redistribution
  • ↑ triglycerides

Miscellaneous

  • allergic reactions including stevens-johnson syndrome (life-threatening)
  • angioedema (life-threatening)
  • immune reconstitution syndrome

Interactions

Drug-Drug interaction

Amprenavir, the active moiety of fosamprenavir is metabolized by CYP3A4 ; it also inhibits and induces this enzyme system. The action of any other medication that is also handled by or affects this system may be altered by concurrent use.↑ blood levels and risk of toxicity from flecainide, propafenone, rifampin, ergot derivatives (dihydroergotamine, ergotamine, ergonovine, methylergonovine ), lovastatin, simvastatin, pimozide, delavirdine, sildenafil (Revatio), alfuzosin, midazolam, or triazolam ; concurrent use contraindicated.Blood levels are ↓ by efavirenz (additional ritonavir may be required when used together), nevirapine, lopinavir/ritonavir, saquinavir, carbamazepine, phenobarbital, phenytoin, dexamethasone, histamine H2-receptor antagonists, and proton-pump inhibitors ; monitor for ↓ antiretroviral activity.Concurrent use with raltegravir may ↓ levels of amprenavir and raltegravir.Levels are ↑ by indinavir and nelfinavir.May ↓ methadone and paroxetine levels.↑ levels and risk of toxicity from amiodarone, lidocaine, quinidine (monitor blood levels), ketoconazole, and itraconazole (dose of itraconazole or ketoconazole should not exceed 200 mg/day when fosamprenavir is used with ritonavir or 400 mg/day when used without), rifabutin (monitor for neutropenia, ↓ rifabutin dose by 50% when used with fosamprenavir or by 75% when used with fosamprenavir with ritonavir), cyclosporine or tacrolimus (monitor blood levels of immunosuppressants), calcium channel blockers (clinical monitoring recommended), some benzodiazepines (alprazolam, clorazepate, diazepam, flurazepam ; dose ↓ of benzodiazepine may be needed), sildenafil, tadalafil, vardenafil (use cautiously; ↓ dose of sildenafil to 25 mg every 48 hr, for tadalafil single dose should not exceed 10 mg in any 72-hr period, dose of vardenafil should not exceed 2.5 mg every 24 hr if used without ritonavir or 2.5 mg every 72 hr with ritonavir with monitoring for toxicity) and tricyclic antidepressants (blood level monitoring recommended).↑ risk of myopathy with atorvastatin ; do not exceed atorvastatin dose of 20 mg/day.May alter the effects of warfarin (monitor INR) or hormonal contraceptives (use alternative method of contraception).May ↑ fluticasone levels; concurrent use not recommended.May ↑ risk of adverse effects with salmeterol ; concurrent use not recommended.May ↑ bosentan levels; initiate bosentan at 62.5 mg once daily or every other day; if patient already receiving bosentan, discontinue bosentan at least 36 hr before initiation of fosamprenavir and then restart bosentan at least 10 days later at 62.5 mg once daily or every other day.May ↑ tadalafil (Adcirca) levels; initiate tadalafil (Adcirca) at 20 mg once daily; if patient already receiving tadalafil (Adcirca), discontinue tadalafil (Adcirca) at least 24 hr before initiation of fosamprenavir and then restart tadalafil (Adcirca) at least 7 days later at 20 mg once daily.May ↑ colchicine levels; ↓ dose of colchicine; do not administer colchicine if patients have renal or hepatic impairment.Concurrent use with telaprevir may ↓ levels of fosamprenavir and telaprevir; avoid concurrent useConcurrent use with boceprevir may ↓ levels of fosamprenavir and boceprevir; avoid concurrent useConcurrent use with maraviroc may ↓ fosamprenavir levels and ↑ maraviroc levels; adjust maraviroc dose to 150 mg twice dailyConcurrent use of St. John's wort is contraindicated; ↓ blood levels and may lead to ↓ virologic response.

Route/Dosage

Oral (Adults) Treatment-naive patients without ritonavir—1400 mg twice daily; Treatment-naive patients with ritonavir—1400 mg once daily with ritonavir 100 or 200 mg once daily, or 700 mg twice daily with ritonavir 100 mg twice daily. Protease inhibitor–experienced patients—700 mg twice daily with ritonavir 100 mg twice daily. If efavirenz is added to a once daily regimen using both fosamprenavir and ritonavir, an additional 100 mg of ritonavir (total of 300 mg) should be given.
Oral (Children ≥4 wk [Treatment-naive] or ≥6 mo [Protease inhibitor-experienced]) ≥20 kg—18 mg/kg twice daily (not to exceed 700 mg twice daily) with ritonavir 3 mg/kg twice daily (not to exceed 100 mg twice daily); 15–19.9 kg—23 mg/kg twice daily (not to exceed 700 mg twice daily) with ritonavir 3 mg/kg twice daily (not to exceed 100 mg twice daily); 11–14.9 kg—30 mg/kg twice daily (not to exceed 700 mg twice daily) with ritonavir 3 mg/kg twice daily (not to exceed 100 mg twice daily); <11 kg—45 mg/kg twice daily (not to exceed 700 mg twice daily) with ritonavir 7 mg/kg twice daily (not to exceed 100 mg twice daily)

Hepatic Impairment

Oral (Adults) Mild hepatic impairment—700 mg twice daily without ritonavir (therapy-naive) or 700 mg twice daily with ritonavir 100 mg once daily (therapy-naive or protease inhibitor experienced); Moderate hepatic impairment—700 mg twice daily without ritonavir (therapy-naive) or 450 mg twice daily with ritonavir 100 mg once daily (therapy-naive or protease inhibitor experienced); Severe hepatic impairment—350 mg twice daily without ritonavir (therapy-naive) or 300 mg twice daily with ritonavir 100 mg once daily (therapy-naive or protease inhibitor experienced).

Availability

Tablets: 700 mg
Oral suspension: 50 mg/mL

Nursing implications

Nursing assessment

  • Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections throughout therapy.
  • Assess patient for allergy to sulfonamides. May exhibit cross-sensitivity.
  • Assess patient for skin reactions throughout therapy. Reactions may be severe and life threatening. Discontinue therapy if severe reactions or moderate rashes with systemic symptoms occur.
  • Lab Test Considerations: Monitor viral load and CD4 cell count regularly during therapy.
    • May cause ↑ serum glucose cholesterol, and triglyceride levels.
    • May cause ↑ AST and ALT levels.
    • May cause neutropenia.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Do not confuse Lexiva with Pexeva (paroxetine).
  • Oral: Tablets may be administered with or without food. Oral suspension should be taken without food in adults and with food in children. Shake suspension vigorously before administering. Refrigeration of suspension may improve taste. If emesis occurs within 30 minutes after dosing, redose.

Patient/Family Teaching

  • Emphasize the importance of taking fosamprenavir as directed. Advise patient to read the Patient Information that comes with the prescription prior to initiation of therapy and with each prescription refill in case of changes. Fosamprenavir must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered if within 4 hr of scheduled dose. If more than 4 hr, skip dose, then return to regular schedule. If a dose is skipped, do not double the next doses.
  • Instruct patient that fosamprenavir should not be shared with others.
  • Inform patient that fosamprenavir does not cure AIDS or prevent associated or opportunistic infections. Fosamprenavir does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of fosamprenavir are unknown at this time.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications because of potentially serious drug interactions.
  • Instruct patient to notify health care professional if nausea, vomiting, diarrhea, or rash occurs.
  • Inform patient that redistribution and accumulation of body fat may occur, causing central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance. The cause and long-term effects are not known.
  • May decrease effectiveness of hormonal contraceptives; advise patient to use a nonhormonal form of contraception during therapy.
  • Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

Evaluation/Desired Outcomes

  • Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
  • Decrease in viral load and increase in CD4 cell counts.

Lexiva

a trademark for fosamprenavir.
References in periodicals archive ?
LEXIVA is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product or to amprenavir.
LEXIVA should be used with caution in patients with a known sulfonamide allergy.
LEXIVA with Epivir(R) (lamivudine) and Abacavir in ART-Naive patients) was announced today by GlaxoSmithKline and Vertex Pharmaceuticals Incorporated , the companies that co-discovered LEXIVA.
Adverse events in this study were consistent with those described in the product information for LEXIVA and Kaletra.
LEXIVA is a protease inhibitor that was co-discovered by GlaxoSmithKline and Vertex Pharmaceuticals Incorporated.
In patients taking Lexiva without ritonavir, FDA recommends that if the original Colcrys regimen was 0.
The FDA-approved "label" for Lexiva (the official prescribing information for physicians) urges caution in using the drug together with proton-pump inhibitors, because experience with other drugs suggested that the blood level of the antiviral might be decreased, making it less effective (no test with Lexiva and Nexium had been done).
Vertex co-discovered the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.
Food and Drug Administration approved once-daily LEXIVA 1400 mg with 100mg of ritonavir in adult patients who had not previously taken a protease inhibitor (PI).
Food and Drug Administration approved the protease inhibitor Lexiva (generic name fosamprenavir, also called 908).
Additional Studies Evaluate a Lower Dose of Ritonavir(R) for Boosting LEXIVA
Lexiva is a registered trademark of the GlaxoSmithKline group of companies.