Fosamprenavir - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Means for the treatment of HIV infection

Included in the formulation

Telzir

pills inwards

VeeV Helsker United Kingdom Limited United Kingdom

Telzir®

suspension inwards

VeeV Helsker United Kingdom Limited United Kingdom

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

АТХ:

J.05.A.E. Protease Inhibitors

J.05.A.E.07 Fosamprenavir

Pharmacodynamics:An antiviral (HIV) agent, a protease inhibitor, an inactive precursor of amprenavir. It hydrolyzes with the formation of inorganic phosphate and active amprenavir. Amprenavir is a non-peptide competitive HIV protease inhibitor that prevents the cleavage of polypeptide precursors necessary for viral replication. Himself fosamprenavir practically does not have antiviral activity, and its active metabolite amprenavir, is highly effectivem selective inhibitor of HIV-1 and HIV-2 replication.

Pharmacokinetics:Absorption is rapid through the intestinal epithelium, pre-hydrolyzed to amprenavir and organic phosphate. Food, when taken in tablets does not affect the pharmacokinetics, when taking the suspension - reduces the AUC by 28%, the maximum concentration by 46%. An empty bowel AUC is the same for any dosage form, maximum concentration 14% higher for the suspension. Maximum concentration - 4.06-5.72 μg / ml, the period of achievement maximum concentration - 0,8-4 h, the minimum concentration - 0,27-0,46 mkg / ml, AUC - 13,8-19,6 mkg h / ml. In liver failure, a 2.5 and 4.5-fold increase in AUC in patients with moderate or severe cirrhosis, respectively. The volume of distribution is 6 l / kg. Linkage with proteins - 90% (mainly with alpha-1-acid glycoprotein, to a lesser extent - with albumin). Metabolized mainly in the liver with the participation of the enzyme CYP3A4. The clearance of amprenavir is significantly reduced in patients with cirrhosis. The half-life is 7.7 hours. It is excreted through the intestine - 75% (in the form of metabolites), kidneys (14% in the form of metabolites, 1% - unchanged).

Indications:HIV as part of combination therapy with other antiretroviral agents.

ICD-10

I.B20-B24 Disease caused by the human immunodeficiency virus [HIV]

Contraindications:Hypersensitivitysimultaneous administration with substrates of cytochrome CYP3A4, with ritonavir and preparations, the metabolism of which depends on CYP2D6 (flecainide, propafenone), with rifampicin, ergotamine, dihydroergotamineom, ergonovine, methylergonovine, cisapride, lovastatin, simvastatin, pimozide, midazolam, triazolam, bepridil; with preparations containing St. John's wort, sildenafil, vardenafil, delavirdine,with ritonavir in patients with severe hepatic impairment.

Carefully:Hypersensitivityto sulphonamides (the possibility of cross- allergies), simultaneous administration with ritonavir and fluticasone or other glucocorticosteroids metabolizingCYP3A4, with atorvastatin, with ritonavir in patients with mild or moderate hepatic impairment.

Pregnancy and lactation:

Recommendations for FDA - Category C. Qualitative and well-controlled studies on humans have not been conducted. When administered to animals, the frequency of miscarriages increases, the development of the bone system is disturbed. Use with caution!

There is no information on the penetration into breast milk.

Dosing and Administration:

Inside, tablets are taken regardless of food intake, suspension - on an empty stomach.

Patients who did not receive protease inhibitor therapy: 1,400 mg twice daily; or 1400 mg once a day in combination with ritonavir 200 mg once a day; or 700 mg twice a day in combination with ritonavir 100 mg twice a day.

Patients who received prior therapy with protease inhibitors: 700 mg twice daily in combination with ritonavir 100 mg twice a day.

Both dosing regimens are suitable for combination therapy with other antiretroviral agents.

For patients with mild or moderate hepatic insufficiency (5-8 on the Child-Pug scale), the daily dose is 1200 mg divided into 2 doses. For patients with severe hepatic insufficiency (9-12 on the Child-Pug scale), the daily dose is 900 mg divided into 2 doses. For patients with renal insufficiency, dose adjustment is not required.

Side effects:

From the side nervous system: often a headache.

From the side digestive system: diarrhea, nausea, vomiting, abdominal pain.

From the side musculoskeletal system: myalgia; myositis; rhabdomyolysis.

From the skin: rash (erythematous or maculopapular, including with itching); Stevens-Johnson syndrome (less than 1%).

From the side metabolism: hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia, development or exacerbation of existing diabetes mellitus.

Other: weakness, redistribution of fat (reduction of subcutaneous tissue on the periphery and in the face, an increase in the abdominal area, hypertrophy of the mammary glands, fat accumulation in the dorso-cervical region, in internal organs); increased spontaneous bleeding in patients with hemophilia.

Laboratory indicators: increased activity of ALT, ACT, creatine phosphokinase, lipase; hypertriglyceridemia, hypercholesterolemia (less than 2%).

Overdose:

Not described.

Treatment is symptomatic.

Interaction:

Abacavir, zidovudine - Induction of glucuronidation, a decrease in their concentration.

Amiodarone, cisapride, dihydroergotamine, ergonovine, methylergonovine, ergotamine, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, simvastatin, St. John's wort (Hypericum perforatum), trazoles - increasing their concentration and the development of severe side effects. Do not use together!

Atovokvon, дивалпроекс, lamotrigine, phenytoin, warfarin - monitoring of joint therapy.

Atorvastatin, bupropoin, carbamazepine, clonazepam, clorazepate, ciclosporin, dexamethasone, diazepam, diltiazem, disopyramide, dronabinol, estazolam, ethosuximide, flurazepam, lidocaine, mexiletine, methamphetamine, metoprolol, nefazodone, nefidipin, perphenazine, prednisone, propoxyphene, risperidone, quinine, selective serotonin reuptake inhibitors, sirolimus, tacrolimus, timolol, thioridazine, tramadol, tricyclic antidepressants, verapamil, zolpidem - monitoring of joint therapy; it is necessary to reduce the dose of these funds.

Didanosine, oral contraceptives containing ethinyl estradiol, methadone, theophylline - decrease in their concentration and effect; should not be used together or it is necessary to change the dose regimen, to carry out pharmacotherapeutic monitoring.

Disulfiram, metronidazole - Development of disulfiram-like reactions in connection with the content of ethanol in the dosage form of fosamprenavir.

Clarithromycin, desipramine, rifabutin, sildenafil, indinavir and saquinavir (in low doses), ketoconazole, meperidine - increasing their concentration (or their metabolites); should reduce the dose.

Rifampicin - reduced concentration and effect of fosamprenavir.

Special instructions:

Little-studied means.

The safety and efficacy of fosamprenavir in children and adolescents has not been established.

Data on the safety of fosamprenavir in patients with impaired liver and / or kidney function are limited.

There are reports that patients with hemophilia type A and B who took protease inhibitors increased hemorrhagic complications, including spontaneous cutaneous hematomas and hemarthroses.Some of these patients were additionally given factor VIII. In more than half of the cases described, treatment with protease inhibitors was continued or resumed after their temporary withdrawal. Patients with hemophilia should be warned about a possible increase in bleeding during treatment with protease inhibitors.

Treatment with antiretroviral drugs, including fosamprenavir, does not prevent the risk of HIV transmission to other people during sexual intercourse or blood transfusion, so patients should take appropriate precautions.

Impact on the ability to drive vehicles and manage mechanisms.

Special studies to study the impact on the ability to drive and work with moving machinery and complex equipment was not carried out.

Instructions

Fosamprenavir (Fosamprenavirum)