Amprenavir (Amprenavirum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
Read on
Clinical and pharmacological group: & nbsp

Means for the treatment of HIV infection

Included in the formulation
АТХ:

J.05.A.E.   Protease Inhibitors

J.05.A.E.05   Amprenavir

Pharmacodynamics:

Competitive inhibition of protease human immunodeficiency virus (HIV): termination of the cleavage of the Gag-Pol polypeptide by viral proteins (reverse transcriptase, proteases and integrases). Formation of inactive virus particles that are not capable of infecting new cells.

Effective at all stages HIVInfections (including early and late stages of the disease) in adults and children, whether not previously taking antiretroviral drugs, or after previous therapy.

Pharmacokinetics:

Bioavailability - 35-90% (decreases with admission with fatty foods). The connection with plasma proteins is 90%. Time to reach of the maximum concentration - 1-2 hours (capsules) and about 0.75 hours (solution). The second peak concentration is observed after 10-12 hours (due to delayed absorption or intestinal-hepatic recirculation). Biotransformation occurs in the liver (CYP3A4). The half-life is 7,1-10,6 hours. It is excreted with feces (75%) and urine (in unchanged form - 3%, in the form of metabolites - 14%).

Indications:

HIV-infection in adults and children (as part of combined antiretroviral therapy).

ICD-10

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

Contraindications:

Individual intolerance.

Simultaneous reception with terfenadine, cisapride, astemizole and rifampicin.

Age to 4 years (solution for oral administration, because of the presence of propylene glycol in it).

Carefully:

Hepatic and / or renal insufficiency.

Deficiency of vitamin K.

Hypersensitivity to sulfonamides.

Pregnancy and lactation:

Use during pregnancy is possible only if the expected effect of therapy exceeds the potential risk to the fetus, because safety is not established (preferably in the form of capsules, since the propylene glycol contained in the solution may have a toxic effect on the fetus).

Action category for the fetus by Food and Drug Administration (US Food and Drug Administration) - C.

For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

HIV infection (as part of a combination therapy): inside (regardless of food intake). At a body weight of more than 50 kg - 1200 mg (in capsules) 2 times a day or 1400 mg (93.3 ml solution for ingestion) 2 times a day; with a body weight of less than 50 kg - 20 mg / kg 2 times a day or 15 mg / kg 3 times (maximum daily dose of 2,400 mg). Solution for ingestion is taken at 225 mg / kg (1.5 ml / kg) 2 times a day or 17 mg / kg (1.1 ml / kg) 3 times (maximum daily dose - 2,800 mg).

If the liver function is impaired, the dose should be reduced: with moderate disruption of the function, 450 mg (in capsules) twice a day, with severe violation, 300 mg twice a day; in the form of a solution for oral administration - 513 mg (34 ml) 2 times a day and 342 mg (23 ml) 2 times (respectively, the degree of impaired function).

Amprenavir in the form of a solution for oral administration is prescribed for children and adults who are difficult to swallow capsules (the solution is stopped as soon as the patient can swallow the capsules).

Side effects:

Digestive system: nausea, vomiting, diarrhea, flatulence.

Nervous system: increased fatigue, headache, oral / perioral paresthesia.

Allergic reactions: rash.

Other: increased levels of transaminases and triglycerides; in isolated cases - Stevens-Johnson syndrome.

Overdose:

In case of an overdose it is recommended to monitor the patient's condition and supportive therapy. Dialysis is ineffective.

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), trazolam - increasing their concentration and development of serious 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 drug formamprenavir.

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

Rifampicin - decreased concentration and effect of amprenavir.

Special instructions:
Instructions
Up