Amprenavir

Chemical name

[(1S,2R)-3-[[(4-Аминофенил)с��льфонил]-(2-метилпропи л)амино]-2-гидрокси-1-(ф��нилметил)пропил]карб��миновой acid ( 3S)-тетрагидро-3-фурани��овый broadcast

Gross

C25-H35-N3-O6-S

Characteristics

Inhibitor Vic-proteaza II generation.

Of drugs

Drugs, the antiviral, ingibirutee proteazu HIV. Ingibiruet (transfected competitive inhibitor) proteazu HIV, blocking its ability to degrade полипротеины-предшес��венники and violates the replication of HIV-1 and VIC-2.V studies in vitro demonstrated synergies with similar nukleozidov (3TC, AZT, abacavir) and the protease inhibitor saquinavir. Coupled with the agricultural Vic-proteaza as indinavir, ritonavir and nelfinavir are additive Effect.effectiven at all stages of HIV infection (including early and late stage of the disease) in adults and children, as had been previously antiretroviral drugs, and the past Terapiu.v previous studies in rats and mice (in tests in vitro and in vivo) has been identified and mutagenna genotoksicski Aguosti.wvedenie with four days nepolowhorelam animals with a very high death rate due to appear weak processes biotransformation and elimination. The animals sexually toxic effect manifested clinically significant liver injury (more liver enzymes increase in mass liver necrosis hepatocytes). However, clinical studies have not shown signs of toxic liver damage both during treatment amprenavirom or thereafter. It has been shown that tertogennogo of the rodents (abnormal elongation thymus gland, incomplete skeletal ossification. The female offspring of mice receiving ddI from 7th day of pregnancy until the 22nd day gain in doses exceeding half therapeutic for a person who was a decrease in body weight by 10 to 20%. In experiments on animals (rats) is the ability amprenavira and / or its metabolites enter breast milk and pass through Platzentu.posle intake of fast and well absorbed from the digestive tract. Absolute bioavailability in humans is unknown, it is a form of medication for a / in the (presumably can reach 90%). When taken in the form of the solution as compared to equivalent doses capsules bioavailability less AUC was decreased by 14%, C_max by 19%. The capsules containing 50 and 150 mg amprenavira, bioekvivalentna. Simultaneous eating reduces AUC at 14-25% and C_max about 30% (the change is not clinically meaningful, it is possible admission as erh, and at the time of delivery). Time to C_max 1-2 hrs (capsules), and about 0.75 hrs (solution). The second peak concentration in a 10-12 hrs (due to delayed state or kishechno-pechenocna recycling). Linking blood protein (mainly alfa_1-kislam glikoproteinom, to a lesser extent, the albuminom) - 90%. The apparent mass of the 430-litres. Content in the spinal fluid is less than 1% of the plasma. metabolised in the liver, with the participation of izofermenta CYP3A4 (is a substrate and inhibitor) zitohroma R450. T_1/2 - 7,1-10,6 displayed at the urine (approximately 14% dose including 3% in unmodified form) and faeces (about 75%). In the long ingestion therapeutic doses substantial cumulation not Nabludaetsa.u patients with moderate and severe violations of the liver 3-4 times increased AUC and decreasing �лиренс.Фармакокинети ческие the children are similar to those in adults.

Indications

HIV infection in adults and children (in a combination antiretroviral therapy).

Restrictions on the use of

Capsule-age up to 4 years (the safety and effectiveness of the children are not identified); Solution for the reception inside is a violation of the liver in children older than 4 years.

Pregnancy and lactation

Perhaps only if the effect of therapy outweighs the potential risk to the fetus, as security has not been established (preferably in the form of capsules, as contained in the solution propilenglikol can have toxic effects on the fetus). At the time of treatment should stop breastfeeding.

Contraindications

Hypersensitivity; Simultaneous with terfenadine, cizapridom, astemizolom and rifampitsinom; Up to 4 years (solution for the reception inside because of the presence of propylene).

Side-Effects

For part of the intestine : nausea, vomiting, diarrhoea, Meteorizm.so the nervous system and sensory organs : fatigue, headache, оральная/периоральна�� Paresthesia.prochie : rashes, raising transaminaz and triglycerides; in a few cases, the syndrome Stevens-Johnson.

Specific guidance

The transition to the reception capsules, as soon as the patient is able to swallow.

Patient interaction

Changes (mutually) farmakokinetiku preparations are inductorami, pesticides or substrates izofermenta CYP3A4 R450 (combined with caution because of the possibility of life-threatening toxic effects). Incompatible with rifampitsinom (decreases the amprenavira plasma 80%), triazolam and midazolam (probably prolongirovanie sedative effect), alkaloids LPV. Oppressing metabolism terfenadina, cizaprida, astemizola (possibly threatening the life of a heart rhythm). Increases AUC (200%) and increased side effects rifabutin (if necessary joint reception should be reduced dose of rifabutin). Increases concentration in the blood (increased activity and toxicity) erythromycin, dapson, itrakonazola, benzodiazepines (alprazolam, diazepam, flurazepam, etc.), blocking calcium channels (diltiazem, nikardeepin, nifedipin, nimodipin), statins (atorvastatin, fluvastatin, lovastatin, pravastatin), clozapina, carbamazepina, zimetidina, loratadina, pimozida, racumin etc. concentration in the blood is reduced to a nenukleozidnykh inhibitors reverse transcriptase (efavirenz, nevirapine). Not recommended simultaneous with preparations containing Hypericum perforatum (Hypericum perforatum), as may reduce amprenavira concentration in the blood, and antatidami (as a result of a solid interval method is not less than 1 hour). Ters effectiveness of hormonal contraceptives.

Overdosing

In the case of an overdose of that monitoring of the patient and supportive therapy. Dialysis weak.

Precautions

It should be borne in mind that an increase bleeding, incl. a spontaneous skin bruises, gemartrozov in patients with hemophilia type A and B. In view of the potential reduction in the effectiveness of hormonal contraception for women of childbearing age should be applied negormonale techniques Beremennosti.dl solution : not recommended by the simultaneous solution (to include propilenglikol) with disulfiram or other drugs that weaken the activity алкогольдегидрогеназ ы (eg, metronidazole), as well as containing ethyl alcohol or propilenglikol. There is a need to monitor the status of children (4 years and older) and adults, especially if there is a violation of the functions of the liver or kidney, as well as genetically determined low алкогольдегидрогеназ ы (eg, in patients belonging to ethnic groups of China and Japan), in connection with the possibility of side effects caused propilenglikolem (convulsions, stalemate, tachycardia, giperosmolarnosti, molernkisly acidosis, a toxic effect on the kidneys, gemoliz). Be wary of patients with impaired kidneys.

Dosing and Administration

Inside, regardless of the meal. Adults and children over 13 years of age (weight 50 kg) : the 1200 mg (capsules), or 1400 mg (solution) twice Sutki.deti 4-12 years, and patients weighing less than 50 kg : capsules - 20 mg / kg twice a day, or 15 mg / kg three times per day; Solution at 22.5 mg / kg twice a day, or 17 mg / kg 3 times a day. The maximum daily dose of 2,400 mg (capsules), 2800 mg (solution). Against the backdrop of liver dysfunction reduce the dose, depending on the extent of violations : at a moderate extent, the 450 mg (capsules), or 513 mg (34 ml) twice a day; with a development-300 mg (capsules), or 342 mg (24 ml) twice a day.

Literature

Recommendations for use of antiretroviral drugs in adults and adolescents infected with the human immunodeficiency virus. January 2000 / / Consilium Medicum-Annex. HIV infection .- 2000 .- T. 1 .- N 3 .- C. 3-22.

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