Description
Pharmacological action
Pharmacodynamics. Alprostadil, the active substance of the drug vasostenone, is a vasodilator. It enhances blood flow through dilatation of arterioles and anterior capillary sphincter. Alprostadil improves microcirculation and rheological properties of blood. After intravenous administration in healthy volunteers and patients, an increase in the elasticity of red blood cells and inhibition of their ex vivo aggregation is observed. Alprostadil effectively inhibits platelet activation in vitro. This effect also extends to the form, aggregation, secretion of substances contained in the granules, and the release of thromboxane – substances facilitating aggregation. The drug leads to a decrease in the formation of arterial blood clots. In humans, it stimulates fibrinolysis and increases certain indicators of endogenous fibrinolysis (plasminogen, plasmin, tissue plasminogen activator activity). Pharmacokinetics After intravenous administration of alprostadil at a dose of 60 Ñg / 2 h, the maximum plasma concentration of healthy volunteers was 6 pg / ml higher than the maximum concentration in the placebo phase (2.4 pg / ml). The half-life of the alpha phase is approximately 0.2 minutes (calculated value), and approximately 8 minutes during the beta phase. Thus, equilibrium concentration is reached shortly after the start of the infusion. Alprostadil is metabolized in the lungs – about 80-90% during the first passage. Primary metabolites which are formed during the first passage – 15-keto-PGE 1, PGE 0 (13.14-dihydroPGE 1) and 15-keto-PGE 0 (13.14-dihydro-15-keto-PGE 1) – in turn, experiencing further decay, in particular by beta oxidation and omega oxidation. Metabolites are excreted in urine (88%) and feces (12%). A full withdrawal takes 72 hours. Primary metabolites of only 15-keto-PGE 0 can be detected in vitro using lung homogenates. After applying alprostadil 60 Ñg / 2 h to healthy volunteers, PGE 0 reaches a maximum plasma concentration of 11.8 pg / ml after the placebo phase (1.7 pg / ml), with a half-life of approximately 2 minutes at the alpha phase and approximately 33 min at the beta phase. T max is achieved after 119 minutes The corresponding values ² ¹ ² ¹for 15-keto-PGE 0 are: C max 151 pg / ml (placebo 8 Ñg / ml), t about 2 min, t 20 min and T max 106 min. Alprostadil is 93% bound to the macromolecular components of blood plasma.
Indications
Treatment of chronic obliterating diseases of the peripheral arteries of stage III and IV in adults, if the procedure is not possible, has a vasodilator effect, or if the procedure was unsuccessful. The introduction is not recommended for the treatment of chronic obliterating diseases of the peripheral arteries of stage IV.
Recommendations for use
Vasostenone is intended for intra-arterial or intravenous administration in the form of a solution. For the introduction of the drug, it is recommended to use an automatic syringe or infusion pump and a catheter for infusion therapy. The dosing schedule contains daily doses calculated for patients with normal renal function, whose body weight is 70 kg. In patients with impaired renal function, if the creatinine level in the blood exceeds the norm (in men> 97 μmol / L, in women> 80 μmol / L), daily doses should be halved at the beginning of therapy. Depending on the clinical condition of the patient, within 2-3 days you can increase the dose to one intended for patients with normal renal function. intraarterial administration With intraarterial administration, the likelihood of adverse reactions is higher in the case of short-term infusion. Based on this, in order to ensure patient safety, it is recommended to start infusion with small doses and, in the absence of adverse reactions, increase the dose. For the prevention of thromboembolic complications, the introduction of 15,000 units of heparin per day is recommended. Intraarterial administration during 12:00. The daily dose is 5-30 μg, the recommended dosage is 0.1 – 0.6 ng / kg / min. When choosing a daily dose (5-30 μg), vasostenone should be diluted in 50 ml of 0.9% NaCl and injected within 12:00 with an automatic syringe. Intraarterial administration within 1-2 hours. The daily dose is 10 – 20 μg, the recommended dosage at a dose of 10 μg is 1.2 ng / kg / min at a dose of 20 μg is 2.4 ng / kg / min. Intra-arterial administration during surgery During reconstructive surgery, 5 40 μg of the drug diluted in 50 ml of 0.9% NaCl is administered intravenously. Introduction Daily dose – 40 micrograms of alprostadil 2 times a day or 60 micrograms of alprostadil 1 time per day. The recommended dosage is 4.7 ng / kg / min. 40 μg of alprostadil should be diluted in 50 – 250 ml of 0.9% NaCl solution and injected into a vein for 2:00 in the morning and evening. 60 μg of alprostadil should be diluted in 50 – 250 ml of 0.9% NaCl solution and injected into a vein within 3:00 1 time per day. Children. Do not use in children.
Special instructions
Patients at risk should be treated with the drug with caution carefully observing the patient during each dose. Patients prone to heart failure by age and patients with coronary heart disease should be monitored in a hospital during treatment and for one day after drug discontinuation. With caution, prescribe the drug for arterial hypotension. To prevent overhydration, infusion volumes should not exceed 50-100 ml per day (administration by means of an infusion device). You should also adhere to the recommendations on the duration of the infusion (see Section “Dosage and Administration”). Monitoring of the parameters of the patient’s cardiovascular system (blood pressure and heart rate), control of body weight, fluid balance, central venous pressure and echocardiography are necessary. The patient can be discharged from the hospital only if stable indicators from the cardiovascular system are established. The same careful supervision (monitoring fluid balance and indicators of renal function) is required for patients with peripheral edema or renal dysfunction (serum creatinine> 1.5 mg / dL or glomerular filtration rate. Caution should be used in patients undergoing hemodialysis period), patients with type 1 diabetes mellitus, especially with severe vascular damage.Vazostenone should be administered only to doctors who have experience in the treatment of obliterating diseases of the peripheral arteries, familiar with modern methods of continuous monitoring of the indicators of the cardiovascular system and have the appropriate equipment for this. Alprostadil should not be used by jet (bolus) administration. In the case of simultaneous use with antihypertensive drugs, vasodilators and antianginal drugs, careful monitoring of the indicators of the cardiovascular system should be carried out (see Section “Interaction with other drugs and other types of interactions”). Use during pregnancy or lactation. Do not use for women of reproductive age and during pregnancy. If necessary, the use of the drug during lactation should be discontinued. Women of reproductive age should use effective contraceptives to prevent pregnancy during the use of the drug. Data from preclinical studies of fertility do not indicate the effect of the drug on fertility when using therapeutic doses of the drug. The ability to influence the reaction rate when driving vehicles or other mechanisms. Like all drugs acting on the cardiovascular system, the drug can adversely affect the ability to drive vehicles and other mechanisms, especially at the beginning of treatment, with increasing doses, stopping the drug, drinking alcohol, can lead to a decrease in systolic blood pressure. Patients should be advised of the need for caution when driving vehicles and working with
Composition
Active substance: Amprostil 20 mg Alprostadil
Side effects
Side effects are classified by frequency as follows: very often ( 1/10), often ( 1/100, <1/10), infrequently ( 1/1000, <1/100), rarely ( 1/10000, <1/1000), very rarely (<1/10000), the frequency is unknown (cannot be estimated from the available data). On the part of the nervous system: often - headache, paresthesia of the limb, on which manipulation was carried out infrequently - confusion rarely - cerebral cramps unknown frequency - stroke. From the gastrointestinal tract: rarely - gastrointestinal diseases, including diarrhea, nausea, vomiting and acceleration of intestinal motility. From the cardiovascular system: infrequently - lowering blood pressure, tachycardia, rarely arrhythmias, heart failure with cases of acute pulmonary edema, which can lead to general heart failure, the frequency is unknown - myocardial infarction. From the digestive system: rarely - violation of the level of liver enzymes. From the respiratory system, chest and mediastinal organs: rarely - pulmonary edema unknown frequency - shortness of breath. On the part of the blood system and lymphatic system: rarely - leukopenia, leukocytosis, thrombocytopenia. Research: infrequently - increased functional parameters of the liver (transaminases): fever, changes in CRP (C-reactive protein) after completion of treatment, these indicators rapidly normalize. On the part of the skin and subcutaneous tissue: often - redness, swelling, hot flashes. General disorders and reactions at the injection site: very often - pain, erythema or edema of the limb, which was infused often - a warming sensation, a swelling sensation, swelling at the injection site, paresthesia, with intravenous administration - redness of the veins at the injection site after intraarterial introduction - a feeling of warming, a feeling of swelling, swelling at the injection site, paresthesia infrequently - increased sweating, chills, fever, after administration - a feeling of warming, a feeling of swelling, swelling at the injection site, paresthesia the known frequency is phlebitis at the injection site, thrombosis at the injection site of the catheter, local bleeding. From the immune system: infrequently - allergic reactions (skin hypersensitivity reactions, including rash, sensation of edema, discomfort in the joints, febrile reaction, sweating, chills) very rarely - anaphylactic or anaphylactoid reactions. From the musculoskeletal system and connective tissue: infrequently - articular symptoms, including pain, very rarely - reversible hyperostosis of the long bones after application of the drug for more than 4 weeks. Reporting on adverse reactions. Reporting on suspected adverse reactions after drug approval is important. This allows you to continue monitoring the benefit / risk balance of the drug. Health workers are asked to report any suspected adverse reactions through the national reporting system. Overdose Symptoms. An overdose of the drug can lead to a decrease in blood pressure and reflex tachycardia due to the effect of vasodilation. Other possible symptoms: vasovagal syncope with pallor of the skin, increased sweating, nausea, vomiting, myocardial ischemia, heart failure. Local reactions are possible: pain, swelling and redness of the limb, in which the infusion is carried out, manifestations of hypersensitivity. The treatment is symptomatic. There is no specific antidote. In case of overdose (severe pain, decrease in blood pressure) should reduce the dose or immediately stop the introduction of infusion. With a decrease in blood pressure, first of all, you need to put the patient on his back, raising the lower limbs. If the symptoms do not disappear, check / monitor the parameters of the cardiovascular system. If necessary, sympathomimetics can be used. Storage conditions Store in a dark place in the original packaging at a temperature of 2 to 8 ° C. Keep out of the reach of children. Expiration 2 years. Deystvuyuschee substances Alprostadil Terms and conditions prescription
