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

The drug prostaglandin E₁ (PgE₁) improves microcirculation and peripheral circulation, has a vasoprotective effect. When systemic administration causes relaxation of smooth muscle fibers,has a vasodilating effect, reduces the overall peripheral vascular resistance without changing blood pressure. At the same time there is a reflex increase in cardiac output and heart rate. Helps increase the elasticity of erythrocytes, reduces platelet aggregation and neutrophil activity, increases fibrinolytic blood activity. Has a stimulating effect on the smooth muscles of the intestine, bladder, uterus; suppresses the secretion of gastric juice.

Pharmacokinetics:

Applicable PgE₁ in combination with alfacyclodextrin intravenously or intraarterially. During the preparation of the solution, the complex of the drug decomposes into constituent parts - PgE₁ and alfacyclodextrin. With intravenous administration, a therapeutically significant concentration of the active substance is reached shortly after the start of the drug administration, and the maximum concentration in the blood plasma is reached within 2 hours from the start of administration. PgE₁ is an endogenous substance with an exceptionally short half-life - the concentration in the blood plasma returns to the baseline level 10 seconds after discontinuation of the drug administration.Biotransformation process PgE₁ occurs mainly in the lungs, with "first passage" through the lungs, 60-90% of the active substance is metabolized with the formation of the main metabolites - 15-KeTO-PgE₁ 15-KeTO-PgE₀ and PgE₀. The main products of kidney metabolism are deduced - 88% and through the gastrointestinal tract - 12% during 72 hours. With blood plasma proteins, 93% PgE_1. Alfacyclodextrin has a half-life of about 7 minutes, is excreted by the kidneys unchanged.

Indications:

Chronic obliterating diseases of arteries of III and IV stages (according to Fontaine's classification) in patients who can not be revascularized or after unsuccessful revascularization.

Intravenous use in the treatment of chronic obliterating diseases of arteries of the IV stage is not recommended.

Contraindications:

Hypersensitivity to alprostadil or other components of the drug;
Chronic heart failure III-IV functional class for NYHA;
Hemodynamically significant violations of the rhythm of the heart;
Exacerbation of the course of coronary heart disease, suffered in the last six months myocardial infarction;
Mitral and / or aortic stenosis and / or insufficiency;
Acute pulmonary edema or pulmonary edema in anamnesis in patients with heart failure;
Severe degree of chronic obstructive pulmonary disease or pulmonary veno-occlusive disease;
Infiltrative lung disease;
Diseases accompanied by an increased risk of bleeding (peptic ulcer and / or duodenal ulcer;
Concomitant therapy with vasodilator or anticoagulant drugs;
Violation of cerebral circulation during the last 6 months;
Severe arterial hypotension;
Impaired renal function (oliguria);
Acute liver failure (increased activity of aspartate aminotransferase, alanine aminotransferase or gamma-glutamyltransferase) or severe hepatic insufficiency, including in the anamnesis;
General contraindications for infusion therapy (eg, chronic heart failure, edema and hyperhydration of the lungs or brain);
Pregnancy and the period of breastfeeding.
Age to 18 years (effectiveness and safety not established).

Carefully:

Arterial hypotension.

Chronic heart failure I-II functional class for NYHA (special attention should be given to controlling the load of the volume of the carrier solution).Patients on hemodialysis (treatment with the drug should be performed in the postdialysis period).

Patients with type 1 diabetes mellitus, especially with extensive vascular lesions (in elderly patients).

Pregnancy and lactation:

Women of reproductive age

Women of reproductive age should use reliable contraceptive methods during treatment.

Pregnancy and lactation

The use of the drug Vazaprostan ® during pregnancy is contraindicated. If it is necessary to appoint in the lactation period, breastfeeding should be discontinued.

Fertility

According to preclinical research alprostadil does not have any undesirable reactions from the part of fertility.

Dosing and Administration:

Enter only intravenously or intraarterially. Intravenous use in the treatment of chronic obliterating diseases of arteries of the IV stage is not recommended.

The solution must be prepared immediately before the infusion. The lyophilizate dissolves immediately after the addition of an isotonic 0.9% solution for injection of sodium chloride. In the beginning, the solution may turn out to be dairy. This effect is created by air bubbles.After a short time, the solution becomes transparent. Do not use the solution after 12 hours after cooking.

Pediatric use:

Vazaprostan® is not recommended for children and adolescents under the age of 18 because the safety and efficacy of the drug in these age groups have not been studied.

Intraarterial administration III and IV stage

Dissolve the contents of one ampoule of the drug Vazaprostan® (corresponding to 60 μg alprostadil) in 50-250 ml isotonic 0.9% solution for injection of sodium chloride.

In the absence of other prescriptions, the contents of 1/6 of the vasaprostan® preparation (corresponding to 10 μg of alprostadil) should be administered intraarterially within 60-120 minutes. when using an infusion device. If necessary, especially in the presence of necrosis, under strict control of drug tolerance, the dose can be increased to 1/3 ampoule (corresponding to 20 μg alprostadil). This dosage is usually used for a single daily infusion.

Intravenous infusion III stage

Dissolve the contents of one ampoule of the drug Vazaprostan® (corresponding to 60 μg of alprostadil) in 50-250 ml of isotonic 0.9% solution for injection of sodium chloride and inject the prepared solution intravenously infusion for 2 hours 1 time per day.

In patients with impaired renal function (serum creatinine concentration greater than 1.5 mg / dL) Intravenous administration of the drug Vazaprostan® begins with 20 mcg (1/3 of the ampoule), injecting it for two hours. When the need after 2-3 days a single dose of 20 mcg is increased to 40-60 mcg.

Patients with renal insufficiency or patients who can be classified as at risk for heart failure, the volume of infusion fluid should be limited to 50-100 ml per day to avoid the appearance of symptoms of hyperhydration. Infusion should be performed with the help of infusion pumps.

The duration of therapy is an average of 14 days, with a positive therapeutic effect, the drug can continue treatment for 7-14 days. The course of treatment should not exceed 3-4 weeks. In the absence of a positive effect within 2 weeks from the start of treatment, further use of the drug should be discontinued.

Side effects:

Possible side effects are given below for body systems and frequency of occurrence: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000), very rarely (<1/10000), unknown (can not be estimated from available data).

When using the drug Vazaprostan^®the following undesirable effects are observed:

Violation of the hematopoietic and lymphatic system:

Rarely: thrombocytopenia, leukopenia, leukocytosis;

Rarely: bleeding, anemia.

Impaired nervous system:

Often: headache;

Rarely: confusion, convulsions of the central genesis;

Rarely: drowsiness, dizziness;

Unknown: disturbance of cerebral circulation.

Heart Disease:

Infrequently: decrease in systolic blood pressure, tachycardia, angina pectoris;

Rarely: arrhythmia, biventricular heart failure, pulmonary edema;

Rarely: acute heart failure, ventricular fibrillation, atrioventricular blockade of degree II, supraventricular arrhythmia;

Unknown: myocardial infarction.

Vascular disorders:

Rarely: shock.

Disturbances from the respiratory system, chest and mediastinal organs:

Rarely: pulmonary edema;

Rarely: bradypnoea, decreased respiratory function, tachypnea, hypercapnia;

Unknown: dyspnoea.

Disorders from the gastrointestinal tract:

Infrequently: diarrhea, nausea, vomiting;

Rarely: peritoneal symptoms.

Disorders from the metabolism and nutrition:

Rarely: hypoglycaemia, hyperkalemia.

Disorders from the liver and bile ducts:

Rarely: increased activity of "hepatic" transaminases, increased activity of gamma-glutamyltransferase;

Rarely: hyperbilirubinemia.

Disorders from the kidneys and urinary tract:

Rarely: disturbance of kidney function, hematuria.

Disturbances from the skin and subcutaneous tissues:

Often: redness, edema, "tide" of blood.

Allergic reactions:

Infrequently: cutaneous hypersensitivity, for example, rash.

Disturbances from the musculoskeletal and connective tissue:

Rarely: tension of the neck muscles, with prolonged use (4 weeks or more), reversible hyperostosis of tubular bones may occur, it is also possible to increase the titer of C-reactive protein;

Infrequently: joint pain.

General disorders and disorders at the site of administration:

Often: pain, headache, after intra-arterial administration: sensation of fever, sensation of raspiraniya, local edema, paresthesia;

Infrequently: after intravenous administration: sensation of fever, sensation of raspiraniya, local edema, paresthesia, fever, increased sweating, chills;

Rarely: anaphylaxis / anaphylactoid reaction, fatigue, general malaise, increased irritability, hypothermia, tachyphylaxis;

Unknown: phlebitis at the site of injection, thrombosis, bleeding at the site of insertion of the catheter.

Overdose:

An overdose of the drug Vazaprostan® can be manifested by a marked decrease in blood pressure and reflex tachycardia. Possible development of vasovagal reactions with pallor of the skin, increased sweating, nausea and vomiting. Possible pain, swelling and redness of the skin at the site of infusion.

If symptoms of an overdose need to reduce the dose of the drug Vazaprostan ® or stop the infusion. With a significant reduction in blood pressure, the patient in the "lying" position should raise his legs. If symptoms persist, sympathomimetics should be used.

Interaction:

Alprostadil can enhance the effect of antihypertensive drugs, vasodilators. The simultaneous use of alprostadil in patients taking anticoagulants and / or antiplatelet agents may increase the chance of bleeding.

Sympathomimetics epinephrine (adrenalin), norepinephrine (noradrenaline) reduce the vasodilating effect.It should be taken into account that drug interactions are possible if the above mentioned drugs were applied shortly before the therapy with Vazaprostan ® was started.

Special instructions:

Vazaprostan® can not be administered bolus!

Vazaprostan ® can be used only by doctors with experience in angiology, who are familiar with modern methods of continuous monitoring of cardiovascular parameters.

Patients with coronary heart disease, as well as patients with peripheral edema and impaired renal function (serum creatinine greater than 1.5 mg / dl) should be monitored in the hospital for one day after discontinuation of the drug.

During the period of treatment, regular monitoring of blood pressure, heart rate, biochemical parameters of blood, coagulating blood system (in case of violations of the blood coagulation system or with simultaneous therapymeans that affect the parameters of the coagulation system), if necessary - control of body weight, fluid balance, measurement of central venous pressure, echocardiography.

Phlebitis (proximal to the place of administration), as a rule, is not a reason for discontinuing therapy, signs of inflammation disappear after a few hours after discontinuation of the infusion or a change in the site of administration of the drug, no specific treatment is required in such cases. Catheterization of the central vein can reduce the incidence of this side effect of the drug.

When the ampoule is damaged, the lyophilizate becomes wet and sticky, and greatly decreases in volume. In this case, the drug can not be used.

Effect on the ability to drive transp. cf. and fur:

Alprostadil can cause a decrease in systolic blood pressure and, thereby, reduces the ability to drive vehicles and engage in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Lyophilizate for the preparation of a solution for infusions of 60 mcg.

Packaging:At 49.5 mg (corresponding to 60 μg alprostadil) in ampoules of neutral glass with a blue dot above the place of the nag and a blue marking ring.
For 10 ampoules together with instructions for use in a pack of cardboard with a special holder for ampoules.
In the case of packaging of the drug pa CJSC "FirmFirma Soteks"
Five ampoules are placed in a contour mesh package made of a polyvinylchloride film and a polymer film or without a polymer film.
2 contour packs of 5 ampoules together with the instructions for use are placed in a pack of cardboard.

Storage conditions:At a temperature not higher than 25 ° C, out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:LSR-001051/08

Date of registration:26.02.2008 / 15.10.2015

Expiration Date:Unlimited

The owner of the registration certificate:YUSB Pharma GmbHYUSB Pharma GmbH Germany

Manufacturer: & nbsp

BAYER PHARMA, AG Germany

Representation: & nbspYUSB FARMA LLC YUSB FARMA LLC Russia

Information update date: & nbsp10.01.2017

Illustrated instructions

Instructions

Vazaprostan® (Vazaprostan®)