Arteris-vero - instructions for use, doses, 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 (OPSS), without changing blood pressure (BP).At the same time there is a reflex increase in cardiac output and heart rate (heart rate). Improves the rheological properties of blood, contributing to the increase in the elasticity of red blood cells and reducing platelet aggregation and neutrophil activity, increases fibrinolytic activity of blood.

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 elimination period - 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 the "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% within 72 hours. With blood plasma proteins, 93% PgE1. Alfacyclodextrin has a half-life of about 7 minutes, is excreted by the kidneys unchanged.

Indications:

Chronic obliterating diseases of the arteries III-IV stage (according to Fontaine's classification) in patients who are unable to undergo revascularization 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, myocardial infarction suffered during the last six months;

- 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;

- disturbance of cerebral circulation during the last six 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 (efficacy and safety not established).

Carefully:

- Arterial hypotension;

- chronic heart failure of I-II functional class in NYHA (special attention should be given to controlling the loading 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 the period of breastfeeding

The use of the drug during pregnancy is contraindicated. If it is necessary to use the drug during breastfeeding, breastfeeding should be discontinued.

Fertility

According to preclinical research alprostadil does not have undesirable reactions to 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, under aseptic conditions. In the vial with lyophilizate add 4 ml of 0.9% solution of sodium chloride for injection, and then the resulting volume is introduced into the vial with 0.9% solution of sodium chloride for injection (taking into account the required amount, 50-250 ml).

The lyophilizate dissolves immediately after the addition of an isotonic 0.9% solution of sodium chloride for injection. Immediately after dissolution, the color of the solution may be dairy. This effect is created by air bubbles. After a short time, the solution becomes transparent. Ready-made solution is recommended to use immediately after preparation. Stability studies have shown that the Arteris-vero ® solution prepared for use can be stored at a temperature of no more than 25 C for up to 12 hours.

Pediatric Use

Alprostadil is not recommended for use in children and adolescents under the age of 18, since its safety and efficacy in these age groups have not been studied. Intraarterial administration III and IV stage

Dissolve the contents of one vial (60 mcg alprostadil) in 50 - 250 ml 0.9% sodium chloride solution for injection. In the absence of other prescriptions, the contents of 1/6 vial (corresponding to 10 μg alprostadil) should be administered intraarterially within 60-120 minutes with the use of an infusion device. If necessary, especially in the presence of necrosis, under strict control of tolerability, the dose can be increased to 1/3 of the vial (20 mcg alprostadil). This dosage is usually used for a single daily infusion.

Intravenous infusion III stage

Dissolve the contents of one vial (60 mcg alprostadil) in 50-250 ml isotonic 0.9% solution of sodium chloride for injection and inject the prepared solution intravenously infusion for 2 hours, once a day.

In patients with impaired renal function (creatinine concentration> 1.5 mg / dl) intravenous administration of Arteris-vero® is started with 20 μg of alprostadil (1/3 vial), injecting it for two hours. If necessary, after 2-3 days a single dose of 20 mcg can be 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 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.

The clinical effect may manifest with a certain delay after the end of the course of treatment.

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), is unknown (it is impossible to estimate from available data).

When alprostadil is used, the following side effects are possible:

Violation of the hematopoietic and lymphatic system:

Rarely: thrombocytopenia, leukopenia, leukocytosis;

Very rarely: bleeding, anemia.

Impaired nervous system:

Often: headache;

Rarely: confusion, convulsions of central genesis;

Very rarely: drowsiness, dizziness;

Unknown: cerebrovascular accident.

Heart Disease:

Infrequently: a 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:

Very rarely: shock.

Disturbances from the respiratory system, organs of the thorax and mediastinum:

Rarely: pulmonary edema;

Very rarely: bradypnoea, decreased respiratory function, tachypnea, hypercapnia;

Unknown: dyspnoea.

Disorders from the gastrointestinal tract:

Infrequently: diarrhea, nausea, vomiting;

Very rarely: peritoneal symptoms.

Disorders from the metabolism and nutrition:

Very rarely: hypoglycemia, hyperkalemia.

Disorders from the liver and bile ducts:

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

Very rarely: hyperbilirubinemia.

Disorders from the kidneys and urinary tract:

Very rarely: a violation of kidney function, hematuria.

Disturbances from the skin and subcutaneous tissues:

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

Allergic reactions:

Infrequent: cutaneous hypersensitivity, for example, skin rash.

Disturbances from the musculoskeletal and connective tissue:

Very rarely: neck muscle strain, with prolonged use (4 weeks or more), there may be reversible hyperostosis of tubular bones, it is also possible to increase the titer of C-reactive protein;

Infrequent: pain in the joints.

General disorders and disorders at the site of administration:

Often: pain, headache, after intra-arterial administration - a feeling of heat, a feeling of bursting, a local edema, paresthesia;

Infrequently: after intravenous administration - a feeling of heat, a feeling of raspiraniya, local edema, paresthesia, fever, increased sweating, chills;

Very 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:

Symptoms: An overdose of alprostadil may 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.

Treatment: If symptoms of an overdose need to reduce the dose of the drug 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 (norepinephrine), reduce the vasodilating effect. It must be taken into account that drug interactions are possible if the above-mentioned drugs were used shortly before alprostadil therapy was started.

Special instructions:

Arteris-vero® should not be administered bolus!

Arteris-vero® 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 renal dysfunction (serum creatinine more than 1.5 mg / dL) should be monitored in the hospital for one day after discontinuation of the drug.

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.

During the treatment period, regular monitoring of blood pressure, heart rate, blood biochemical parameters, blood coagulation system (for disorders of the blood coagulation system or for simultaneous therapy with drugs 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. Central vein catheterization can reduce the incidence of this side effect.

If the vial is damaged, the lyophilizate becomes wet and sticky and decreases greatly in volume. In this case, you can not use the drug.

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 solution for infusion, 60 mcg.

Packaging:

By 60 μg of the active substance in the bottles of colorless glass, hermetically sealed with rubber stoppers, with capping of aluminum or aluminum-plastic caps.

For 10 vials with instructions for use are placed in a pack with partitions or special nests of cardboard.

For 70 or 100 bottles with an equal number of instructions for use are placed in a box of cardboard (for hospitals).

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004489

Date of registration:10.10.2017

Expiration Date:10.10.2022

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Information update date: & nbsp21.11.2017

Illustrated instructions

Instructions

Arters-Vero® (Arteris-vero)