Arteris-vero 60 mcg, 10 pcs.

The drug prostaglandin E1 (PgE1) improves microcirculation and peripheral blood flow, has a vasoprotective effect. When administered systemically, it causes relaxation of smooth muscle fibers, has a vasodilator effect, reduces total peripheral vascular resistance (PPR), without changing blood pressure (BP). There is a reflex increase in cardiac output and heart rate (HR). It improves the rheological properties of blood by increasing the elasticity of erythrocytes and reducing platelet aggregation and neutrophil activity, increases blood fibrinolytic activity.

It has a stimulating effect on the smooth muscles of the intestine, bladder, uterus; it suppresses the secretion of gastric juice.

Indications

Chronic arterial obliterative disease stage III-IV (according to Fontaine classification) in patients who cannot be revascularized or after unsuccessful revascularization.

Intravenous use in the treatment of chronic obliterating arterial disease of stage IV is not recommended.

Active ingredient

Composition

1 vial contains:

The active ingredient: alprostadil 60 mcg.

Excipients: alphadex 1940.0 µg; lactose monohydrate, in terms of anhydrous lactose 47.5 mg.

The weight of the contents of the bottle is 49.5 mg.

How to take, the dosage

Inject only intravenously or intraarterially.

Intravenous use is not recommended in the treatment of stage IV chronic arterial obliterative disease.

The solution should be prepared immediately before infusion under aseptic conditions. In a bottle with lyophilizate add 4 ml of 0.9% sodium chloride solution for injection, and then the obtained volume is injected into a bottle with 0.9% sodium chloride solution for injection (taking into account the required amount, 50-250 ml).

The lyophilizate dissolves immediately after adding isotonic 0.9% sodium chloride solution for injection. Immediately after dissolution the color of the solution may be milky. This effect is created by air bubbles. After a short time, the solution becomes clear. It is recommended to use the prepared solution immediately after preparation. Stability tests have shown that ready-to-use Arteris-vero® solution can be stored at a temperature not exceeding 25 C for up to 12 hours.

Pediatric use

Alprostadil is not recommended for use in children and adolescents under 18 years of age because its safety and efficacy in these age groups have not been studied. Intra-arterial administration of stage III and IV

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

Stage III intravenous infusion

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

In patients with impaired renal function (creatinine concentration > 1.5 mg/dL) the intravenous administration of Arteris-vero® is started with 20 mcg alprostadil (1/3 vial) administered intravenously for two hours. If necessary, the single dose of 20 mcg may be increased to 40-60 mcg after 2-3 days. In patients with renal insufficiency or patients who can be classified as a group of risk due to cardiac dysfunction, the volume of fluid administered during infusion should be limited to 50-100 ml per day to avoid the occurrence of symptoms of hyperhydration. Infusion should be performed using infusion pumps.

The duration of therapy is an average of 14 days; in case of positive therapeutic effect the drug can be continued for 7-14 days more. The course of treatment should not exceed 4 weeks. If there is no positive effect within 2 weeks from the start of treatment, further use of the drug should be discontinued.

The clinical effect may appear with some delay at the end of the course of treatment.

Interaction

Special Instructions

Arteris-vero® must not be administered bolus!

The use of Arteris-vero® is restricted to physicians experienced in angiology who are familiar with current methods of continuous monitoring of the cardiovascular system.

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 a hospital setting for one day after discontinuation of the drug.

In patients with renal insufficiency or patients who may be classified as being at risk due to cardiac dysfunction, the volume of fluid infusion should be limited to 50-100 ml per day to avoid symptoms of hyperhydration.

Any regular control of blood pressure, heart rate, biochemical parameters of blood, coagulation system (in case of coagulation disorders or concurrent therapy with the drugs that affect coagulation system parameters), if necessary – control of body weight, fluid balance, central venous pressure, echocardiographic study are required during the treatment.

Phlebitis (proximal to the injection site) is usually not a reason for discontinuation of therapy, signs of inflammation disappear within a few hours after cessation of infusion or change of the site of drug administration, 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 moist and sticky and strongly decreases in volume. In this case the drug should not be used.

Alprostadil may decrease systolic blood pressure and thereby decrease ability to operate motor vehicles and engage in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

– Hypersensitivity to alprostadil or other components of the drug;

– chronic heart failure III-IV functional class according to NYHA;

– hemodynamically significant heart rhythm disturbances;

– exacerbation of coronary heart disease, myocardial infarction within the last six months;

– mitral and/or aortic stenosis and/or insufficiency;

– acute pulmonary edema or a history of pulmonary edema in patients with heart failure;

– severe chronic obstructive pulmonary disease or pulmonary veno-occlusive disease;

– infiltrative lung disease;

– diseases with increased risk of bleeding (gastric and/or duodenal ulcer);

– concomitant therapy with vasodilators or anticoagulant drugs;

– impaired cerebral circulation within the last six months;

– severe arterial hypotension;

– renal dysfunction (oliguria);

– acute liver failure (increased aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyltransferase activity) or severe liver failure, including a history;

– general contraindications for infusion therapy (e.g., chronic heart failure, pulmonary or cerebral edema and hyperhydration);

– pregnancy and breastfeeding period;

– age under 18 years (effectiveness and safety not established).

– Arterial hypotension;

– Chronic heart failure I – II functional class according to NYHA (special attention should be paid to control the load of the carrier solution volume);

– Patients on hemodialysis (treatment with the drug should be performed in the post-dialysis period);

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

Side effects

Possible side effects are listed below by body system and frequency of occurrence: Very common (>1/10), common (>1/100, <1/10), infrequent (>1/1000, <1/100), rare (>1/10000, <1/1000), very rare (<1/10000), unknown (cannot estimate from available data).

The following side effects are possible when using alprostadil:

Disorders of the hematopoietic and lymphatic system:

Rare: thrombocytopenia, leukopenia, leukocytosis;

Very rare: bleeding, anemia.

Nervous system disorders:

Often: headache;

Rarely: confusion, convulsions of central genesis;

Very rarely: drowsiness, dizziness;

Unknown: impaired cerebral circulation.

Cardiac disorders:

Infrequent: decreased systolic blood pressure, tachycardia, angina; Rare: arrhythmia, biventricular heart failure, pulmonary edema;

Very rare: Acute heart failure, ventricular fibrillation, grade II atrioventricular block, supraventricular arrhythmia;

Unknown: myocardial infarction.

vascular disorders:

very rarely: shock.

Respiratory system, chest and mediastinum disorders:

Rare: pulmonary edema;

Very rare: bradypnea, decreased respiratory function, tachypnea, hypercapnia;

Unknown: dyspnea.

Gastrointestinal tract disorders:

Infrequent: diarrhea, nausea, vomiting;

Very rare: peritoneal symptoms.

Disorders of metabolism and nutrition:

Very rare: hypoglycemia, hyperkalemia.

Hepatic and biliary tract disorders:

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

Very rare: hyperbilirubinemia.

Renal and urinary tract disorders:

Very rare: impaired renal function, hematuria.

Skin and subcutaneous tissue disorders:

Often: redness, swelling, “rush” of blood.

Allergic reactions:

Infrequent: skin hypersensitivity, such as skin rash.

Musculoskeletal and connective tissue disorders:

Very rare: Neck muscle strain, with prolonged use (4 weeks or more) reversible tubular bone hyperostosis may occur, also possible increase in C-reactive protein titer;

Infrequent: joint pain.

General disorders and disorders at the site of administration:

Often: pain, headache, after intra-arterial injection – feeling of heat, feeling of tumescence, local swelling, paresthesia;

Infrequently: After intravenous administration – Feeling of fever, feeling of tumescence, local edema, paresthesia, fever, increased sweating, chills;

Very rarely: Anaphylaxis/anaphylactoid reaction, fatigue, general malaise, increased irritability, hypothermia, tachyphylaxis;

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

Overdose

Symptoms: Overdose with alprostadil may manifest as a marked decrease in blood pressure and reflex tachycardia. Vasovagal reactions with pale skin, increased sweating, nausea and vomiting may develop. Pain, swelling and redness of the skin at the site of infusion are possible.

Treatment: In case of symptoms of overdose the drug dose should be reduced or the infusion should be stopped. If there is a significant decrease in blood pressure, the patient in “lying” position should be elevated legs. If symptoms persist, sympathomimetics should be used.

Similarities