Vazostenon^® (Concentrate) Instructions for Use

Marketing Authorization Holder

Pharmsintez OJSC (Russia)

Manufactured By

Kevelt AS (Estonia)

ATC Code

C01EA01 (Alprostadil)

Active Substance

Alprostadil (Rec.INN registered by WHO)

Dosage Form

Vazostenon®

Concentrate for solution for infusion 20 mcg/1 ml: amp. 5, 10, or 20 pcs.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion in the form of a transparent, colorless liquid.

Excipients : anhydrous ethanol – up to 1 ml.

1 ml – glass ampoules (5) – contour cell packaging (1) – cardboard packs.
1 ml – glass ampoules (5) – contour cell packaging (2) – cardboard packs.
1 ml – glass ampoules (5) – contour cell packaging (4) – cardboard packs.

Clinical-Pharmacological Group

Vasodilator drug – synthetic prostaglandin E₁ analogue

Pharmacotherapeutic Group

Vasodilating agent – synthetic prostaglandin E₁ analogue

Pharmacological Action

Prostaglandin E₁ drug. It improves microcirculation and peripheral blood circulation and has an angioprotective effect.

When administered systemically, it causes relaxation of smooth muscle fibers, has a vasodilating effect, reduces total peripheral vascular resistance, and lowers blood pressure. A reflex increase in cardiac output and heart rate is noted. It improves the rheological properties of blood by increasing the elasticity of erythrocytes and reducing platelet aggregation and neutrophil activity, and increases the fibrinolytic activity of blood.

It affects metabolism, increases the utilization of glucose and oxygen, suppresses the release of free radicals and lysosomal enzymes from granulocytes and macrophages, stimulates protein synthesis, has a beneficial effect on lipid metabolism (by suppressing cholesterol synthesis and reducing the concentration of LDL), and inhibits the proliferation of smooth muscle cells.

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

When administered intracavernosally, it blocks α₁-adrenergic receptors in the tissues of the penis, has a relaxing effect on the smooth muscles of the cavernous bodies, promotes increased blood flow and improved microcirculation.

Dilation of the cavernous arteries and vessels of the trabecular smooth muscle of the cavernous bodies leads to a rapid increase in blood inflow and dilation of the lacunar spaces in the cavernous bodies. Venous outflow through the vessels located under the tunica albuginea is limited, which stimulates the development of an erection (the “corporal veno-occlusive mechanism”). Onset of action is 5-10 minutes, duration is 1-3 hours.

Pharmacokinetics

When administered intravenously, Alprostadil is rapidly metabolized.

During a single pass through the lungs, 60-90% is metabolized. Enzymatic oxidation produces 3 biologically active metabolites: 15-keto-PGE₁, 15-keto-13,14-dihydro-PGE₁, and 13,14-dihydro-PGE₁. The keto-metabolites have a lower biological effect compared to alprostadil, the metabolite 13,14-dihydro-PGE₁ has an effect comparable to PGE₁. The pharmacodynamic effect is mainly due to this biologically active metabolite. The T_1/2 of 13,14-dihydro-PGE₁ is about 1 min. The main metabolites are excreted primarily in the urine and to a lesser extent in the feces.

When administered intracavernosally, the concentration of alprostadil and its main metabolite, 15-oxo-13,14-dihydro-PgE₁, is determined only in the cavernous bodies.

After intracavernosal administration of 20 mcg of alprostadil, the content of the main metabolite in the peripheral bloodstream increased and reached a maximum 30 minutes after injection, and then returned to the initial level 60 minutes after injection, while the levels of alprostadil in the peripheral bloodstream were slightly higher than the initial ones. Alprostadil, when entering the systemic circulation during intracavernosal administration, is very rapidly metabolized. It is excreted in the form of metabolites.

Indications

The need for temporary maintenance of the arterial duct function until corrective surgery for congenital ductus-dependent heart defects in newborns (including mitral atresia, pulmonary artery atresia, tricuspid atresia, tetralogy of Fallot).

Chronic obliterating arterial diseases of stages III-IV (according to the Fontaine classification). Obliterating endarteritis with a severe degree of intermittent claudication (when surgical revascularization of the lower limb is impossible), obliterating atherosclerosis, diabetic angiopathy, obliterating thromboangiitis (Buerger’s disease), Raynaud’s syndrome with trophic disorders, vasculitis, scleroderma, calf muscle cramps, damaging effects of physical factors, especially excessive vibration.

Treatment of erectile dysfunction of neurogenic, vascular, psychogenic, or mixed etiology; performing a pharmacological test as part of diagnostic tests for erectile dysfunction.

ICD codes

Dosage Regimen

Determine the dosage regimen individually based on the indication, route of administration, and patient condition.

For neonatal ductus arteriosus maintenance, administer as a continuous intravenous infusion. Initiate therapy at an infusion rate of 0.05-0.1 mcg/kg/minute. Titrate the dosage downward to the lowest effective rate, which is typically 0.01-0.025 mcg/kg/minute. Continuously monitor blood pressure and respiratory status.

For chronic critical limb ischemia (Fontaine stages III-IV), administer by intra-arterial infusion or prolonged intravenous infusion. The typical daily dose for intra-arterial administration is 40 mcg dissolved in 50-250 ml of sodium chloride 0.9% over 1-2 hours. For intravenous infusion, administer 60-80 mcg diluted in 250-500 ml of sodium chloride 0.9% or dextrose 5% over 3-6 hours. The treatment course duration is typically 2-4 weeks.

For erectile dysfunction diagnosis and treatment, use only the appropriate formulation for intracavernosal injection. For the pharmacological diagnostic test, initiate with a low dose, such as 2.5 mcg. If the response is inadequate, titrate the dose upward in increments (e.g., 5 mcg, 10 mcg, 20 mcg) at subsequent visits to determine the minimum effective dose. For treatment, the recommended starting dose is 2.5 mcg. Adjust the dose based on individual response and tolerability. The maximum recommended frequency of administration is once daily and no more than three times per week, with at least 24 hours between injections.

Prepare the infusion solution immediately prior to administration. Dilute the concentrate in sodium chloride 0.9% or dextrose 5% solution. Discard any unused solution. For intracavernosal use, strictly follow aseptic preparation and administration techniques. Instruct patients on proper self-injection technique, including site rotation. Monitor for signs of priapism; seek immediate medical attention for any erection lasting more than 4 hours.

Adverse Reactions

From the digestive system diarrhea, nausea, vomiting, increased transaminase activity; rarely – hyperbilirubinemia, peritoneal symptoms.

From the cardiovascular system arterial hypotension, tachycardia, pain in the heart area; rarely – heart failure, cardiac arrhythmias, AV block, acute pulmonary edema.

From the central and peripheral nervous system headache, psychoses, seizures of central origin, paresthesia; rarely – lethargy.

From the respiratory system rarely – tachypnea, respiratory distress syndrome.

From the hematopoietic system and blood clotting system leukocytosis, leukopenia; rarely – bleeding, hypochromic anemia, thrombocytopenia.

From the urinary system rarely – anuria, renal failure, hematuria.

From metabolism rarely – hypoglycemia, hypercapnia.

From the musculoskeletal system joint pain, neck muscle tension, reversible hyperostosis of tubular bones.

Allergic reactions skin rash, itching.

Other hyperthermia, skin redness, increased sweating, swelling of the limb into which the infusion is performed are possible.

With intracavernosal administration pain in the penis, prolonged erection and priapism are possible; rarely – fibrosis, edema, feeling of heat, numbness, rashes on the penis, balanitis, hemorrhages, itching and swelling at the injection site, bleeding from the urethra, fungal infection, phimosis, painful erection and impaired ejaculation, pain in the testicles, testicular swelling, pain and tension in the scrotum, frequent urination, urinary incontinence, pain in the buttocks, legs, abdomen, pain in the pelvic area, lower back, flu-like syndrome, hypesthesia, myasthenia.

Contraindications

Chronic heart failure, pulmonary edema, cardiac arrhythmias, myocardial infarction within the last 6 months; infiltrative changes in the lungs, bronchial asthma; impaired liver function, liver diseases (including in the anamnesis); history of ulcerative lesions of the gastrointestinal tract; hypersensitivity to alprostadil; pregnancy, lactation.

For intracavernosal administration: diseases predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia); anatomical deformities of the penis (angulation, cavernous fibrosis, Peyronie’s disease). Not used in patients with a penile implant, as well as when sexual intercourse is contraindicated.

Use in Pregnancy and Lactation

Alprostadil is contraindicated during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Contraindication: impaired liver function, liver diseases (including in the anamnesis).

Pediatric Use

In newborns, it should be used under constant blood pressure monitoring, with mandatory availability of conditions for artificial ventilation.

Currently, there is no experience with intracavernosal administration in patients under 18 years of age.

Geriatric Use

Currently, there is no experience with intracavernosal administration in patients over 75 years of age.

Use intra-arterially and intravenously with caution in cases of extensive vascular lesions in diabetes mellitus (in elderly patients).

Special Precautions

Use intra-arterially and intravenously with caution in acute and subacute myocardial infarction, in myocardial infarction within the last 6 months, in severe or unstable angina, decompensated chronic heart failure, in arterial hypotension, cardiovascular failure, in pulmonary edema, severe arrhythmias, broncho-obstructive syndrome (severe degree with signs of respiratory failure), in infiltrative changes in the lungs, liver failure (including in the anamnesis), with an increased risk of bleeding (including with gastric or duodenal ulcer, severe cerebrovascular disease, proliferative retinopathy with a tendency to bleeding, extensive trauma), hemodialysis, type 1 diabetes mellitus, especially with extensive vascular lesions (in elderly patients); against the background of the use of vasodilators or anticoagulants; in newborns (risk of bradypnea, arterial hypotension, tachycardia or hyperthermia).

Administer intracavernosally with caution in thrombocytopenia, polycythemia, thrombophlebitis, venous thrombosis (including in case of predisposition), increased blood viscosity, balanitis, urethritis.

Should not be used in patients with a tendency to drug addiction and/or mental or intellectual impairments.

In case of blood clotting system disorders or during simultaneous therapy with drugs that affect the clotting system, blood clotting parameters should be regularly monitored during treatment with alprostadil. With systemic administration, monitoring of central hemodynamic parameters and blood biochemical parameters is necessary.

With prolonged continuous administration, the development of apnea, a negative effect on the structure of the arterial duct wall with an increased risk of its rupture, and thinning of the muscular layer of the pulmonary artery are possible. With treatment duration of more than 4 weeks, reversible cortical proliferation of tubular bones is possible.

In newborns, it should be used under constant blood pressure monitoring, with mandatory availability of conditions for artificial ventilation.

Currently, there is no experience with intracavernosal administration in patients under 18 years of age and over 75 years of age.

Alprostadil is not intended for simultaneous use with other drugs for the treatment of erectile dysfunction.

The correspondence of the used dosage form of alprostadil to the specific indications for its use should be strictly observed.

Drug Interactions

With simultaneous use, Alprostadil enhances the effect of antihypertensive agents and vasodilators, anticoagulants, and antiplatelet agents.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.