Arteris-vero^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Veropharm, LLC (Russia)

ATC Code

C01EA01 (Alprostadil)

Active Substance

Alprostadil (Rec.INN registered by WHO)

Dosage Form

Arteris-vero®

Lyophilizate for preparation of solution for infusion 60 mcg: fl. 10 pcs.

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of solution for infusion in the form of a hygroscopic, lyophilized mass of white color.

Excipients: alphadex – 1940 mcg, lactose monohydrate (calculated as anhydrous lactose) – 47.5 mg.

The mass of the vial contents is 49.5 mg.

Colorless glass vials (10) – cardboard packs.

Clinical-Pharmacological Group

Vasodilator drug – synthetic prostaglandin E₁ analogue

Pharmacotherapeutic Group

Vasodilating agent – synthetic prostaglandin E₁ analogue

Pharmacological Action

Prostaglandin E₁ drug. Improves microcirculation and peripheral circulation, 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. Improves the rheological properties of blood by increasing the elasticity of erythrocytes and reducing platelet aggregation and neutrophil activity, 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 gastric juice secretion.

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 muscles 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 (“corporeal 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 passage through the lungs, 60-90% is metabolized. During enzymatic oxidation, 3 biologically active metabolites are formed: 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. 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 the injection, and then returned to the initial level 60 minutes after the 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 severe 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 and route of administration.

For temporary maintenance of the arterial duct in newborns with congenital heart defects, administer a continuous intravenous infusion. Initiate therapy at an initial dose of 0.05-0.1 mcg/kg/min. Titrate the dosage downward to the lowest effective level. Continuously monitor blood pressure and ensure facilities for artificial lung ventilation are available.

For chronic obliterating arterial diseases (Fontaine stages III-IV), administer the drug intravenously or intra-arterially. The typical daily dose for intravenous infusion is 20-40 mcg diluted in 250-500 ml of 0.9% sodium chloride solution. For intra-arterial administration, use a dose of 10-20 mcg diluted in 20-50 ml of 0.9% sodium chloride solution, infused over 1-2 hours. The standard treatment course duration is 2-4 weeks.

For the treatment of erectile dysfunction, use the intracavernosal route of administration. Initiate therapy under medical supervision. The initial dose is 5-10 mcg. If the response is inadequate, increase the dose in 5-10 mcg increments until a satisfactory erection is achieved, not exceeding 60 mcg. The maximum frequency of administration is once daily and no more than three times per week. For diagnostic purposes, use a single dose.

Reconstitute the 60 mcg lyophilisate with 1 ml of 0.9% sodium chloride solution for injection. Gently agitate to dissolve. Use the prepared solution immediately. Do not administer the solution if particulate matter or discoloration is observed.

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-blockade, 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 coagulation 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 lung 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.

Intra-arterial and intravenous administration should be used with caution in extensive vascular lesions in diabetes mellitus (in elderly patients).

Special Precautions

Intra-arterial and intravenous administration should be used 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 insufficiency, 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).

Intracavernosal administration should be used 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 disorders.

In case of blood coagulation system disorders or during simultaneous therapy with drugs that affect the coagulation system, blood coagulation 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 a 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 lung 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.