Alprostadil (Lyophilisate) Instructions for Use

ATC Code

C01EA01 (Alprostadil)

Active Substance

Alprostadil (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Vasodilator drug – synthetic prostaglandin E₁ analogue

Pharmacotherapeutic Group

Drugs for the treatment of heart diseases; other drugs for the treatment of heart diseases; prostaglandins

Pharmacological Action

A prostaglandin E₁ drug. It improves microcirculation and peripheral 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; it 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”). The onset of action is 5-10 minutes, and the 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, and 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 minute. 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, then returned to the baseline level 60 minutes after the injection, while the levels of alprostadil in the peripheral bloodstream were slightly higher than baseline. Alprostadil, upon entering the systemic circulation during intracavernosal administration, is very rapidly metabolized. It is excreted as metabolites.

Indications

The need for temporary maintenance of the patency of the arterial duct until a corrective operation is performed 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 individually based on the indication, route of administration, and patient response.

For neonatal ductus arteriosus patency, administer a continuous intravenous infusion. Initiate therapy at 0.05-0.1 mcg/kg/minute. Titrate the infusion rate to the lowest effective dose maintaining the desired clinical effect. The maximum recommended infusion rate is 0.4 mcg/kg/minute.

For chronic critical limb ischemia (Fontaine stages III-IV), administer via intra-arterial infusion. The initial dose is 0.1-0.2 ng/kg/minute for 60-120 minutes. Gradually increase the dose based on tolerability. The maintenance dose typically ranges from 1-2 ng/kg/minute administered over several hours daily. The total daily dose should not exceed 30-40 mcg.

For the treatment of erectile dysfunction, use the intracavernosal injection route. The initial dose in the physician’s office is 2.5 mcg. If the response is inadequate, increase the dose in 2.5 mcg increments. If there is a partial response, a 5 mcg dose may be tried. The maximum single dose for self-injection is 60 mcg. Do not administer more than once daily or exceed three times weekly.

For the diagnostic test for erectile dysfunction, administer an intracavernosal injection of 10 mcg. If the response is insufficient, a second dose of 20 mcg may be given after 1 hour. Do not exceed a total of 30 mcg for the diagnostic procedure.

Reconstitute the lyophilisate strictly according to the manufacturer’s instructions using the provided solvent. Use the solution immediately after preparation. Discard any unused solution. Monitor blood pressure and heart rate during systemic administration. In neonates, maintain facilities for artificial ventilation.

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 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 administered 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 history); 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 history).

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 with signs of respiratory failure), in infiltrative changes in the lungs, liver failure (including history), with an increased risk of bleeding (including peptic ulcer of the stomach or duodenum, severe cerebrovascular disease, proliferative retinopathy with a tendency to bleed, extensive trauma), hemodialysis, type 1 diabetes mellitus, especially with extensive vascular lesions (in elderly patients); while using 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 prone to drug addiction and/or with mental or intellectual impairments.

In case of blood coagulation disorders or during concomitant 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, 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 may develop. 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.

Strict adherence to the correspondence of the used dosage form of alprostadil to specific indications for its use must be 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.