VAP 20 concentrate 20 µg/ml 1 ml, 5 pcs.

The analogue of natural PHE1 (prostaglandin E1), has vasodilator (at the level of arterioles, precapillary sphincters, muscular arteries), anti-aggregant and angioprotective action.

It improves microcirculation and peripheral circulation, promotes the opening of collateral vessels. It reduces the overall peripheral vascular resistance and the blood pressure and reflexively increases the heart rate resulting in the increase of the minute blood volume.

It improves rheological properties of blood by promoting elasticity of erythrocytes and reducing platelet adhesion/aggregation. It has a fibrinolytic effect.

Stimulates smooth muscles of the intestine, bladder and uterus; inhibits secretion of gastric juice.

Indications

Chronic obliterating arterial diseases of stages III and IV (according to Fontaine classification).

Active ingredient

Composition

Composition 1 ampoule contains:

the active ingredient:

alprostadil* 20 mcg

auxiliary substances:

ethanol&

*Alprostadil = PGE1 (prostaglandin E1).

How to take, the dosage

It is administered intravenously. The solution should be prepared immediately before administration. 1-2 ampoules (20 mcg or 40 mcg) are dissolved in 0.9% sodium chloride solution or 5% dextrose solution to a volume of 100-250 ml. The solution, ready to use, is suitable for 24 hours if stored in refrigerator (2-8°C) in a light-protected place. Do not use the solution prepared more than 24 hours ago.

50-250 ml ready-to-use infusion solution, 40 µg alprostadil concentration, administered intravenously over 2 hours (333 ng/min), infusion rate 0.4-2 ml/min. VAP20 is administered once a day, in case of severe clinical symptoms it is possible to administer VAP20 2 times a day. The average duration of treatment is 14 days; if the effect is positive the drug may be continued for another 7-14 days. The course of treatment should not exceed 4 weeks. If there is no positive effect within 2 weeks of the start of treatment, further use of the drug should be stopped.

In case of impaired renal function (creatinine concentration in serum is more than 1.5 mg/dL) intravenous administration should be started from 20 mcg. If necessary, after 2-3 days a single dose is increased to 40-60 mcg. For patients with renal insufficiency and heart failure, the maximum volume of administered liquid is 50-100 ml/day. The course of treatment is 4 weeks.

Interaction

Alprostadil may increase the effect of hypotensive drugs, vasodilators and antianginal agents.

Concomitant use of alprostadil in patients taking agents that prevent blood clotting (anticoagulants, antiaggregants) may increase the likelihood of bleeding. In combination with cefamandole, cefoperazone, cefotetan and thrombolytics – the risk of bleeding increases. Adrenomimetics – epinephrine, norepinephrine – reduce the vasodilatory effect.

It should be noted that drug interactions are also possible if the above agents were used shortly before therapy with the drug was started.

Special Instructions

Alprostadil may only be administered by a physician experienced in angiology who is familiar with modern methods of continuous monitoring of the cardiovascular system and who has the appropriate equipment for this purpose.

The prepared solution is recommended to be used immediately after preparation; temporary storage of the prepared solution for not more than 24 hours at 2 to 8 ºC is possible.

At the time of treatment it should be monitored:

Contraindications

Chronic heart failure, marked cardiac rhythm disturbances, exacerbation of coronary heart disease, myocardial infarction or stroke within the last 6 months.

Pulmonary edema, infiltrative pulmonary disease, and chronic obstructive pulmonary disease.

Hepatic dysfunction (increased aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyltransferase activity) and severe liver diseases in the history, as well as diseases accompanied by an increased risk of bleeding (peptic ulcer, duodenal disease, extensive trauma).

Companion therapy with vasodilators and anticoagulants.

Pregnancy and lactation period.

General contraindications for infusion therapy, such as decompensated heart failure, pulmonary or cerebral edema, functional renal impairment (oliguria), and hyperhydration.

Children under 18 years of age.

The use of VAP20 in arterial hypotension, cardiovascular insufficiency, in patients on hemodialysis (treatment with the drug should be performed in the post-dialysis period), in patients with diabetes, especially in diabetic angiopathy.

Side effects

In infusion

Nervous system and sensory organs: headache, dizziness, paresthesia, seizure syndrome, increased fatigue, malaise, impaired skin and mucosal sensitivity; rarely – confusion, psychosis.

Cardiovascular system and blood (hematopoiesis, hemostasis): BP decrease, tachycardia, cardialgia, cardiac rhythm disorders, AV blockade, redness of skin; rarely – development or deepening of heart failure, leukopenia or leukocytosis.

Respiratory system: dyspnea; rarely – respiratory distress syndrome, acute pulmonary edema.

Gastrointestinal system disorders: feeling of discomfort in the epigastric region, nausea, vomiting, diarrhea, increased liver transaminase activity; rarely – hyperbilirubinemia.

Urogenital system disorders: rarely – renal failure, hematuria.

Musculoskeletal system: arthralgia; with prolonged continuous use (more than 4 weeks) – reversible hyperostosis of tubular bones.

Allergic reactions: skin rashes, urticaria, itching.

Others: increased sweating, hyperthermia, chills, swelling of the limb into the vein of which the infusion is carried out; rarely – increased titer of C-reactive protein; reactions at the injection site – pain, edema, erythema, impaired sensitivity, phlebitis proximal to the place of injection (up to 40% of patients).

Extremely rare (up to 1% of cases): Shock, acute heart failure, hyperbilirubinemia, bleeding, somnolence, bradypnea, decreased respiratory function, tachypnea, anuria, impaired renal function, hypoglycemia, cardiac ventricular fibrillation, grade II AV block, supraventricular arrhythmia, neck muscle tension, increased irritability, hypothermia, hypercapnia, skin hyperemia, hematuria, peritoneal symptoms, tachyphylaxis, hyperkalemia, thrombocytopenia, anemia.

In newborns: Apnea (frequency 10-12%), fever (14%), skin hyperemia (about 10%, especially with IV administration), bradycardia (7%), decreased BP (4%), seizures (4%), tachycardia (3%); about 2%, diarrhea, sepsis; about 1%, cardiac arrest, edema, DIC syndrome, hypokalemia; ≤1% – cerebral hemorrhage, excessive neck extension, hypothermia, nervous agitation, lethargy, congestive heart failure, grade II AV block, supraventricular tachycardia, ventricular fibrillation, bradypnoea, stridor, hypercapnia, respiratory depression, tachypnoea, regurgitation of gastric contents, hyperbilirubinemia, anemia, bleeding, thrombocytopenia, anuria, hematuria, peritoneal symptoms, hypoglycemia, hyperkalemia; hyperostosis in the bones of the lower extremities has been reported with a prolonged course of treatment (over several weeks) (see See also “Precautions”).

In intracavernosal administration

Local reactions: Penile pain (37%), excessively long erections (up to 4-6 h – 4%), hematoma (3%) and ecchymosis (2%) at the injection site (associated with improper insertion technique), fibrous nodules formation and Peyronie’s disease (3-8%), penile edema (1%), penile rash (1%); Less than 1% – priapism (0.4%), balanitis, hemorrhages at the injection site; inflammation, itching and swelling at the injection site, urethral bleeding, penile disorders, includingincluding penile heat, numbness, fungal infection, irritation, hypersensitivity, phimosis, rash, erythema, venous discharge, painful erections, ejaculation disorders.

Systemic effects (rare): Pain and swelling of the scrotum and testicles, increased urination, urinary incontinence, BP fluctuations (increase or decrease), tachycardia, supraventricular extrasystole, peripheral circulation disorders, fatigue, headache, hypoesthesia, leg swelling, hyperhidrosis, nausea, dry mouth, increased serum creatinine levels, cramping of the calf muscles, weakness in the buttocks, localized pain (in the chest, buttocks, pelvis, legs, genitals, abdomen), mydriasis, flu-like syndrome.

Overdose

Symptoms: overdose of the drug may be manifested by decreased blood pressure and increased heart rate. Vasovagal reactions with pale skin, increased sweating, nausea and vomiting may develop, which may also be accompanied by myocardial ischemia and symptoms of heart failure, and there may be pain, swelling and reddening of the tissue at the site of infusion.

Treatment: the drug dose should be reduced or the infusion should be stopped. If there is a pronounced decrease in blood pressure, the patient should elevate his legs while lying down.

Pregnancy use

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

Paediatric use

In newborns should be used under continuous monitoring of BP, with mandatory ventilatory support.

There is currently no experience with intracavernous administration in patients less than 18 years of age.

Similarities