Vap 20.

Vap 20 contains the substance alprostadil. It belongs to the group of prostaglandins.

Indications Wapa 20.

It is used to eliminate obliterating pathologies of the 3-4th degree of chronic type (the Fontaine classification is used), which are not subject to revascularization (or if revascularization in such people has not yielded results).

The drug is not recommended for use in the treatment of obliterating pathologies (chronic type) in the area of peripheral arteries of the 4th degree.

Release form

Released as a concentrate for the preparation of infusion in glass ampoules with a volume of 1 ml (type I Ph.EUR). A separate pack contains 5 or 10 ampoules with the medicine.

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Pharmacodynamics

The active component of the drug alprostadil is a vasodilator that helps to increase blood circulation, performing the process of dilation of precapillary sphincters with arterioles. The drug has a positive effect on microcirculation processes, as well as rheological parameters of the blood.

After intravenous infusion, there is an increase in erythrocyte elasticity, as well as suppression of their aggregation in ex vivo indications. At the same time, alprostadil effectively inhibits the process of platelet activation when acting in vitro. This effect extends to the properties of changing the type of platelets, as well as aggregation and release of components located inside the granules, as well as the release of the substance thromboxane (helps aggregation processes). The drug helps reduce the formation of arterial thrombi in in vivo tests on animals.

The use of drugs activates fibrinolysis processes, increasing its individual internal values (plasmin with plasminogen, and in addition, the action of the plasminogen activator inside the tissues).

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Pharmacokinetics

Alprostadil is a synthetic analogue of natural PG: E1, which has a short half-life. When taking the drug orally at a dose of 60 mcg, after 2 hours the peak plasma level in a healthy person was higher by 6 pg / ml than the maximum value at the placebo stage (is 2.4 pg / ml). The half-life in the α-stage is approximately 0.2 minutes (calculated value), and in the β-stage - about 8 minutes. As a result, the drug reaches the equilibrium level quite soon after the onset of the infusion.

Alprostadil is metabolized in the lungs – about 80-90% in the first pass. The primary breakdown products formed in the first pass are 15-keto-PGE 1, and also PGE 0 (the so-called 13,14-dihydro-PGE 1) with the element 15-keto-PGE 0 (which is 13,14-dihydro-15-keto-PGE 1) – then continue to be broken down (among other things, β-oxidation and ω-oxidation processes occur).

The decay products are excreted in urine (88%) and feces (12%). Complete excretion takes 72 hours. Of the primary decay products, only the element 15-keto-PGE 0 can be determined by in vitro exposure using lung homogenates.

When alprostadil is taken in the amount of 60 mcg, PGE 0 reaches a peak plasma level in a healthy person in 2 hours - 11.8 pg / ml after the placebo stage (equal to 1.7 pg / ml), while the half-life is approximately 2 minutes at the α stage, and about 33 minutes during the β stage. The maximum value is observed after 119 minutes. At the same time, the corresponding indicators for the element 15-keto-PGE 0 are: peak level - 151 pg / ml (while placebo is 8 mcg / ml), α half-life is about 2 minutes, and β half-life is 20 minutes; the peak is reached in 106 minutes.

Synthesis of alprostadil with macromolecular elements within plasma is 93%.

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Dosing and administration

The drug should be administered intravenously or intraarterially, provided that the doctor performing the procedure has experience in the field of angiology, is familiar with modern methods of regular monitoring of cardiovascular values, and has the equipment required for these purposes. The solution cannot be administered intravenously by bolus method.

For intravenous treatment of grade 3 pathologies.

The following intravenous treatment regimen is used: dissolve the contents of 2 ampoules (equal to 40 mcg of the drug) in a sodium chloride solution (0.9%; take 50-250 ml), and then administer the resulting substance over a period of 2 hours. This dosage is used 2 times a day.

Alternative method: single daily infusion over 3 hours. Three ampoules (60 mcg alprostadil) should be administered, which are dissolved using the same amount of the above solvent.

For people with renal dysfunction (renal insufficiency with CC values >1.5 mg/dl), intravenous therapy should be started with the introduction of 1 ampoule twice a day (twice 20 mcg of Vap 20). Each procedure lasts 2 hours. Taking into account the overall clinical picture, it is allowed to increase the dosage to the standard portion indicated above over a period of 2-3 days.

For individuals with renal insufficiency, as well as those who fall into the risk category for cardiac dysfunction, it is necessary to limit the daily infusion volume to 50-100 ml, and the administration must be carried out using an infusion device.

Treatment of pathologies of the 3rd and 4th degree by introducing drugs into the arterial area.

Below is the following scheme of intra-arterial treatment course: dissolve 1 ampoule (20 mcg of the substance) in sodium chloride solution (0.9%). In this case, the volume of the finished solution will be half of the medicinal ampoule (in 25 ml of this solution - 10 mcg of the drug). Infusion is carried out using a special device for 1-2 hours. If the tolerance of the drug remains satisfactory, it is allowed to increase the dose to 1 ampoule (or 20 mcg of the active component), especially if there are necroses on the body. Often 1 infusion is required per day.

When infusing via an inserted catheter, taking into account the severity of the disease and the tolerance of the drug, a dosage of 0.1-0.6 ng/kg/minute is prescribed (approximately a quarter/half of an ampoule with the drug). In this case, the duration of infusion using the device is 12 hours.

After 3 weeks of therapy, it is necessary to determine the advisability of further use of the drug. If there is no result, the drug must be discontinued. The therapeutic course may last no more than 1 month.

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Use Wapa 20. during pregnancy

The drug should not be prescribed to pregnant women, and if it is necessary to use it during lactation, breastfeeding should be discontinued for the duration of treatment.

Women of reproductive age should use effective contraception while using the drug to avoid pregnancy.

Preclinical testing data demonstrate that Vap 20 does not affect fertility when taken in recommended medicinal doses.

Contraindications

Main contraindications:

• the presence of hypersensitivity to alprostadil or other components of the drug;
• in case of disorders in the functioning of the heart: decompensated heart failure (stages 3 and 4 according to the NYHA classification); inadequate therapy of cardiac arrhythmia and heart failure; arrhythmia of various origins (including those that cause the development of hemodynamic disorders); aortic/mitral stenosis/insufficiency; improperly controlled coronary heart disease; coronary heart disease and a recent (within the last six months) myocardial infarction;
• suspicion of the development of pulmonary edema (in chronic or acute form), made after an X-ray or clinical examination, as well as a history of pulmonary edema or pulmonary infiltration;
• chronic obstructive pulmonary pathologies in severe degrees, and in addition, pulmonary embolism;
• persons with documented liver disease (including those who have symptoms of acute liver failure - elevated GGT or transaminase levels) or severe liver failure (this includes a history of it);
• kidney dysfunction (oliguria);
• the presence of a tendency to develop bleeding (multiple injuries, as well as bleeding/erosive ulcerative pathology of the duodenum or stomach in acute form);
• history of stroke within the last six months;
• severely low blood pressure;
• the presence of general contraindications regarding infusion procedures (including congestive heart failure, cerebral or pulmonary edema, and hyperhydria);
• children and adolescents under 18 years of age.

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Side effects Wapa 20.

The use of the drug may cause the following side effects:

• disorders of the nervous system: mainly paresthesia of the limb on which the procedure was performed, as well as headaches. Rarely, cerebral seizures and a feeling of confusion occur. Development of psychosis or stroke and dizziness are possible;
• Gastrointestinal disorders: Gastrointestinal disorders are occasionally observed, including vomiting with diarrhea and nausea, as well as increased intestinal peristalsis (an effect caused by alprostadil). Abdominal pain with heartburn and anorexia may occur;
• manifestations of the cardiovascular system: in some cases, angina or tachycardia may occur and a decrease in blood pressure may be observed. Rarely, arrhythmia or heart failure occurs, as a result of which acute pulmonary edema begins, which may cause general heart failure. Blockades and myocardial infarction may be observed;
• reactions of the digestive system: liver enzyme levels may occasionally be disturbed;
• manifestations of the respiratory system: pulmonary edema is occasionally observed. Dyspnea may occur;
• disorders in the functioning of the hematopoietic system: anemia or leukocytosis, as well as thrombocytopenia or leukopenia are occasionally observed;
• laboratory test results: sometimes an increase in temperature or transaminase levels is observed. CRP values may also change, but they quickly return to normal after the end of therapy;
• reactions of the subcutaneous layer and skin: swelling, redness and hot flashes often occur;
• systemic disorders and manifestations at the infusion site: swelling and an increase in temperature with edema in the area of administration are often observed; in addition, reddening of the veins and the development of paresthesia are observed. Less often, chills with fever and hyperhidrosis begin. Phlebitis may appear at the infusion site, and in addition, thrombosis in the area of catheter insertion. Local bleeding, a feeling of malaise and a disorder of the sensitivity of the mucous membranes with the skin may also occur;
• immune disorders: sometimes allergic reactions develop (increased skin sensitivity – rashes, swelling, hyperhidrosis, discomfort in the joints with chills, as well as a pyrogenic reaction). Rarely – development of anaphylactoid or anaphylactic symptoms. Anaphylaxis is possible;
• disorders in the functioning of muscles and bones: sometimes signs of disorders in the joint area appear (including pain). Curable hyperostosis in the area of long tubular bones is observed sporadically (when using the drug for a period longer than 1 month);
• others: increased fatigue, anuria with vasalgia, a feeling of general weakness, renal failure and orthostatic collapse may be observed.

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Overdose

Manifestations of overdose are a decrease in blood pressure, as well as reflex tachycardia due to vasodilation. Other possible signs are: hyperhidrosis, vomiting, vasovagal syncope accompanied by pallor, as well as heart failure, nausea and myocardial ischemia. Local symptoms may develop: redness and swelling of the limb where the infusion is performed, as well as intolerance reactions.

Therapy should be symptomatic. The drug has no specific antidote. If the blood pressure drops or severe pain occurs when the required dose is exceeded, the infusion should be reduced or stopped immediately. If blood pressure drops, the victim should first be laid on his back, with his legs slightly raised. If the symptoms of the disorder do not go away, the cardiovascular system should be monitored. Sympathomimetic drugs should be prescribed if necessary.

Interactions with other drugs

During the use of Vap 20, potentiation of the properties of antihypertensive drugs, as well as antianginal drugs and vasodilators, may be observed. The combination of these drugs with alprostadil or use simultaneously with other vasodilators requires constant monitoring of the cardiovascular system (this includes monitoring blood pressure).

Adrenaline with noradrenaline, as well as sympathomimetic agents, weaken the vasodilatory effect of the drug.

Combination with antithrombotic drugs (drugs that inhibit platelet aggregation, anticoagulants and thrombolytics) can increase the tendency to bleeding. Given the weak inhibitory effect of Bap 20 on platelet aggregation in vitro, it should be used with caution in combination with anticoagulants.

Concomitant use with the drugs cefatetan and cefoperazone with cefamendole weakens the effect of alprostadil.

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Storage conditions

Vap 20 should be kept in a place protected from light and inaccessible to small children. Temperature conditions – within 2-8°C.

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Shelf life

Vap 20 is permitted for use within 3 years from the date of manufacture of the drug.

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