VAP 500 - instructions for use, dose, side effects, contraindications

Active substanceAlprostadilAlprostadil

Similar drugsTo uncover

Alprostan® Zentiva

concentrate d / infusion

Zentiva c.s. Czech Republic

Arters-Vero®

lyophilizate d / infusion

VEROPHARM SA Russia

Vazaprostan®

lyophilizate d / infusion

YUSB Pharma GmbH Germany

Vazaprostan®

lyophilizate d / infusion

YUSB Pharma GmbH Germany

VAP® 20

concentrate d / infusion

SEM Pharmaceuticals Limited Cyprus

VAP 500

concentrate d / infusion

SEM Pharmaceuticals Limited Cyprus

Kaverdzhekt®

lyophilizate in / cavern.

Pfizer IFG Belgium N.V. Belgium

Dosage form: & nbspconcentrate for solution for infusion

Composition:

1 ampoule contains:

active substance: Alprostadil * 500 μg

Excipients: ethanol &

* Alprostadil = PGE₁ (Prostaglandin E₁)

Description:Transparent colorless liquid with a characteristic smell of ethanol.

Pharmacotherapeutic group:Vasodilating agent (Prostaglandin E1)

ATX: & nbsp

G.04.B.E.01 Alprostadil

Pharmacodynamics:

The most important pharmacological effects of prostaglandin E₁ (PGE₁) relate vasodilation, blocking of aggregation and activation of platelets.

Maintenance of patency of the open arterial duct

Due to the effect on the smooth muscle fibers of the arterial duct (ductus arteriosus botalli) alprostadil interferes with the functional closure of the arterial duct shortly after birth or reopens it,It is also believed that a decrease in pulmonary vascular resistance occurs, which improves pulmonary blood flow in those newborns who have pulmonary vascular resistance in congenital heart disease. Alprostadil improves hemodynamics in congenital cyanotic heart disease

In infants with interruption of the aortic arch or with severe coarctation of the aorta alprostadil allows to maintain distal aortic perfusion, providing blood flow through the arterial duct from the pulmonary artery to the aorta. In infants with coarctation of the aorta alprostadil reduces aortic narrowing, relaxing the tissue of the aortic wall or increasing the diameter of the aorta by expanding the duct.

In infants with such anomalies of the aortic arch, the systemic blood flow to the trunk and extremities increases, improving the supply of tissues with oxygen and kidney blood flow.

The time from the beginning of infusion to the maximum effect in children with coarctation of the aorta is usually about 3 hours (15 minutes - 11 hours), in children with interruption of the aortic arch of about 1.5 hours (15 minutes - 4 hours), and in children with cyanotic heart pockets about 30 minutes.

Severe chronic heart failure in patients awaiting heart transplantation

For these serious patients, the most important pharmacological effect of alprostadil is the improvement of hemodynamics, which is manifested by:

- increase in stroke volume and cardiac index

- decrease in systemic arterial pressure, pulmonary pressure, pressure in the right atrium and pulmonary capillary vascular resistance.

Pharmacokinetics:

Biotransformation process PGE₁ occurs mainly in the lungs, with "first passage" through the lungs, about 80% of the active substance is metabolized (mainly β and ω-oxidation). Metabolites are excreted by the kidneys within 24 hours.

Indications:

The need for temporary maintenance of the functioning of the arterial duct until the moment of corrective surgery with congenital ductus-dependent heart defects in newborns (including with pulmonary atresia, pulmonary artery stenosis, tricuspid atresia, tetralogy of Fallot, coarctation of the aorta, atresia of the left heart, interrupted aortic arch with valve stenosis, transposition of the great arteries, combined or not with other shirts).

Severe chronic heart failure in patients waiting for a heart transplant, with severe symptoms and unstable hemodynamics, despite the therapy (cardiac glycosides, diuretics, ACE inhibitors).

Contraindications:

Hypersensitivity to alprostadil or other components of the drug.

Also, in the case of maintaining the patency of the open arterial duct:

Respiratory distress syndrome, spontaneous opening of the ductus arteriosus

Also in the case of severe chronic heart failure in patients waiting heart transplant:

Pronounced violations of the rhythm of the heart, exacerbation of coronary heart disease.

Myocardial infarction or stroke for 6 months before the start of therapy.

Clinical or radiologic signs of developing pulmonary edema or initial signs of edema, expressed ventilation disorders due to chronic obstructive pulmonary diseases.

Acute hepatic insufficiency (increased activity of transaminases or gamma-glutamyltransferase) or severe liver disease in the anamnesis.

High risk of bleeding (gastric or duodenal ulcer, multiple trauma).

Pregnancy, lactation.

Pregnancy and lactation:Use during pregnancy is contraindicated. It should be canceled breastfeeding.

Dosing and Administration:

Cooking solution should be immediately before the infusion. Do not use a solution cooked more than 24 hours ago. Enter through the central venous catheter, using an automatic infusion pump. The drug is dissolved in a solution of glucose 5% or in a 0.9% solution of sodium chloride

Do not directly contact the concentrate with plastic surfaces. Therefore, it is recommended to inject the concentrate into a ready solution of glucose or sodium chloride, in order to avoid contact with the walls of the container

Maintenance of patency of the open arterial duct:

Initial dose PGE₁ - 50 - 100 ng / kg / min. After the effect is achieved, with an improvement in oxygenation or with an increase in systemic blood pressure and blood pH, the infusion rate can be reduced to the lowest dose while maintaining the effect.

Usually 1 ml of the drug is diluted with 0.9% sodium chloride solution or 5% aqueous glucose solution to a final volume of 100-250 ml. The solution thus prepared contains 500 mcg PGE₁.

For infusion rate of 50 ng / kg / min:

Solution for infusion, including volume of ampoule (ml)	The concentration of alprostadil in solution (μg / ml)	Infusion rate (ml / kg / h)
250	2	1,5
100	5	0,6

The drug is used 2-3 days before the scheduled date of the operation. However, after careful correlation of benefit and risk, therapy can be administered for a longer period (up to 3 weeks).

Severe chronic heart failure v patients waiting for a heart transplant

The effective and tolerated dose is determined individually by catheterization of the right heart for 24-72 hours. The dose is selected according to the standard step: 2.5; 5; 10; 15; 20; 25; thirty; 35; 40 ng / kg / min. Before each dose increase, all hemodynamic parameters (heart rate, peripheral arterial pressure, central venous pressure, pulmonary artery wedge pressure and cardiac output) are measured by thermodilution. Dose is increased at an interval of 15 minutes. An increase in the cardiac index by at least 20% is estimated as an effective hemodynamic change. The maximum dose is 5-40 ng / kg / min. If side effects occur, the dose is reduced by at least 50% (up to an average initial dose of 2.5-20 ng / kg / min).In a number of cases with repeated individual side effects or with the development of pulmonary edema during continuous therapy PGE₁ (vasodilating effect) with simultaneous clinical improvement of heart failure symptoms, a gradual dose reduction of up to 1-5 ng / kg / min is possible.

Usually the preparation is dissolved to a final volume of 100 ml. The solution is injected for 48 hours.

For infusion rate 2.5 ng / kg / min:

Solution for infusion (ml)	The concentration of alprostadil in solution (μg / ml)	Infusion rate (ml / kg / h)
100	5	0,03

In severe chronic heart failure, the duration of therapy depends on the clinical condition.

Side effects:

Maintaining open arterial duct:

Often: Apnea, fever (as an effect on the central nervous system), facial hyperemia, decreased blood pressure, bradycardia, tachycardia, seizure or convulsive muscle twitching.

In 1% of patients (or less often):

From the cardiovascular system: hypovolemic shock, congestive heart failure, cardiac arrest, atrioventricular blockade of degree II, supraventricular tachycardia, ventricular fibrillation, edema and hyperemia of the skin.

From the respiratory system: bradypnoe, tachypnea, respiratory distress, including respiratory depression.

Metabolism: hypercapnia, hyperkalemia or hypokalemia, hypocalcemia, hypoglycemia, ketoacidotic hyperglycemia (in newborns whose mothers have diabetes mellitus)

From the digestive system: necrotizing enterocolitis.

From the nervous system: tension of the neck muscles, increased excitability, nervousness, inhibition.

Laboratory indicators: Anemia, thrombocytopenia, bleeding, disseminated intravascular coagulation.

From the genitourinary system: renal failure, anuria, hematuria.

From the side of the liver: increasing the level of bilirubin.

Other: infection, hypothermia, urticaria.

Children with a body weight of less than 2 kg at birth have a predisposition to certain side effects from the cardiovascular system, as well as respiratory depression. Children with cyanosis have a predisposition to respiratory depression.

With long-term treatment, hyperostosis of tubular bones can occur, reversible after discontinuation of treatment.In addition, there was damage to the arterial duct, pulmonary artery or aorta (weakening of the wall with the formation of edema, cracks or even aneurysms).

In some cases it is necessary to track the occurrence of dose-dependent hyperplasia of the mucous membrane of the pylorus.

Severe chronic heart failure in patients awaiting heart transplantation

Very often (more often 10%); redness, anxiety, general malaise, pain (joint, muscle, headache), vomiting, fever.

Often (up to 10%): erythema of the skin, lowering blood pressure, abdominal pain, tachycardia, diarrhea, chills, increasing serum creatinine.

In addition, patients with peripheral arterial disease with intravenous administration of low doses PGE1 the following side effects can occur:

Chills, sweating, gastrointestinal symptoms (nausea, anorexia), skin reactions (allergic symptoms, itching), paresthesia, joint pain, dizziness and fatigue, tachyarrhythmia, palpitations, pain behind the sternum.

In some cases, there were manifestations of acute pulmonary edema or circulatory insufficiency.

With prolonged treatment for more than 2-4 weeks, single cases of reversible hyperostosis of tubular bones were described.

Deviations from laboratory parameters (increase in the titer of the C-reactive protein, increase in the activity of transaminases, thrombocytosis and changes in the leukocyte formula) returned to normal values after discontinuation of the infusion.

Overdose:

In newborns and infants:

Overdose of the drug may manifest as apnea, bradycardia, hyperthermia, lowering blood pressure, hyperemia. In the case of apnea and bradycardia, the infusion should be stopped and symptomatic therapy started. In the case of hyperthermia, lowering blood pressure or hyperemia, treatment is continued, being careful, the speed of infusion should be reduced to the disappearance of symptoms.

In adults:

Overdose can be manifested by lowering blood pressure and reflex tachycardia due to the vasodilating effect of the drug. In this case, it is necessary to reduce the dose of the drug or stop the infusion.

Usually, treatment is not required, given the rapid metabolism of the drug.

Interaction:

Alprostadil can enhance the effect of antihypertensive drugs, vasodilators.The simultaneous use of alprostadil in patients taking anti-clotting drugs (oral anticoagulants, heparin, antiaggregants and thrombolytic drugs) may increase the chance of bleeding. In combination with cefamandole, cefoperazone, cefotetan and thrombolytic - increases the risk of bleeding. Alpha-adrenomimetics - metameninol, epinephrine, phenylephrine - reduce the vasodilating effect.

Special instructions:

Maintenance of patency of the open arterial duct

The drug can be used in children only in pediatric clinics, equipped with cardiac diagnostic equipment and intensive care unit.

In children with congenital malformations, the following indicators are regularly determined: arterial blood gases (P₀₂, R_C02), arterial blood pH, blood pressure, ECG, heart rate, respiratory rate, respiratory status (continuous monitoring).

Children with an anomaly of the arch of the aorta should be additionally monitored: blood pressure (in the descending part of the aorta or on the lower limbs), pulsation of the femoral artery palpation, diuresis.

In newborns with cyanogen with a body weight at birth less than 2 kg, apnea may occur during the first hours of infusion. If necessary, it should be possible to perform intubation and connect to an artificial respiration apparatus. To achieve the desired effect PGE₁ should be administered at the lowest possible dose in the shortest time interval. The benefit and risk of long-term treatment should be assessed in seriously ill newborns.

In newborns receiving the drug for more than 5 days, it is necessary to monitor the potential rapid dose-dependent hyperplasia of the gastric pylorus mucosa.

Absolutely contraindicated application PGE₁ In newborns with respiratory distress syndrome, which is sometimes mistaken for a cyanotic heart disease!

It is necessary to monitor newborns with a penchant for hemorrhages (umbilical artery catheter, auscultation, Doppler sensor).

In the case of a marked reduction in blood pressure (more than 2 standard deviations of more than 30 minutes), it is necessary to immediately reduce the infusion rate.

Severe chronic heart failure in patients awaiting heart transplantation

The drug can be used only in centers that have experience in the treatment of patients who are candidates for heart transplant, the possibility of invasive monitoring of hemodynamic parameters within 48-72 hours.

For optimal hemodynamic action PGE₁ on the total blood flow it is necessary to ensure a positive fluid balance with continuous monitoring of hemodynamic parameters. 12 hours after the administration of the optimal individual maintenance dose, it is necessary to re-evaluate hemodynamics. At this point in time, as a sufficient improvement, maintenance of an increase in the cardiac index by 20% (at least) from the baseline level (before administration PGE₁), as well as a decrease in pulmonary vascular resistance by at least 4 units of Wood (Wood).

Calculation of Wood's units: (mean pressure in the pulmonary artery - wedging pressure of pulmonary capillaries) / cardiac output.

If this drug is well tolerated, then the use of chronic infusion therapy is justified. For this, a permanent catheter connected to a portable perfusor is placed in the central vein.

In the course of chronic infusion therapy, outpatients should monitor the condition of patients in the clinic every month and every month during the first month.

This variant of long-term use preparation requires a high level of interaction on the part of the patient, for example, with aseptic preparation of the infusion solution, thoroughness with self-administered infusion, careful handling of the catheter. The physician should conduct the necessary instruction and training of the patient, especially on the aseptic preparation of the infusion solution. The patient should explain that a constant infusion of the drug is vital and that even short breaks in the infusion therapy can lead to a rapid resumption of the symptoms. It must be understood that such therapy must be carried out without interruption and for a sufficiently long time. The patient's adherence to such treatment is a prerequisite for the use of the drug.

Effect on the ability to drive transp. cf. and fur:The drug may affect the ability to actively participate in street traffic or management mechanisms, especially at the beginning of treatment,with increasing dose and drug withdrawal.

Form release / dosage:

Concentrate for the preparation of solution for infusions of 0.5 mg / ml.

Packaging:

For 1.0 ml in a neutral neutral glass ampoule (type I Ph. Eur.) with a ring of yellow color.

For 5 or 10 ampoules together with instructions for use in a cardboard box with a special holder for ampoules.

Storage conditions:

List B.

At a temperature of 2 to 8 ° C (in the refrigerator), in a place protected from light.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:LSR-004848/10

Date of registration:28.05.2010 / 13.03.2013

Expiration Date:Unlimited

The owner of the registration certificate:SEM Pharmaceuticals LimitedSEM Pharmaceuticals Limited Cyprus

Manufacturer: & nbsp

DREHM Pharma GmbH, Austria Austria

Representation: & nbspSEM Pharmaceuticals LimitedSEM Pharmaceuticals LimitedRussia

Information update date: & nbsp22.01.2017

Illustrated instructions

Instructions

VAP 500 (Vap 500)