Alprostan Zentiva - instructions for use, dose, side effects, contraindications

Alprostadil (synthetic analogue of natural prostaglandin E₁(PGE₁)) is a vasodilator, angioprotective drug. Acts in a complex way, improving microcirculation and peripheral circulation, causes vasodilation at the level of arterioles, precapillary sphincters, muscular arteries.Improves the rheological properties of blood, promoting the increase in the elasticity of red blood cells; has an effect on hemocoagulation, reducing the adhesion and aggregation of platelets. Has a fibrinolytic effect. It has an antiatherogenic effect, slowing the activation of neutrophils, excessive proliferation of cells of the vascular wall.

Reduces the overall peripheral vascular resistance, arterial pressure, reflexively increases the heart rate, which leads to an increase in cardiac output. Stimulates the smooth muscles of the intestine, bladder and uterus, inhibits the secretion of gastric juice.

Pharmacokinetics:

The half-life is about 10 seconds. Metabolized in the lungs at a single passage to 60-90%, as a result of enzymatic oxidation, three biologically active metabolites are formed: 15-keto-PGE₁ 15-keto-13,14-dihydro-PGE₁ and 13,14-dihydro-PEE₁ (PGE₀). Keto metabolites have a lower biological effect compared to alprostadil, the metabolite 13,14-dihydro-PGE₁ (PGE₀) is comparable with PGE₁ action. It is important that the PGE₀ lasts longer, its half-life is about 1 min (alpha-phase) and 30 min (beta phase).

In all likelihood, the pharmacodynamic effect is mainly caused by this biologically active stable metabolite. The main metabolites are excreted by the kidneys - up to 88% and intestines - up to 12%.

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 pulmonary atresia, pulmonary artery stenosis, tricuspid atresia, tetralogy of Fallot, coarctation of the aorta, atresia of the left heart, interruption of the aortic arch with stenosis of the valve, transposition of the trunk, arteries combined or not with other vices).

- Chronic obliterating diseases of the arteries III - IV stage (according to Fontaine's classification).

Contraindications:

In chronic obliterating diseases of the arteries

- Hypersensitivity to alprostadil or to any auxiliary substance of the drug;

- pregnancy and the period of breastfeeding;

- myocardial infarction during the last six months, subacute myocardial infarction, severe stable form of angina or unstable angina, chronic heart failure in the stage of decompensation, severe heart rhythm disturbances;

- broncho-obstructive syndrome of severe degree with signs of respiratory failure; pulmonary edema; infiltrative changes in the lungs, confirmed with the help of clinical and radiological examination;

- severe chronic liver dysfunction or acute liver failure;

- simultaneous application with vasodilating and anticoagulant agents;

- cerebral edema;

- oliguria;

- hyperhydration;

- the existing risk of hemorrhagic complications (hemorrhagic stroke, peptic ulcer of the stomach or duodenum, poliferative retinopathy with bleeding, multiple injuries, etc.).

In newborns

- hypersensitivity to alprostadil or to any auxiliary substance of the drug;

- respiratory distress syndrome;

- persistent open arterial duct.

Carefully:

With arterial hypotension, cardiovascular failure (special attention should be paid to reducing the load due to the volume of the solvent). Caution should be used with ALPROSTAN® ZENTIVA in patients with type 1 diabetes mellitus receiving insulin, especially with diabetic angiopathy; in patients,(treatment with the drug should be carried out in the post-dialysis period).

Care should be taken in newborns, especially in the case of bradypnoea, arterial hypotension, tachycardia, and febrile conditions.

Prostaglandin E₁ is a serious blocker of platelet aggregation, so the drug ALPROSTAN® ZENTIVA should be used in newborns with great care in connection with the risk of bleeding.

Pregnancy and lactation:

The use of the drug during pregnancy and during breastfeeding is contraindicated.

Dosing and Administration:

Recommended dilution of the drug ALPROSTAN® ZENTIVA, concentrate for solution for infusion.

The solution must be prepared immediately before the infusion is performed, with aseptic conditions. The solution is recommended to be used immediately after preparation, it is possible to temporarily store the resulting solution for not more than 24 hours at a temperature of 2-8 ° C.

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.

1 ampoule of the drug ALPROSTAN® ZENTIVA (0.2 ml) is diluted in 9.8 ml of 0.9% sodium chloride solution or 5% or 10% glucose solution, thus obtaining a concentration of 100 μg alprostadil in 10 ml of the solution. For administration, this stock solution is diluted with 0.9% sodium chloride solution or 5% aqueous glucose solution to a final volume of 100-250 ml.

Maintenance of patency of the open arterial duct in newborns.

The initial dose of ALPROSTAN® Zentiva is 0.01-0.05 μg / kg / min. Enter through the central venous catheter (or through the umbilical artery into the arterial duct), using an automatic infusion pump. 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 (0.01-0.02 μg / kg / min) while maintaining the effect. In exceptional cases, if the initial dosage has no effect, it is possible to increase the dose to 0.1 μg / kg / min. Serious side effects are the reason for lower dosage.

When taking it is necessary to monitor vital functions, hemodynamic parameters and acid-base balance and gas composition of the blood.

The drug is used 2-3 days before the scheduled date of the operation.However, after a thorough evaluation of the benefits and risks to the patient, therapy can be given for a longer period (up to 3 weeks).

In the treatment of adult patients with chronic obliterating diseases of the arteries limbs, the drug ALPROSTAN® ZENTIVA is administered intravenously at a dose of 50 μg to 200 μg once a day. As a solvent, 200-500 ml of a 0.9% solution of sodium chloride or 5% or 10% glucose solution is used, the infusion should last at least 2 hours. The solution should be prepared immediately before administration. The duration of treatment is an average of 14 days, with a positive effect, treatment with the drug can continue for another 7-14 days. The course of treatment should not exceed 4 weeks. In the absence of a positive effect within 2 weeks from the beginning of therapy, further use of the drug should be discontinued.

If the kidney function is violated (the concentration of creatinine in the blood serum is more than 150 μmol / L), intravenous administration starts with 20 μg. If necessary, after 2-3 days, the single dose is increased to 40-60 μg. For patients with renal and heart failure, the maximum volume of injected fluid is 50-100 ml / day. The course of treatment is 4 weeks.

Side effects:

The frequency of adverse reactions was determined according to the following gradation (classification of the World Health Organization): very frequent - more than 1/10, frequent - more than 1/100 to less than 1/10, infrequent - more than 1/1000 to less than 1/100, rare - from more than 1/10000 to less than 1/1000, very rare - from less than 1/10000, including individual messages, frequency is unknown - according to available data, determine the incidence rate a side effect is not possible.

In chronic obliterating diseases of the arteries

Immune system disorders: rare - allergic reaction.

Impaired nervous system: frequent - headache, dizziness.

Violations from the blood and lymphatic system: rare - leukocytosis, leukopenia.

Heart Disease: rare - tachycardia, stenocardia, acute heart failure, cardiac arrest.

Vascular disorders: frequent - lowering of arterial pressure, orthostatic hypotension.

Disturbances from the respiratory system, organs of the thorax and mediastinum: rare - pulmonary edema.

Disorders from the gastrointestinal tract: frequent - a feeling of discomfort in the epigastric region, nausea, vomiting, diarrhea.

Disturbances from musculoskeletal and connective tissue: frequency unknown - hyperostosis.

Disorders from the kidneys and urinary tract: infrequent - anuria, hematuria, renal insufficiency.

General disorders and disorders at the site of administration: very frequent - the appearance of signs of phlebitis proximal to the site of introduction, signs of inflammation disappear after several hours after stopping the infusion or changing the place of injection; frequent - a feeling of indisposition; frequency is unknown - chills, fatigue.

Disturbances from the skin and subcutaneous tissues: frequency unknown - increased sweating, skin rash, itching, hives.

Laboratory and instrumental data: infrequent - hyperkalemia or hypokalemia, hypoglycemia, transient increase in the activity of "hepatic" transaminases in the blood serum; frequency unknown - an increase in the titer of the C-reactive protein in the blood plasma.

If side effects occur, the dose should be reduced.

Neonatal application

Violations from the blood and lymphatic system: frequent - disseminated intravascular coagulopathy; frequency unknown - anemia, thrombocytopenia.

Disruption from the metabolism and nutrition: frequency is unknown - hypoglycemia.

Impaired nervous system: frequent - convulsions; frequency unknown - drowsiness.

Disorders of the psyche: frequency unknown - irritability.

Heart Disease: frequent - bradycardia, tachycardia; infrequent - acute heart failure, ventricular fibrillation, atrioventricular block of the 2nd degree, supraventricular tachycardia.

Vascular disorders: frequent - a decrease in blood pressure; infrequent - fragility of blood vessels; frequency unknown - shock, bleeding, flushing of the skin.

Disturbances from the respiratory system, chest and mediastinal organs: very frequent - respiratory failure, respiratory arrest; infrequent - bradypnoe, dyspnea, tachypnea, including respiratory depression.

Disorders from the gastrointestinal tract: frequent - diarrhea; infrequent - dose-dependent hyperplasia of the mucous membrane of the pylorus of the stomach, obstruction of the pylorus of the stomach, hypertrophy of the gastric mucosa; frequency is unknown - peritoneal symptoms.

Disturbances from musculoskeletal and connective tissue: infrequent - exostosis of tubular bones; frequency unknown - hyperostosis, neck muscle strain.

Disorders from the liver and bile ducts: infrequent - hyperbilirubinemia.

Disorders from the kidneys and urinary system: infrequent - anuria, hematuria, renal insufficiency.

General disorders and disorders at the site of administration: very frequent - transient fever, hyperthermia; frequent - the expansion of subcutaneous vessels (hyperemia); infrequent - hypothermia, tachyphylaxis.

Laboratory and instrumental data: infrequent - hypercapnia, hyperkalemia.

Overdose:

In newborns

Symptoms: apnea, bradycardia, hyperthermia, lowering of arterial pressure, hyperemia of the skin. In the case of apnea and bradycardia, the infusion should be stopped.

Treatment: symptomatic therapy. 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 case of signs of oppression of the respiratory center, artificial ventilation is indicated.

In adults

Symptoms: decrease in blood pressure, hyperemia of the skin, general weakness, increased frequency of heartbeats. Possible development of vasovagal reactions with pallor of the skin, increased sweating, nausea and vomiting, which may be accompanied by myocardial ischemia and symptoms of heart failure, as well as pain, swelling and redness of the tissue at the site of infusion.

Treatment: When symptoms of an overdose need to reduce the dose of the drug or stop the infusion. If the patient's blood pressure is significantly lowered, it is necessary to put and raise his legs. If symptoms persist, sympathomimetics should be used.

Interaction:

With the simultaneous use of alprostadil, the effect of antihypertensive and vasodilating drugs is enhanced. With the simultaneous use of alprostadil with anticoagulant and antiplatelet agents, the risk of bleeding increases.

In combination with cefamandole, cefoperazone, cefatetan and thrombolytics, the risk of bleeding increases.

Adrenomimetics - adrenaline, noradrenaline - reduce the vasodilating effect of alprostadil.

There is no data on the interaction between alprostadil and standard therapy used in newborns (or infants) with congenital heart defects. Standard therapy includes antibiotics such as penicillin or gentamicin, vasoconstrictor drugs, such as dopamine or isoproterenol, cardiac glycosides and diuretics, such as furosemide.

Special instructions:

The drug ALPROSTAN® ZENTIVA can be used only by physicians with experience in angiology, familiar with modern methods of continuous monitoring of the cardiovascular system and having for this purpose appropriate equipment and equipment for children's resuscitation.

During the period of treatment, it is necessary to control the hemodynamic parameters of the acid-base balance, the biochemical parameters of the blood, the coagulating blood system (in case of disorders of the blood coagulation system or with simultaneous therapy with drugs that affect the coagulation system).

In 10-12% of newborns with congenital heart defects, breathing may stop when exposed to alprostadil. Apnea is most often observed in newborns weighing less than 2 kg at birth, and most often occurs during the first hour of drug administration.Therefore, the drug ALPROSTAN® ZENTIVA should be used under constant monitoring of blood pressure, under conditions for carrying out artificial ventilation (IVL).

The drug ALPROSTAN® ZENTIVA should be administered in the shortest time and in the smallest dosage, capable of leading to the desired therapeutic effect. The risk of prolonged administration should be assessed in relation to the benefits of administering to a patient of infantile age.

With prolonged administration of alprostadil, neonatal cortical growth of tubular bones was observed. Cortical growth in children was reversed after the drug was withdrawn.

The drug ALPROSTAN® ZENTIVA is contraindicated for use in newborns (or infants) with respiratory distress syndrome. A differential diagnosis should always be made between respiratory distress syndrome and congenital heart disease with cyanosis (limiting pulmonary blood flow). The diagnosis should be based on the presence of cyanosis (an indicator of the partial pressure of oxygen in the blood (pO₂) less than 40 mm Hg) and the presence of radiologic signs of the limitation of pulmonary blood flow.

Arterial pressure should be controlled by a catheter in the umbilical artery, auscultatory or by doplerography. If the blood pressure drops significantly, the rate of administration should be immediately reduced. The use of the drug ALPROSTAN® ZENTIVA in newborns (or infants) can lead to obstruction of the pylorus of the stomach against the background of hyperplasia of the mucous membrane of the antral part of the stomach. The occurrence of this phenomenon is associated with the duration of treatment and the total dose of the drug. For newborns (or infants) who receive alprostadil in recommended doses for more than 120 hours, it is necessary to monitor possible manifestations of antral hyperplasia of the mucosa and obstruction of the pylorus.

In newborns (or infants) with reduced pulmonary blood flow, oxygen saturation increases inversely with the value of pO₂i.e. The best response to therapy occurs in patients with low pO values₂ (less than 40 mm Hg), while patients with high pO values₂ (more than 40 mm Hg) usually have a minimal response. In newborns (or infants) with reduced pulmonary blood flowthe effectiveness of alprostadil is determined by an increase in the saturation of blood with oxygen, an increase in systemic blood pressure and blood pH.

Patients with coronary heart disease, renal insufficiency (serum creatinine greater than 150 μmol / L) should be monitored in the hospital during treatment with ALPROSTAN® ZENTIVA and within 1 day after discontinuation of treatment. To avoid the appearance of symptoms of hyperhydration in such patients, the volume of the injected fluid, if possible, should not exceed 50-100 ml per day. It is necessary to monitor the patient's condition dynamically (control of blood pressure and heart rate), if necessary - control of body weight, fluid balance, measurement of central venous pressure or echocardiography.

In patients with chronic obliterating diseases of the arteries of the lower limbs, the use of ALPROSTAN® ZENTIVA is part of a comprehensive treatment, the clinical effect is long-lasting and may occur with a certain delay after the end of the course of treatment.

Phlebitis (proximal to the injection site), as a rule, is not a reason for discontinuing therapy,signs of inflammation disappear after a few hours after stopping the infusion or changing the place of administration, specific treatment in such cases is not required. Catheterization of the central vein can reduce the incidence of this side effect of the drug.

Effect on the ability to drive transp. cf. and fur:

It should be noted that the use of the drug ALPROSTAN® ZENTIVA may be accompanied by potential systemic manifestations in the form of lowering blood pressure, dizziness, or increased fatigue, which usually disappear shortly after the infusion is stopped due to the short biological half-life of the active substance. Therefore, care must be taken when managing vehicles and mechanisms and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Concentrate for the preparation of a solution for infusions of 0.1 mg / 0.2 ml.

Packaging:For 0.2 ml of the drug in ampoules of colorless glass. 5 ampoules are placed in a molded container made of PVC.Two molded containers (10 ampoules), together with instructions for use, are placed in a cardboard box.

Storage conditions:

Store at a temperature of 1 to 5 ° C. Do not freeze!

Keep out of the reach of children.

Shelf life:

2 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012232 / 01

Date of registration:14.10.2011 / 04.02.2014

Expiration Date:Unlimited

The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic

Manufacturer: & nbsp

ZENTIVA, k.s. Czech Republic

Representation: & nbspZENTIVA ZENTIVA Czech Republic

Information update date: & nbsp13.07.2017

Illustrated instructions

Instructions

Alprostan® Zentiva (Alprostan® Zentiva)