Vasaprostan lyophilisate for preparation of solution for infusion 60mkg / dose, No. 10

• Chronic obliterating arterial disease of stages III and IV (according to Fontaine's classification) in patients who cannot undergo revascularization or after unsuccessful revascularization.

• Intravenous use in the treatment of chronic obliterating stage IV arterial diseases is not recommended.

Administer intravenously or intra-arterially only. Intravenous use in the treatment of chronic obliterating stage IV arterial diseases is not recommended.

It is necessary to prepare the solution immediately before the infusion. The lyophilisate is dissolved immediately after adding isotonic 09% sodium chloride injection solution. At the beginning, the solution may turn out to be milky. This effect is created by air bubbles. After a short time, the solution becomes clear. Do not use the solution after 12 hours after preparation.

Application in pediatrics:

VasaprostanЃ is not recommended for children and adolescents under the age of 18, since the safety and efficacy of the drug in these age groups have not been studied.

Intra-arterial injection stage III and IV

Dissolve the contents of one ampoule of VasaprostanЃ (corresponds to 60 ?g of alprostadil) in 50-250 ml of isotonic 09% sodium chloride injection solution.

In the absence of other prescriptions, the contents of a 1/6 ampoule of VasaprostanЃ (corresponding to 10 ?g of alprostadil) should be administered intra-arterially for 60-120 minutes. when using an infusion device. If necessary, especially in the presence of necrosis under strict control of the tolerability of the drug, the dose can be increased to 1/3 of the ampoule (corresponds to 20 ?g of alprostadil). This dosage is usually given as a single daily infusion.

IV infusion stage III

Dissolve the contents of one ampoule of VasaprostanЃ (corresponds to 60 ?g of alprostadil) in 50-250 ml of isotonic 09% sodium chloride injection solution and inject the prepared solution intravenously for 2 hours 1 time a day.

In patients with impaired renal function (serum creatinine concentration more than 15 mg / dL), intravenous administration of VasaprostanЃ begins with 20 ?g (1/3 of an ampoule) administered for two hours. If necessary, after 2-3 days, a single dose of 20 mcg is increased to 40-60 mcg.

Patients with renal insufficiency or patients who can be attributed to a risk group due to impaired heart function, the volume of fluid administered during infusion should be limited to 50-100 ml per day in order to avoid the appearance of symptoms of overhydration. Infusion should be done using infusion pumps.

The duration of therapy is on average 14 days with a positive therapeutic effect, drug treatment can be continued for another 7-14 days. The course of treatment should not exceed 3-4 weeks. In the absence of a positive effect within 2 weeks from the start of treatment, further use of the drug should be discontinued.

1 ampoule contains:

Active ingredient: alprostadil (clathrate complex with alphadex 1: 1) - 60 mcg;

Excipients: alfadex (a-cyclodextrin) 1940.0 ?g, anhydrous lactose 47.5 mg.

Alprostadil = PGE1 (prostaglandin E1), INN

Alphadex = a-cyclodextrin (a-cd), INN

• Hypersensitivity to alprostadil or other components of the drug;

• Chronic heart failure III-IV functional class according to NYHA;

• Hemodynamically significant heart rhythm disturbances;

• Exacerbation of the course of coronary heart disease, myocardial infarction suffered in the last six months;

• Mitral and / or aortic stenosis and / or insufficiency;

• Acute pulmonary edema or a history of pulmonary edema in patients with heart failure;

• Severe chronic obstructive pulmonary disease or pulmonary veno-occlusive disease;

• Infiltrative lung disease;

• Diseases accompanied by an increased risk of bleeding (peptic ulcer and / or duodenal ulcer;

• Concomitant therapy with vasodilator or anticoagulant drugs;

• Violation of cerebral circulation during the last 6 months;

• Severe arterial hypotension;

• Renal dysfunction (oliguria);

• Acute liver failure (increased activity of aspartate aminotransferase alanine aminotransferase or gamma-glutamyltransferase) or severe liver failure, including a history;

• General contraindications for fluid resuscitation (eg, chronic heart failure, pulmonary or cerebral edema and hyperhydration);

• Pregnancy and the period of breastfeeding.

• Age up to 18 years (efficacy and safety have not been established).

Carefully:

Arterial hypotension.

Chronic heart failure of NYHA functional class I-II (special attention should be paid to controlling the load of the volume of the carrier solution). Patients on hemodialysis (treatment with the drug should be carried out in the post-dialysis period).

Patients with type 1 diabetes mellitus, especially with extensive vascular lesions (in elderly patients).

Trade name of the drug

VasaprostanЃ

International non-proprietary name

Alprostadil

Dosage form

lyophilisate for preparation of solution for infusion

Description

Hygroscopic white lyophilic mass.

Pharmacotherapeutic group

Vasodilating agent - prostaglandin E1, synthetic analogue

ATX code

G04BE01

Pharmacodynamics:

The drug prostaglandin E1 (PgE1) improves microcirculation and peripheral circulation has a vasoprotective effect. When administered systemically, it causes relaxation of smooth muscle fibers; it has a vasodilating effect; it reduces the total peripheral vascular resistance without changing blood pressure. In this case, a reflex increase in cardiac output and heart rate is noted. Promotes an increase in the elasticity of erythrocytes, reduces platelet aggregation and the activity of neutrophils increases the fibrinolytic activity of the blood. Has a stimulating effect on the smooth muscles of the intestines of the bladder of the uterus; suppresses the secretion of gastric juice.

Pharmacokinetics:

PgE1 is used in combination with alphacyclodextrin intravenously or intraarterially. During the preparation of the solution, the complex of the drug disintegrates into its constituent parts - PgE1 and alphacyclodextrin. When administered intravenously, a therapeutically significant concentration of the active substance is reached shortly after the start of drug administration, and the maximum concentration in blood plasma is reached within 2 hours from the start of administration. PgE1 is an endogenous substance with an extremely short half-life - the concentration in the blood plasma returns to the initial level 10 seconds after stopping the administration of the drug. The process of biotransformation of PgE1 occurs mainly in the lungs during the 'first pass' through the lungs, 60-90% of the active substance is metabolized with the formation of the main metabolites - 15-KeTO-PgE1 15-KeTO-PgE0 and PgE0.The main metabolic products are excreted by the kidneys - 88% and through the gastrointestinal tract - 12% within 72 hours. 93% of PgE1 binds to blood plasma proteins. Alphacyclodextrin has a half-life of about 7 minutes and is excreted unchanged by the kidneys.

Indications:

• Chronic obliterating arterial disease of stages III and IV (according to Fontaine's classification) in patients who cannot undergo revascularization or after unsuccessful revascularization.

• Intravenous use in the treatment of chronic obliterating stage IV arterial diseases is not recommended.

Contraindications:

• Hypersensitivity to alprostadil or other components of the drug;

• Chronic heart failure III-IV functional class according to NYHA;

• Hemodynamically significant heart rhythm disturbances;

• Exacerbation of the course of coronary heart disease, myocardial infarction suffered in the last six months;

• Mitral and / or aortic stenosis and / or insufficiency;

• Acute pulmonary edema or a history of pulmonary edema in patients with heart failure;

• Severe chronic obstructive pulmonary disease or pulmonary veno-occlusive disease;

• Infiltrative lung disease;

• Diseases accompanied by an increased risk of bleeding (peptic ulcer and / or duodenal ulcer;

• Concomitant therapy with vasodilator or anticoagulant drugs;

• Violation of cerebral circulation during the last 6 months;

• Severe arterial hypotension;

• Renal dysfunction (oliguria);

• Acute liver failure (increased activity of aspartate aminotransferase alanine aminotransferase or gamma-glutamyltransferase) or severe liver failure, including a history;

• General contraindications for fluid resuscitation (eg, chronic heart failure, pulmonary or cerebral edema and hyperhydration);

• Pregnancy and the period of breastfeeding.

• Age up to 18 years (efficacy and safety have not been established).

Carefully:

Arterial hypotension.

Chronic heart failure of NYHA functional class I-II (special attention should be paid to controlling the load of the volume of the carrier solution). Patients on hemodialysis (treatment with the drug should be carried out in the post-dialysis period).

Patients with type 1 diabetes mellitus, especially with extensive vascular lesions (in elderly patients).

Pregnancy and lactation:

Women of reproductive age

Women of reproductive age should use reliable contraceptive methods during treatment.

Pregnancy and lactation

The use of VasaprostanЃ during pregnancy is contraindicated. If necessary, the appointment during lactation, breastfeeding should be discontinued.

Fertility

According to preclinical studies, alprostadil does not have any adverse reactions from fertility.

Method of administration and dosage:

Administer intravenously or intra-arterially only. Intravenous use in the treatment of chronic obliterating stage IV arterial diseases is not recommended.

It is necessary to prepare the solution immediately before the infusion. The lyophilisate is dissolved immediately after adding isotonic 09% sodium chloride injection solution. At the beginning, the solution may turn out to be milky. This effect is created by air bubbles. After a short time, the solution becomes clear. Do not use the solution after 12 hours after preparation.

Application in pediatrics:

VasaprostanЃ is not recommended for children and adolescents under the age of 18, since the safety and efficacy of the drug in these age groups have not been studied.

Intra-arterial injection stage III and IV

Dissolve the contents of one ampoule of VasaprostanЃ (corresponds to 60 ?g of alprostadil) in 50-250 ml of isotonic 09% sodium chloride injection solution.

In the absence of other prescriptions, the contents of a 1/6 ampoule of VasaprostanЃ (corresponding to 10 ?g of alprostadil) should be administered intra-arterially for 60-120 minutes. when using an infusion device. If necessary, especially in the presence of necrosis under strict control of the tolerability of the drug, the dose can be increased to 1/3 of the ampoule (corresponds to 20 ?g of alprostadil). This dosage is usually given as a single daily infusion.

IV infusion stage III

Dissolve the contents of one ampoule of VasaprostanЃ (corresponds to 60 ?g of alprostadil) in 50-250 ml of isotonic 09% sodium chloride injection solution and inject the prepared solution intravenously for 2 hours 1 time a day.

In patients with impaired renal function (serum creatinine concentration more than 15 mg / dL), intravenous administration of VasaprostanЃ begins with 20 ?g (1/3 of an ampoule) administered for two hours. If necessary, after 2-3 days, a single dose of 20 mcg is increased to 40-60 mcg.

Patients with renal insufficiency or patients who can be attributed to a risk group due to impaired heart function, the volume of fluid administered during infusion should be limited to 50-100 ml per day in order to avoid the appearance of symptoms of overhydration. Infusion should be done using infusion pumps.

The duration of therapy is on average 14 days with a positive therapeutic effect, drug treatment can be continued for another 7-14 days. The course of treatment should not exceed 3-4 weeks. In the absence of a positive effect within 2 weeks from the start of treatment, further use of the drug should be discontinued.

Side effects:

Possible side effects are listed below by body system and frequency of occurrence: very often (> 1/10) often (> 1/100 <1/10) infrequently (> 1/1000 <1/100) rarely (> 1/10000 <1 / 1000) very rarely (<1/10000) unknown (cannot be estimated from the available data).

When using the drug VasaprostanЃ, the following undesirable effects are observed:

Violation of the hematopoietic and lymphatic system:

Rarely: thrombocytopenia; leukopenia; leukocytosis;

Very rare: bleeding anemia.

Nervous system disorders:

Often: headache;

Rarely: confusion of consciousness, convulsions of central genesis;

Very rare: drowsiness; dizziness;

Unknown: cerebrovascular accident.

Heart disorders:

Uncommon: decreased systolic blood pressure; tachycardia; angina pectoris;

Rarely: arrhythmia, biventricular heart failure, pulmonary edema;

Very rare: acute heart failure; ventricular fibrillation; atrioventricular block II degree; supraventricular arrhythmia;

Unknown: myocardial infarction.

Vascular disorders:

Very rare: shock.

Respiratory system disorders of the chest and mediastinal organs:

Rarely: pulmonary edema;

Very rare: bradypnea; decreased respiratory function; tachypnea; hypercapnia;

Unknown: dyspnea.

Gastrointestinal disorders:

Uncommon: diarrhea, nausea, vomiting;

ќчень редко: перитонеальные симптомы.

Ќарушени¤ со стороны обмена веществ и питани¤:

ќчень редко: гипогликеми¤ гиперкалиеми¤.

Ќарушени¤ со стороны печени и желчевывод¤щих путей:

–едко: повышение активности 'печеночных' трансаминаз повышение активности гамма-глутамилтрансферазы;

ќчень редко: гипербилирубинеми¤.

Ќарушени¤ со стороны почек и мочевывод¤щих путей:

ќчень редко: нарушение функции почек гематури¤.

Ќарушени¤ со стороны кожи и подкожных тканей:

„асто: покраснение отЄк 'прилив' крови.

јллергические реакции:

Ќечасто: кожна¤ гиперчувствительность например сыпь.

Ќарушени¤ со стороны скелетно-мышечной и соединительной ткани:

ќчень редко: напр¤жение мышц шеи при длительном применении (4 недели и более) может возникать обратимый гиперостоз трубчатых костей также возможно увеличение титра —-реактивного белка;

Ќечасто: боль в суставах.

ќбщие расстройства и нарушени¤ в месте введени¤:

„асто: боль головна¤ боль после внутриартериального введени¤: ощущение жара ощущение распирани¤ локальный отЄк парестези¤;

Ќечасто: после внутривенного введени¤: ощущение жара ощущение распирани¤ локальный отЄк парестези¤ лихорадка повышенное потоотделение озноб;

ќчень редко: анафилакси¤/ анафилактоидна¤ реакци¤ утомл¤емость общее недомогание повышенна¤ раздражительность гипотерми¤ тахифилакси¤;

Ќеизвестно: флебит на участке инъекции тромбоз кровотечение в месте введени¤ катетера.

ѕередозировка:

ѕередозировка препаратом ¬азапростанЃ может про¤вл¤тьс¤ выраженным снижением артериального давлени¤ и рефлекторной тахикардией. ¬озможно развитие вазовагальных реакций с бледностью кожных покровов повышенным потоотделением тошнотой и рвотой. ¬озможны боль отек и покраснение кожи в месте инфузии.

ѕри симптомах передозировки необходимо уменьшить дозу препарата ¬азапростанЃ или прекратить инфузию. ѕри значительном снижении артериального давлени¤ пациенту в положении 'лежа' необходимо приподн¤ть ноги. ѕри сохранении симптомов необходимо использовать симпатомиметики.

¬заимодействие:

јлпростадил может усиливать эффект гипотензивных средств вазодилататоров. ќдновременное применение алпростадила у пациентов принимающих антикоагул¤нты и/или антиагреганты может увеличить веро¤тность кровотечени¤.

—импатомиметики эпинефрин (адреналин) норэпинефрин (норадреналин) снижают вазодилатирующий эффект. Ќеобходимо учитывать что взаимодействи¤ препаратов возможны и в том случае если вышеперечисленные средства примен¤лись незадолго до того как была начата терапи¤ препаратом ¬азапростанЃ.

ќсобые указани¤:

¬азапростанЃ нельз¤ вводить болюсно!

¬азапростанЃ могут примен¤ть только врачи имеющие опыт работы в ангиологии знакомые с современными методами непрерывного контрол¤ за показател¤ми сердечно-сосудистой системы.

ѕациенты с ишемической болезнью сердца а также пациенты с периферическими отеками и нарушением функции почек (сывороточный креатинин более 15 мг/дл) должны находитьс¤ под наблюдением в стационаре в течение одного дн¤ после прекращени¤ применени¤ препарата.

ѕациентам с почечной недостаточностью или пациентам которых можно отнести к группе риска в св¤зи с нарушением функции сердца объем вводимой при инфузии жидкости следует ограничить до 50-100 мл в сутки во избежание по¤влени¤ симптомов гипергидратации.

¬ период лечени¤ необходим регул¤рный контроль артериального давлени¤ частоты сердечных сокращений биохимических показателей крови свертывающей системы крови (при нарушени¤х свертывающей системы крови или при одновременной терапии средствами которые вли¤ют на показатели свертывающей системы) при необходимости - контроль массы тела баланса жидкости измерение центрального венозного давлени¤ проведение эхокардиографического исследовани¤.

‘лебит (проксимальнее места введени¤) как правило не ¤вл¤етс¤ причиной дл¤ прекращени¤ терапии признаки воспалени¤ исчезают через несколько часов после прекращени¤ инфузии или изменени¤ места введени¤ препарата специфического лечени¤ в подобных случа¤х не требуетс¤.  атетеризаци¤ центральной вены позвол¤ет снизить частоту про¤влени¤ данного побочного действи¤ препарата.

ѕри повреждении ампулы лиофилизат становитс¤ влажным и клейким и сильно уменьшаетс¤ в объеме. ¬ этом случае препарат использовать нельз¤.

¬ли¤ние на способность управл¤ть трансп. ср. и мех.:

јлпростадил может вызывать снижение систолического артериального давлени¤ и тем самым снижает способность к управлению транспортными средствами и зан¤тию другими потенциально опасными видами де¤тельности требующими повышенной концентрации внимани¤ и быстроты психомоторных реакций.

‘орма выпуска/дозировка:

Ћиофилизат дл¤ приготовлени¤ раствора дл¤ инфузий 60 мкг.

”паковка:

495 mg (corresponding to 60 ?g of alprostadil) in neutral glass ampoules with a blue dot above the cut and a blue marking ring.
10 ampoules, together with instructions for use, in a cardboard box with a special holder for ampoules.
In the case of packaging of the drug by ZAO FirmFirma Sotex,
5 ampoules are placed in a blister strip made of polyvinyl chloride film and polymer film or without polymer film.
2 blister packs of 5 ampoules, together with instructions for use, are placed in a cardboard box.

Storage conditions:

At a temperature not exceeding 25 ? C, out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date!

Vacation conditions

On prescription