Expiration date: 02/2025

The composition and form of issue:

Lyophilisate for preparation of infusion solution (48.2 mg). 1 ampoule contains:

alprostadil (in combination with alfadex) 20 or 60 mcg

excipients: lactose alphadex 

in carton 1 contour cell pack with 10 vials.

Feature:

Lyophilisate white assembled on the bottom of the ampoule, forms a layer with a thickness of about 3 mm. After complete dissolution of the lyophilisate in physiological solution is a clear, colorless liquid.

Pharmacological action:

PGE1 the drug improves microcirculation and peripheral circulation, has vasoprotective action. With systemic administration causes relaxation of smooth muscle fibers, exerts vasodilating effect, reduces round without changes AD. It is noted a reflex increase in cardiac output and heart rate. Contributes to the elasticity of red blood cells, reduces platelet aggregation and activity of neutrophils, increases the fibrinolytic activity of blood. Has a stimulating effect on smooth muscles of intestines, bladder, uterus, suppresses gastric acid secretion.

Pharmacokinetics:

PGE1 used in combination with alpha-cyclodextrin in/in or/as. During the preparation of the solution complex of the drug disintegrates into its component parts — PGE1 and alpha - cyclodextrin. At/in the introduction of a therapeutically significant concentration of active substance is achieved shortly after the start of drug administration, Cmax in plasma within 2 h from the beginning of the introduction. PGE 1 is an endogenous substance with a very short T1/2 — plasma concentration of blood returns to the original level within 10 s after the cessation of administration. The process of biotransformation PGE 1 occurs mainly in the lungs, in the "first pass" through the lungs is metabolized in 60-90% of the active substance with the formation of the major metabolites, 15-keto — PGE1, 15 - keto — PGE1 and PGE0. The main products of metabolism are excreted by kidneys 88% via the gastrointestinal tract — 12% within 72 hours the plasma protein binds 93% PGE1. Alpha-cyclodextrin has a T1/2 approximately 7 min, displayed kidneys in an unmodified form.

Indications:

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

Contraindications:

Hypersensitivity to alprostadil and other components of the drug, congestive heart failure, severe heart rhythm disturbances, exacerbation of ischemic heart disease, myocardial infarction (within the next 6 months), pulmonary edema, infiltrative lung disease, chronic obstructive pulmonary disease, liver dysfunction (elevated levels of AST, ALT or GGT) and liver disease in the anamnesis as well as diseases associated with the increased risk of bleeding and hemorrhage (gastric ulcer or duodenal ulcer, severe damage of brain vessels, proliferative retinopathy with a tendency to hemorrhage, extensive trauma, etc.), concomitant therapy of anticoagulant and vasodilator remedies, pregnancy, breastfeeding.

Application of pregnancy and breast-feeding:

Contraindicated in pregnancy. At the time of treatment should stop breastfeeding.

Side effects:

From the nervous system: headache, convulsions, dizziness, increased fatigue, feeling of malaise, violation of sensitivity of skin and mucous membranes.

From the side of cardiovascular system: decrease in blood pressure, chest pain, cardiac arrhythmia, AV blockade.

From the digestive system: discomfort in epigastralna area, diarrhoeal phenomenon, diarrhoea, nausea, vomiting.

From the musculoskeletal: hyperostosis of long bones (in the treatment of more than 4 weeks).

Local reactions: pain, swelling, erythema, impaired sensitivity, phlebitis (proximal to the point on/in the introduction).

Laboratory findings: leukocytosis, leukopenia, increased titer of C-reactive protein, increased level of transaminases.

Other: increased sweating, hyperthermia, swelling of the limbs, in the vein that is being infused.

Rare: joint pain, confusion, convulsions of Central origin, fever, chills, bradypnea, arthralgia, psychosis, renal failure, anuria. There have been several reported cases of development of pulmonary edema and acute left ventricular failure.

Extremely rare (1% of cases): shock, acute heart failure, hyperbilirubinemia, bleeding, drowsiness, bradypnea, reduced respiratory function, tachypnea, anuria, impaired renal function, hypoglycemia, ventricular fibrillation of the heart, AV blockade II degree, supraventricular arrhythmia, muscle tension neck, irritability, hypothermia, hypercapnia, flushing of skin integument, hematuria, peritoneal symptoms, tachyphylaxis, hyperkalemia, thrombocytopenia, anemia.

Allergic reactions: skin rash, itching.

Side effects associated with the drug or the procedure of catheterization disappear after reducing the dose or termination of infusion.

Drug interactions:

Vasaprostan may increase the effect of antihypertensive drugs, vasodilators and antianginal drugs. The simultaneous use of Vasaprostan in patients taking drugs that prevent blood clotting (anticoagulants, thrombocyte aggregation inhibitors), may increase the likelihood of bleeding. In combination with cefamandole, cefoperazone, and cefotetan with thrombolytic drugs increases the risk of bleeding. Sympathomimetics — epinephrine, norepinephrine, reduces vazodilatiruushimi effect.

Be aware that the drug interaction is possible in the case if these drugs were used just before had started therapy with Vasaprostan.

Method of application and dose:

In/and the introduction. Dissolve the contents of 1 ampoule of lyophilisate Vasaprostan (corresponds to 20 mcg alprostadila) in 50 ml of saline.

In the absence of other provisions half ampoules Vasaprostan content (corresponding to 10 µg alprostadila) is administered in over 60-120 min when using the device for infusion. If necessary, especially in the presence of necrosis, under strict control tolerability may increase the dose to 20 mg alprostadila (contents of 1 ampoule). This dosage is usually applied to a single daily infusion.

If/and infusion is introduced through the catheter, depending on patient tolerance and severity of disease, recommended dose of 0.1–0.6 ng/kg/min infusion for 12 h when using the device for infusion (corresponds to 0.25–1.5 vials Vasaprostan).

The on/in infusion. Dissolve the contents of 2 vials lyophilisate Vasaprostan (corresponds to 40 µg alprostadila) in 50-250 ml of physiological saline solution and injected the resulting solution V/V for 2 hours 2 times daily or 3 capsules (60 mg alprostadila) for 3 hours 1 time a day.

In patients with impaired renal function (renal failure when creatinine level more than 1.5 mg/DL)/introduction begin with 20 mcg for 2 h. If necessary, after 2-3 days, a single dose of 40-60 mcg.

For patients with renal and heart failure maximum volume of fluid injected — 50-100 ml/day. The course of treatment is 4 weeks.

The treatment lasts an average of 14 days, with a positive effect of the treatment can be continued for 7-14 days. In the absence of a positive effect within 2 weeks of starting treatment further use of the drug should be discontinued.

Preparation of the solution. To prepare the solution to be immediately before infusion. Lyophilisate dissolved immediately after the addition of saline. At the beginning of the solution can be obtained milky turbid. This effect is created by air bubbles and has no value. After a short time the solution becomes transparent. You can't use the solution prepared more than 12 hours ago.

Overdose:

Symptoms: decreased blood pressure, increased heart rate. May develop vasovagal reactions with pallor, increased perspiration, nausea and vomiting that may be accompanied by myocardial ischemia and symptoms of heart failure, as well as possible pain, swelling and redness of the tissue at the site of infusion.

Treatment: it is necessary to reduce the dose or discontinue the infusion. In marked decrease in blood pressure to the patient in the supine position to raise the legs. If symptoms persist, you must use a sympathomimetic.

Precautions:

With careful use Vasaprostan hypotension, cardiovascular failure (particular attention should be paid to control load volume of solution vehicle), patients on hemodialysis (treatment with the drug should be postdializnom period), in patients with diabetes mellitus type 1, especially with extensive lesions of the vessels.

Vasaprostan can affect the ability to actively participate in traffic or operate machinery, especially at the beginning of treatment with increasing doses and withdrawal, as well as at simultaneous reception of alcohol.

Special instructions:

Alprostadil may be used only by physicians with experience in angiology familiar with modern methods of continuous monitoring of the cardiovascular system and with the appropriate equipment.

During treatment requires monitoring blood pressure, heart rate, blood biochemistry, blood coagulation system (in violation of blood coagulation system or in concurrent therapy with drugs that affect the clotting).

Patients of IBS, and patients with peripheral edema and renal dysfunction (serum creatinine >1.5 mg/DL) should be monitored in hospital during treatment Vasaprostan within 1 day after stopping its use.

In order to avoid symptoms of fluid overload in patients with renal insufficiency, the volume of introduced fluid should not exceed 50-100 ml/day. Necessarily dynamic monitoring of patient: monitor blood pressure and heart rate, if necessary, control body weight, fluid balance, measurement of Central venous pressure or holding echocardiography.

Phlebitis (proximal to the injection site), as a rule, is not a cause for discontinuation of therapy, signs of inflammation disappear in a few hours after cessation of the infusion, or change the place of administration of the drug, specific treatment in such cases is not required. Catheterization of a Central vein allows to reduce the frequency of manifestations of this side effect of the drug.

If the damage vials lyophilisate becomes wet and sticky, and greatly reduced in volume. In this case, the drug cannot be used.