Composition, form of production and packaging
Lyophilizate for the preparation of a solution for infusions in the form of hygroscopic white mass.
1 amp.
alprostadil (clathrate complex with alfadex) 20 Ојg
Excipients: alfadex (? -cyclodextrin), lactose anhydrous.
Ampoules glass (10) - packs cardboard.
Lyophilizate for the preparation of a solution for infusions in the form of hygroscopic white mass.
1 amp.
alprostadil (clathrate complex with alfadex) 60 Ојg
Excipients: alfadex (? -cyclodextrin), lactose anhydrous.
Ampoules glass (10) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
The product description was approved by the manufacturer for the 2009 print edition.
PHARMACHOLOGIC EFFECT
Preparation of prostaglandin E 1 (PG E 1 ). Improves microcirculation and peripheral circulation, has vasoprotective action.
When systemic administration causes relaxation of smooth muscle fibers, has a vasodilating effect, reduces OPSS without changing blood pressure. At the same time there is a reflex increase in cardiac output and heart rate.
Helps increase the elasticity of erythrocytes, reduces platelet aggregation and neutrophil activity, increases fibrinolytic blood activity.
Has a stimulating effect on the smooth muscles of the intestine, bladder, uterus; suppresses the secretion of gastric juice.
PHARMACOKINETICS
It is used in combination with alfacyclodextrin IV or in / a. During the preparation of the solution, the complex of the drug decomposes into its constituent parts - PG E 1 and alfacyclodextrin.
Suction
With IV administration, a therapeutically significant concentration of the active substance is reached shortly after the start of the drug administration, and C max in the blood plasma is reached within 2 hours from the start of administration.
Distribution
PG E 1 binds to plasma proteins by 93%.
Metabolism
The process of biotransformation of PG E 1 occurs mainly in the lungs, 60-90% of the active substance is metabolized through the lungs at the "first passage" through the lungs to form the main metabolites - 15-keto-PG E 1 , 15-keto-PG E 0 and PG E 0 .
Excretion
PG E 1 is an endogenous substance with an exceptionally short T 1/2 . Concentration in the blood plasma returns to the baseline level 10 seconds after discontinuation of administration. It is excreted in the form of metabolites with urine (88%) and through the gastrointestinal tract (12%) for 72 hours.
T 1/2 alfa - cyclodextrin is about 7 minutes, is excreted in the urine unchanged.
INDICATIONS
- chronic obliterating diseases of arteries of III and IV stages (according to Fontaine's classification).
DOSING MODE
Cooking solution should be immediately before the infusion. The lyophilizate dissolves immediately after the addition of saline. In the beginning, the solution may turn out to be milky-cloudy. This effect is created by air bubbles and does not matter. After a short time, the solution becomes transparent.
Do not use a solution prepared more than 12 hours ago.
Intraarterial administration
Lyophilizate for solution for infusion: 1 amp / 20 Ојg alprostadil
To obtain a solution for intravenous administration, the contents of 1 ampoule of lyophilizate (corresponding to 20 Ојg of alprostadil) should be dissolved in 50 ml of saline. In the absence of other prescriptions, half of the vasaprostan ampoule (corresponding to 10 Ојg of alprostadil) should be administered intraperitoneally for 60-120 minutes using an infusion device. If necessary, especially in the presence of necrosis, under strict control of tolerability, the dose can be increased to 1 ampoule (20 Ојg alprostadil). This dose is usually used for a single daily infusion.
If intravenous administration of the drug is carried out through an established catheter, depending on the tolerability and severity of the disease, a dose of 0.1-0.6 ng / kg / min is recommended with the administration of the drug for 12 hours when using an infusion device (corresponding to 1/4 -1 1 1 / 2 ampoules of Vazaprostana).
Lyophilizate for solution for infusion: 1 amp / 60 Ојg alprostadil
To obtain a solution for intravenous administration, the contents of 1 ampoule of lyophilizate (corresponding to 60 Ојg of alprostadil) should be dissolved in 50-250 ml of saline. In the absence of other prescriptions, 1/6 of the vasaprostan ampoule (corresponding to 10 Ојg of alprostadil) should be administered intraperitoneally for 60-120 minutes using an infusion device. If necessary, especially in the presence of necrosis, under strict control of tolerability, the dose can be increased to 1/3 of the ampoule (20 Ојg alprostadil). This dose is usually used for a single daily infusion.
If intravenous administration of the drug is carried out through an established catheter, depending on the tolerability and severity of the disease, a dose of 0.1-0.6 ng / kg / min is recommended with the administration of the drug for 12 hours when using an infusion device (corresponding to 1/12 to 1 / 2 ampoules of Vazaprostana).
Intravenous administration
Lyophilizate for solution for infusion: 1 amp / 20 Ојg alprostadil
To obtain a solution for intravenous administration, the contents of 2 ampoules of lyophilizate (corresponding to 40 Ојg of alprostadil) should be dissolved in 50-250 ml of physiological solution and the resulting solution is injected iv for 2 hours. This dose is applied 2 times / day.
Either the contents of 3 ampoules (corresponding to 60 Ојg of alprostadil) are dissolved in 50-250 ml of physiological solution and injected intravenously for 3 hours 1 time / day.
The duration of treatment on average is 14 days, with a positive effect, the drug can be continued for 7-14 days. In the absence of a positive effect within 2 weeks from the start of treatment, further use of the drug should be discontinued.
Lyophilizate for solution for infusion: 1 amp / 60 Ојg alprostadil
To obtain a solution for intravenous administration, the contents of 1 ampoule of lyophilizate (corresponding to 60 Ојg of alprostadil) should be dissolved in 50-250 ml of physiological saline and injected with iv solution for 3 hours 1 time / day.
The duration of treatment on average is 14 days, with a positive effect, the drug can be continued for 7-14 days. In the absence of a positive effect within 2 weeks from the start of treatment, further use of the drug should be discontinued.
In patients with renal insufficiency (serum creatinine> 1.5 mg / dl) IV administration of Vazaprostan should be started with 20 Ојg (1 amp 20 Ојg or 1/3 amp at 60 Ојg) for 2 hours. If necessary, 3 days a single dose is increased to 40-60 mcg.
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 EFFECT
From the central nervous system and the peripheral nervous system: headache, dizziness, convulsive syndrome, increased fatigue, a feeling of malaise, a violation of the sensitivity of the skin and mucous membranes.
On the part of the cardiovascular system: lowering blood pressure, chest pain, heart rhythm disturbances, AV blockade.
From the digestive system: a feeling of discomfort in the epigastrium, nausea, vomiting, diarrhea.
From the musculoskeletal system: hyperostosis of long tubular bones (with therapy more than 4 weeks).
Allergic reactions: skin rash, itching.
Local reactions: erythema, edema, pain, sensitivity disorder, phlebitis (proximal to the site of intravenous administration).
Other: increased sweating, hyperthermia, puffiness of the extremity, the vein of which is infusion.
Laboratory indicators: leukocytosis, leukopenia, increase in the titer of C-reactive protein, increase in the level of transaminases.
Rarely: arthralgia, confusion, convulsions of the central genesis, fever, chills, bradypnoe, psychosis, renal failure, anuria. Several cases of pulmonary edema and acute left ventricular failure were reported.
Very rarely (up to 1% of cases): shock, acute heart failure, hyperbilirubinemia, bleeding, drowsiness, bradypnoea, decreased respiratory function, tachypnea, anuria, renal dysfunction, hypoglycaemia, ventricular fibrillation, grade II AV block, supraventricular arrhythmia, stress neck muscles, increased irritability, hypothermia, hypercapnia, skin flushing, hematuria, peritoneal symptoms, tachyphylaxis, hyperkalemia, thrombocytopenia, anemia.
The side effects associated with the use of the drug or with the procedure itself of the catheterization are reversible after a dose reduction or termination of the infusion.
CONTRAINDICATIONS
- chronic heart failure in the stage of decompensation;
- marked violations of the rhythm of the heart;
- exacerbation of IHD;
- transferred to the last 6 months myocardial infarction;
- pulmonary edema;
- infiltrative lung diseases;
- chronic obstructive pulmonary disease;
- dysfunction of the liver (increase in the level of AST, ALT, GGT);
- liver disease in history;
- diseases accompanied by an increased risk of bleeding (peptic ulcer of the stomach and duodenum, severe damage to the brain vessels, proliferative retinopathy with a tendency to bleeding, extensive trauma);
- concomitant therapy with vasodilating and anticoagulant drugs;
- Pregnancy;
- the period of lactation (breastfeeding);
- age under 18 years (effectiveness and safety not established);
- hypersensitivity to alprostadil and other components of the drug.
With caution should appoint vazaprostan with arterial hypotension, cardiovascular insufficiency (it is necessary to control the load of the volume of the carrier solution), patients on hemodialysis (treatment should be performed in the postdialysis period), patients with type 1 diabetes mellitus, especially with extensive vascular lesions.
PREGNANCY AND LACTATION
The use of vasaprostan during pregnancy is contraindicated.
If it is necessary to use the drug during lactation, breastfeeding should be stopped.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function (serum creatinine more than 1.5 mg / dl) IV injection of Vazaprostan should be started with 20 mcg for 2 hours. If necessary, after 2-3 days, the dose can be increased to 40-60 mcg.
For patients with renal and heart failure, the maximum volume of injected fluid is 50-100 ml / day. The duration of the course of treatment is 4 weeks.
During the treatment with Vasaprostane, in order to avoid the appearance of symptoms of hyperhydration in patients with renal insufficiency, the volume of the injected fluid should be limited to 50-100 ml / day. Dynamic monitoring of the patient's condition is necessary (control of blood pressure and heart rate), if necessary - control of body weight, fluid balance, measurement of central venous pressure or echocardiography.
Patients with IHD, peripheral edema and renal dysfunction (serum creatinine more than 1.5 mg / dL) during treatment with Vasaprostan and for 1 day after discontinuation of the drug should be monitored in the hospital.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in cases of violations of the liver (increase in the level of AST, ALT, GGT), liver diseases in the anamnesis.
APPLICATION FOR CHILDREN
Contraindication: age under 18 years (efficacy and safety not established).
SPECIAL INSTRUCTIONS
Vazaprostan can only be used by physicians with experience in angiology, familiar with modern methods of continuous monitoring of the cardiovascular system and having appropriate equipment for this.
When carrying out therapy, Vasaprostan should monitor blood pressure, heart rate, blood biochemical parameters, blood coagulability (for disorders of the blood coagulation system or for simultaneous therapy with drugs that affect the coagulation system).
During the treatment with Vasaprostane, in order to avoid the appearance of symptoms of hyperhydration in patients with renal insufficiency, the volume of the injected fluid should be limited to 50-100 ml / day. Dynamic monitoring of the patient's condition is necessary (control of blood pressure and heart rate), if necessary - control of body weight, fluid balance, measurement of central venous pressure or echocardiography.
Patients with IHD, peripheral edema and renal dysfunction (serum creatinine> 1.5 mg / dL) during treatment with Vasaprostan and within 1 day after discontinuation of the drug should be monitored in the hospital.
Phlebitis (proximal to the injection site), as a rule, is not a reason for stopping therapy, inflammation symptoms disappear after several hours after stopping the infusion or changing the place of administration of the drug. Specific treatment in such cases is not required. Catheterization of the central vein can reduce the incidence of this side effect of the drug.
Impact on the ability to drive vehicles and manage mechanisms
Vazaprostan can affect the ability to actively participate in street traffic, driving vehicles or controlling mechanisms, especially at the beginning of treatment, with increasing doses and withdrawal of the drug, as well as with the simultaneous intake of alcohol.
OVERDOSE
Symptoms: decreased blood pressure, increased heart rate, possible development of vaso-vagal reactions (pallor of the skin, increased sweating, nausea, vomiting), which may be accompanied by myocardial ischemia and symptoms of heart failure; possible pain, swelling and redness of the tissue at the site of infusion.
Treatment: it is necessary to reduce the dose of the drug or stop the infusion. At the expressed depression of a BP the patient in a prone position it is necessary to raise legs. If symptoms persist, sympathomimetics should be used.
DRUG INTERACTION
With the simultaneous use of vasaprostan can enhance the effect of antihypertensive drugs, peripheral vasodilators, antianginal drugs.
With the combined use of vasaprostan with anticoagulants, platelet aggregation inhibitors, cefamandole, cefoperazone, cefotetan, thrombolytics, the risk of bleeding increases.
With the simultaneous use of vasaprostan with epinephrine (adrenaline), norepinephrine (noradrenaline), the vasodilating effect is reduced.
It should be taken into account that the interaction is possible if the above drugs were used shortly before the therapy was started by Vasaprostan.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 4 years.
If the ampoule is damaged, the lyophilizate becomes wet and sticky, greatly reduced in volume. In this case, you can not use the drug.
