Alprostadil, active agent formulation Vazostenon is vasodilators. It enhances the blood flow by dilation of the arterioles and sphincters peredkapilyarni. Alprostadil improves microcirculation and blood rheology. After intravenous administration in healthy volunteers and patients have increasing flexibility of red blood cells and inhibition of platelet aggregation ex vivo. Alprostadil effectively inhibits in vitro platelet activation.
This effect also applies to the shape, aggregation, secretion of substances contained in the granules and the release of thromboxane – a substance that promotes aggregation. The drug reduces the cases of formation of arterial thrombi. In humans it causes stimulation of fibrinolysis and improving certain indices of endogenous fibrinolysis (plasminogen, plasmin, plasminogen activator activity of tissue).
After intravenous administration of alprostadil in a dose of 60 mg / 2 hours the maximum concentration in the plasma of healthy volunteers 6 pg / ml exceeded the maximum concentration in the placebo phase (2.4 pg / ml). The half-life during the alpha phase is about 0.2 m (estimated value), and during the beta phase – about 8 minutes.
Thus, the equilibrium concentration is reached soon after the beginning of infusion. Alprostadil is metabolized in the lungs – about 80-90% in the first pass. The primary metabolites that are formed during the first pass – 15-keto-PGE-1, PGE-0 (13.14 digidroPGE-1) and 15-keto-PGE 0 (13,14-dihydro-15-keto-PGE 1) – in turn, experiencing further disintegration, in particular by beta-oxidation and omega-oxidation.
The metabolites are excreted in urine (88%) and the feces (12%). Complete withdrawal is carried out for 72 hours. Primary metabolites only 15-keto-PGE 0 can be detected in vitro using lung homogenates. After application of alprostadil 60 micrograms / 2 hours in healthy volunteers PGE 0 reaches a maximum concentration of 11.8 pg / ml after placebo phase (1.7 pg / ml) in the blood plasma, the half-life of approximately 2 minutes at the alpha phase and about 33 min with beta-phase. T max is reached after 119 min.
The corresponding values for 15-keto-PGE 0 are: C max 151 pg / ml (placebo 8 .mu.g / ml), t ½α about 2 minutes, t ½ß 20 min and 106 min T max. Alprostadil 93% is associated with the macromolecular components of blood plasma.
Kevelt JSC, Estonia
For adults on prescription
1 ampoule contains 20 ug
Treatment of chronic peripheral arterial occlusive diseases III and IV in the adult stage, in case it is impossible to conduct the procedure has vasodilator action, or if the holding of such a procedure is not successful.
Introduction not recommended for the treatment of chronic peripheral arterial occlusive disease stage IV.
Hypersensitivity to alprostadil or other components of the formulation; cardiac dysfunction: decompensated heart failure class III and IV according to the classification of the New York Heart Association (NYHA) heart failure is due to a previous treatment failures;
arrhythmia of various etiologies, including arrhythmia, which causes hemodynamic disturbances;
cardiac arrhythmia due to previous treatment failures; insufficiency and / or stenosis, aortic and / or mitral valves;
inadequately controlled by coronary heart disease; coronary artery disease;
recent myocardial infarction (within the last 6 months);
suspected acute / chronic pulmonary edema, by clinical or radiological studies, pulmonary edema, or a history of pulmonary infiltration;
severe chronic obstructive pulmonary disease, thrombosis, pulmonary disease; liver disease, including signs of acute liver failure (elevated transaminases or gamma-glutamyl) or severe liver failure (including history);
renal dysfunction, bleeding tendency (acute erosive or bleeding stomach ulcer and / or duodenal ulcers, polytrauma) stroke within the last 6 months, severe hypotension;
General contraindications to infusion therapy (e.g. congestive heart failure, pulmonary edema or brain and hyperhydration) during pregnancy and breastfeeding child.
Side effects classified by frequency as follows: very often (≥ 1/10), often (≥ 1/100, < 1/10), rare (≥ 1/1000, < 1/100), rare (≥ 1 / 10000, < 1/1000), very rare (< 1/10000), unknown frequency (can not be estimated from the available data).
From the nervous system: often – headache, paresthesia limbs on which the manipulation was carried out; rarely – confusion; seldom – cerebral convulsions unknown frequency – stroke.
On the part of the gastrointestinal tract: rarely – gastrointestinal diseases, including diarrhea, nausea, vomiting and accelerate intestinal peristalsis.
From the cardiovascular system: infrequently – lowering of blood pressure, tachycardia, angina rarely arrhythmia, heart failure cases of acute pulmonary edema, which can lead to total heart failure is unknown frequency – myocardial infarction.
From the digestive system: rarely – a violation of liver enzymes.
The respiratory system, thorax and mediastinum: rare – swelling of the lungs; unknown frequency – shortness of breath.
From the blood system and lymphatic system: rarely – leukopenia, leukocytosis, thrombocytopenia. Explorer infrequently – increasing functional in liver (transaminase): increasing the temperature indicator changes CRP (C-reactive protein) after completion of treatment is rapid normalization of these parameters.
Skin and subcutaneous tissue: common – redness, swelling, flushing.
General disorders and reactions at the injection site: very often – pain, erythema and swelling of the limbs, which were administered an infusion; often – warming sensation, sensation of swelling at the injection site swelling, paresthesias, when administered intravenously – redness at the site of venous infusion; after intra-arterial administration – warming sensation, a feeling of swelling, swelling at the injection site, paresthesia; Infrequent – increased sweating, chills, fever, after the introduction – sensation warming sensation of swelling, swelling at the injection site, paresthesia; unknown frequency – at the injection site phlebitis, thrombosis at the site of catheter insertion, local bleeding.
Immune system: infrequently – allergic reactions (hypersensitivity skin reaction including rash, swelling feeling discomfort in the joints, febrile reaction, sweats and chills), very rarely – anaphylactic or anaphylactoid reactions.
On the part of the musculoskeletal system and connective tissue disorders: uncommon – joint symptoms, including pain, very rarely – reversible hyperostosis of long bones after treatment for more than 4 weeks.
Reporting of adverse reactions. Reporting of suspected adverse reactions after the approval of the drug is important. This allows you to continue to monitor the balance of the benefit / risk of the drug. Medical professionals are asked to report any suspected adverse reactions via the national reporting system.
Store in a dark place in its original packaging at a temperature of 2 to 8 ° C
Keep out of the reach of children.
In the treatment the drug may be enhanced effect antihypertensive drugs, vasodilators, and antianginal drugs. With simultaneous use of these drugs with Alprostadil the use of other vasodilators requires careful control of the cardiovascular system, including blood pressure monitoring.
Sympathomimetics epinephrine, norepinephrine reduce the vasodilator effect of the drug. Simultaneous use of the drug and antithrombotics (anticoagulants, platelet aggregation inhibitors, thrombolytic agents) may increase bleeding tendency.
Given the weak inhibitory effects of alprostadil on in vitro platelet aggregation, should be used with caution in patients who are concurrently taking anticoagulants. The simultaneous use of cefamandole, tsefaperazon, tsefatetanom Vazostenon reduces the effect of the drug.
Patients at risk of drug therapy should be done with caution, watching the patient for each dose input. Patients prone to heart failure at his age, and in patients with coronary heart disease should be kept under observation in the hospital during treatment and within one day after the cessation of drug therapy. With care prescribe a drug and hypotension.
To prevent overhydration infusion volumes should not exceed 50-100 ml per day (introduction via infusion device). Also, should follow the recommendations of the duration of infusion (see. Section “Dosage and Administration”). Monitoring parameters needed cardiovascular system of the patient (blood pressure and heart rate) monitoring body weight, fluid balance, central venous pressure and echocardiography.
The patient can be discharged from the hospital only in the case of stable performance of the cardiovascular system. The same thorough supervision (control fluid balance and indices of renal function) in patients with peripheral edema is required, or renal dysfunction (creatinine serum levels > 1,5 mg / dl or glomerular filtration rate
With caution in patients on hemodialysis (treatment carried out in pislyadializny period), the patients with diabetes of type I, especially in patients with severe vascular lesions.
Vazostenon should enter only doctors who have experience in the treatment of occlusive peripheral arterial disease, familiar with modern methods of continuous monitoring of indicators of the cardiovascular system and have the appropriate equipment for this purpose. alprostadil should not be used by the jet (bolus) administration.
In the case of simultaneous application with antihypertensive drugs, vasodilators and antianginal drugs should be closely monitored parameters of the cardiovascular system (see. Section “interaction with other drugs and other types of interactions”).
Use during pregnancy or lactation. Do not use for women of childbearing age and during pregnancy. If necessary, use during lactation should be discontinued. Women of childbearing age should use effective contraception to prevent pregnancy during the use of the drug.
These preclinical studies did not show fertility effect of the drug on fertility when using therapeutic doses of medicament.
Ability to influence the reaction rate when driving or operating other machinery.
As with all drugs acting on the cardiovascular system, the drug may negatively affect the ability to drive vehicles and other mechanisms, especially at the beginning of treatment, when increasing the dose, discontinuation of the drug, the use of alcohol can lead to a decrease in systolic blood pressure.
Should inform patients about the need to observe caution when driving and operating machinery
Recommendations for use
Vazostenon for intraarterial or intravenous administration in solution form. For the administration of the drug is recommended to use an automatic syringe or an infusion pump and a catheter for infusion therapy. The dosing schedule presented daily dose calculated for patients with normal renal function, the body mass of 70 kg.
Patients with impaired renal function when blood creatinine level exceeds the norm (males > 97 umol / L in women > 80 pmol / l), at the beginning of therapy should decrease the daily doses twice.
Depending on the clinical condition of the patient within 2-3 days, the dose can be increased to such an intended for patients with normal renal function. When intraarterial intraarterial administration likelihood of adverse reactions in the above case, the short infusion. Accordingly, to ensure safety of the patient, the infusion is recommended to start with low doses and in the absence of adverse reactions – increasing the dose. For the prevention of thromboembolic complications recommended administration 15,000 units of heparin per day. Intraarterial administration over 12.00.
The daily dose – 5-30mkg recommended dosage of 0.1 – 0.6 ng / kg / min. When selecting a daily dose (5 – 30 mcg) Vazostenon should be diluted in 50 ml 0,9% NaCl and do administration for 12:00 with an automatic syringe.
Intraarterial administration for 1-2 hours. The daily dose – 10 – 20 micrograms, the recommended dose at the dose of 10 mg – 1.2 ng / kg / min; at a dose of 20 mg – 2.4 ng / kg / min. Intraarterial administration during operation time during reconstructive surgery intravenously administered 5 – 40 micrograms drug, diluted in 50 ml 0,9% NaCl.
The daily dose – 40 micrograms alprostadil 2 times a day or 60 .mu.g of alprostadil 1 time per day. Recommended dosage – 4.7 ng / kg / min. 40 .mu.g of alprostadil should be diluted in 50 – 250 ml of 0,9% NaCl solution and administered intravenously over a 2 o’clock in the morning and evening. 60 .mu.g of alprostadil should be diluted in 50 – 250 ml of 0,9% NaCl solution and administered intravenously over 1 3:00 once a day. Children. Do not apply to children.
Symptoms. An overdose of the drug may result in reduced blood pressure and reflex tachycardia due to vasodilation effect.
Other possible symptoms are: syncope vazovagusnye with pale skin, sweating, nausea, vomiting, myocardial ischemia, heart failure. There are local reactions: pain, swelling and redness of the extremities, which were infused, the manifestations of hypersensitivity.
Treatment is symptomatic. No specific antidote. In the case of an overdose (severe pain, reduction in blood pressure) or reduced dose should immediately stop the introduction of infusion.
By reducing blood pressure in the first place to put the patient on his back, lifting the lower limbs. If the symptoms do not disappear, you should check / control the parameters of the cardiovascular system. If necessary, it can be used sympathomimetics.