Clinical and pharmacological group: & nbsp

Vasodilators

Included in the formulation
  • Alprostan® Zentiva
    concentrate d / infusion 
    Zentiva c.s.     Czech Republic
  • Arters-Vero®
    lyophilizate d / infusion 
    VEROPHARM SA     Russia
  • Vazaprostan®
    lyophilizate d / infusion 
    YUSB Pharma GmbH     Germany
  • Vazaprostan®
    lyophilizate d / infusion 
    YUSB Pharma GmbH     Germany
  • VAP® 20
    concentrate d / infusion 
  • VAP 500
    concentrate d / infusion 
  • Kaverdzhekt®
    lyophilizate in / cavern. 
  • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    G.04.B.E.01   Alprostadil

    Pharmacodynamics:

    Synthetic analogue of prostaglandin E1; direct vasodilating action on arterioles, precapillary sphincters, arteries of muscle type; relaxation of the muscles of spongy bodies, which causes rapid blood flow and dilatation of lacunar spaces of cavernous bodies, difficulty in venous outflow from spongy bodies.

    Pharmacological effects

    Vasodilator: used to temporarily maintain the functioning of the arterial duct. The medication for the treatment of impotence, diagnosis of erectile dysfunction.

    Pharmacokinetics:

    Relationship with plasma proteins 81-99%. T1 / 2 - 5-10 minutes. Biotransformation: with intravenous injection - in the lungs (with a single passage through the lungs to 60-90%); with intracavernous injection - in the cavernous bodies, urethra, prostate.Elimination by the kidneys in the form of metabolites.

    Indications:

    The need for temporary maintenance of the functioning of the arterial duct until the corrective operation is performed with congenital ductus-dependent heart defects in newborns (including mitral atresia, pulmonary atresia, tricuspid atresia, tetralogy of Fallot).

    Chronic obliterating diseases of arteries of III-IV stage (according to Fontaine's classification). Obliterating endarteritis with a severe degree of "intermittent" lameness (with impossible surgical revascularization of the lower limb), obliterating atherosclerosis, diabetic angiopathy, obliterating thromboangiitis (Burger's disease), Raynaud's syndrome with trophic disorders, vasculitis, scleroderma, spasms of the calf muscles, especially over-limit vibration.

    Treatment of erectile dysfunction of neurogenic, vascular, psychogenic or mixed etiology; conducting a pharmacological test in a complex of diagnostic tests for erectile dysfunction.

    V.F50-F59.F52.2   Insufficiency of the genital reaction

    IX.I70-I79.I73.0   Raynaud's syndrome

    IX.I70-I79.I73.1   Obliterating thromboangitis [Berger's disease]

    IX.I70-I79.I73.9   Peripheral vascular disease, unspecified

    IX.I70-I79.I79.2 *   Peripheral angiopathy in diseases classified elsewhere

    XIII.M30-M36.M31   Other necrotizing vasculopathies

    XIII.M30-M36.M34   Systemic sclerosis

    XIV.N40-N51.N48.4   Impotence of organic origin

    XVIII.R25-R29.R25.2   Cramp and spasm

    XXI.Z40-Z54.Z42   Follow-up care with restorative surgery

    Contraindications:

    Hypersensitivity, pregnancy, breast-feeding, respiratory depression (in newborns), RDS of newborns, spontaneous stable-open ductus arteriosus (in newborns); to intracavernous introduction - sickle cell anemia, myeloma, leukemia, thrombocytopenia, polycythemia, thrombophlebitis, venous thrombosis, including predisposition to it, increased blood viscosity; anatomical deformations of the penis: angulation, cavernous fibrosis, Peyronie's disease, urethral stricture; to intracavernous introduction - hypospadias, balanitis, urethritis, age younger than 18 and over 75 years old, implant of the penis.

    Carefully:

    C use caution in / a and / in acute and subacute myocardial infarction, with myocardial infarction, transferred during the last 6 months, with a severe or unstable form of angina,decompensated chronic heart failure, with arterial hypotension, cardiovascular insufficiency, with pulmonary edema, severe arrhythmias, bronchial obstructive syndrome (severe degree with signs of respiratory failure), with infiltrative changes in the lungs, liver failure (including in the anamnesis), at an increased risk of bleeding (including with peptic ulcer of the stomach or duodenum, severe damage to the vessels of the brain, proliferative retinopathy with a tendency bleeding, major trauma), hemodialysis, type 1 diabetes, especially in extensive lesions of vessels (in the elderly); on the background of the use of vasodilators or anticoagulants; in newborns (risk of developing bradypnoea, arterial hypotension, tachycardia, or hyperthermia).

    C caution should be given intracavernously with thrombocytopenia, polycythemia, thrombophlebitis, venous thrombosis (including in case of predisposition), increased blood viscosity, balanitis, urethritis.

    Pregnancy and lactation:

    Pregnancy

    FDA recommendations for suppositories of category C, for injection forms - not defined.Qualitative controlled studies in humans have not been conducted. When vaginal administration of alprostadil to pregnant rabbits at a dose of 4000 μg / day (12.5 times the maximum recommended for humans) adverse effects on the fetus is not documented. When vaginal administration in doses, many times exceeding those used for erectile dysfunction, toxic effect on the embryo and the maternal organism was noted. Men who use alprostadil in candles, during sexual intercourse with a pregnant woman, it is necessary to use a condom to protect the woman and the fetus from the effects of the drug. Since it is not known how the alprostadil on the embryo in the early stages of pregnancy, it is recommended that women of reproductive age use contraceptives.

    Lactation

    There is no information on the penetration into breast milk. Do not apply!

    Dosing and Administration:

    Obliterating diseases of the arteries (III and IV stages according to Fontaine's classification, accompanied by pain at rest or trophic changes); obliterating endarteritis with severe intermittent claudication in the presence of contraindications to revascularization surgery.Improves the quality of life and increases the physical capabilities of patients with obliterating diseases of the arteries: 60 μg intravenously drip for 2 hours. Inferior to the effectiveness of iloprost. Intermittent claudication: according to RCT, prostaglandin E1 in comparison with pentoxifylline (PGE1 - 40 μg in 250 ml of 0.9% sodium chloride solution intravenously drip for 2 hours 2 times a day, pentoxifylline - in 250 ml of 0.9% solution of sodium chloride intravenously drip for 2 hours 2 times a day) significantly increased the painless walking distance (average distance 416 m, 95% CI 28-804), but did not affect the maximum walking distance (1 RCT, 29 participants). In other studies, there is no standard deviation, so it is not possible to analyze the effect of drugs on the walking distance. According to these studies (2 RCTs, 240 participants), there was no difference in the ankle-brachial pressure index between the groups. PGE1 increased the average painless walking distance from 83 to 264 m in one study and from 89 to 195 m in the other, pentoxifylline - from 84 to 188 m and from 78 to 149 m, respectively.

    Atherosclerosis. 120 mcg / day intravenously. Diabetic angiopathy: ineffective. Berger's disease.Reynaud's syndrome with trophic disorders. 60 μg intravenously drip for 3 hours daily. Vasculitis. Systemic scleroderma. 60 mcg iv in for 3 h daily. Sucks in gastrocnemius muscles.

    Damage by physical factors, especially extreme vibration. Intraarterially (with the help of an infusion pump) 10-20 mcg for 1-2 hours once a day or 0.1-0.6 ng / kg × min (5-10 mcg) through the established catheter for 12 hours. Intravenous by 40 μg 2 times a day (after preliminary dissolving the contents of the ampoule in 50 ml of 0.9% sodium chloride solution) or 50-200 μg once a day (in more severe conditions, 50-100 μg twice a day); duration of infusion - at least 2 hours. In the absence of a positive effect within 2 weeks after the start of treatment, further use is stopped.

    If renal function is impaired (creatinine concentration in the blood serum> 1.5 mg / l), intravenous administration starts with a dose of 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 - 4 weeks. The clinical effect is long-term and may occur with some delay after the end of the course of treatment.

    Violations of the erection of neurogenic, vascular, psychogenic or mixed etiology.

    Intracavernous 5-10 mcg once a week, 125-1000 mcg transurethral in 4 doses for a 2-4-week period. Treatment with self-injections at home should start with a dose set in the doctor's office, no more than 1 time per day and 3 times a week. The onset of action is 5-10 minutes, duration 1-3 hours.

    The dose is selected individually before the minimum effective dose (the appearance of an erection sufficient for sexual intercourse, but no more than 1 hour), under the supervision of a doctor until the erection disappears. If the first dose is ineffective, the second, higher, is administered after 1 hour. If the second dose is ineffective, the third, even higher, is administered no earlier than 1 day later. In cases of erectile dysfunction of a neurogenic genesis (for example, with damage to the spinal cord), the initial dose is 1.25 μg. With each subsequent administration, the dose is doubled, but not more than 5 μg, until the minimum effective dose is reached. In cases of erectile dysfunction of vascular, psychogenic or mixed etiology, the initial dose is 2.5 μg. For each subsequent administration, the dose should be doubled, but not more than 5-10 μg, until the minimum effective dose is reached.Intraurethral in the form of suppositories, the initial dose of 125-250 mcg; if necessary, the dose is gradually raised or lowered until an erection sufficient for a sexual intercourse arises. The maximum frequency of application is 2 times a day. Effective for erectile dysfunction of various etiologies. Intracavernous administration at a dose of 40-1000 μg is superior in effectiveness to intraurethral injection, but more difficult to apply. It surpasses the efficiency of moxizilite chlor-hydrate; comparable to a vacuum device. Inferior to sodium nitroprusside in a dose of 300-400 micrograms intracavernous. Intraurethral, ​​in the form of applications is ineffective; possible use in combination with phentolamine intracavernous.

    Psychogenic erectile dysfunction: intracavernous 2.5-5.0 mcg is more economical than psychotherapy.

    Erectile dysfunction after treatment of prostate cancer - the most convincing evidence is obtained for oral PDE-5 inoculants after radiotherapy for prostate cancer and radical prostatectomy. In the transurethral administration of alprostadil, 270 participants from 384 reported an acceptable improvement in erection, 35% had an effective dose of 1000 μg, 31% had 500 μg, 17% had 250 μg and 17% had 125 μg.270 men were divided into two groups - alprostadil treatment group and placebo group. The OR of successful coitus was at least 1 time for 3 months and was significant in favor of treatment - 18.96 (95% CI 8.85-40.65), a wide confidence interval indicates insufficient research opportunities and the need to interpret its results carefully. Significantly more often in the treatment group alprostadil there was pain in the penis (OR - 75.73, 95% CI 10.27-558.4), pain and burning in the urethra (OR 4.66, 95% CI 1.91-12, 42). In the active group, 2% experienced dizziness. According to the authors' conclusions, PDE-5 inhibitors are effective in the treatment of secondary erectile dysfunction after treatment of prostate cancer. Other methods need further investigation.

    Carrying out a pharmacological test in a complex of diagnostic tests for erectile dysfunction: once in a dose that causes an erection.

    Use in children

    The need to temporarily maintain the functioning of the arterial duct before the corrective operation for congenital heart defects in newborns (including mitral atresia, pulmonary atresia, tricuspid valve, tetralogy of Fallot).Intravenous drip: for newborns the initial dose is 50-100 ng / kg × min, then it is reduced to the minimum effective. Lower doses (10 ng / kg × min) may be more effective and safer. Continuously through the umbilical arterial catheter (brought directly to the mouth of the arterial duct) or one of the large veins with an initial rate of 0.05-0.1 (up to 0.4) μg / kg × min. After reaching the therapeutic effect, 0.01-0.02 μg / kg × min (0.005-0.01 C21). When there are significant side effects, the dose should be reduced.

    Side effects:

    When parenteral administration of patients with heart defects.

    Apnea (10-12%) 22, fever of hypothalamic genesis (14%), flushing of blood to the face and hands (10%), decrease in calcium concentration, bradycardia (7%).

    With intracavernous injection.

    Decreased calcium concentration (15%), hypotension (dose-dependent - 0.5% at 125 mcg, 0.7% at 250 mcg, 0.7% at 500 mcg, and 2.4% at 1000 mcg, 4.2-42 , 2%

    - with intraurethral injection), fibrosis of the penis (5.2%), pain in the penis during erection (dose-dependent - 9.1% at 125 mcg and up to 18.3% - at 1000 mcg, 10.8% intraurethral injection).

    Overdose:

    With intravascular injection - hypotension, flushing of the skin, weakness; in newborns - apnea, bradycardia, fever. Treatment is symptomatic, mechanical ventilation.

    With intracavernosal injection - hypertension, tachycardia, fatigue, pelvic pain, pain in the penis, prolonged erection and / or priapism. Treatment: with an erection longer than 4 hours - intracavernous ephedrine, epinephrine, phenylephrine or aspiration of blood from cavernous bodies; surgical treatment.

    Interaction:

    Anticoagulant drugs, cefoperazone, cefotetan, heparin, thrombolytic agents - an increased risk of bleeding.

    Vasodilators - strengthening effect, hypotension.

    Sympathomimetic drugs, α-adrenomimetics - antagonism with alprostadil.

    Special instructions:

    Must be weighed the potential risks and benefits of alprostadil in acute and subacute myocardial infarction within the past 6 months, severe or unstable angina, congestive heart failure, pulmonary edema, cardiac arrhythmias, hypotension, broncho-obstructive syndrome, infiltrative changes in the lungs, liver insufficiency ( including in history), the risk of bleeding, concomitant therapy with α-agonists over a prolonged erection, vasodilator, anticoagulant agents E, MAO inhibitors, with bradypnea (neonates), hypotension, tachycardia, hyperthermia or (neonates).

    Monitoring for heart defects COS, AD, ECG, heart rate, FHR, body temperature; with coarctation of the aorta in addition - blood pressure on the limbs below the constriction of the aorta, pulsation of the femoral artery, diuresis.

    For patients participating in the self-injection treatment program, a physician is examined once every 3 months, dosage adjustment is performed only by a doctor. Introduce the dorsolateral part of the proximal third of the penis, periodically change the side of the injection, avoid getting into the visible veins.

    The solution is used immediately after preparation, stored no more than 24 hours at a temperature of 2-8 ° C.

    Instructions
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