Pharmacological properties of the drug Alprostadil
Prostaglandin E1. It has a vasodilating, angioprotective effect, improves microcirculation and peripheral circulation, and promotes the appearance of collaterals. By causing relaxation of the smooth muscles of the corpora cavernosa of the penis, it helps to increase blood flow and improve microcirculation. Improves the rheological properties of blood, reducing adhesion and aggregation of platelets, helping to increase the elasticity of red blood cells. It has an antiatherogenic effect, slowing down the activation of neutrophil granulocytes, the proliferation of vessel wall cells and the deposition of cholesterol in it, and has a fibrinolytic effect. Rapidly metabolized. The main metabolites are excreted in urine (88%) and feces (12%).
Indications for use of the drug Alprostadil
Obliterating diseases of the arteries of the extremities - obliterating endarteritis, intermittent claudication, damage to peripheral arteries due to atherosclerosis, diabetes mellitus, Buerger's disease, Raynaud's syndrome with trophic disorders due to vasculitis, systemic scleroderma, exposure to physical factors (vibration); congenital ductus-dependent heart defects in newborns with indications for surgical reconstruction to maintain temporary patency of the ductus arteriosus before corrective surgery. Treatment of erectile dysfunction of neurogenic, vascular, psychogenic or mixed etiology; conducting a pharmacological test as part of a set of diagnostic tests for erectile dysfunction.
Alprostan® Zentiva
The drug ALPROSTAN® ZENTIVA can only be used by doctors with experience in angiology, familiar with modern methods of continuous monitoring of the state of the cardiovascular system and who have the appropriate equipment and equipment for pediatric resuscitation.
During the treatment period, it is necessary to monitor hemodynamic parameters of the acid-base balance, biochemical parameters of the blood, and the blood coagulation system (in case of disorders of the blood coagulation system or during simultaneous therapy with drugs that affect the coagulation system).
10-12% of newborns with congenital heart defects may experience respiratory arrest when exposed to alprostadil. Apnea is most often observed in newborns weighing less than 2 kg at birth, and most often occurs during the first hour of drug administration. Therefore, the drug ALPROSTAN® ZENTIVA should be used under constant monitoring of blood pressure, in the presence of conditions for artificial pulmonary ventilation (ALV).
ALPROSTAN® ZENTIVA should be administered in the shortest possible time and in the smallest dosage that can lead to the desired therapeutic effect. The risk of prolonged administration should be weighed against the benefit obtained when administered to an infant patient.
With prolonged administration of alprostadil, cortical growth of tubular bones was observed in newborns. Cortical growth in children reversed after discontinuation of the drug.
ALPROSTAN® ZENTIVA is contraindicated for use in newborns (or infants) with respiratory distress syndrome. A differential diagnosis should always be made between respiratory distress syndrome and congenital heart disease with cyanosis (restriction of pulmonary blood flow). The diagnosis should be based on the presence of cyanosis (partial pressure of oxygen in the blood (pO2) less than 40 mm Hg) and the presence of radiological signs of pulmonary blood flow restriction.
Blood pressure should be monitored by an umbilical artery catheter, auscultation, or Doppler ultrasound. If blood pressure drops significantly, the rate of administration should be immediately reduced. The use of ALPROSTAN® ZENTIVA in newborns (or infants) can lead to obstruction of the pylorus of the stomach against the background of hyperplasia of the mucous membrane of the antrum of the stomach. The occurrence of this phenomenon is associated with the duration of treatment and the total dose of the drug. Neonates (or infants) receiving alprostadil at recommended doses for more than 120 hours should be monitored for possible manifestations of antral mucosal hyperplasia and pyloric obstruction.
In newborns (or infants) with reduced pulmonary blood flow, oxygen saturation increases in inverse proportion to the pO2 value, i.e. The best response to therapy occurs in patients with low pO2 values (less than 40 mm Hg), while patients with high pO2 values (more than 40 mm Hg) usually have minimal response. In newborns (or infants) with reduced pulmonary blood flow, the effectiveness of alprostadil is determined by an increase in blood oxygen saturation, an increase in systemic blood pressure and blood pH.
Patients with coronary heart disease, renal failure (serum creatinine more than 150 µmol/l) should be monitored in the hospital during treatment with ALPROSTAN® ZENTIVA and for 1 day after stopping treatment. To avoid the appearance of symptoms of overhydration in such patients, the volume of fluid administered should, if possible, not exceed 50-100 ml per day. Dynamic monitoring of the patient's condition is necessary (monitoring blood pressure and heart rate), and, if necessary, monitoring body weight, fluid balance, measuring central venous pressure or echocardiography.
In patients with chronic obliterating diseases of the arteries of the lower extremities, the use of ALPROSTAN® ZENTIVA is part of a complex treatment; the clinical effect is long-lasting and may appear with a certain delay after completion of the course of treatment.
Phlebitis (proximal to the injection site), as a rule, is not a reason to discontinue therapy; signs of inflammation disappear a few hours after stopping the infusion or changing the injection site; specific treatment is not required in such cases. Central vein catheterization can reduce the incidence of this side effect of the drug.
Use of the drug Alprostadil
In adults, for diseases of peripheral arteries, it is used according to an intermittent multi-week regimen. The recommended dose is from 50 to 200 mcg once a day or from 50 to 100 mcg twice a day for more severe conditions. Injected intravenously over 2 hours in 100–500 ml of 0.9% sodium chloride solution or 5% glucose solution. The course of treatment is 14 days, when a therapeutic effect is achieved, treatment is continued for another 7–14 days, the total duration of the course of treatment should not exceed 4 weeks. If the therapeutic effect is not achieved within 2 weeks of treatment, alprostadil is discontinued. Newborns are administered intravenously by drip or through the umbilical artery at an initial rate of 0.01-0.05 mcg/kg per 1 min; after achieving a therapeutic effect, maintenance treatment is carried out at the minimum effective dose (usually 0.01–0.02 mcg/kg per 1 min). If necessary, the initial dose can be increased to 0.1 mcg/kg per 1 minute. The dose for intracavernous administration is selected for each patient individually by careful titration under the supervision of a physician. For erectile dysfunction of neurogenic origin, the recommended initial dose is 1.25 mcg. With each subsequent administration, the dose of the drug can be doubled, but not by more than 5 mcg, until the minimum effective dose is reached, causing a sufficient erection lasting no more than 60 minutes. For erectile dysfunction of vascular, psychogenic or mixed etiology, the initial dose is 2.5 mcg. With each subsequent administration, the dose is doubled, but not more than by 5-10 mcg until the minimum effective dose is reached. If a certain dose does not cause an effect, then the next, higher dose can be administered after 1 hour. If there is an effect, the interval between doses should be at least 1 day. As a rule, the dose should not exceed 60 mcg. The frequency of injections is no more than 1 time per day and 3 times per week. When using alprostadil as a diagnostic agent, it is recommended to use a single dose that induces an erection.
Alprostadil (Alprostadilum)
Obliterating diseases of the arteries (stages III and IV 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 arterial diseases: 60 mcg intravenously over 2 hours. Inferior to iloprost in effectiveness. Intermittent claudication: according to RCTs, prostaglandin E1 compared with pentoxifylline (PGE1 - 40 mcg in 250 ml of 0.9% sodium chloride solution intravenously for 2 hours 2 times a day, pentoxifylline - in 250 ml of 0.9% sodium solution chloride intravenous drip for 2 hours twice a day) significantly increased pain-free walking distance (mean distance 416 m, 95% CI 28-804), but had no effect on maximum walking distance (1 RCT, 29 participants). Other studies do not provide standard deviation, so the effect of medications on walking distance cannot be analyzed. According to these studies (2 RCTs, 240 participants), there was no difference in ankle-brachial pressure index between groups. PGE1 increased the average pain-free walking distance from 83 to 264 m in one study and from 89 to 195 m in another, and pentoxifylline from 84 to 188 m and from 78 to 149 m, respectively.
Atherosclerosis. 120 mcg/day intravenously. Diabetic angiopathy: ineffective. Berger's disease. Raynaud's syndrome with trophic disorders. 60 mcg intravenously over 3 hours daily. Vasculitis. Systemic scleroderma. 60 mcg IV over 3 hours daily. Cramps of the calf muscles.
Damage due to physical factors, especially extreme vibration. Intra-arterial (using an infusion pump) 10-20 mcg for 1-2 hours 1 time per day or 0.1-0.6 ng/kg×min (5-10 mcg) through an installed catheter for 12 hours. Intravenously according 40 mcg 2 times a day (after dissolving the contents of the ampoule in 50 ml of 0.9% sodium chloride solution) or 50-200 mcg 1 time per day (for more severe conditions - 50-100 mcg 2 times a day); the duration of the infusion is at least 2 hours. If there is no positive effect within 2 weeks after the start of treatment, further use is stopped.
If renal function is impaired (serum creatinine concentration ›1.5 mg/l), intravenous administration begins with a dose of 20 mcg. If necessary, after 2-3 days the single dose is increased to 40-60 mcg. For patients with renal and heart failure, the maximum volume of administered fluid is 50-100 ml/day. The course of treatment is 4 weeks. The clinical effect is long-term and may appear with some delay after completion of the course of treatment.
Erection disorders of neurogenic, vascular, psychogenic or mixed etiology.
Intracavernous 5-10 mcg once a week, 125-1000 mcg transurethral in 4 doses over a 2-4 week period. Self-injection treatment at home should begin with the dose prescribed in the doctor's office, no more than 1 time per day and 3 times per week. Onset of action is 5-10 minutes, duration is 1-3 hours.
The dose is selected individually until the minimum effective dose is achieved (the appearance of an erection sufficient for sexual intercourse, but not more than 1 hour), under the supervision of a doctor until the erection disappears. If the first dose is ineffective, a second, higher dose is administered after 1 hour. If the second dose is ineffective, a third, even higher dose is administered no earlier than 1 day later. For erectile dysfunction of neurogenic origin (for example, with spinal cord damage), the initial dose is 1.25 mcg. With each subsequent administration, the dose is doubled, but not by more than 5 mcg, until the minimum effective dose is reached. For erectile dysfunction of vascular, psychogenic or mixed etiology, the initial dose is 2.5 mcg. With each subsequent administration, double the dose, but not by more than 5-10 mcg, until the minimum effective dose is reached. Intraurethral in the form of suppositories, initial dose 125-250 mcg; if necessary, the dose is gradually increased or decreased until an erection sufficient for sexual intercourse occurs. The maximum frequency of use is 2 times a day. Effective for erectile dysfunction of various etiologies. Intracavernous administration in a dose of 40-1000 mcg is more effective than intraurethral administration, but is more difficult to use. Surpasses the effectiveness of moxisilite chlorine hydrateρB; comparable to a vacuum deviceB. Inferior to sodium nitroprusside at a dose of 300-400 mcg intracavernosally. Intraurethral, in the form of applications, is ineffective; Can be used in combination with phentolamine intracavernosally.
Psychogenic erectile dysfunction: intracavernous 2.5-5.0 mcg is more cost-effective than psychotherapy.
Erectile dysfunction after treatment for prostate cancer—the most compelling evidence comes from oral PDE5 inhibitors after radiation therapy for prostate cancer and radical prostatectomy. With transurethral alprostadil, 270 of 384 participants reported acceptable erectile improvement, with the 1000 mcg dose effective in 35%, 500 mcg in 31%, 250 mcg in 17%, and 125 mcg in 17%. 270 men were divided into two groups - an alprostadil treatment group and a placebo group. The OR for successful coitus at least once within 3 months was significant and in favor of treatment - 18.96 (95% CI 8.85-40.65), a wide confidence interval indicates insufficient power of the study and the need to interpret its results carefully. Significantly more often in the alprostadil treatment group 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' findings, PDE5 inhibitors are effective in the treatment of secondary erectile dysfunction after treatment for prostate cancer. Other methods need further research.
Carrying out a pharmacological test as part of a set of diagnostic tests for erectile dysfunction: once in a dose that causes an erection.
Use in children
The need to temporarily support the functioning of the ductus arteriosus before performing corrective surgery 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 x min, then it is reduced to the minimum effective. Lower doses (10 ng/kg x min) may be more effective and safer. Continuously through an umbilical arterial catheter (connected directly to the mouth of the ductus arteriosus) or one of the large veins with an initial rate of 0.05-0.1 (up to 0.4) mcg/kg x min. After achieving a therapeutic effect - 0.01-0.02 mcg/kg×min (0.005-0.01C21). If severe side effects occur, the dose should be reduced.
Contraindications to the use of the drug Alprostadil
During pregnancy and breastfeeding; relative contraindications - acute and subacute period of myocardial infarction, severe or unstable angina; broncho-obstructive syndrome, impaired liver function, risk of bleeding (peptic ulcer of the stomach and duodenum, pathology of cerebral vessels, proliferative retinopathy with a tendency to bleeding, polytrauma, etc.), severe arterial hypotension, increased sensitivity to the drug. For intracavernous administration: diseases predisposing to the occurrence of priapism (sickle cell anemia, myeloma, leukemia); anatomical deformations of the penis (angulation, cavernous fibrosis, Peyronie's disease).
Side effects of the drug Alprostadil
Irritation of the vein proximal to the injection site, headache, dizziness, fatigue, malaise, sweating, discomfort in the epigastric region, nausea, vomiting, diarrhea, swelling of the limb into which the drug is administered, arterial hypotension, orthostatic reactions, tachycardia, fever, allergic reactions , reversible hyperostosis of long bones with prolonged treatment (4 weeks or more), leukocytosis or leukopenia, increased CRP titer; in newborns - fever, diarrhea, arterial hypotension, hypoventilation, apnea, bradycardia or tachycardia, skin reactions, extremely rarely - convulsions and disseminated intravascular coagulation syndrome. With intracavernous injection, pain in the penis, prolonged erection and priapism, fibrosis, swelling and rashes on the penis, balanitis, hemorrhages at the injection site, inflammation, itching and swelling at the injection site, bleeding from the urethra, a feeling of heat in the penis, numbness are possible. , fungal infection, irritation, hypersensitivity, phimosis, erythema, venous discharge, painful erection and ejaculation disorder. If the injection technique is violated, a hematoma may appear at the injection site. Pain in the testicular area, swelling of the testicles, pain and tension in the scrotum, increased urination, and urinary incontinence are rarely noted; possible fluctuations in blood pressure, supraventricular extrasystole, peripheral vascular disorders; dizziness, headache, hyperesthesia; weakness of the gluteal muscles, localized pain (in the gluteal muscles, lower extremities, genitals, abdomen), pain in the lumbar region, flu-like syndrome.
Instructions for use ALPROSTAN
The incidence of adverse reactions increases with increasing dose, concentration and infusion rate.
In adult patients:
From the cardiovascular system:
An increase in infusion volume is limited to patients with severe heart failure (risk of developing pulmonary edema or severe heart failure). The following side effects have been reported in less than 1%:
- arterial and orthostatic hypotension, tachycardia, angina pectoris.
From the central nervous system:
The following side effects have been reported in less than 1%:
- weakness, dizziness, headache, hyperthermia.
From the digestive system:
The following side effects have been reported in less than 1%:
- feeling of discomfort in the epigastric region, nausea, vomiting, diarrhea.
Other adverse reactions:
The following side effects have been reported in less than 1%:
- increased sweating, allergic reactions.
From the musculoskeletal system:
a long course of treatment (4 weeks or more) may be complicated by reversible hyperostosis of the tubular bones.
From the hematopoietic organs:
changes in the blood are possible in the form of leukocytosis, leukopenia.
Laboratory indicators:
changes in laboratory parameters may be observed in patients on Alprostan therapy (increased levels of C-reactive proteins, transaminases, increased platelet counts, as well as changes in white blood cell counts), and return to normal levels after discontinuation of therapy.
Due to the antiplatelet effect of prostaglandins, the effect of platelet aggregation inhibitors and fibrinolytics may be reduced.
Local reactions:
swelling of the limb is possible, into the vein of which the drug solution is infused. When treating limb ischemia, intravenous administration of alprostadil may be complicated by the appearance of signs of phlebitis proximal to the injection site (in 40% of patients); signs of inflammation disappear a few hours after stopping the infusion or changing the injection site; specific treatment is not required in such cases. Central vein catheterization can reduce the incidence of this side effect of the drug, but its use is not an integral part of treatment.
In newborns:
From the central nervous system:
apnea occurs in 12% of newborns treated with Alprostan. The most common side effects are also hyperthermia (approximately 14% of newborns) and seizures (approximately 4%). The following side effects have been reported in less than 1% of newborns:
- cerebral bleeding, hypertonicity of the neck muscles, increased irritability, hypothermia, syndrome of increased neuro-reflex excitability, drowsiness and rigidity.
From the cardiovascular system:
the most common are: facial flushing (flushing) (in 10% of newborns, most often after intra-arterial injection), bradycardia (7%), hypotension (4%), tachycardia (3%), cardiac arrest and edema (1% ). The following side effects have been reported in less than 1% of newborns:
- congestive heart failure, hyperemia, AV block, shock, right ventricular infundibulospasm, supraventricular tachycardia and ventricular fibrillation.
From the respiratory system:
The following side effects have been reported in less than 1% of newborns:
- bradypnea, bronchial wheezing, hypercapnia, respiratory depression, tachypnea, respiratory distress.
From the digestive system:
the most common adverse reaction is diarrhea (about 2% of patients). The following side effects have been reported in less than 1% of newborns:
- gastric regurgitation, hyperbilirubinemia.
From the hematopoietic organs:
the most common adverse reaction is generalized thrombohemorrhagic syndrome (about 1% of patients). The following side effects have been reported in less than 1% of newborns:
- anemia, bleeding and thrombocytopenia.
From the urinary system:
anuria and hematuria have been reported in less than 1% of newborns.
From the musculoskeletal system:
Cases of cortical proliferation of long bones have been reported.
Other adverse reactions:
sepsis (in approximately 2% of newborns), hypokalemia (about 1%), peritonitis, hypoglycemia and hyperkalemia (less than 1%).
If side effects occur, the dose of the drug should be reduced.
Alprostadil overdose, symptoms and treatment
If signs of overdose appear (decrease in blood pressure, skin hyperemia, weakness), reduce the infusion rate or discontinue alprostadil. As a rule, no specific treatment is required. If there are signs of depression of the respiratory center in newborns, mechanical ventilation is performed. With intracavernous administration, in the event of prolonged erection and/or priapism, sympathomimetic amines are injected intracavernosally, aspiration is performed, and, if necessary, surgical treatment is used.
List of pharmacies where you can buy Alprostadil:
- Moscow
- Saint Petersburg
