Composition, structure and packing
Concentrate for solution for infusion in the form of a transparent colorless liquid.
1 amp. alprostadil 100 mcg.
Excipients: ethanol - up to 0.2 ml.
Clinico-pharmacological group: preparation of prostaglandin E1, which improves peripheral circulation.
Pharmacological action
The preparation of prostaglandin E1. Has vasodilator and angioprotective action. It improves the microcirculation and peripheral circulation, causing vasodilation at the level of arterioles, precapillary sphincters, the arteries.
With the introduction intrakavernoznom relaxes smooth muscles of the corpora cavernosa, thereby increasing blood flow and improve microcirculation in them. When intra-arterial injection promotes the temporary preservation of a functioning ductus arteriosus in neonates. It improves the rheological properties of blood, increasing the flexibility of red blood cells.
Affect the process of blood clotting, reducing the adhesion and aggregation of platelets.
It has fibrinolytic effects and antiatherogenic properties, slowing the activation of neutrophils, excessive proliferation of cells of the vascular wall.
Reduces TPVR, blood pressure, reflex increases in heart rate, which leads to an increase in cardiac output.
It stimulates the smooth muscles of the intestine, bladder, uterus, suppresses the secretion of gastric juice.
Pharmacokinetics
Metabolism
Following in / introduction of alprostadil quickly biotransformiruetsya. For a single passage through the lungs is metabolized to 60-90%. When enzymatic oxidation formed three biologically active metabolite: 15-keto-PGE1, 15-keto-13 ,14-dihydro-PGE1 and 13,14-dihydro-PGE1. Keto-metabolites have a lower than alprostadilom pharmacological activity, and metabolite 13,14-dihydro-PGE1 - comparable. Pharmacodynamic effects of the drug is due mainly just that pharmacologically active metabolite.
Withdrawal
The main metabolites excreted in the urine (88%) and feces (12%). T1 / 2 alprostadil is about 10 seconds. T1 / 2 13,14-dihydro-PGE1 is about 1 min (α-phase) and 30 min (β-phase).
Statement
chronic obliterating peripheral arterial disease stage III-IV (Fontaine classification), accompanied by pain in the limbs at rest or trophic disturbances (occlusive disease with severe intermittent claudication, which is not shown surgery, atherosclerosis of arteries of extremities, Raynaud's syndrome with trophic ulcers, diabetic angiopathy , Berger disease, vasculitis in systemic sclerosis, violations of peripheral circulation as a result of exposure sverhpredelnymi vibration);
the need for temporary preservation of a functioning blood flow to the reconstructive cardiac surgery for congenital heart defects duktuszavisimyh newborns.
Dosage regimen
Adults with chronic obliterating arterial diseases Alprostan appointed in / infusion dose of 50-200 mg 1 time / day or in more severe states of 50-100 mg 2 times / day. The solvent used 200-500 ml of saline, 5% or 10% glucose solution. The duration of infusion - at least 2 h. The solution should be prepared immediately before administration.
Duration of therapy averaged 14 days, with the positive effect of treatment can continue for a further 7-14 days. The maximum duration of treatment - 4 weeks.
In the absence of a positive effect within 2 weeks of starting treatment continued use of the drug should be discontinued.
When congenital malformations in newborns duktuszavisimyh Alprostan injected by constant infusion through the large veins or through the umbilical artery directly into the mouth of the ductus arteriosus. The initial dose is 0.01-0.05 mg / kg / min.
If necessary, the dose may be increased to 0.1 mg / kg / min.
When the therapeutic effect of the dose is reduced to the minimum maintenance (0.01-0.02 mg / kg / min).
Terms of preparing infusion solution
At dilution of 1 mg (0.2 ml) of concentrate for infusion of 9.8 ml of solvent (5% or 10% glucose solution, saline solution) obtained a solution with a concentration of alprostadil mkg/10 100 ml.
The resulting solution can be further diluted with large amounts of solvent. Also note that the resulting infusion solution should be used immediately after preparation, probably deposited within 24 hours at a temperature of from 2 to 8 ° C.
Side effect
From the CNS: headache, dizziness, fatigue, feeling of malaise.
On the part of the digestive system: a feeling of discomfort, nausea, vomiting, diarrhea, increase in liver transaminases, hyperbilirubinemia.
Since the cardiovascular system: tachycardia, hypotension, seizures, angina, cardiac arrhythmias, AV-block, pulmonary edema, cardio-vascular insufficiency.
The part of the hemopoietic system: leucopenia, leukocytosis. Allergic reactions: urticaria.
Other: increased sweating, hyperthermia body, increasing the titer of C-reactive protein, prolonged treatment (from 4 or more weeks) - hyperostosis of tubular bones; hematuria. Local reaction: swelling of limbs, in the vein received infusions.
Babies: From CNS: irritability, convulsions, drowsiness.
On the part of the digestive system: peritoneal symptoms, hyperbilirubinemia, diarrhea.
Since the cardiovascular system: arterial hypotension, bradycardia, tachycardia, shock, acute heart failure, cardiac arrhythmias, AV-block.
The respiratory system: respiratory depression (up to apnea), lower respiratory function (bradypnea, tachypnea).
On the part of the hemopoietic system: DIC-syndrome, bleeding, thrombocytopenia, anemia.
From the urinary system: reduction of renal function, anuria, hematuria. Allergic reactions: skin rash, tachyphylaxis.
Other: hyper-or hypothermia of the skin, flushing of the skin, hypo-or hyperglycemia, hypertonicity of the neck muscles, hypercapnia. With long-term therapy (several weeks) may cause hyperostosis of the bones of the lower extremities. With the development of side effects dose should be reduced.
Contraindications
acute and subacute myocardial infarction;
severe or unstable form of angina pectoris;
bronchial obstruction with signs of severe respiratory failure, edema or infiltrative changes in the lungs;
marked disturbances of liver function;
state, characterized by risk of bleeding (peptic ulcer and duodenal ulcer in acute, severe carotid arteries, proliferative retinopathy with a tendency to bleeding, major trauma);
co-administration of vasodilator and anticoagulant funds;
Pregnancy
lactation (breastfeeding);
Hypersensitivity to alprostadilu;
the age of 18 years (except for the neonatal period) and over 75 years.
In neonatology:
inhibition of respiratory function;
respiratory distress syndrome;
state of spontaneous staunchly ductus arteriosus;
Hypersensitivity to alprostadilu.
Pregnancy and lactation
Alprostan contraindicated in pregnancy. If necessary, use during lactation should decide on the termination of breastfeeding.
Application for violations of liver function
Contraindications disturbancies liver function.
Application for violations of renal function
In patients on hemodialysis treatment for drug should be conducted in postdializnom period.
Cautions
Particular caution should be exercised when administering the drug to patients with arterial hypotension, cardiovascular disease (should take into account the volume of infusion solution, increased infusion should be limited to patients with severe heart failure due to the risk of developing pulmonary edema and possible heart failure), in elderly patients with insulin-dependent diabetes mellitus, especially in extensive vascular damage, with the appointment of newborns in the case bradypnea, arterial hypotension, tachycardia, hyperthermia.
During treatment Alprostanom need to monitor hemodynamic parameters, acid-base balance, blood biochemistry parameters of coagulation (disorders of blood coagulation system or while taking medications that affect blood clotting).
In order to avoid the onset of symptoms in these patients overhydration volume of fluid injected, if possible, should not exceed 50-100 mg / day. Need dynamic monitoring of the patient (control of blood pressure, heart rate), if necessary - control of body weight, fluid balance, the measurement of central venous pressure, or echocardiography.
In the appointment of the drug for the treatment of chronic obliterating arterial diseases should be aware that therapy Alprostanom is a necessary part of complex treatment.
Clinical effect of long-term nature and can occur with some delay after the end of treatment. In patients on hemodialysis treatment for drug should be conducted in postdializnom period. The newborn drug should be used under the constant supervision of blood pressure in the presence of conditions for mechanical ventilation.
Overdose
Symptoms: reduction of blood pressure, flushing of the skin, weakness.
Treatment: infusion should be slowed down or stopped. Necessary for the specific treatment, there is usually no. If you suspect depression of the respiratory center in newborns should resort to artificial ventilation.
Drug Interactions
With simultaneous application Alprostana with anticoagulants and antiagregantami increased risk of bleeding. With simultaneous application Alprostan intensifies the effect of antihypertensive agents and vasodilators.
Pharmaceutical interactions
Concentrate for infusion pharmaceutically incompatible with other solutions (except for normal saline, 5% and 10% dextrose).
Terms and Conditions of storage
The drug should be stored in a dry, dark place at temperatures from 1 ° to 5 ° C; not freeze. Shelf life - 2 years. The prepared solution should be stored no longer than 24 hours at a temperature of 2 ° to 8 ° C.
Concentrate for solution for infusion in the form of a transparent colorless liquid.
1 amp. alprostadil 100 mcg.
Excipients: ethanol - up to 0.2 ml.
Clinico-pharmacological group: preparation of prostaglandin E1, which improves peripheral circulation.
Pharmacological action
The preparation of prostaglandin E1. Has vasodilator and angioprotective action. It improves the microcirculation and peripheral circulation, causing vasodilation at the level of arterioles, precapillary sphincters, the arteries.
With the introduction intrakavernoznom relaxes smooth muscles of the corpora cavernosa, thereby increasing blood flow and improve microcirculation in them. When intra-arterial injection promotes the temporary preservation of a functioning ductus arteriosus in neonates. It improves the rheological properties of blood, increasing the flexibility of red blood cells.
Affect the process of blood clotting, reducing the adhesion and aggregation of platelets.
It has fibrinolytic effects and antiatherogenic properties, slowing the activation of neutrophils, excessive proliferation of cells of the vascular wall.
Reduces TPVR, blood pressure, reflex increases in heart rate, which leads to an increase in cardiac output.
It stimulates the smooth muscles of the intestine, bladder, uterus, suppresses the secretion of gastric juice.
Pharmacokinetics
Metabolism
Following in / introduction of alprostadil quickly biotransformiruetsya. For a single passage through the lungs is metabolized to 60-90%. When enzymatic oxidation formed three biologically active metabolite: 15-keto-PGE1, 15-keto-13 ,14-dihydro-PGE1 and 13,14-dihydro-PGE1. Keto-metabolites have a lower than alprostadilom pharmacological activity, and metabolite 13,14-dihydro-PGE1 - comparable. Pharmacodynamic effects of the drug is due mainly just that pharmacologically active metabolite.
Withdrawal
The main metabolites excreted in the urine (88%) and feces (12%). T1 / 2 alprostadil is about 10 seconds. T1 / 2 13,14-dihydro-PGE1 is about 1 min (α-phase) and 30 min (β-phase).
Statement
chronic obliterating peripheral arterial disease stage III-IV (Fontaine classification), accompanied by pain in the limbs at rest or trophic disturbances (occlusive disease with severe intermittent claudication, which is not shown surgery, atherosclerosis of arteries of extremities, Raynaud's syndrome with trophic ulcers, diabetic angiopathy , Berger disease, vasculitis in systemic sclerosis, violations of peripheral circulation as a result of exposure sverhpredelnymi vibration);
the need for temporary preservation of a functioning blood flow to the reconstructive cardiac surgery for congenital heart defects duktuszavisimyh newborns.
Dosage regimen
Adults with chronic obliterating arterial diseases Alprostan appointed in / infusion dose of 50-200 mg 1 time / day or in more severe states of 50-100 mg 2 times / day. The solvent used 200-500 ml of saline, 5% or 10% glucose solution. The duration of infusion - at least 2 h. The solution should be prepared immediately before administration.
Duration of therapy averaged 14 days, with the positive effect of treatment can continue for a further 7-14 days. The maximum duration of treatment - 4 weeks.
In the absence of a positive effect within 2 weeks of starting treatment continued use of the drug should be discontinued.
When congenital malformations in newborns duktuszavisimyh Alprostan injected by constant infusion through the large veins or through the umbilical artery directly into the mouth of the ductus arteriosus. The initial dose is 0.01-0.05 mg / kg / min.
If necessary, the dose may be increased to 0.1 mg / kg / min.
When the therapeutic effect of the dose is reduced to the minimum maintenance (0.01-0.02 mg / kg / min).
Terms of preparing infusion solution
At dilution of 1 mg (0.2 ml) of concentrate for infusion of 9.8 ml of solvent (5% or 10% glucose solution, saline solution) obtained a solution with a concentration of alprostadil mkg/10 100 ml.
The resulting solution can be further diluted with large amounts of solvent. Also note that the resulting infusion solution should be used immediately after preparation, probably deposited within 24 hours at a temperature of from 2 to 8 ° C.
Side effect
From the CNS: headache, dizziness, fatigue, feeling of malaise.
On the part of the digestive system: a feeling of discomfort, nausea, vomiting, diarrhea, increase in liver transaminases, hyperbilirubinemia.
Since the cardiovascular system: tachycardia, hypotension, seizures, angina, cardiac arrhythmias, AV-block, pulmonary edema, cardio-vascular insufficiency.
The part of the hemopoietic system: leucopenia, leukocytosis. Allergic reactions: urticaria.
Other: increased sweating, hyperthermia body, increasing the titer of C-reactive protein, prolonged treatment (from 4 or more weeks) - hyperostosis of tubular bones; hematuria. Local reaction: swelling of limbs, in the vein received infusions.
Babies: From CNS: irritability, convulsions, drowsiness.
On the part of the digestive system: peritoneal symptoms, hyperbilirubinemia, diarrhea.
Since the cardiovascular system: arterial hypotension, bradycardia, tachycardia, shock, acute heart failure, cardiac arrhythmias, AV-block.
The respiratory system: respiratory depression (up to apnea), lower respiratory function (bradypnea, tachypnea).
On the part of the hemopoietic system: DIC-syndrome, bleeding, thrombocytopenia, anemia.
From the urinary system: reduction of renal function, anuria, hematuria. Allergic reactions: skin rash, tachyphylaxis.
Other: hyper-or hypothermia of the skin, flushing of the skin, hypo-or hyperglycemia, hypertonicity of the neck muscles, hypercapnia. With long-term therapy (several weeks) may cause hyperostosis of the bones of the lower extremities. With the development of side effects dose should be reduced.
Contraindications
acute and subacute myocardial infarction;
severe or unstable form of angina pectoris;
bronchial obstruction with signs of severe respiratory failure, edema or infiltrative changes in the lungs;
marked disturbances of liver function;
state, characterized by risk of bleeding (peptic ulcer and duodenal ulcer in acute, severe carotid arteries, proliferative retinopathy with a tendency to bleeding, major trauma);
co-administration of vasodilator and anticoagulant funds;
Pregnancy
lactation (breastfeeding);
Hypersensitivity to alprostadilu;
the age of 18 years (except for the neonatal period) and over 75 years.
In neonatology:
inhibition of respiratory function;
respiratory distress syndrome;
state of spontaneous staunchly ductus arteriosus;
Hypersensitivity to alprostadilu.
Pregnancy and lactation
Alprostan contraindicated in pregnancy. If necessary, use during lactation should decide on the termination of breastfeeding.
Application for violations of liver function
Contraindications disturbancies liver function.
Application for violations of renal function
In patients on hemodialysis treatment for drug should be conducted in postdializnom period.
Cautions
Particular caution should be exercised when administering the drug to patients with arterial hypotension, cardiovascular disease (should take into account the volume of infusion solution, increased infusion should be limited to patients with severe heart failure due to the risk of developing pulmonary edema and possible heart failure), in elderly patients with insulin-dependent diabetes mellitus, especially in extensive vascular damage, with the appointment of newborns in the case bradypnea, arterial hypotension, tachycardia, hyperthermia.
During treatment Alprostanom need to monitor hemodynamic parameters, acid-base balance, blood biochemistry parameters of coagulation (disorders of blood coagulation system or while taking medications that affect blood clotting).
In order to avoid the onset of symptoms in these patients overhydration volume of fluid injected, if possible, should not exceed 50-100 mg / day. Need dynamic monitoring of the patient (control of blood pressure, heart rate), if necessary - control of body weight, fluid balance, the measurement of central venous pressure, or echocardiography.
In the appointment of the drug for the treatment of chronic obliterating arterial diseases should be aware that therapy Alprostanom is a necessary part of complex treatment.
Clinical effect of long-term nature and can occur with some delay after the end of treatment. In patients on hemodialysis treatment for drug should be conducted in postdializnom period. The newborn drug should be used under the constant supervision of blood pressure in the presence of conditions for mechanical ventilation.
Overdose
Symptoms: reduction of blood pressure, flushing of the skin, weakness.
Treatment: infusion should be slowed down or stopped. Necessary for the specific treatment, there is usually no. If you suspect depression of the respiratory center in newborns should resort to artificial ventilation.
Drug Interactions
With simultaneous application Alprostana with anticoagulants and antiagregantami increased risk of bleeding. With simultaneous application Alprostan intensifies the effect of antihypertensive agents and vasodilators.
Pharmaceutical interactions
Concentrate for infusion pharmaceutically incompatible with other solutions (except for normal saline, 5% and 10% dextrose).
Terms and Conditions of storage
The drug should be stored in a dry, dark place at temperatures from 1 ° to 5 ° C; not freeze. Shelf life - 2 years. The prepared solution should be stored no longer than 24 hours at a temperature of 2 ° to 8 ° C.
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