Composition, structure and packing
The solution for infusion, clear, yellowish.
1 bottle contains 5 mg. nifedipine (active substance) in 50 ml infusion rasctvora.
Excipients: ethanol 96%, macrogol 400, sodium hydroxide, 0,1 N, water for injection.
Clinico-pharmacological group: blocker "slow" calcium channels.
Pharmacological action
Nifedipine - a selective blocker of the "slow" calcium channels, a derivative of 1,4-dihydropyridine. Has antianginal and hypotensive action. Reduces the current of calcium ions through the slow calcium channels within cells, primarily into cardiomyocytes, smooth muscle cells of coronary and peripheral arteries, lowering the peripheral vascular resistance and increasing coronary arteries, particularly the larger supplying vessels, and even intact segments of the walls partially stenosed vessels. In addition, the nifedipine lowers the tone of smooth muscles of coronary arteries, thus prevents angiospasm, increases blood flow in poststenotic regions of the vessels and increases oxygen delivery to the myocardium, decreases myocardial oxygen demand by reducing peripheral vascular resistance (afterload), and prolonged admission, he capable of preventing the development of new atherosclerotic lesions in coronary arteries.
Nifedipine lowers the tone of smooth muscles of arterioles, thereby reducing the increased peripheral vascular resistance and hence blood pressure (BP). In the early treatment of nifedipine may be a temporary reflex increase in heart rate and, consequently, the values of cardiac output. However, this increase is not so much to compensate for the expansion of blood vessels. In addition, nifedipine at short and long-term use increases the excretion of sodium and water from the body. Hypotensive effect of nifedipine is especially pronounced in patients with arterial hypertension.
Pharmacokinetics
Distribution
After intravenous administration of nifedipine rapidly distributed in the body, 50% of the administered dose is distributed in the body after a 5-6 min. Connect to plasma proteins (albumin) at 95%.
Metabolism
After parenteral administration of nifedipine is almost completely metabolized in the liver to the inactive metabolites.
Withdrawal
Excreted by the kidneys mainly as inactive metabolites, to a lesser extent (of 5-15%) with bile. In urine only traces (less than 1%) of the unmodified active agent.
The half-life (T1 / 2) nifedipine after parenteral administration is 1.7 hours in patients with impaired renal function, the pharmacokinetics of nifedipine are not significantly altered.
In hepatic failure showed a significant lengthening of T1 / 2 of the drug and reduce its total clearance, which may require dose reduction.
Penetrates through the placental barrier, excreted in breast milk.
Hemodialysis and peritoneal dialysis does not affect the pharmacokinetics of nifedipine, plasmapheresis enhances its elimination.
Statement
Prinzmetal angina
hypertensive crisis
Dosage regimen
50 ml of solution Adalat ® intravenously infusion for about 4-8 hours (at a rate 6,3-12,5 ml / h, which corresponds to 0,63-1,25 mg of nifedipine / h).
The maximum dose of the drug, administered within 24 hours should not exceed 150-300 ml (which corresponds to 15-30 mg nifedipina/24 h).
In patients with renal impairment dose adjustment is required. Infusion may be carried out continuously for 3 days. Then we recommend switching to oral therapy nifedipine.
Instructions for the introduction of solution for infusion Adalat:
Ready-to-use infusion solution Adalat should be imposed only through a special syringe and vascular system brand
Perfusors Inzhektomat, or annexed to the solution. Subject to the use of prescribed infusion supplies loss nifedipine through conducting system can not be afraid.
Nifedipine, the active substance infusion solution Adalat, highly sensitive to light, so it is necessary to protect the solution from this exposure. Supplied with a protective plastic shell vial must be removed from the packaging only immediately before use.
When the hybrid infusion must also provide protection solution Adalat from light, so it must be injected directly into the infusion tube which has received another solution, with the introduction of the system should be as close as possible to the place of puncture a vein. Never mix the solution in one bottle Adalat with other solutions.
If the solution is stored in the refrigerator, before the introduction of its temperature must be brought to room temperature.
Side effect
Since the cardiovascular system:
tachycardia, decrease blood pressure, "tides" of blood to the face, accompanied by a sensation of heat.
From the side of the central nervous system:
headache.
The part of the digestive system:
nausea.
Chronic administration of nifedipine into the description the following side effects: peripheral edema, abdominal pain, asthenia, palpitations, malaise, angina, blood pressure reduction, including postural hypotension, in some cases marked, until the development of ventricular fibrillation and prolong the interval QT, heart rate , constipation, diarrhea, dry mouth, dyspepsia, agitation, tremor, shortness of breath, itching, rash, sweating, allergic reactions, visual disturbances, syncope, anreksiya, flatulence, vomiting, hyperglycemia, myalgia, hypesthesia, somnolence, insomnia, paresthesia, polyuria, gum hyperplasia, increased activity of "liver" enzymes, agranulocytosis, thrombocytopenic purpura, thrombocytopenia, exfoliative dermatitis, gynaecomastia, photosensitivity, urticaria.
Contraindications
Hypersensitivity to nifedipine;
pregnancy and lactation;
cardiogenic shock;
unstable angina;
Acute myocardial infarction (within the first 4 weeks of illness);
co-administration with rifampicin;
age of 18 years (safety and efficacy not established)
Use of the drug with caution:
Chronic heart failure, severe aortic stenosis, subaortalny stenosis, marked bradycardia, hepatic impairment, severe impairment of cerebral blood flow, expressed as hypotension (systolic blood pressure below 90 mm Hg), elderly, patients with malignant hypertension and hypovolaemia, held on hemodialysis.
Pregnancy and lactation
The use of nifedipine is contraindicated during the entire period of pregnancy as possible embryotoxic, fetotoksicheskoe and teratogenic effect of the drug.
Nifedipine penetrates into breast milk, so if its reception is required, then breastfeeding should be discontinued.
Cautions
Dosage Adalat ® must be selected individually based on disease severity and patient response to treatment, as well as to strictly control the level of blood pressure and heart rate.
Avoid the simultaneous application of solution for infusion Adalat ®, and β-adrenoceptor blockers, because of the risk of significant decrease of blood pressure, and in some cases - worsening symptoms of heart failure.
Infusion solution Adalat ® should not be given to patients who have assumed the relationship of pain of ischemic nature of previous therapy nifedipine.
In the application of nifedipine may occur very rarely attacks of angina and may worsen during the worsening of angina, elongation and increased frequency of seizures, especially in the beginning of treatment.
In some cases reported the development of myocardial infarction, however, this is not possible to establish a causal link with the disease receiving nifedipine as myocardial infarction may occur as a result of the natural history of coronary heart disease.
Patients with disorders of the liver with the introduction Adalat require careful monitoring, and in some cases, you must decrease the dose.
To avoid burning in the area of the injection should be made slowly.
Nifedipine causes false positive increase in the concentration of vanillylmandelic acid in urine in the determination of the spectrophotometric method and does not affect the result of this reaction using the method of high performance liquid chromatography (HPLC).
Solution for infusion Adalat in a plastic container is stable in daylight for 1 hour, and in artificial light for 6 hours.
Overdose
Symptoms
Loss of consciousness up to coma and BP decrease, tachycardia / bradycardia, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock, accompanied by swelling of the lungs.
Treatment
Withdrawal of nifedipine from the body and the restoration of stable hemodynamics.
When bradycardia - β-sympathomimetic, in life-threatening bradycardia - implantation of temporary artificial pacemaker.
In marked decrease in blood pressure should slow intravenous injection of 10-20 ml of 10% solution of calcium gluconate (allowed re-introduction), in which the inefficiency - the appointment of vasoconstrictor sympathomimetics (dopamine and norepinephrine).
The doses of these drugs are selected depending on the obtained therapeutic effect. Introduction of fluid should be limited to the risk of overloading the heart.
Hemodialysis is pointless, because nifedipine is not displayed during dialysis, we recommend conducting plasmapheresis.
Drug Interactions
Antihypertensive effect of nifedipine could worsen, while the use of drugs to lower blood pressure, as well as prazozina and other alpha-blockers, due to the suppression of their metabolism.
Antihypertensive effect of reducing: sympathomimetic, non-steroidal anti-inflammatory drugs (NSAIDs), because of the suppression of the synthesis of prostaglandins in the kidneys, as well as delays of sodium and fluids in the body, estrogens (water retention), and calcium preparations. Since nifedipine is metabolized by the enzyme cytochrome P450 3A4, then drugs that inhibit or induce these enzymes may interact with nifedipine in its ingestion, in violation of clearance and metabolism of "first pass" through the liver. These interactions are more typical for nifedipine oral.
Digoxin
Nifedipine reduces the clearance of digoxin, which leads to an increase in its concentration in plasma, so patients need careful monitoring for symptoms of an overdose of cardiac glycosides, and the dose if necessary, should be reduced.
Quinidine
Nifedipine reduces the concentration of quinidine in blood plasma, however, with its abolition content quinidine may increase substantially, requiring adjustments to the dose. In some cases, may increase the concentration of nifedipine in blood plasma, so if the testimony should reduce its dosage. During concomitant therapy is necessary to monitor the concentration of quinidine in blood plasma and blood pressure level. At the same time taking with nifedipine increases the risk lengthening the interval QT.
Procainamide
When combined with procainamide risk long QT interval and increased the negative inotropic effect of both drugs.
Phenytoin
Induces enzymes cytochrome P450 3A4 and reduces the bioavailability of nifedipine and, consequently, reduces its effectiveness, which may require increasing the dose.
Cimetidine
Inhibits cytochrome P450 3A4 systems and causes an increased concentration of nifedipine in blood plasma, thereby enhancing its hypotensive action.
Rifampicin
Refers to a potent inducer of liver enzymes, accelerating the metabolism of nifedipine, which leads to a weakening of its effectiveness.
Diltiazem
Slows the removal of nifedipine from the body, so the combination therapy should be very cautiously, if necessary, reducing the dose of nifedipine.
Tsizaprid
Increasing concentrations of nifedipine in plasma, so you should monitor the level of blood pressure, and if necessary to reduce the dose of nifedipine.
Grapefruit juice
inhibits cytochrome P450 3A4 system and increases the concentration of nifedipine in plasma, because of lower metabolism "first pass" through the liver.
Valproic acid
Because valproic acid causes an increase in plasma concentrations of nimodipine, the structure is close to nifedpinu, blocker "slow" calcium channels, it is not excluded increase in plasma concentrations of nifedipine and increased its effectiveness.
Acetylsalicylic acid
Nifedipine does not alter the antiplatelet properties of aspirin in a dose of 100 mg (platelet aggregation and duration of bleeding). Acetylsalicylic acid, in turn, does not affect the pharmacokinetic parameters of nifedipine.
Carbamazepine, Phenobarbital
Since carbamazepine and fenabarbital cause a reduction in plasma concentration of nimodipine, the structure close to nifedipine, blockers "slow" calcium channels, it may decrease in plasma concentration of nifedipine and decrease its effectiveness. Nifedipine may displace from its association with protein drugs characterized by a high degree of binding (indirect anticoagulants - derivatives of coumarin and indandiona, quinine, sulfinpirazon), followed by the possible increase of their concentration in plasma. Since erythromycin, fluoxetine, ritonavir, indinavir, amprenavir, Nelfinavir, saquinavir, ketoconazole, itraconazole, fluconazole, inhibits the enzyme cytochrome P450 3A4, it is not ruled out increasing the concentration of nifedipine in blood plasma as a result of their interaction. It is recommended to control blood pressure level and if necessary to reduce the dose of nifedipine. In case of simultaneous appointment with dizopiramid and flekainamidom may gain a negative inotropic effect of both drugs.
Aymalin, omeprazole, benazepril, irbesartan, orlistat, ranitidine, rosiglitazone, doxazosin, pantoprazole, talinolol, triamterene, hydrochlorothiazide did not affect the pharmacokinetics of nifedipine.
Infusion solution Adalat contains 18% by volume of ethanol that must be considered in combination with drugs that are incompatible with ethanol. Solution for infusion Adalat ® compatible with the following solutions:
0,9% solution of sodium chloride
5% dextrose
5% solution of fructose
Infusion rate for glucose Adalat 10 ml / h, and in conjunction with the compatibility of the solution - 40 ml / h.
Combination with other infusion solutions is not recommended.
Terms and Conditions of storage
Store at temperatures not above 25 ° C, protected from light and the reach of children.
Shelf life 2 years.
The solution for infusion, clear, yellowish.
1 bottle contains 5 mg. nifedipine (active substance) in 50 ml infusion rasctvora.
Excipients: ethanol 96%, macrogol 400, sodium hydroxide, 0,1 N, water for injection.
Clinico-pharmacological group: blocker "slow" calcium channels.
Pharmacological action
Nifedipine - a selective blocker of the "slow" calcium channels, a derivative of 1,4-dihydropyridine. Has antianginal and hypotensive action. Reduces the current of calcium ions through the slow calcium channels within cells, primarily into cardiomyocytes, smooth muscle cells of coronary and peripheral arteries, lowering the peripheral vascular resistance and increasing coronary arteries, particularly the larger supplying vessels, and even intact segments of the walls partially stenosed vessels. In addition, the nifedipine lowers the tone of smooth muscles of coronary arteries, thus prevents angiospasm, increases blood flow in poststenotic regions of the vessels and increases oxygen delivery to the myocardium, decreases myocardial oxygen demand by reducing peripheral vascular resistance (afterload), and prolonged admission, he capable of preventing the development of new atherosclerotic lesions in coronary arteries.
Nifedipine lowers the tone of smooth muscles of arterioles, thereby reducing the increased peripheral vascular resistance and hence blood pressure (BP). In the early treatment of nifedipine may be a temporary reflex increase in heart rate and, consequently, the values of cardiac output. However, this increase is not so much to compensate for the expansion of blood vessels. In addition, nifedipine at short and long-term use increases the excretion of sodium and water from the body. Hypotensive effect of nifedipine is especially pronounced in patients with arterial hypertension.
Pharmacokinetics
Distribution
After intravenous administration of nifedipine rapidly distributed in the body, 50% of the administered dose is distributed in the body after a 5-6 min. Connect to plasma proteins (albumin) at 95%.
Metabolism
After parenteral administration of nifedipine is almost completely metabolized in the liver to the inactive metabolites.
Withdrawal
Excreted by the kidneys mainly as inactive metabolites, to a lesser extent (of 5-15%) with bile. In urine only traces (less than 1%) of the unmodified active agent.
The half-life (T1 / 2) nifedipine after parenteral administration is 1.7 hours in patients with impaired renal function, the pharmacokinetics of nifedipine are not significantly altered.
In hepatic failure showed a significant lengthening of T1 / 2 of the drug and reduce its total clearance, which may require dose reduction.
Penetrates through the placental barrier, excreted in breast milk.
Hemodialysis and peritoneal dialysis does not affect the pharmacokinetics of nifedipine, plasmapheresis enhances its elimination.
Statement
Prinzmetal angina
hypertensive crisis
Dosage regimen
50 ml of solution Adalat ® intravenously infusion for about 4-8 hours (at a rate 6,3-12,5 ml / h, which corresponds to 0,63-1,25 mg of nifedipine / h).
The maximum dose of the drug, administered within 24 hours should not exceed 150-300 ml (which corresponds to 15-30 mg nifedipina/24 h).
In patients with renal impairment dose adjustment is required. Infusion may be carried out continuously for 3 days. Then we recommend switching to oral therapy nifedipine.
Instructions for the introduction of solution for infusion Adalat:
Ready-to-use infusion solution Adalat should be imposed only through a special syringe and vascular system brand
Perfusors Inzhektomat, or annexed to the solution. Subject to the use of prescribed infusion supplies loss nifedipine through conducting system can not be afraid.
Nifedipine, the active substance infusion solution Adalat, highly sensitive to light, so it is necessary to protect the solution from this exposure. Supplied with a protective plastic shell vial must be removed from the packaging only immediately before use.
When the hybrid infusion must also provide protection solution Adalat from light, so it must be injected directly into the infusion tube which has received another solution, with the introduction of the system should be as close as possible to the place of puncture a vein. Never mix the solution in one bottle Adalat with other solutions.
If the solution is stored in the refrigerator, before the introduction of its temperature must be brought to room temperature.
Side effect
Since the cardiovascular system:
tachycardia, decrease blood pressure, "tides" of blood to the face, accompanied by a sensation of heat.
From the side of the central nervous system:
headache.
The part of the digestive system:
nausea.
Chronic administration of nifedipine into the description the following side effects: peripheral edema, abdominal pain, asthenia, palpitations, malaise, angina, blood pressure reduction, including postural hypotension, in some cases marked, until the development of ventricular fibrillation and prolong the interval QT, heart rate , constipation, diarrhea, dry mouth, dyspepsia, agitation, tremor, shortness of breath, itching, rash, sweating, allergic reactions, visual disturbances, syncope, anreksiya, flatulence, vomiting, hyperglycemia, myalgia, hypesthesia, somnolence, insomnia, paresthesia, polyuria, gum hyperplasia, increased activity of "liver" enzymes, agranulocytosis, thrombocytopenic purpura, thrombocytopenia, exfoliative dermatitis, gynaecomastia, photosensitivity, urticaria.
Contraindications
Hypersensitivity to nifedipine;
pregnancy and lactation;
cardiogenic shock;
unstable angina;
Acute myocardial infarction (within the first 4 weeks of illness);
co-administration with rifampicin;
age of 18 years (safety and efficacy not established)
Use of the drug with caution:
Chronic heart failure, severe aortic stenosis, subaortalny stenosis, marked bradycardia, hepatic impairment, severe impairment of cerebral blood flow, expressed as hypotension (systolic blood pressure below 90 mm Hg), elderly, patients with malignant hypertension and hypovolaemia, held on hemodialysis.
Pregnancy and lactation
The use of nifedipine is contraindicated during the entire period of pregnancy as possible embryotoxic, fetotoksicheskoe and teratogenic effect of the drug.
Nifedipine penetrates into breast milk, so if its reception is required, then breastfeeding should be discontinued.
Cautions
Dosage Adalat ® must be selected individually based on disease severity and patient response to treatment, as well as to strictly control the level of blood pressure and heart rate.
Avoid the simultaneous application of solution for infusion Adalat ®, and β-adrenoceptor blockers, because of the risk of significant decrease of blood pressure, and in some cases - worsening symptoms of heart failure.
Infusion solution Adalat ® should not be given to patients who have assumed the relationship of pain of ischemic nature of previous therapy nifedipine.
In the application of nifedipine may occur very rarely attacks of angina and may worsen during the worsening of angina, elongation and increased frequency of seizures, especially in the beginning of treatment.
In some cases reported the development of myocardial infarction, however, this is not possible to establish a causal link with the disease receiving nifedipine as myocardial infarction may occur as a result of the natural history of coronary heart disease.
Patients with disorders of the liver with the introduction Adalat require careful monitoring, and in some cases, you must decrease the dose.
To avoid burning in the area of the injection should be made slowly.
Nifedipine causes false positive increase in the concentration of vanillylmandelic acid in urine in the determination of the spectrophotometric method and does not affect the result of this reaction using the method of high performance liquid chromatography (HPLC).
Solution for infusion Adalat in a plastic container is stable in daylight for 1 hour, and in artificial light for 6 hours.
Overdose
Symptoms
Loss of consciousness up to coma and BP decrease, tachycardia / bradycardia, hyperglycemia, metabolic acidosis, hypoxia, cardiogenic shock, accompanied by swelling of the lungs.
Treatment
Withdrawal of nifedipine from the body and the restoration of stable hemodynamics.
When bradycardia - β-sympathomimetic, in life-threatening bradycardia - implantation of temporary artificial pacemaker.
In marked decrease in blood pressure should slow intravenous injection of 10-20 ml of 10% solution of calcium gluconate (allowed re-introduction), in which the inefficiency - the appointment of vasoconstrictor sympathomimetics (dopamine and norepinephrine).
The doses of these drugs are selected depending on the obtained therapeutic effect. Introduction of fluid should be limited to the risk of overloading the heart.
Hemodialysis is pointless, because nifedipine is not displayed during dialysis, we recommend conducting plasmapheresis.
Drug Interactions
Antihypertensive effect of nifedipine could worsen, while the use of drugs to lower blood pressure, as well as prazozina and other alpha-blockers, due to the suppression of their metabolism.
Antihypertensive effect of reducing: sympathomimetic, non-steroidal anti-inflammatory drugs (NSAIDs), because of the suppression of the synthesis of prostaglandins in the kidneys, as well as delays of sodium and fluids in the body, estrogens (water retention), and calcium preparations. Since nifedipine is metabolized by the enzyme cytochrome P450 3A4, then drugs that inhibit or induce these enzymes may interact with nifedipine in its ingestion, in violation of clearance and metabolism of "first pass" through the liver. These interactions are more typical for nifedipine oral.
Digoxin
Nifedipine reduces the clearance of digoxin, which leads to an increase in its concentration in plasma, so patients need careful monitoring for symptoms of an overdose of cardiac glycosides, and the dose if necessary, should be reduced.
Quinidine
Nifedipine reduces the concentration of quinidine in blood plasma, however, with its abolition content quinidine may increase substantially, requiring adjustments to the dose. In some cases, may increase the concentration of nifedipine in blood plasma, so if the testimony should reduce its dosage. During concomitant therapy is necessary to monitor the concentration of quinidine in blood plasma and blood pressure level. At the same time taking with nifedipine increases the risk lengthening the interval QT.
Procainamide
When combined with procainamide risk long QT interval and increased the negative inotropic effect of both drugs.
Phenytoin
Induces enzymes cytochrome P450 3A4 and reduces the bioavailability of nifedipine and, consequently, reduces its effectiveness, which may require increasing the dose.
Cimetidine
Inhibits cytochrome P450 3A4 systems and causes an increased concentration of nifedipine in blood plasma, thereby enhancing its hypotensive action.
Rifampicin
Refers to a potent inducer of liver enzymes, accelerating the metabolism of nifedipine, which leads to a weakening of its effectiveness.
Diltiazem
Slows the removal of nifedipine from the body, so the combination therapy should be very cautiously, if necessary, reducing the dose of nifedipine.
Tsizaprid
Increasing concentrations of nifedipine in plasma, so you should monitor the level of blood pressure, and if necessary to reduce the dose of nifedipine.
Grapefruit juice
inhibits cytochrome P450 3A4 system and increases the concentration of nifedipine in plasma, because of lower metabolism "first pass" through the liver.
Valproic acid
Because valproic acid causes an increase in plasma concentrations of nimodipine, the structure is close to nifedpinu, blocker "slow" calcium channels, it is not excluded increase in plasma concentrations of nifedipine and increased its effectiveness.
Acetylsalicylic acid
Nifedipine does not alter the antiplatelet properties of aspirin in a dose of 100 mg (platelet aggregation and duration of bleeding). Acetylsalicylic acid, in turn, does not affect the pharmacokinetic parameters of nifedipine.
Carbamazepine, Phenobarbital
Since carbamazepine and fenabarbital cause a reduction in plasma concentration of nimodipine, the structure close to nifedipine, blockers "slow" calcium channels, it may decrease in plasma concentration of nifedipine and decrease its effectiveness. Nifedipine may displace from its association with protein drugs characterized by a high degree of binding (indirect anticoagulants - derivatives of coumarin and indandiona, quinine, sulfinpirazon), followed by the possible increase of their concentration in plasma. Since erythromycin, fluoxetine, ritonavir, indinavir, amprenavir, Nelfinavir, saquinavir, ketoconazole, itraconazole, fluconazole, inhibits the enzyme cytochrome P450 3A4, it is not ruled out increasing the concentration of nifedipine in blood plasma as a result of their interaction. It is recommended to control blood pressure level and if necessary to reduce the dose of nifedipine. In case of simultaneous appointment with dizopiramid and flekainamidom may gain a negative inotropic effect of both drugs.
Aymalin, omeprazole, benazepril, irbesartan, orlistat, ranitidine, rosiglitazone, doxazosin, pantoprazole, talinolol, triamterene, hydrochlorothiazide did not affect the pharmacokinetics of nifedipine.
Infusion solution Adalat contains 18% by volume of ethanol that must be considered in combination with drugs that are incompatible with ethanol. Solution for infusion Adalat ® compatible with the following solutions:
0,9% solution of sodium chloride
5% dextrose
5% solution of fructose
Infusion rate for glucose Adalat 10 ml / h, and in conjunction with the compatibility of the solution - 40 ml / h.
Combination with other infusion solutions is not recommended.
Terms and Conditions of storage
Store at temperatures not above 25 ° C, protected from light and the reach of children.
Shelf life 2 years.
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