pharmachologic effect
Selective class II calcium channel blocker, dihydropyridine derivative. Inhibits the flow of calcium into cardiomyocytes and vascular smooth muscle cells. Has antianginal and hypotensive effects. Reduces the tone of vascular smooth muscles. Dilates coronary and peripheral arteries, reduces peripheral vascular resistance, blood pressure and slightly reduces myocardial contractility, reduces afterload and myocardial oxygen demand. Improves coronary blood flow. It has virtually no antiarrhythmic activity. Does not inhibit myocardial conductivity.
Calcigard Retard tablets PPO Prolong 20mg No. 100
Compound
1 tablet contains:
Tablet core: active substance:
nifedipine 20 mg,
excipients:
lactose monohydrate 20.00 mg, starch 13.44 mg, microcrystalline cellulose 15.00 mg, polysorbate-80 1.00 mg, macrogol 6000 1.00 mg, stearic acid 1.00 mg, povidone (K-30) 6.00 mg, magnesium stearate 1.56 mg, sodium lauryl sulfate 2.00 mg.
Film coating: hypromellose (15 cps) 2.66 mg, ethylcellulose 0.40 mg, diethyl phthalate 0.26 mg, titanium dioxide 0.26 mg, chocolate brown varnish 0.40 mg, talc 0.02 mg.
Pharmacokinetics
Absorption is high (more than 92-98%). Bioavailability - 40-60%. Eating increases bioavailability. Has a first pass effect through the liver.
Penetrates the blood-brain barrier and is excreted in breast milk.
Penetrates the blood-brain barrier and is excreted in breast milk.
Completely metabolized in the liver. The isoenzymes CYP3A4, CYP3A5 and CYP3A7 are involved in the metabolism of the drug. The half-life (T1/2) is 3.8-16.9 hours. In patients with liver failure, total clearance decreases and T1/2 increases.
There is no cumulative effect. Chronic renal failure, hemodialysis and peritoneal dialysis do not affect pharmacokinetics. With prolonged use, tolerance to the action of the drug develops. Plasmapheresis may enhance elimination.
Indications for use
Coronary heart disease - angina pectoris of exertion and rest (including variant).
Arterial hypertension (as monotherapy or in combination with other antihypertensive drugs).
Contraindications
Symptoms:
headache, facial skin flushing, decreased blood pressure, suppression of sinus node activity, bradycardia, arrhythmia.
Treatment:
gastric lavage with the administration of activated charcoal, symptomatic therapy aimed at stabilizing the activity of the cardiovascular system. The antidote is calcium; slow intravenous administration of a 10% solution of calcium chloride or calcium gluconate is indicated, followed by switching to a long-term infusion.
With a pronounced decrease in blood pressure, intravenous administration of dopamine or dobutamine. In case of conduction disturbances, the administration of atropine, isoprenaline or the installation of an artificial pacemaker is indicated. With the development of heart failure - intravenous administration of strophanthin. Catecholamines should be used only in case of life-threatening circulatory failure (due to their reduced effectiveness, a high dosage is required, which increases the risk of increasing the tendency to arrhythmia due to intoxication). It is recommended to control blood glucose and electrolytes (potassium and calcium ions), as insulin release is impaired. Hemodialysis is not effective.
Directions for use and doses
The dosage regimen is set individually depending on the severity of the disease and the response to the therapy. It is recommended to take the drug during or after meals with a small amount of water.
Initial dose: 1 tablet (20 mg) twice a day. If necessary, the dose can be increased. The maximum daily dose of the drug is 120 mg.
In elderly patients or patients receiving combination (antianginal or antihypertensive) therapy, with impaired liver function, in patients with severe cerebrovascular accidents, the dose should be reduced.
Storage conditions
List B. At a temperature not exceeding 30 C in a dry place, protected from light.
Keep out of the reach of children.
Best before date
3 years. Do not use after the date indicated on the package.
special instructions
During the treatment period it is necessary to refrain from taking ethanol.
It is recommended to stop treatment with the drug gradually.
It should be borne in mind that angina pectoris may occur at the beginning of treatment, especially after recent abrupt withdrawal of beta-blockers (the latter should be withdrawn gradually).
The simultaneous administration of beta-blockers must be carried out under conditions of careful medical supervision, as this may cause an excessive decrease in blood pressure, and in some cases, aggravation of symptoms of heart failure.
In case of severe heart failure, the drug is dosed with great caution.
The diagnostic criteria for prescribing the drug for vasospastic angina are: the classic clinical picture, accompanied by an increase in the ST segment, the occurrence of ergonovine-induced angina or coronary artery spasm, the detection of coronary spasm during angiography or the identification of an angiospastic component without confirmation (for example, with a different voltage threshold or with unstable angina, when electrocardiogram data indicate transient vasospasm).
For patients with severe obstructive cardiomyopathy, there is a risk of an increase in the frequency, severity and duration of angina attacks after taking nifedipine; in this case, discontinuation of the drug is necessary.
In patients on hemodialysis with high blood pressure, irreversible kidney failure, and a reduced total blood volume, the drug should be used with caution; a sharp drop in blood pressure may occur.
Patients with impaired liver function are closely monitored and, if necessary, reduce the dose of the drug and/or use other dosage forms of nifedipine.
If during therapy the patient requires surgery under general anesthesia, it is necessary to inform the anesthesiologist about the nature of the therapy being performed.
During treatment, positive results are possible when performing a direct Coombs test and laboratory tests for antinuclear antibodies.
Caution should be used when co-administering disopyramide and flecainamide due to a possible increase in inotropic effect.
Description
Round, biconvex, brown, film-coated tablets with a score on one side.
Conditions for dispensing from pharmacies
On prescription
Dosage form
extended-release film-coated tablets
Manufacturer and organization accepting consumer complaints
Manufacturer: TORRENT PHARMACEUTICALS LTD. Torrent House, Off Ashram Road, Ahmedabad 380 009, India
Representative office in Russia: Moscow 117418 st. Novocheremushkinskaya, 61 tel/31 fax: (495) 232 94 09
Pharmacodynamics
Selective blocker of slow calcium channels, 1,4-dihydropyridine derivative. It has a vasodilating, antianginal and hypotensive effect. Reduces the Ca2+ current into cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries, and in high doses suppresses the release of Ca2+ from intracellular stores. Reduces the number of functioning channels without affecting the time of their activation, inactivation and recovery. It uncouples the processes of excitation and contraction in the myocardium, mediated by tropomyosin and troponin, and in vascular smooth muscles, mediated by calmodulin. In therapeutic doses, it normalizes the transmembrane Ca2+ current, which is disturbed in a number of pathological conditions, primarily in arterial hypertension. Does not affect the tone of the veins. Strengthens coronary blood flow, improves blood supply to ischemic areas of the myocardium without developing the steal phenomenon, and activates the functioning of collaterals. By dilating the peripheral arteries, it reduces the total peripheral vascular resistance, myocardial tone, afterload, myocardial oxygen demand and increases the duration of diastolic relaxation of the left ventricle. It has virtually no effect on the sinoatrial and atrioventricular nodes and does not have antiarrhythmic activity. Increases renal blood flow, causes moderate natriuresis. The negative chrono-, dromo- and inotropic effects are overlapped by reflex activation of the sympathoadrenal system and an increase in the number of heart contractions in response to peripheral vasodilation.
The onset of effect is 20 minutes when taken orally, the duration of the effect is 12-24 hours (long-term retard form).
Side effects
From the cardiovascular system:
Manifestations of excessive vasodilation (asymptomatic decrease in blood pressure, development or worsening of heart failure, flushing of the facial skin, flushing of the facial skin, feeling of heat), tachycardia, palpitations, arrhythmia, peripheral edema, chest pain. Rarely - excessive decrease in blood pressure, fainting; in some patients, especially at the beginning of treatment, angina attacks may occur, which requires discontinuation of the drug; isolated cases of myocardial infarction have been described.
From the central nervous system:
Headache, dizziness, increased fatigue, weakness, drowsiness. With long-term oral administration in high doses, paresthesia of the limbs, depression, anxiety, extrapyramidal (parkinsonian) disorders (ataxia, mask-like face, shuffling gait, stiffness in the movements of the arms and legs, tremor of the hands and fingers, difficulty swallowing).
From the digestive system:
Dry mouth, increased appetite, dyspepsia (nausea, diarrhea or constipation). Rarely - gum hyperplasia (bleeding, pain, swelling). With long-term use - liver dysfunction (intrahepatic cholestasis, increased activity of liver enzymes).
From the hematopoietic organs:
Anemia, asymptomatic agranulocytosis, thrombocytopenia, thrombocytopenic purpura, leukopenia.
Allergic reactions:
Rarely - itching, urticaria, exanthema, exfoliative dermatitis, photodermatitis. Very rarely - autoimmune hepatitis.
From the musculoskeletal system:
arthritis, arthralgia (rare), joint swelling, myalgia, cramps of the upper and lower extremities.
From the urinary system:
increased daily diuresis, deterioration of renal function (in patients with renal failure).
Other:
Rarely - difficulty breathing, cough, very rarely - visual impairment (including transient blindness at the maximum concentration of nifedipine in the blood plasma), gynecomastia (in elderly patients, completely disappearing after discontinuation of the drug), hyperglycemia, galactorrhea, pulmonary edema, bronchospasm, weight gain.
Use during pregnancy and breastfeeding
Prescription of nifedipine for pregnant women is indicated only if the expected benefit to the mother outweighs the potential risk to the fetus. Nifedipine is not recommended for use during the first 20 weeks of pregnancy.
The drug is excreted in breast milk, so it is recommended to stop breastfeeding while taking the drug. There are no data on the use of Calcigard retard by nursing women.
Interaction
The severity of the decrease in blood pressure increases with the simultaneous use of other antihypertensive drugs, nitrates, cimetidine (to a lesser extent, ranitidine), inhalational anesthetics and tricyclic antidepressants.
Medicines from the group of slow calcium channel blockers can further enhance the negative inotropic effect (decreased force of heart contraction) of antiarrhythmic drugs such as amiodarone and quinidine.
Nifedipine causes a decrease in the concentration of quinidine in the blood plasma; after discontinuation of nifedipine, a sharp increase in the concentration of quinidine may occur.
Increases the plasma concentration of digoxin and theophylline, and therefore the clinical effect and the content of digoxin and theophylline in the blood plasma should be monitored.
Inducers of microsomal liver enzymes (rifampicin, etc.) reduce the concentration of nifedipine.
In combination with nitrates, tachycardia increases. The hypotensive effect is reduced by sympathomimetics, non-steroidal anti-inflammatory drugs (suppression of Pg synthesis in the kidneys and Na+ and fluid retention in the body), estrogens (fluid retention in the body). Calcium supplements may reduce the effect of slow calcium channel blockers.
Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, non-steroidal anti-inflammatory drugs, quinine, salicylates, sulfinpyrazone), as a result of which their concentration in the blood plasma may increase .
Suppresses the metabolism of prazosin and other alpha-blockers, as a result of which the hypotensive effect may be enhanced.
Nifedipine inhibits the elimination of vincristine from the body and may cause increased side effects of vincristine; if necessary, the dose of vincristine is reduced.
Lithium preparations can increase toxic effects (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Procainamide, quinidine and other drugs that cause prolongation of the Q-T interval may increase the risk of a significant prolongation of the Q-T interval. Grapefruit juice suppresses the metabolism of nifedipine in the body, and therefore their simultaneous use is contraindicated.
Overdose
Symptoms:
headache, facial skin flushing, decreased blood pressure, suppression of sinus node activity, bradycardia, arrhythmia.
Treatment:
gastric lavage with the administration of activated charcoal, symptomatic therapy aimed at stabilizing the activity of the cardiovascular system. The antidote is calcium; slow intravenous administration of a 10% solution of calcium chloride or calcium gluconate is indicated, followed by switching to a long-term infusion.
With a pronounced decrease in blood pressure, intravenous administration of dopamine or dobutamine. In case of conduction disturbances, the administration of atropine, isoprenaline or the installation of an artificial pacemaker is indicated. With the development of heart failure - intravenous administration of strophanthin. Catecholamines should be used only in case of life-threatening circulatory failure (due to their reduced effectiveness, a high dosage is required, which increases the risk of increasing the tendency to arrhythmia due to intoxication). It is recommended to control blood glucose and electrolytes (potassium and calcium ions), as insulin release is impaired. Hemodialysis is not effective.
Impact on the ability to drive vehicles and operate machinery
In some patients, especially at the beginning of treatment, the drug may cause dizziness, which reduces the ability to drive a car or use other machinery. In the future, the degree of restrictions is determined depending on the individual tolerability of the drug.
Directions for use and doses
Individual. For oral administration, the initial dose is 10 mg 3-4 times a day. If necessary, the dose is gradually increased to 20 mg 3-4 times a day. In special cases (variant angina, severe arterial hypertension), for a short time the dose can be increased to 30 mg 3-4 times a day. To relieve a hypertensive crisis, as well as an attack of angina, 10-20 mg (rarely 30 mg) can be used sublingually.
IV to relieve an attack of angina or hypertensive crisis - 5 mg for 4-8 hours.
Intracoronary to relieve acute spasms of the coronary arteries, a bolus of 100-200 mcg is administered. For stenosis of large coronary vessels, the initial dose is 50-100 mcg.
Maximum daily doses: when taken orally - 120 mg, when administered intravenously - 30 mg.
special instructions
Nifedipine should be used only in a clinical setting under the strict supervision of a physician for acute myocardial infarction, severe cerebrovascular accidents, diabetes mellitus, liver and kidney dysfunction, malignant arterial hypertension and hypovolemia, as well as in patients on hemodialysis. In patients with impaired liver and/or kidney function, the use of nifedipine in high doses should be avoided. Elderly patients are more likely to have decreased cerebral blood flow due to acute peripheral vasodilation.
When taken orally, nifedipine can be chewed to accelerate the effect.
If chest pain occurs during treatment, nifedipine should be discontinued. Nifedipine should be discontinued gradually, since withdrawal syndrome may develop if it is suddenly stopped (especially after long-term treatment).
When administered intracoronarily in the presence of stenosis of two vessels, nifedipine cannot be administered into the third open vessel due to the danger of a pronounced negative inotropic effect.
During the course of treatment, avoid drinking alcohol due to the risk of excessive reduction in blood pressure.
Impact on the ability to drive vehicles and machinery
At the beginning of treatment, you should avoid driving vehicles and other potentially dangerous activities that require rapid psychomotor reactions. In the process of further treatment, the degree of restrictions is determined depending on the individual tolerance of nifedipine.
Calcigard® retard
Pharmacokinetic interactions
Medicines that affect the metabolism of nifedipine
Nifedipine is metabolized by isoenzymes CYP3A3A4/5, which are located in the intestinal mucosa and liver. Drugs that inhibit or induce this enzyme system may have an effect on the hepatic first pass effect (after oral administration) or the clearance of nifedipine. Inducers of the CYP3A4 isoenzyme
Rifampicin
Rifampin is a potent inducer of the CYP3A4 isoenzyme. When used simultaneously with rifampicin, the bioavailability of nifedipine is significantly reduced and, accordingly, its effectiveness is reduced. Therefore, the simultaneous use of nifedipine with rifampicin is contraindicated.
Antiepileptic drugs that induce CYP3A4 (eg, phenytoin, carbamazepine, phenobarbital)
Phenytoin induces the CYP3A4 isoenzyme. With the simultaneous use of nifedipine and phenytoin, the bioavailability of nifedipine is reduced and its effectiveness is reduced. When using this combination simultaneously, it is necessary to monitor the clinical response to nifedipine therapy and, if necessary, increase its dose. If the dose of nifedipine is increased with simultaneous use of both drugs, the dose of nifedipine should be reduced after discontinuation of phenytoin.
Clinical studies examining the potential interaction between nifedipine and carbamazepine or phenobarbital have not been conducted. Since both drugs reduce the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of a decrease in the concentration of nifedipine in the blood plasma and a decrease in its effectiveness cannot be excluded.
CYP3A4 isoenzyme inhibitors
Macrolide antibiotics (for example, erythromycin)
Clinical studies on the interaction of nifedipine and macrolide antibiotics have not been conducted. Some macrolides are known to inhibit the CYP3A4 isoenzyme. As a result, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and macrolide antibiotics.
Azithromycin, a macrolide antibiotic, does not inhibit the CYP3A4 isoenzyme.
HIV protease inhibitors (eg, ritonavir)
Clinical studies examining the interaction of nifedipine and HIV protease inhibitors have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. In addition, drugs of this class have been shown to suppress the metabolism of nifedipine mediated by the CYP3A4 isoenzyme in vitro.
When used simultaneously with nifedipine, a significant increase in the concentration of nifedipine in the blood plasma cannot be ruled out due to a decrease in the effect of “first pass” through the liver and slower elimination.
Azole antifungals (eg, ketoconazole)
Clinical studies examining the interaction of nifedipine and azole antifungals have not been conducted. It is known that drugs of this class inhibit the CYP3A4 isoenzyme. When used simultaneously with nifedipine, a significant increase in the systemic bioavailability of nifedipine is possible by reducing the effect of “first pass” through the liver.
Cimetidine and ranitidine
It has been established that cimetidine and ranitidine inhibit the CYP3A4 isoenzyme and cause an increase in the concentration of nifedipine in the blood plasma (by 80% and 70%, respectively), thereby enhancing its antihypertensive effect.
Diltiazem
Diltiazem reduces the clearance of nifedipine. This combination should be used with caution. A dose reduction of nifedipine may be required.
Fluoxetine
Clinical studies examining the interaction of nifedipine and fluoxetine have not been conducted. It is known that fluoxetine in vitro suppresses the metabolism of nifedipine, mediated by the action of the CYP3A4 isoenzyme. Therefore, the possibility of an increase in the concentration of nifedipine in the blood plasma cannot be excluded with the simultaneous use of nifedipine and fluoxetine.
Nefazodone
Clinical studies examining the interaction between nifedipine and nefazodone have not been conducted. Nefazodone is known to inhibit the metabolism of other drugs mediated by the CYP3A4 isoenzyme. Therefore, the possibility of increased plasma concentrations of nifedipine cannot be excluded with simultaneous use of nifedipine and nefazodone.
Quinidine
Increased plasma concentrations of quinidine have been reported when administered concomitantly with quinidine. Therefore, when using quinidine and nifedipine simultaneously, careful monitoring of blood pressure is necessary. If necessary, the dose of nifedipine should be reduced.
Quinupristin/dalfopristin
Concomitant use of quinupristin/dalfopristin and nifedipine may lead to increased plasma concentrations of nifedipine.
Valproic acid
Clinical studies examining the interaction of nifedipine and valproic acid have not been conducted. Since valproic acid increases the concentration of nimodipine in the blood plasma, which is structurally similar to BMCC, the possibility of increasing the concentration of nifedipine in the blood plasma and enhancing its effectiveness cannot be excluded.
Grapefruit juice
Grapefruit juice inhibits the CYP3A4 isoenzyme and suppresses the metabolism of nifedipine. The simultaneous use of nifedipine with grapefruit juice leads to an increase in the concentration of nifedipine in the blood plasma and a prolongation of its action due to the effect of “primary passage” through the liver and a decrease in clearance. This may enhance the antihypertensive effect of nifedipine. With regular consumption of grapefruit juice, this effect can last for 3 days after the last consumption of the juice. The consumption of grapefruit/grapefruit juice during treatment with nifedipine is contraindicated.
CYP3A4 isoenzyme substrates
Substrates of the CYP3A4 isoenzyme (for example, cisapride, tacrolimus, benzodiazepines, imipramine, propafenone, terfenadine, warfarin), when used simultaneously with nifedipine, may act as CYP3A4 inhibitors and increase the concentration of nifedipine in the blood plasma.
Cisapride
Concomitant use of cisapride and nifedipine may lead to increased plasma concentrations of nifedipine.
Effect of nifedipine on other drugs
Quinidine
Nifedipine causes a decrease in the concentration of quinidine in the blood plasma. After discontinuation of nifedipine, a sharp increase in the concentration of quinidine in the blood plasma may occur. Therefore, when using nifedipine as an additional therapy or discontinuing nifedipine, the concentration of quinidine in the blood plasma should be monitored and, if necessary, its dose should be adjusted.
Digoxin
The simultaneous use of nifedipine and digoxin may lead to a decrease in the clearance of digoxin and, consequently, to an increase in the concentration of digoxin in the blood plasma. The patient should be carefully monitored for symptoms of glycoside overdose and, if necessary, reduce the dose of digoxin, taking into account its concentration in the blood plasma.
Theophylline
Nifedipine increases plasma concentrations of theophylline, and therefore the concentration of theophylline in blood plasma should be monitored. The clinical effect of both drugs when used together does not change.
Tacrolimus
Tacrolimus is metabolized with the participation of the CYP3A4 isoenzyme. Recently published data indicate the possibility of increased plasma concentrations of tacrolimus in selected cases when co-administered with nifedipine. When using tacrolimus and nifedipine simultaneously, the concentration of tacrolimus in the blood plasma should be monitored and, if necessary, its dose should be reduced.
Vincristine
Nifedipine slows down the elimination of vincristine from the body and may cause increased side effects of vincristine. If simultaneous use is necessary, reduce the dose of vincristine.
Protein-binding drugs
Nifedipine can displace drugs characterized by a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, non-steroidal anti-inflammatory drugs, quinine, salicylates, sulfinpyrazone), as a result of which their concentration in the blood plasma may increase .
Cephalosporins
With the simultaneous administration of cephalosporins (for example, cefixime) and nifedipine in probands, the bioavailability of the cephalosporin increased by 70%.
Medicines that lower blood pressure
The antihypertensive effect of nifedipine may be enhanced when used simultaneously with antihypertensive drugs, such as diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARA II), other BMCCs, alpha-blockers, phosphodiesterase-5 inhibitors, methyldopa.
When using nifedipine and beta-blockers simultaneously, it is necessary to carefully monitor the patient's condition, since in some cases the course of chronic heart failure may worsen.
The severity of the decrease in blood pressure increases with the simultaneous use of inhalational anesthetics and tricyclic antidepressants.
Nitrates
When used simultaneously with nitrates, tachycardia increases.
Antiarrhythmic drugs
BMCCs can enhance the negative inotropic effect of antiarrhythmic drugs such as amiodarone and quinidine. Caution should be exercised when prescribing nifedipine concomitantly with disopyramide and flecainamide due to the possible enhancement of the inotropic effect.
Magnesium sulfate
It is necessary to carefully monitor blood pressure in pregnant women while using nifedipine with intravenous magnesium sulfate due to the possibility of an excessive decrease in blood pressure, which is dangerous for both the mother and the fetus.
Fentanyl
The simultaneous use of nifedipine and fentanyl can lead to severe arterial hypotension. If possible, it is recommended that nifedipine be discontinued at least 36 hours before fentanyl-based anesthesia.
Calcium preparations
Reduced effectiveness of nifedipine.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs reduce the antihypertensive effect of nifedipine due to suppression of prostaglandide synthesis, sodium and fluid retention in the body.
Sympathomimetics
Sympathomimetics reduce the antihypertensive effect of nifedipine.
Estrogens
Estrogens reduce the antihypertensive effect of nifedipine due to fluid retention in the body.
Lithium preparations
When BMCC is used together with lithium drugs, it is possible to increase the manifestation of the neurotoxicity of the latter (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Note
Adequate and strictly controlled studies of the safety of nifedipine during pregnancy have not been conducted. The use of nifedipine during pregnancy is not recommended.
Since nifedipine is excreted in breast milk, its use should be avoided during lactation or breastfeeding should be discontinued during treatment.
Experimental studies revealed the embryotoxic, fetotoxic and teratogenic effects of nifedipine.
The drug is available with a prescription.
