Calcigard retard tablets 20 mg 100 pcs. in Balashikha

Calcigard retard

From the cardiovascular system: tachycardia, arrhythmias, peripheral edema (ankles, feet, legs), manifestations of excessive vasodilation (asymptomatic decrease in blood pressure, “flushes” of blood to the facial skin, flushing of the facial skin, feeling of heat), excessive decrease in blood pressure (rarely), fainting , development or worsening of heart failure (usually worsening of an existing one). In some patients (especially with severe obstructive lesions of the coronary arteries), at the beginning of treatment or when the dose is increased, attacks of angina pectoris may occur, including the development of myocardial infarction (requires discontinuation of the drug).

From the nervous system: headache, dizziness, increased fatigue, asthenia, drowsiness. With long-term ingestion in high doses - paresthesia of the limbs, tremor, extrapyramidal (parkinsonian) disorders (ataxia, mask-like face, shuffling gait, stiffness of the arms or legs, tremor of the hands and fingers, difficulty swallowing), depression.

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 transaminases).

From the musculoskeletal system: rarely - arthralgia, swelling of the joints, myalgia.

From the hematopoietic organs: anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura, asymptomatic agranulocytosis.

From the urinary system: increased daily diuresis, deterioration of renal function (in patients with renal failure).

Allergic reactions: rarely - itching, urticaria, exanthema, autoimmune hepatitis.

Local reactions: burning at the site of intravenous administration.

Other: rarely - visual impairment (including transient loss of vision against the background of Cmax in plasma), gynecomastia (in elderly patients, completely disappearing after withdrawal), galactorrhea, hyperglycemia, pulmonary edema (difficulty breathing, cough, wheezing), weight gain. Overdose. Symptoms: headache, flushing of the facial skin, prolonged pronounced decrease in blood pressure, suppression of sinus node function, bradycardia, bradyarrhythmia.

Treatment: in case of severe poisoning (collapse, depression of the sinus node), gastric lavage is performed and activated charcoal is prescribed. The antidote is Ca2+ preparations: slow intravenous administration of 10% CaCl2 or calcium gluconate is indicated, followed by switching to a long-term infusion.

With a pronounced decrease in blood pressure, dopamine or dobutamine is administered intravenously. For conduction disorders - atropine, isoprenaline or an artificial pacemaker. With the development of heart failure - intravenous administration of strophanthin. Catecholamines should be used only when there is a threat to life (due to their reduced effectiveness, a high dosage is required, which increases the risk of developing arrhythmia). It is recommended to monitor blood concentrations of glucose (insulin release may decrease) and electrolytes (K+, Ca2+).

Hemodialysis is ineffective.

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).

Calcigard retard tablets 20 mg 100 pcs. in Balashikha

Pharmacological action: Blocks calcium channels, inhibits the transmembrane flow of calcium ions into smooth muscle cells of arterial vessels and cardiomyocytes. Dilates peripheral, mainly arterial, vessels, incl. coronary, lowers blood pressure (slight reflex tachycardia and increased cardiac output are possible), reduces peripheral vascular resistance and afterload on the heart. Increases coronary blood flow, reduces the strength of heart contractions, heart function and myocardial oxygen demand. Improves myocardial function and helps reduce heart size in chronic heart failure. Reduces pressure in the pulmonary artery and has a positive effect on cerebral hemodynamics. Inhibits platelet aggregation, has antiatherogenic properties (especially with long-term use), improves poststenotic circulation in atherosclerosis. Increases the excretion of sodium and water, reduces myometrial tone (tocolytic effect). Long-term use (2–3 months) is accompanied by the development of tolerance. For long-term therapy of arterial hypertension, it is advisable to use fast-acting dosage forms in a dose of up to 40 mg/day (with increasing doses, the development of concomitant reflex reactions is more likely). In patients with bronchial asthma, it can be used with other bronchodilators (sympathomimetics) for maintenance treatment.

When taken orally, it is quickly and completely absorbed. The bioavailability of all dosage forms is 40–60% due to the “first pass” effect through the liver. About 90% of the dose taken is bound to plasma proteins. With intravenous administration, T1/2 is 3.6 hours, volume of distribution is 3.9 l/kg, plasma Cl is 0.9 l/min, constant concentration is 17 ng/ml. After oral administration, Cmax in plasma is created within 30 minutes, T1/2 - 2-4 hours. About 80% is excreted by the kidneys in the form of inactive metabolites and approximately 15% in feces. In small quantities it passes through the blood-brain barrier and the placental barrier and penetrates into breast milk. In patients with impaired liver function, total Cl decreases and T1/2 increases. When capsules are taken orally, the effect appears within 30–60 minutes (chewing accelerates the development of the effect) and lasts 4–6 hours; when administered sublingually, it occurs within 5–10 minutes and reaches a maximum within 15–45 minutes. The effect of tablets with two-phase release develops after 10–15 minutes and lasts 21 hours. It does not have mutagenic or carcinogenic activity.