Calcigard^® Retard (Tablets) Instructions for Use

Marketing Authorization Holder

Torrent Pharmaceuticals, Ltd. (India)

ATC Code

C08CA05 (Nifedipine)

Active Substance

Nifedipine (Rec.INN registered by WHO)

Dosage Form

Calcigard® Retard

Film-coated prolonged-release tablets 20 mg: 30, 60, or 100 pcs.

Dosage Form, Packaging, and Composition

Prolonged-release film-coated tablets brown in color, biconvex, with a score on one side.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

Calcium channel blockers; selective calcium channel blockers with predominant vascular action; dihydropyridine derivatives

Pharmacological Action

Selective class II calcium channel blocker, a dihydropyridine derivative. It inhibits the influx of calcium into cardiomyocytes and vascular smooth muscle cells. It has antianginal and antihypertensive effects. It reduces the tone of vascular smooth muscle.

It dilates coronary and peripheral arteries, reduces total peripheral resistance, blood pressure, and, to a minor extent, myocardial contractility, decreases afterload and myocardial oxygen demand. It improves coronary blood flow. It has virtually no antiarrhythmic activity. It does not depress myocardial conduction.

Pharmacokinetics

When taken orally, it is rapidly absorbed from the gastrointestinal tract. It undergoes first-pass metabolism in the liver. Protein binding is 92-98%. It is metabolized in the liver to form inactive metabolites.

The elimination half-life (T_1/2) is about 2 hours. It is excreted primarily by the kidneys as metabolites and in trace amounts unchanged; 20% is excreted through the intestines as metabolites.

Indications

Prevention of angina attacks (including vasospastic angina), in some cases – relief of angina attacks; arterial hypertension, hypertensive crises; Raynaud’s disease.

ICD codes

Dosage Regimen

The dosage is individualized. For oral administration, the initial dose is 10 mg 3-4 times/day. If necessary, the dose is gradually increased to 20 mg 3-4 times/day.

In special cases (variant angina, severe arterial hypertension), the dose can be increased for a short time to 30 mg 3-4 times/day. For relief of a hypertensive crisis, as well as an angina attack, 10-20 mg (rarely 30 mg) can be used sublingually.

Intravenous for relief of an angina attack or hypertensive crisis – 5 mg over 4-8 hours.

Intracoronary for relief of acute spasms of the coronary arteries, administer a bolus of 100-200 mcg. For stenoses of large coronary vessels, the initial dose is 50-100 mcg.

Maximum daily doses for oral administration – 120 mg, for intravenous administration – 30 mg.

Adverse Reactions

From the cardiovascular system skin flushing, feeling of warmth, tachycardia, arterial hypotension, peripheral edema; rarely – bradycardia, ventricular tachycardia, asystole, increased frequency of angina attacks.

From the digestive system nausea, heartburn, diarrhea; rarely – impaired liver function; in isolated cases – gingival hyperplasia. With long-term use in high doses, dyspeptic symptoms, increased activity of liver transaminases, intrahepatic cholestasis are possible.

From the central and peripheral nervous system headache. With long-term use in high doses, paresthesia, muscle pain, tremor, mild visual disturbances, sleep disorders are possible.

From the hematopoietic system in isolated cases – leukopenia, thrombocytopenia.

From the urinary system increased daily diuresis. With long-term use in high doses, impaired renal function is possible.

From the endocrine system in isolated cases – gynecomastia.

Allergic reactions skin rash.

Local reactions with intravenous administration, burning at the injection site is possible.

Within 1 minute after intracoronary administration, manifestation of the negative inotropic effect of nifedipine, increased heart rate, arterial hypotension are possible; these symptoms gradually disappear within 5-15 minutes.

Contraindications

Arterial hypotension (systolic blood pressure below 90 mm Hg), collapse, cardiogenic shock, severe heart failure, severe aortic stenosis; hypersensitivity to nifedipine.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies on 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 during lactation should be avoided or breastfeeding should be discontinued during treatment.

In experimental studies, embryotoxic, fetotoxic, and teratogenic effects of nifedipine were identified.

Use in Hepatic Impairment

In cases of impaired liver function, Nifedipine should be used only in a clinical setting under strict medical supervision. In patients with impaired liver function, the use of nifedipine in high doses should be avoided.

Use in Renal Impairment

In cases of impaired renal function, Nifedipine should be used only in a clinical setting under strict medical supervision. In patients with impaired renal function, the use of nifedipine in high doses should be avoided.

Geriatric Use

In elderly patients, a decrease in cerebral blood flow due to sharp peripheral vasodilation is more likely.

Special Precautions

Nifedipine should be used only in a clinical setting under strict medical supervision in cases of acute myocardial infarction, severe cerebrovascular accidents, diabetes mellitus, impaired liver and kidney function, 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. In elderly patients, a decrease in cerebral blood flow due to sharp peripheral vasodilation is more likely.

For oral administration, to accelerate the effect, Nifedipine can be chewed.

If chest pain occurs during treatment, Nifedipine should be discontinued. Nifedipine should be withdrawn gradually, as abrupt discontinuation (especially after long-term treatment) may lead to withdrawal syndrome.

With intracoronary administration, in the presence of stenosis of two vessels, Nifedipine should not be injected into the third open vessel due to the risk of a pronounced negative inotropic effect.

During the course of treatment, alcohol consumption should be avoided due to the risk of excessive blood pressure reduction.

Effect on ability to drive vehicles and operate machinery

At the beginning of treatment, driving vehicles and engaging in other potentially hazardous activities requiring quick psychomotor reactions should be avoided. During further treatment, the degree of restrictions is determined based on individual tolerance to nifedipine.

Drug Interactions

With simultaneous use with antihypertensive drugs, diuretics, phenothiazine derivatives, the antihypertensive effect of nifedipine is enhanced.

With simultaneous use with anticholinergic agents, memory and attention disturbances are possible in elderly patients.

With simultaneous use with beta-blockers, the development of pronounced arterial hypotension is possible; in some cases – the development of heart failure.

With simultaneous use with nitrates, the antianginal effect of nifedipine is enhanced.

With simultaneous use with calcium preparations, the effectiveness of nifedipine decreases due to antagonistic interaction caused by an increase in the concentration of calcium ions in the extracellular fluid.

Cases of muscle weakness development have been described with simultaneous use with magnesium salts.

With simultaneous use with digoxin, a slowdown in the elimination of digoxin from the body and, consequently, an increase in its plasma concentration is possible.

With simultaneous use with diltiazem, the antihypertensive effect is enhanced.

With simultaneous use with theophylline, changes in the plasma concentration of theophylline are possible.

Rifampicin induces the activity of liver enzymes, accelerating the metabolism of nifedipine, which leads to a decrease in its effectiveness.

With simultaneous use with phenobarbital, phenytoin, carbamazepine, the plasma concentration of nifedipine decreases.

There are reports of an increase in the plasma concentration of nifedipine and an increase in its AUC with simultaneous use with fluconazole, itraconazole.

With simultaneous use with fluoxetine, an enhancement of the side effects of nifedipine is possible.

In some cases, with simultaneous use with quinidine, a decrease in the plasma concentration of quinidine is possible, and upon discontinuation of nifedipine, a significant increase in the concentration of quinidine is possible, which is accompanied by QT interval prolongation on the ECG.

Cimetidine and, to a lesser extent, ranitidine increase the plasma concentration of nifedipine and thus enhance its antihypertensive effect.

Ethanol may enhance the effect of nifedipine (excessive arterial hypotension), causing dizziness and other adverse reactions.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.