Corinfar^® UNO (Tablets) Instructions for Use

ATC Code

C08CA05 (Nifedipine)

Active Substance

Nifedipine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

A selective calcium channel blocker, a derivative of 1,4-dihydropyridine. It has antianginal and antihypertensive effects. It reduces the influx of extracellular calcium into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries; in high doses, it inhibits the release of calcium from intracellular stores. It decreases the number of functioning calcium channels without affecting their activation, inactivation, and recovery time. 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 flow of calcium ions, which is impaired in a number of pathological conditions, primarily in arterial hypertension. It does not affect venous tone. It enhances 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 peripheral arteries, it reduces systemic vascular resistance, myocardial tone, and afterload. It has almost no effect on the sinoatrial and AV nodes and has weak antiarrhythmic activity. It enhances renal blood flow and causes moderate natriuresis. The negative chronotropic, dromotropic, and inotropic effects are outweighed by reflex activation of the sympathoadrenal system in response to peripheral vasodilation.

The time to onset of the clinical effect is 30 minutes, and its duration is 12-24 hours. With long-term use (2-3 months), tolerance to the drug’s action develops.

Pharmacokinetics

Absorption

After oral administration, Nifedipine is highly absorbed from the gastrointestinal tract (more than 90%). Bioavailability is 40-60% and increases when taken with food. The modified-release tablet formulation provides gradual release of the active substance into the systemic circulation. C_max in plasma is reached in 2.3-7.7 hours and is 17-41.4 ng/ml.

Distribution

It penetrates the blood-brain barrier and placental barrier and is excreted in breast milk. Plasma protein binding is 90%. There is no cumulative effect.

Metabolism and Excretion

It undergoes first-pass effect through the liver. It is completely metabolized in the liver. It is excreted by the kidneys as inactive metabolites (70-80% of the administered dose). 20% is excreted in the bile.

Pharmacokinetics in Special Clinical Cases

In patients with hepatic insufficiency, total clearance decreases and the half-life increases.

Indications

• Stable angina (angina pectoris);
• Variant angina (Prinzmetal’s angina);
• Arterial hypertension.

ICD codes

Dosage Regimen

Tablets

Individual. 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. To relieve a hypertensive crisis, as well as an attack of angina, it can be used sublingually at 10-20 mg (rarely 30 mg).

Intravenously to relieve an attack of angina or hypertensive crisis – 5 mg over 4-8 hours.

Intracoronary to relieve 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: flushing, facial skin hyperemia, feeling of heat, tachycardia, arrhythmia, peripheral edema (ankles, feet, legs), excessive decrease in blood pressure, syncope, heart failure; in some patients, especially at the beginning of treatment, the appearance of angina attacks is possible, which requires discontinuation of the drug. Isolated cases of myocardial infarction have been described.

From the central and peripheral nervous system: headache, dizziness, general weakness, increased fatigue, drowsiness, paresthesia. With long-term use in high doses – extrapyramidal (parkinsonian) disorders (ataxia, mask-like face, shuffling gait, stiffness of movements of the arms and legs, tremor of the hands and fingers, difficulty swallowing), depression.

From the digestive system: dry mouth, increased appetite, dyspepsia (nausea, diarrhea or constipation), gingival hyperplasia (completely disappearing after discontinuation of the drug). With long-term use, impaired liver function (intrahepatic cholestasis, increased activity of liver enzymes) is possible.

From the musculoskeletal system: arthritis, myalgia; rarely – arthralgia, joint swelling.

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

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

Allergic reactions: itching, urticaria, exanthema, exfoliative dermatitis, photodermatitis, autoimmune hepatitis, acute generalized allergic reactions – swelling of the mucous membranes, laryngeal edema, bronchospasm (up to the development of life-threatening dyspnea).

Other: visual impairment (including transient blindness when reaching the maximum concentration of nifedipine in plasma), gynecomastia (in elderly patients, completely disappearing after discontinuation of the drug), galactorrhea, hyperglycemia, pulmonary edema, weight gain.

Contraindications

• Cardiogenic shock;
• Acute phase of myocardial infarction (within the first 4 weeks);
• Unstable angina;
• Severe aortic stenosis;
• Severe arterial hypotension (systolic blood pressure below 90 mm Hg);
• Concomitant use of rifampicin;
• Pregnancy;
• Lactation (breastfeeding);
• Age under 18 years (efficacy and safety have not been established);
• Hypersensitivity to nifedipine and other derivatives of 1,4-dihydropyridine.

The drug should be used with caution in severe mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, sick sinus syndrome, in chronic heart failure, in mild or moderate arterial hypotension, in severe cerebrovascular accidents, gastrointestinal obstruction, renal and hepatic insufficiency (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure), and in elderly individuals.

Use in Pregnancy and Lactation

The drug is contraindicated for use during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

The drug should be used with caution in hepatic insufficiency.

Use in Renal Impairment

The drug should be used with caution in renal insufficiency (especially in patients on hemodialysis due to the high risk of excessive and unpredictable decrease in blood pressure).

Pediatric Use

The efficacy and safety of the drug in children under 18 years of age have not been established.

Geriatric Use

Caution should be exercised in elderly patients due to the high probability of age-related renal impairment.

Special Precautions

The patient should be warned about the need to take the drug regularly, regardless of how they feel.

In patients on hemodialysis, with high blood pressure and irreversible renal impairment and with a reduced total blood volume, the drug should be used with caution, as a sharp drop in blood pressure is possible.

In case of impaired liver function, patients require careful monitoring and, if necessary, a reduction in the dose of the drug or the use of other dosage forms of nifedipine.

In severe heart failure, the selection of the nifedipine dose should be carried out with caution.

Concomitant administration of beta-blockers should 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 heart failure symptoms.

During treatment, positive results may occur when performing a direct Coombs test and laboratory tests for antinuclear antibodies.

It should be borne in mind that at the beginning of treatment, angina may occur, especially after a recent abrupt withdrawal of beta-blockers (the latter should be withdrawn gradually).

Diagnostic criteria for prescribing the drug for vasospastic angina are: a classic clinical picture accompanied by ST segment elevation, the occurrence of ergonovine-induced angina or coronary artery spasm, the detection of coronary spasm during angiography, or the detection of an angiospastic component without confirmation (for example, with different stress thresholds or in unstable angina when ECG data indicate transient angiospasm).

It should be prescribed with caution simultaneously with disopyramide and flecainide due to a possible increase in the inotropic effect.

If a patient requires surgical intervention under general anesthesia, the anesthesiologist must be informed about the nature of the therapy being conducted.

Caution should be exercised in elderly patients due to the high probability of age-related renal impairment.

Alcohol should not be consumed during therapy.

Effect on the ability to drive vehicles and operate machinery

During the treatment period, it is necessary to refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: headache, facial skin hyperemia, prolonged pronounced decrease in blood pressure, suppression of sinus node activity, bradycardia and/or tachycardia, bradyarrhythmia; in severe overdose – loss of consciousness, coma.

Treatment: gastric and small intestinal lavage. Calcium preparations are the antidote; intravenous administration of a 10% solution of calcium chloride or calcium gluconate followed by a long-term infusion is indicated. For a pronounced decrease in blood pressure – slow intravenous administration of dopamine, dobutamine, epinephrine (adrenaline) or norepinephrine (noradrenaline). For conduction disorders – atropine, isoprenaline, or an artificial pacemaker. It is recommended to monitor blood glucose levels (insulin release may decrease) and electrolytes (potassium, calcium). Hemodialysis is not effective.

Drug Interactions

The antihypertensive effect of nifedipine is enhanced when used simultaneously with other antihypertensive agents, nitrates, cimetidine (to a lesser extent – with ranitidine), agents for inhalation anesthesia, and diuretics.

It should be taken into account that calcium channel blockers may enhance the negative inotropic effect of amiodarone and quinidine.

When used together, Nifedipine causes a decrease in the plasma concentration of quinidine; after discontinuation of nifedipine, a sharp increase in the concentration of quinidine may occur.

When used simultaneously, Nifedipine increases the plasma concentration of digoxin and theophylline (the use of such a combination requires monitoring of clinical efficacy and the content of digoxin and theophylline in plasma).

Inducers of liver microsomal enzymes (including rifampicin) reduce the concentration of nifedipine.

When nifedipine is used together with nitrates, tachycardia increases.

The antihypertensive effect of nifedipine is reduced when used simultaneously with sympathomimetics, NSAIDs, estrogens, and calcium preparations.

Nifedipine can displace from protein binding drugs characterized by a high degree of binding (including indirect anticoagulants – coumarin and indandione derivatives, anticonvulsants, NSAIDs, quinine, salicylates, sulfinpyrazone), as a result, their concentration in plasma may increase.

When used together, Nifedipine suppresses the metabolism of prazosin and other alpha-blockers, which may lead to an increase in the antihypertensive effect.

Nifedipine inhibits the excretion of vincristine from the body and may enhance the side effects of vincristine (if necessary, the dose of vincristine is reduced).

When used together, lithium preparations may enhance toxic effects (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

With simultaneous administration of cephalosporins (for example, cefixime) and nifedipine, the bioavailability of the cephalosporin increases by 70%.

Procainamide, quinidine, and other drugs that cause QT interval prolongation enhance the negative inotropic effect and increase the risk of significant QT interval prolongation.

Diltiazem suppresses the metabolism of nifedipine in the body (the use of such a combination requires careful monitoring and, if necessary, a reduction in the dose of nifedipine).

Grapefruit juice suppresses the metabolism of nifedipine in the body, and therefore it is contraindicated to use it with nifedipine.

Storage Conditions

The drug should be stored in a light-protected place, out of the reach of children, at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.