Nitrendipine (Tablets) Instructions for Use

ATC Code

C08CA08 (Nitrendipine)

Active Substance

Nitrendipine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

Calcium channel blocker, a dihydropyridine derivative. It has antianginal and hypotensive action. It reduces the flow of extracellular calcium into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries. It reduces the number of functioning 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 transmembrane calcium current. The negative inotropic effect is masked by a reflex increase in heart rate.

In heart failure, due to its peripheral vasodilating action, it increases the left ventricular ejection fraction. It contributes to a reduction in heart size. The hypotensive effect is also associated with the inhibition of aldosterone secretion. It does not affect venous tone.

It relaxes vascular smooth muscle, causes dilation of peripheral and coronary arteries, reduces total peripheral resistance and, to a small extent, myocardial contractility. It decreases preload and afterload and myocardial oxygen demand.

By enhancing coronary blood flow, it improves the blood supply to ischemic areas of the myocardium without developing the “steal” phenomenon, activates the functioning of collaterals. It does not depress myocardial conduction. It enhances renal blood flow and has a moderate natriuretic effect.

Pharmacokinetics

After oral administration, more than 90% of nitrendipine is absorbed; its bioavailability is 60-70%; plasma protein binding is 98%. C_max in plasma is reached within 1-2 hours and is 9-40 ng/ml. It is metabolized in the liver by oxidation.

T_1/2 is 8-12 hours; it is excreted by the kidneys and with bile in the form of four polar metabolites ( 30%). Total clearance is 1.3 l/min. In elderly patients, an increase in T_1/2 is observed; in liver cirrhosis – an increase in AUC and plasma concentration.

Indications

Arterial hypertension, angina pectoris (effort angina, stable angina without angiospasm, stable vasospastic angina, unstable vasospastic angina when beta-blockers and nitrates are ineffective), Raynaud’s syndrome (symptomatic therapy).

ICD codes

Dosage Regimen

Determine the dosage individually for each patient based on the therapeutic response and tolerability.

For the initial treatment of arterial hypertension or angina pectoris, administer 10 mg once daily.

If the clinical response is inadequate after 2-4 weeks, increase the dose to 20 mg once daily.

For maintenance therapy, the usual effective dose is 20 mg once daily.

In some patients, a higher maintenance dose of 40 mg daily may be required; administer this total dose as 20 mg twice daily.

The maximum recommended daily dose is 40 mg.

Administer tablets orally, with a small amount of fluid, with or without food.

For elderly patients or those with hepatic impairment, initiate therapy at the lower end of the dosage range.

Monitor blood pressure closely during dosage titration and after reaching a maintenance dose.

Do not abruptly discontinue therapy; gradually reduce the dose under medical supervision.

Adverse Reactions

From the central and peripheral nervous system: dizziness, headache, paresthesia, feeling of fatigue, asthenia, drowsiness, extrapyramidal (parkinsonian) disorders (ataxia, mask-like face, shuffling gait, stiffness of arms or legs, tremor of hands and fingers, difficulty swallowing), depression.

From the cardiovascular system: tachycardia, angina pectoris, development or worsening of heart failure, flushing of the skin of the face and upper body, manifestations of precapillary vasodilation (swelling in the ankle area, gum swelling, peripheral edema), asymptomatic arrhythmia (including ventricular flutter and fibrillation); rarely – excessive decrease in blood pressure.

From the digestive system: nausea, vomiting, constipation or diarrhea, increased appetite, hepatitis, increased activity of liver transaminases; rarely – gingival hyperplasia (bleeding, swelling, soreness), dry mouth.

From the musculoskeletal system: arthritis (arthralgia, joint pain and swelling), myalgia.

From the hematopoietic system: leukopenia, anemia, asymptomatic thrombocytopenia, asymptomatic agranulocytosis.

Allergic reactions: skin rash.

Other: visual impairment (including transient vision loss against the background of C_max), pulmonary edema (difficulty breathing, cough, stridor breathing), weight gain, galactorrhea.

Contraindications

Tachycardia, arterial hypotension (systolic BP <90 mm Hg), collapse, vascular and cardiogenic shock, the first week of acute myocardial infarction, severe heart failure, pregnancy, lactation (breastfeeding), hypersensitivity to dihydropyridine derivatives.

Use in Pregnancy and Lactation

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

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

Use with caution in patients under 18 years of age (efficacy and safety of use have not been studied).

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Use with caution in hypertrophic obstructive cardiomyopathy, sick sinus syndrome, with aortic or mitral stenosis, chronic heart failure, myocardial infarction with left ventricular insufficiency, with arterial hypotension, with chronic liver diseases, with hepatic insufficiency, renal insufficiency, in elderly patients, in patients under 18 years of age (efficacy and safety of use have not been studied).

Before discontinuing treatment, a gradual dose reduction is recommended.

During the use of nitrendipine, alcohol consumption should be avoided.

Effect on ability to drive vehicles and operate machinery

During the treatment period, one should refrain from potentially hazardous activities requiring increased attention and high speed of psychomotor reactions.

Drug Interactions

With simultaneous use with antihypertensive drugs, beta-blockers, an enhancement of the antihypertensive effect is possible; with digoxin – a slight increase in the plasma concentration of digoxin is possible.

With simultaneous use with cimetidine, ranitidine, the bioavailability of nitrendipine increases in the absence of hemodynamic changes.

A decrease in the antihypertensive effect of nitrendipine is possible with its simultaneous use with NSAIDs (due to sodium ion retention in the body and blockade of prostaglandin synthesis by the kidneys), with estrogens (sodium retention), sympathomimetics, inducers of liver microsomal enzymes (including rifampicin).

Calcium preparations may reduce the effectiveness of slow calcium channel blockers.

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.