Nitrendipine instructions for use. Medicinal reference book geotar. Use during pregnancy and lactation

Pharmacological action - antianginal, vasodilating, hypotensive, nephroprotective.
Specifically binds to membrane receptors that regulate the function of voltage-gated L-type calcium channels, reduces the flow of calcium ions into the cell during membrane depolarization. Predominantly affects vascular smooth muscle cells (less coronary than td;). It has a highly selective long-term vasodilating effect. It causes systemic vasodilation, a decrease in peripheral vascular resistance, and, as a result, hypotension. Lowers blood pressure in proportion to the dose, does not cause orthostatic hypotension and the development of tolerance, does not violate the circadian rhythm of blood pressure changes. Expands the vessels of the kidneys, increases the blood levels of atrial natriuretic peptide, increases the excretion of sodium and water, does not activate the sympathoadrenal (heart rate usually does not change) and renin-aldosterone (the content of angiotensin and renin in plasma does not increase significantly) systems. However, at the beginning of therapy, short-term reflex tachycardia may occur. Does not affect the sinus and AV nodes. After taking 20 mg of nitrendipine in patients with mild to moderate hypertension, there is a decrease in SBP and diastolic blood pressure by 15-20%.
It is effective both in monotherapy and in combination with hypothiazide and propranolol. Long-term therapy contributes to the reverse development of left ventricular hypertrophy and the manifestation of a nephroprotective effect. The greatest hypotensive effect is observed in elderly patients with low plasma renin levels. In elderly patients (60 years and older) with isolated systolic hypertension (systolic blood pressure of at least 160 mm BP with diastolic blood pressure below 95 mm) when used for 2 years (initial dose - 10 mg / day, then up to 20-40 mg / day in 2 doses) prevents the development of cardiovascular complications: it reduces the overall frequency of cerebral strokes by 42%, the frequency of cardiac complications (heart failure, myocardial infarction, sudden death) - by 26%, the frequency of all cardiovascular complications - by 31%. With sublingual application, the possibility of stopping a hypertensive crisis has been shown. At a dose of 10-20 mg / day, it is effective (especially with continuous therapy for many years) to prevent attacks of vasospastic angina and improve long-term prognosis.
When taken orally, it is rapidly and almost completely absorbed. Bioavailability - 60-70%. Cmax in plasma is reached after 1-2 hours, the plasma level is 9-42 ng / ml, it binds to blood proteins by 98%. Almost completely metabolized in the liver by oxidation. Excreted in the urine (30%) in the form of four polar metabolites, T1 / 2 ranges from 8-24 Total Cl - 1.3 l / min. In the elderly and patients with cirrhosis of the liver, T1 / 2 and blood concentrations increase (a decrease in the daily dose is required). It has a teratogenic effect.

- a drug of the calcium channel blockers group, is a derivative of dihydropyridine.

Description of the pharmacological properties of the drug Nitrendipine

The drug has a hypotensive, vasodilating, nephroprotective and antianginal effect.

It has a predominant effect on the cells of the ugly muscles of the vessels (to a lesser extent - coronary).

Nitrendipine lowers blood pressure without causing orthostatic hypotension, without disturbing the circadian rhythm of changes in blood pressure. Also, the drug dilates the renal vessels, promotes an increase in the blood of atrial natriuretic peptide substance. In addition, the active ingredient increases the excretion of water and sodium without activating the sympathoadrenal system. But at the beginning, during treatment, reflex short-term tachycardia can be observed. Has a teratogenic effect. By oxidation, it is almost completely metabolized in the liver cells.

Indications for use

The drug Nitrendipine is indicated in cases of heart failure, angina pectoris (stable without angiospasm), vasospastic angina, unstable vasospastic, as well as ineffectiveness of nitrates and beta-blockers, with (shown as a symptomatic treatment).

Analogues of Nitrendipine

Analogues of the drug Nitrendipine in this case are drugs that have the same active ingredient nitrendipine.

These are drugs such as:

• Bypress;
• Lusopress;
• Nitrepin;
• Unipress;
• Octidipine.

All these medicines have the same indications for use as the drug in question.

tab. 20 mg: 30 pcs. Reg. No.: P No. 012848/01-2001

Clinico-pharmacological group:

Calcium channel blocker

Release form, composition and packaging

15 pcs. - cellular contour packings (2) - packs of cardboard.

Description of the active ingredients of the drug Nitrendipine»

pharmachologic effect

Calcium channel blocker, dihydropyridine derivative. It has antianginal, hypotensive effect. Reduces the current of extracellular calcium in cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries. Reduces the number of functioning channels without affecting the time of their activation, inactivation and recovery. Dissociates the processes of excitation and contraction in the myocardium, mediated by tropomyosin and troponin, and in vascular smooth muscle, mediated by calmodulin. In therapeutic doses, it normalizes the transmembrane current of calcium. The negative inotropic effect is masked by a reflex increase in heart rate.

In heart failure, due to the peripheral vasodilating effect, it increases the ejection fraction of the left ventricle. Helps reduce the size of the heart. The hypotensive effect is also associated with inhibition of aldosterone secretion. Does not affect the tone of the veins. It relaxes vascular smooth muscles, causes expansion of peripheral and coronary arteries, reduces OPSS and slightly - myocardial contractility. Reduces pre- and afterload and myocardial oxygen demand. By enhancing coronary blood flow, it improves blood supply to ischemic areas of the myocardium without the development of the “steal” phenomenon, and activates the functioning of collaterals. Does not inhibit conduction in the myocardium. Enhances renal blood flow, has a moderate natriuretic effect.

Indications

Arterial hypertension, angina pectoris (tension, stable without angiospasm, stable angiospastic, unstable angiospastic with the ineffectiveness of beta-blockers and nitrates), Raynaud's syndrome (symptomatic therapy).

Dosing regimen

Set individually. The daily dose is 10-40 mg in 1-2 doses.

Side effect

From the side of the central nervous system and peripheral nervous system: dizziness, headache, paresthesia, fatigue, asthenia, drowsiness, 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 side of the cardiovascular system: tachycardia, angina, development or aggravation of heart failure, flushing of the skin of the face and upper body, manifestations of precapillary vasodilation (swelling in the ankle joints, swelling of the gums, peripheral edema), asymptomatic arrhythmia (including flutter and ventricular fibrillation); rarely - an excessive decrease in blood pressure.

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

From the musculoskeletal system: arthritis (arthralgia, soreness and swelling of the joints), myalgia.

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

Allergic reactions: skin rash.

Others: visual impairment (including transient loss of vision against the background of C max), pulmonary edema (difficulty breathing, coughing, stridor breathing), weight gain, galactorrhea.

Contraindications

Tachycardia, arterial hypotension (systolic blood pressure<90 мм рт.ст.), коллапс, сосудистый и кардиогенный шок, первая неделя острого инфаркта миокарда, выраженная сердечная недостаточность, беременность, лактация (грудное вскармливание), повышенная чувствительность к производным дигидропиридина.

Pregnancy and lactation

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

Application for violations of liver function

Use with caution in liver failure.

Application for violations of kidney function

Use with caution in renal failure.

Use in the elderly

Use with caution in elderly patients.

Application for children

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

special instructions

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

Against the background of the use of nitrendipine, alcohol should be avoided.

Influence on the ability to drive vehicles and control mechanisms

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

drug interaction

drug interaction

With simultaneous use with antihypertensive drugs, beta-blockers, it is possible to increase the antihypertensive effect; with digoxin - a slight increase in the concentration of digoxin in plasma 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 a delay in the body of sodium ions and blockade of prostaglandin synthesis by the kidneys), with estrogens (sodium retention), sympathomimetics, inducers of microsomal liver enzymes (including rifampicin).

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

Instruction

Tradename

Nitresan

international title

Nitrendipine

Dosage form

Tablets 10mg, 20mg

Compound

One tablet contains

active substance- nitrendipine 10 mg, 20 mg,

Excipients: lactose monohydrate, corn starch, microcrystalline cellulose, povidone 25, docusate sodium, magnesium stearate.

Description

Yellow, flat-surfaced tablets with score on one side and dosage on the other side, about 7.0 mm in diameter (for dosages of 10 mg and 20 mg).

Pharmacotherapeutic group

Blockers of "slow" calcium channels are selective.

dihydropyridine derivatives.

ATC code C08CA08

Pharmacological properties

Pharmacokinetics

When administered orally, nitrendipine is rapidly and almost completely absorbed, bioavailability is approximately 88%. The biological half-life of absorption is 30-60 minutes. Peak plasma concentration is reached within 1-3 hours after taking the drug, the average maximum concentration (Cmax) is about 6.1-19 mcg / l. Considering the significant influence of the first passage through the liver (first-pass effect), the systemic availability of nitrendipine is 20-30%.

96-98% of nitrendipine binds to plasma proteins (albumin) and therefore does not undergo dialysis. Nitrendipine cannot be eliminated by hemodialysis or peritoneal dialysis. The volume of distribution at steady state is about 5-9 l/kg of body weight.

When taken orally, nitrendipine undergoes significant metabolic changes already during the first passage through the liver (first-pass effect), and is almost completely metabolized as a result of oxidative processes in the liver. Its metabolites are pharmacodynamically ineffective. Less than 0.1% of an oral dose is excreted unchanged in the urine. Nitrendipine in the form of metabolites is mainly excreted by the kidneys (about 77% of the oral dose), the rest is excreted in the bile and stool.

The elimination half-life of nitrendipine taken as a tablet is about 8-12 hours. The accumulation of the active substance or its metabolites in the body after reaching a steady state is not observed.

Since nitrendipine is excreted mainly as metabolites, in patients with chronic liver disease, its excretion from the body is much slower: the biological half-life is extended by 2-3 times. In patients with impaired renal function, no special dosage adjustment is required.

Pharmacodynamics

Nitresan is a 1,4-dihydropyridine type calcium channel blocker that acts as an antihypertensive agent.

Nitresan inhibits the transmembrane passage of calcium ions into vascular smooth muscle cells. This leads to protection against excessive calcium penetration into the cell, inhibition of calcium-dependent myogenic contractions of vascular smooth muscles, a decrease in peripheral vascular resistance, a decrease in pathologically elevated blood pressure, and a slight natriuretic effect, especially at the beginning of treatment.

Indications for use

Treatment of essential (primary) hypertension

Dosage and administration

Treatment is strictly individual in accordance with the severity of the disease, as a rule, long-term treatment.

Tablets are taken orally in the morning after meals, without chewing and drinking plenty of water. Do not drink grapefruit juice. The active substance Nitrendipine is sensitive to light, so the tablets should be removed from the blister immediately before use.

For adults, nitresan is prescribed 10 mg (1 tablet) 2 times a day in the morning and evening (20 mg / day) or 20 mg (1 tablet) once a day, in the morning. In case of insufficient reduction in blood pressure, the doctor during treatment can double the daily dose, 20 mg (2 tablets of 10 mg) 2 times a day (40 mg / day) or 20 mg (1 tablet of 20 mg) 2 times a day. day (40 mg / day).

The average therapeutic single dose is 10 mg, the average therapeutic daily dose is 20 mg.

The maximum single dose is 20 mg, the maximum daily dose is 40 mg.

In elderly patients and patients with liver dysfunction, the metabolism of nitrendipine may be slowed down, which may lead to unwanted hypotension. Since the effect of nitrendipine in such patients may be enhanced and / or continued, it is recommended to start treatment with low doses (10 mg / day) with careful monitoring of the patient's condition. With a strong decrease in pressure in these cases, even at low doses, it is necessary to change the treatment.

The duration of therapy is determined by the doctor.

In patients with renal insufficiency, no special dose adjustments are required.

Side effects

Highlyoften (>1/10)

Headache (especially at the beginning of treatment, passing)

Hot flashes (especially at the beginning of treatment, passing)

Peripheral edema (especially at the beginning of treatment, passing)

Often (≥ 1% up to< 10 %)

- at the beginning of treatment, attacks of angina pectoris (chest pain) or in patients suffering from angina pectoris may increase the frequency, duration and severity of attacks

Palpitations, tachycardia, varicose veins

Flatulence

Infrequently(≥ 0.1% up to< 1 %)

- paresthesia, dizziness, fatigue, syncope, nervousness, migraine, drowsiness, tinnitus

- abnormal vision, blurred vision

Dry mouth, nausea, vomiting, abdominal pain, diarrhea, constipation, dyspepsia, gastroenteritis

Increased urge to urinate, polyuria

Hypersensitive skin reactions: pruritus, urticaria, rash, photosensitivity

Myalgia, arthralgia

hypotension

Weight gain, sweating

Rarely(≥ 0.01% up to< 0,1 %)

Leukocytoclastic vasculitis (allergic cutaneous vasculitis)

Impaired liver function (increased concentration of transaminases)

Very rarely (<1/10000)

myocardial infarction

Leukopenia, agranulocytosis

Gingival hyperplasia (bleeding, swelling, soreness)

Exfoliative dermatitis, angioedema

Fever

Erectile dysfunction, gynecomastia, menorrhagia

Contraindications

Hypersensitivity to the active substance (nitrendipine), to

other calcium antagonist of the 1,4-dihydropyridine type or other

drug components

Cardiogenic shock

Severe aortic valve stenosis

Recent acute myocardial infarction (during the previous

4 weeks)

Unstable angina

Pregnancy and lactation

Children and adolescents up to 18 years of age

Drug Interactions

Nitrendipine is metabolized by the cytochrome P450 3A4 enzyme system, localized in the intestinal mucosa and in the liver. Drugs that inhibit or stimulate this enzymatic system may modify the first-pass effect or clearance of nitrendipine. Medicinal products that inhibit the CYP 3A4 system and therefore may lead to an increase in the plasma concentrations of nitrendipine, for example:

macrolide antibiotics (eg erythromycin),

HIV protease inhibitors (eg ritonavir)

azole antifungals (eg ketoconazole),

antidepressants, nefazodone and fluoxetine,

quinupristin / dalfopristin,

valproic acid,

cimetidine and ranitidine

With simultaneous use with these agents, it is necessary to monitor blood pressure and, if necessary, consider reducing the dose of nitresan.

With the simultaneous use of nitresan increases: the concentration in the blood plasma of quinidine, theophylline and digoskin (almost twice).

The hypotensive effect of nitresan is weakened by:

Non-steroidal anti-inflammatory drugs (NSAIDs) - retain Na + and block the synthesis of prostaglandin (Pg) by the kidneys;

Estrogens - retain Na +;

Sympathomimetics, inducers of microsomal liver enzymes, incl. rifampicin, rifampin, phenytoin, carbamazepine and phenobarbital - significantly reduce the bioavailability of nitrendipine;

Ca2+ preparations.

The hypotensive effect of nitresan is enhanced by:

Alpha and beta-blockers and / or other antihypertensive drugs: by reducing hepatic blood flow, increase the concentration of nitrendipine in plasma;

inhalation anesthetics;

Diuretics: May lead to increased urinary sodium excretion;

Muscle relaxants (pancuronium, vecuronium): the duration and intensity of their effects are increased in patients taking nitrendipine;

Cimetidine and ranitidine: although to a lesser extent, cause an increase in plasma levels of nitrendipine;

Nitrates, Li + preparations increase toxic effects (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

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

Grapefruit juice inhibits the oxidative metabolism of nitresan, which leads to an increase in the plasma level of nitrendipine and an enhanced antihypertensive effect. With regular use of grapefruit juice, the effect may appear even after 3 days have passed since its last intake.

Detailed studies evaluating potential drug-drug interactions involving the cytochrome P450 system such as: phenytoin, phenobarbital, carbamazepine, ketoconazole, itraconazole, fluconazole, nefazodone, valproic acid, erythromycin, troleandomycin, clarithromycin, roxithromycin, amprenavir, atazanavir, ritonavir, indinavir, nelfinavir, saclinavir, quinuprestin/dalfopristin have not yet been carried out or the potential risk has not been confirmed. However, with complex treatment regimens, with the appointment of several drugs, it is advisable to consult a clinical pharmacologist. This takes into account the relative risk associated with the choice of different drugs or side effects.

special instructions

In patients with severe liver dysfunction, the effect of Nitresan may be enhanced and/or prolonged. In such cases, treatment should be started at a low dose and the patient should be closely monitored by a physician during treatment. In cases of uncompensated cardiac activity, as well as in the syndrome of weakness of the sinus node, in the absence of cardiostimulation, special attention to the patient's condition and careful monitoring of cardiac activity are required when taking Nitresan.

Elderly patients should be especially careful when increasing the dose.

The composition of the excipients of the drug includes lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take the drug.

Application in pediatrics

Given the lack of data on the safety and efficacy of the drug in pediatric practice, it is recommended to refrain from prescribing it in children under 18 years of age.

Use during pregnancy and lactation

The safety of the drug during pregnancy has not been tested, so its use during pregnancy is not recommended. Nitrendipine passes into breast milk. Given the lack of experience in its use by women during lactation, the drug is not recommended for use during lactation.

Features of the effect of the drug on the ability driving vehicles and potentially dangerous mechanisms

During the period of treatment of arterial hypertension, care must be taken when driving vehicles or be careful when working with various mechanisms and machines. This is especially true at the beginning of treatment, with increasing doses, when switching to another therapy and while using the drug with alcohol.

Overdose

Symptoms: hot flashes, headache, hypotension (circulatory collapse), and changes in heart rate (tachycardia or bradycardia)

Treatment: measures for poisoning: gastric lavage, followed by the intake of activated charcoal. Careful monitoring of the state of vital functions. With a marked decrease in blood pressure , followed by intravenous administration of dopamine or norepinephrine. It is recommended to pay attention to the possible negative effects of catecholamines (especially in violation of the heart rhythm). For bradycardia, atropine or orciprenaline should be used. A rapid improvement in the condition occurs after repeated intravenous administration of 10 ml of 10% calcium gluconate or 10% calcium chloride, followed by a long-term infusion of calcium (avoiding the possible development of hypercalcemia). Catecholamines are also effective, but at much higher doses. Subsequent treatment should focus on leveling the most pronounced symptoms. Hemodialysis is ineffective, it is possible that hemoperfusion and plasmapheresis will not be effective.

Release form and packaging

pharmachologic effect

Indications for use

Mode of application

Side effects

Contraindications

Release form

Storage conditions

Synonyms

Active substance:

The authors

Links

• The official instructions for the drug Nitrendipine.
• Modern drugs: a complete practical guide. Moscow, 2000. S. A. Kryzhanovsky, M. B. Vititnova.