Nifedipine - instructions for use, dose, side effects, contraindications

auxiliary substances (core): lactose monohydrate (sugar milk) - 58.0 mg, microcrystalline cellulose - 15.0 mg, potato starch - 5.6 mg, croscarmellose sodium 2.0 mg, magnesium stearate 0.9 mg, povidone (polyvinylpyrrolidone) 3 , 5 mg.

auxiliary substances (shell): hypromellose - 2.38 mg, macrogol 4000 - 0.56 mg, titanium dioxide - 1.0 mg, dye quinoline yellow - 0.06 mg.

Description:The tablets are biconvex, covered with a film coating of yellow color, on a fracture of uniform color.

Pharmacotherapeutic group:blocker of "slow" calcium channels.

ATX: & nbsp

C.08.C.A.05 Nifedipine

Pharmacodynamics:

NIFEDIPIN is a selective blocker of "slow" calcium channels, the 1,4-dihydropyridine derivative. Has vasodilating, antianginal and hypotensive action.Reduces the current of extracellular calcium ions inside cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses, suppresses the release of calcium ions from the intracellular depot. Reduces the number of functioning channels, without affecting the time of their activation, inactivation and recovery.

Separates the processes of excitation and contraction in the myocardium mediated by tropomyosin and troponin, and in smooth muscles of vessels, mediated by calmodulin. In therapeutic doses normalizes the transmembrane current of calcium ions, disrupted in a number of pathological conditions, especially in hypertension. Does not affect the tone of the veins. Reduces spasm and dilates coronary and peripheral (mainly arterial) vessels, lowers arterial pressure, general peripheral vascular resistance, reduces afterload, myocardial tone, myocardial oxygen demand and prolongs the duration of diastolic left ventricular relaxation. Increases coronary blood flow, improves the blood supply of ischemic zones of the myocardium without the development of the phenomenon of "stealing," activates the functioning of collaterals.Virtually does not affect the sinoatrial and atrioventricular nodes and does not have antiarrhythmic activity. Negative chrono-, dromo- and inotropic action is blocked by reflex activation of the sympathoadrenal system and an increase in the heart rate in response to peripheral vasodilation. It enhances kidney blood flow, causes a moderate natriuresis. The time of clinical effect is 20 minutes, the duration of the clinical effect is 4-6 hours.

Pharmacokinetics:

Nifedipine quickly and almost completely (from 92% to 98%) is absorbed from the gastrointestinal tract. After ingestion, its bioavailability is 40-60%. Eating increases bioavailability. Has the effect of "first pass" through the liver. The maximum concentration in the blood plasma is observed after 1-3 hours and is 65 ng / ml. Connection with blood plasma proteins - 90%. Penetrates through the blood-brain and placental barrier, excreted in breast milk. It is completely metabolized in the liver. In the metabolism of the drug, isozymes participate CYP3A4, CYP3A5 and CYP3A7. It is excreted by the kidneys in the form of inactive metabolites (approximately 80% of the dose taken) and with bile 20%. The half-life (T1/2) is 2-4 hours.In patients with hepatic insufficiency, the overall clearance decreases and increases T1/2.

There is no cumulative effect. Chronic renal failure, hemodialysis and peritoneal dialysis do not affect the pharmacokinetics. At long reception (within 2 3 months) tolerance to action of a preparation develops. Plasmapheresis can enhance elimination.

Indications:

- angina of tension and rest (including variant angina);

- Arterial hypertension (in the form of monotherapy or in combination with other antihypertensive drugs).

Contraindications:

- hypersensitivity,

- arterial hypotension (systolic blood pressure below 90 mm Hg),

- cardiogenic shock, collapse,

- pronounced aortic or subaortic stenosis,

- unstable angina,

- acute period of myocardial infarction (within the first 4 weeks),

- syndrome of weakness of the sinus node,

- AV blockade II-III century,

- pregnancy (up to 20 weeks), lactation period,

- age to 18 years (efficacy and safety of use not investigated).

- hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (due to the presence of lactose in the composition).

Carefully:Aortic stenosis (especially with concomitant use with beta-blockers), mitral stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, chronic heart failure, severe disorders of cerebral circulation, myocardial infarction with left ventricular failure, hepatic insufficiency, chronic renal failure (especially patients, who are on hemodialysis - a high risk of excessive and unpredictable lowering of blood pressure), simultaneous reception of beta-adrenoblockers and cardiac glycosides, pregnancy (after 20 weeks), advanced age.

Pregnancy and lactation:

The administration of nifedipine to pregnant women (after the 20th week) is only indicated if the intended benefit to the mother exceeds the potential risk to the fetus.

The drug is excreted in breast milk, therefore during its reception it is necessary to stop breastfeeding.

Dosing and Administration:

The dosage regimen is set individually, depending on the degree of severity of the disease and the patient's response to ongoing therapy.It is recommended to take the drug inside during or after eating, squeezed with a small amount of water.

Initial dose: 1 tablet (10 mg) 2-3 times a day. If necessary, the dose of the drug can be increased to 2 tablets (20 mg) - 1-2 times a day. The maximum daily dose is 40 mg. In elderly patients or patients receiving combined (antianginal or antihypertensive) therapy, as well as in violation of liver function, in patients with severe impairment of cerebral circulation, the dose should be reduced.

Side effects:

From the cardiovascular system: symptoms of excessive vasodilatation (asymptomatic decrease in blood pressure (BP), development or exacerbation of congestive heart failure (often aggravating already existing), "tides" of blood to the skin, facial flushing, burning sensation), tachycardia, peripheral edema (ankles, feet, legs) , arrhythmia, syncope; rare - an excessive fall in blood pressure, fainting, in some patients, especially early in treatment, may cause strokes, until the development of myocardial infarction, which requires discontinuation of the drug.

From the nervous system: headache, dizziness, fatigue, weakness, drowsiness, sleep disturbances (including insomnia), nervousness, anxiety, hypoesthesia, muscle cramps.

From the gastrointestinal tract, liver: dry mouth, increased appetite, dyspeptic disorder (nausea, diarrhea, or constipation); rarely - gingival hyperplasia (bleeding, soreness, swelling), with prolonged admission - violations of the liver (intrahepatic cholestasis, increased activity of "liver" transaminases).

From the musculoskeletal system: arthritis, rarely - arthralgiaI, puffiness of the joints, myalgia.

Allergic reactions: skin itching, hives, exanthema, exfoliative dermatitis, photodermatitis, angioedema, anaphylactoid reactions; very rarely - autoimmune hepatitis,

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

From the urinary system: an increase in daily diuresis, impaired renal function (in patients with renal insufficiency), dysuria.

Other: rarely - difficulty breathing,cough; very rarely - visual impairment (including transient blindness against the maximum concentration of nifedipine in blood plasma), gynecomastia (in elderly patients, completely disappearing after drug withdrawal), hyperglycemia, galactorrhea, pulmonary edema, bronchospasm, weight gain, chills, nasal bleeding, nasal congestion, erythema.

Overdose:

Symptoms: headache, hyperemia of the facial skin, lowering blood pressure, suppressing the activity of the sinus node, bradycardia, arrhythmia.

Treatment: gastric lavage with the appointment of activated charcoal, symptomatic therapy aimed at stabilizing the activity of the cardiovascular system. The antidote is calcium, a slow intravenous injection of 10% calcium chloride or calcium gluconate at a dose of 0.2 ml / kg (but not more than 10 ml) for 5 minutes is shown, with ineffectiveness it is possible to re-administer the concentration of calcium in serum, Switch to a constant infusion at a rate of 0.2 ml / kg / h, but not more than 10 ml / h.

At the expressed depression of arterial pressure - intravenous introduction of a dopamine ordobutaminea. In conduction disorders, the administration of atropine, isoprenaline or the establishment of an artificial pacemaker is indicated. With the development of heart failure - intravenous strophanthin. Catecholamines should be used only in the case of circulatory insufficiency, life-threatening (due to their reduced efficacy, a high dosage is required, which increases the risk of an increase in the tendency to arrhythmia due to intoxication). It is recommended to monitor the blood glucose content (insulin release may decrease) and electrolytes (potassium ions, calcium).

Hemodialysis is not effective.

Interaction:

The severity of lowering blood pressure is enhanced by the simultaneous administration of nifedipine with other antihypertensive drugs, nitrates, cimetidine, ranitidine (to a lesser extent), inhalational anesthetics, diuretics and tricyclic antidepressants.

Medicines from the group of blockers of the "slow" calcium channels can further increase the negative inotropic effect (reducing the force of cardiac contraction) of such antiarrhythmic agents as amiodarone and quinidine.

Under the influence of nifedipine, the concentration of quinidine in the blood serum is significantly reduced, which is apparently due to a decrease in the bioavailability of quinidine, induction of enzymes inactivating it, increased blood flow in the liver and kidneys, an increase in the distribution of the drug, and a change in hemodynamics. With the withdrawal of nifedipine after its simultaneous use with quinidine, a transient increase in the concentration (approximately 2-fold) of the latter in the serum is observed, which reaches a maximum level 3-4 days after cancellation, as well as the lengthening of the interval QT on the ECG.

In combination with nitrates, tachycardia and hypotensive effect of nifedipine are enhanced. Calcium preparations can reduce the effect of blockers of "slow" calcium channels. When combined with nifedipine, anticoagulant activity of coumarin derivatives increases.

Combination with prazosin increases the risk of orthostatic hypotension. Procainamide, quinidine and other drugs that cause lengthening of the interval QT, may increase the risk of significant lengthening of the interval QT.

Grapefruit juice inhibits the metabolism of nifedipine in the body, in connection with which, their simultaneous reception is contraindicated.

Increasing the concentration of digoxin in plasma and therefore should be controlled clinical effect and / or a content of digoxin in plasma.

Rifampicin weakens the action of nifedipine (accelerates the metabolism of the latter by inducing the activity of liver enzymes).

Inhibitors-isoenzymes CYP3A cytochrome P450 systems, such as macrolides (for example, erythromycin), fluoxetine, nefazodone, peptidase inhibitors (e.g., amprenavir, indinavir, nelfinavir, ritonavir or saquinavir); antifungal agents (ketoconazole, itraconazole or fluconazole) lead to an increase in the level of nifedipine in blood plasma.

Taking into account the experience of using the blocker of "slow" calcium channels of nimodipine, the following interactions with nifedipine can not be ruled out: carbamazepine, phenobarbital - decrease in the concentration of nifedipine in blood plasma; valproic acid - Increase in the concentration of nifedipine in blood plasma.

Nifedipine inhibits the excretion of vincristine from the body and may cause an increase in side effects of vincristine, if necessary, reduce the dose of vincristine.

It can displace medicinal products characterized by a high degree of binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsant drugs, quinine, salicylates,sulfinpyrazone), which may increase their plasma concentrations. Suppresses the metabolism of prazosin and other alpha-adrenoblockers, as a result of which the hypotensive effect may increase. Simultaneous use with magnesium sulfate in pregnant women can cause blockade of neuromuscular synapses.

Special instructions:

During the treatment it is necessary to refrain from taking ethanol.

Cancellation of the drug is gradual (the risk of developing the syndrome of "withdrawal").

It should be borne in mind that at the beginning of treatment angina may occur, especially after the recent abrupt cancellation of beta-blockers (the latter should be abolished gradually). Simultaneous prescribing of beta-blockers should be carried out in conditions of careful medical control, as this can lead to too pronounced decrease in LD, and in some cases - aggravation of symptoms of heart failure.With severe heart failure, the drug is dosed with great care. Diagnostic criteria for prescribing the drug with vasospastic angina are: a classic clinical picture, accompanied by an increase in the segment ST, appearance ergonovine-induced angina, or coronary artery spasm, coronary spasm detection by angiography or detection angiospastic component without acknowledgment (e.g., with different threshold voltage or unstable angina, when electrocardiogram data demonstrate transient vasoconstriction).

For patients with severe obstructive cardiomyopathy, there is a risk of increased frequency, severity, and duration of angina attacks after taking nifedipine; in this case, it is necessary to cancel the drug.

In patients who are on hemodialysis, with high blood pressure, irreversible failure of kidney function, with a decrease in the volume of circulating blood, the drug should be used cautiously, there may be a sharp drop in blood pressure.

Patients with impaired liver function are carefully monitored and, if necessary, reduce the dose of the drug and / or use other dosage forms of nifedipine.

If during the therapy the patient is required to undergo surgery under general anesthesia, it is necessary to inform the anesthesia doctor about the nature of the therapy.

During treatment, positive results are possible with a direct Coombs reaction and laboratory tests for antinuclear antibodies.

With caution should be prescribed simultaneously with disopyramide and flecainide due to the possible enhancement of the inotropic effect.

The use of the drug before 20 weeks of pregnancy is unsafe (the risk of fetal anomalies at the stage of organogenesis), after 20 weeks of pregnancy is possible only with an acceptable ratio of benefit and risk.

With in vitro fertilization in some cases, blockers of "slow" calcium channels caused changes in the head of the spermatozoa, which can lead to a disruption of the functions of spermatozoa. In cases in which repeated in vitro fertilization was not carried out for an unclear reason, blockers of "slow" calcium channels,including nifedipine, are considered a possible cause of failure.

In the spectrophotometric evaluation nifedipine can lead to an incorrect detection of an increased content of vanillyl-mandelic acid in the urine, the study using high-performance liquid chromatography (HPLC) has no effect.

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:

Tablets, film-coated 10 mg.

For 10, 25, 50 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered. By 10, 20, 30, 40, 50 or 100 tablets into a polymer container for medicines. One container or 1, 2, 3, 4, 5 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

List B. Store in a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001945/09

Date of registration:16.03.2009

The owner of the registration certificate:OZONE, LLC OZONE, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp14.12.2010

Illustrated instructions

Instructions

Nifedipine (Nifedipine)