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

Selective blocker of "slow" calcium channels (BCCC), a derivative of 1,4-dihydropyridine. Has vasodilating, antianginal and hypotensive action. Reduces the current of calcium ions in 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 muscle 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. Strengthens the coronary blood flow, improves the blood supply of the ischemic zones of the myocardium without the development of the phenomenon of "stealing", activates the functioning of collaterals. Expanding the peripheral arteries, reduces the overall peripheral resistance of the vessels, myocardial tone, postload, the need for myocardium in oxygen and prolongs the duration of diastolic relaxation of the left ventricle. Virtually does not affect the sinoatrial and atrioventricular node and does not have antiarrhythmic activity. It enhances kidney blood flow, causes a moderate natriuresis. Negative chrono-, dromo- and inotropic action is blocked by reflex activation of the sympathoadrenal system and an increase in the heart rate (HR) in response to peripheral vasodilation.

Time of onset of the effect with ingestion of 20 minutes, the duration of the effect: 4-6 hours.

Pharmacokinetics:

Absorption is high (more than 92-98%). Bioavailability is 40-60%. Eating increases bioavailability. Has the effect of "first pass" through the liver. The time to reach the maximum concentration in the blood plasma is 1-3 hours, the maximum concentration in the blood plasma of 65 mg / ml. Connection with blood plasma proteins - 90%.

Penetrates through the blood-brain barrier 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. The half-life is 2-4 hours. In patients with hepatic insufficiency, the overall clearance decreases and the half-life period increases. It is excreted as inactive metabolites in the main kidneys (80%) and bile (20%). There is no cumulative effect. Chronic renal failure, hemodialysis and peritoneal dialysis do not affect the pharmacokinetics. At long reception (2-3 months) tolerance to action of a preparation develops. Plasmapheresis can enhance elimination.

Indications:

- Ischemic heart disease - angina of tension (including variant);

- arterial hypertension (in monotherapy or in combination with other antihypertensive agents).

Contraindications:

- Hypersensitivity to nifedipine and other derivatives dihydropyridine series, other components of the preparation;

- acute stage of myocardial infarction (first 4 weeks);

- unstable angina;

- cardiogenic shock (risk of myocardial infarction); collapse;

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

- chronic heart failure (in the stage of decompensation);

- severe stenosis of the aortic valve;

- idiopathic hypertrophic subaortic stenosis;

- at combinations with rifampicin (see. Interacting with a friendtheir medicinal products);

- pregnancy up to 20 weeks, lactation period;

- age under 18 years (effectiveness and safety not established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully:

In patients with stenosis of the aortic or mitral valve mouth, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, weakness syndrome of the sinus node,myocardial infarction with left ventricular failure, marked violations of the liver and / or kidney function; severe disorders of cerebral circulation, malignant arterial hypertension; patients who are on hemodialysis (due to the risk of arterial hypotension), in old age, during pregnancy after the 20th week.

Pregnancy and lactation:

The administration of nifedipine to pregnant women after 20 weeks is only indicated if the intended benefit to the mother exceeds the potential risk to the fetus if other ongoing therapy is ineffective.

Nifedipine is contraindicated in pregnancy up to 20 weeks.

The drug is excreted in breast milk, so it is recommended to stop breastfeeding while taking the drug.

Dosing and Administration:

Inside.

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 during or after a meal, 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: tachycardia, arrhythmias, peripheral edema (ankles, feet, shins), excessive vasodilation (asymptomatic decrease in blood pressure, blood flushes to the skin of the face, heat), excessive lowering of blood pressure (rarely), fainting, developing or exacerbation of heart failure (often exacerbation of existing). In some patients (especially with severe obstructive coronary artery disease) at the beginning of treatment or with an increase in the dose, angina attacks may occur, up to the development of myocardial infarction (requires drug discontinuation).

From the central nervous system: headache, dizziness, fatigue, weakness, drowsiness, sleep disturbances (including insomnia), nervousness, anxiety, hypoesthesia, muscle cramps.With prolonged ingestion in high doses - paresthesia of the extremities, depression, tremor.

From the digestive system: dryness of the oral mucosa, increased appetite, indigestion (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: rarely - arthralgia, swelling of the joints, myalgia.

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

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

Allergic reactions: rarely - skin itching, hives, exanthema, autoimmune hepatitis.

Other: rarely - visual impairment (including transient loss of vision against the maximum concentration of the drug in the blood plasma), gynecomastia (in elderly patients, completely disappearing after withdrawal), galactorrhea, hyperglycemia, pulmonary edema (difficulty breathing, coughing, breath), increase body weight.

Overdose:

Symptoms: headache, hyperemia of the facial skin, a long pronounced decrease in blood pressure, suppression of the sinus node function, bradycardia, bradyarrhythmia.

Treatment:

- in case of severe poisoning (collapse, suppression of the sinus node), gastric lavage is performed, Activated carbon. Antidote are calcium preparations: 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, in case of inefficiency, it is possible to re-administer the concentration of calcium in the blood serum, when the symptoms resume, you can switch to a constant infusion at a rate of 0.2 ml / kg / h, but not more than 10 ml / h.

- with a pronounced decrease in blood pressure - intravenous dopamine or dobutamine.

- in case of conduction disturbances - atropine, isoprenaline or an artificial pacemaker.

- with the development of heart failure - intravenous injection of strophanthin. Catecholamines should be used only in the case of circulatory insufficiency, life-threatening (due to their reduced efficacy, a high dose is required, which increases the risk of an increase in the tendency to arrhythmia due to intoxication).

It is recommended to control the concentration of glucose in the blood (insulin release may decrease) and electrolytes (potassium, calcium).

Hemodialysis is ineffective.

Interaction:

The severity of lowering blood pressure is enhanced by the simultaneous use of other antihypertensive agents, nitrates, cimetidine (to a lesser extent ranitidine), inhalational anesthetics and tricyclic antidepressants. Drugs from the BCCI group can further enhance the negative inotropic effect (reducing the force of cardiac contraction) of antiarrhythmics such as amiodarone and quinidine.

Under the influence of nifedipine, the concentration of quinidine in serum is significantly reduced, which is apparently due to a decrease in the bioavailability of quinidine, induction of enzymes that inactivate it, increased blood flow in the liver and kidneys, an increase in the volume of the drug distribution, and changes in hemodynamic parameters. 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 on day 3-4 after cancellation, as well as the lengthening of the interval QT on the ECG.

Increases the plasma concentration of digoxin and theophylline, and therefore it is necessary to monitor the clinical effect and the content of digoxin and theophylline in the blood plasma. Inductors of microsomal liver enzymes (rifampicin and others) reduce the concentration of nifedipine.

In combination with nitrates, tachycardia increases. The hypotensive effect is reduced by sympathomimetics, non-steroidal anti-inflammatory drugs (suppression of prostaglandin synthesis in the kidneys and retention of sodium and liquid ions in the body), estrogens (fluid retention in the body). Calcium preparations can reduce the effect of BCCC. Nifedipine can displace from the association with proteins preparations characterized by a high degree of binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, nonsteroidal anti-inflammatory drugs, quinine, salicylates, sulfinpyrazone), so that their concentration in the blood plasma can increase.

Suppresses the metabolism of prazosin and other alpha-adrenoblockers, as a result of which the hypotensive effect may increase.

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.

Lithium preparations can enhance toxic effects (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

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.

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 (alcohol).

Discontinue drug treatment is recommended gradually.

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 administration of beta-blockers should be carried out in conditions of careful medical control, as this can lead to an excessive decrease in blood pressure, and in some cases, to worsening of symptoms of heart failure.

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 on hemodialysis, with high blood pressure and irreversible kidney deficiency with a reduced total blood, the drug should be used cautiously, a sudden drop in blood pressure may occur.

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, the anesthesiologist should be informed that the patient is taking Nifedipine.

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

Caution should be given concomitantly with disopyramide and flecainamide because of the possible increase in inotropic effect.

Form release / dosage:

Tablets 10 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 50 tablets in cans of polymer complete with lids.

Each jar, 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

List B.

In dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N002407 / 01

Date of registration:24.11.2009

Expiration Date:Unlimited

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Information update date: & nbsp23.06.2018

Illustrated instructions

Instructions

Nifedipine (Nifedipine)