Expiration date: 01/2025

Composition and form of release:

Prolonged-acting tablets, film-coated 1 table.

active substance:

nifedipine 10 mg

excipients (tablet core): lactose monohydrate — 15, 8 mg, potato starch — 15, 7 mg MKC — 15, 5 mg povidone K25 — 2, 7 mg magnesium stearate — 0, 3 mg 

shell tablets: hypromellose — 2, 88 mg, macrogol 6000 — 0, 48 mg macrogol 35000 — 0, 22 mg of the dye quinoline yellow (E104) — 0, 27 mg titanium dioxide (E171) — 0, 77 mg talc — 0, 38 mg

in a blister PVC / aluminum 10 pcs. in a pack of cardboard 3 blisters, or in bottles of brown glass with a white cork made of LDPE with a relief inscription "AWD" 50 or 100 pcs. there is 1 bottle in a cardboard pack.

Description of the dosage form:

Round, biconvex yellow tablets, film-coated, with beveled edges.

View on the break: a homogeneous mass of yellow color.

Pharmacokinetics:

Absorption is high (more than 90%). Bioavailability — 50-70%. Eating increases bioavailability. It has the effect of the first passage through the liver. Cmax of nifedipine in blood plasma after a single oral administration 2 table. (corresponds to 20 mg of nifedipine) is reached after 1-3 hours, and its value is on average 28.3 ng / ml.

Penetrates through the BBB and placental barrier, is excreted with breast milk. The relationship with plasma proteins (albumins) is 95%. It is completely metabolized in the liver.

It is excreted by the kidneys as an inactive metabolite (60-80% of the dose taken), 20% with bile. T1/2 is 2-5 hours.

There is no cumulative effect. Chronic renal failure, hemodialysis and peritoneal dialysis do not affect pharmacokinetics.

In patients with hepatic insufficiency, the total clearance decreases and T1/2 increases.

With prolonged use (2-3 months), tolerance to the action of the drug develops.

Description of pharmacological action:

Selective blocker of "slow" calcium channels (BMCC), a derivative of 1,4-dihydropyridine. It has an antianginal and hypotensive effect. Reduces the flow of extracellular Ca2+ into cardiomyocytes and smooth muscle cells of coronary and peripheral arteries in high doses inhibits the release of Ca2+ from intracellular depots. In therapeutic doses, it normalizes the transmembrane current Ca2+, which is disrupted in a number of pathological conditions, primarily in arterial hypertension. It does not affect the tone of the veins. Enhances coronary blood flow, improves blood supply to ischemic areas of the myocardium without the development of the phenomenon of "stealing", activates the functioning of collaterals. By expanding peripheral arteries, it reduces heart rate, myocardial tone, postload and myocardial oxygen demand. Practically does not affect the sinoatrial and atrioventricular nodes, has weak antiarrhythmic activity. Increases renal blood flow, causes moderate natriuresis. Negative chrono-, dromo- and inotropic effects are overlapped by reflex activation of the sympathoadrenal system and an increase in heart rate in response to peripheral vasodilation.

The time of onset of the clinical effect is 20 minutes, its duration is 4-6 hours.

Indications:

• chronic stable angina pectoris (tension angina pectoris)
• Prinzmetal's angina pectoris (variant angina pectoris)
• arterial hypertension.

Contraindications:

• hypersensitivity to nifedipine and other derivatives of 1, 4-dihydropyridine or other components of the drug
• arterial hypotension (SAD below 90 mmHg)
• cardiogenic shock, collapse
• chronic heart failure in the decompensation stage, severe aortic stenosis
• unstable angina
• acute myocardial infarction (first 4 weeks)
• pregnancy (I trimester)
• lactation period
• combined use with rifampicin.

With caution: mitral valve stenosis, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, sinus node weakness syndrome, malignant arterial hypertension, hypovolemia, severe cerebral circulatory disorders, myocardial infarction with left ventricular insufficiency, gastrointestinal obstruction, renal and hepatic insufficiency, hemodialysis (due to the risk of arterial hypotension), pregnancy (II and III trimesters), age up to 18 years (efficacy and safety have not been established), simultaneous administration of beta-blockers, digoxin.

Side effect:

From the side of the CCC: tachycardia, palpitations, arrhythmias, peripheral edema (ankles, feet, shins), manifestations of excessive vasodilation (asymptomatic decrease in blood pressure, development or aggravation of heart failure, flushes of blood to the skin of the face, hyperemia of the skin of the face, a feeling of heat), pronounced decrease in blood pressure (rarely), syncope. In some patients, especially at the beginning of treatment or with an increase in the dose, angina attacks may occur and, in isolated cases, the development of myocardial infarction, which requires discontinuation of the drug.

From the central nervous system: headache, dizziness, general weakness, fatigue, drowsiness. With prolonged use of the drug in high doses - paresthesia of the extremities, tremor, extrapyramidal (Parkinsonian) disorders (ataxia, masked face, shuffling gait, tremor of the hands and fingers, difficulty swallowing), depression.

From the digestive system: dyspepsia (nausea, diarrhea or constipation), dry mouth, flatulence, increased appetite. Rarely - gum hyperplasia, completely disappearing after discontinuation of the drug. With prolonged use - liver dysfunction (intrahepatic cholestasis, increased activity of hepatic transaminases).

From the musculoskeletal system: arthritis, myalgia, swelling of the joints, convulsions of the upper and lower extremities.

Allergic reactions: rarely - itching of the skin, urticaria, exanthema, autoimmune hepatitis, exfoliative dermatitis, photodermatitis, anaphylactic reactions.

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

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

Other: rarely - visual disturbances (including transient blindness at the maximum concentration of nifedipine in blood plasma), gynecomastia (in elderly patients, completely disappearing after withdrawal), galactorrhea, hyperglycemia, pulmonary edema, bronchospasm, weight gain.

Drug interaction:

With the simultaneous use of other antihypertensive agents, as well as tricyclic antidepressants, nitrates, cimetidine, inhalation anesthetics, diuretics, the hypotensive effect of nifedipine may increase.

BMCC can further enhance the negative inotropic effect of antiarrhythmic agents such as amiodarone and quinidine.

When combining nifedipine with nitrates, tachycardia increases.

Diltiazem suppresses the metabolism of nifedipine in the body, which may require simultaneous administration of these drugs to reduce the dose of nifedipine.

Reduces the concentration of quinidine in blood plasma.

Increases the concentration of digoxin and theophylline in blood plasma.

Rifampicin accelerates the metabolism of nifedipine, co-administration is not recommended.

With simultaneous administration with cephalosporins (for example, cefixime), the concentration of cephalosporins in the blood may increase.

Sympathomimetics, NSAIDs (suppression of PG synthesis in the kidneys and retention of sodium ions and fluid in the body), estrogens (fluid retention in the body) reduce the hypotensive effect.

Nifedipine can displace drugs with a high degree of binding from protein binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, NSAIDs, quinine, salicylates, sulfinpyrazone), as a result of which their concentration in blood plasma may increase.

Nifedipine suppresses the metabolism of prazosin and other alpha-blockers, which can lead to an increased hypotensive effect.

If necessary, the dose of vincristine is reduced, because nifedipine inhibits its excretion from the body, which can cause increased side effects.

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

With simultaneous administration of procainamide, quinidine and other drugs that cause prolongation of the QT interval, the risk of significant prolongation of the QT interval increases.

Grapefruit juice suppresses the metabolism of nifedipine in the body, so it is contraindicated during treatment with nifedipine.

Nifedipine is metabolized by the cytochrome P450 3A system, in this regard, the simultaneous use of drugs that inhibit this system can lead to the interaction of this drug and nifedipine: for example, macrolides, antiviral drugs (e.g. amprenavir, indinavir, nelfinavir, ritonavir or saquinavir) antifungal agents of the azole group (ketoconazole, itraconazole or fluconazole) cause an increase in the concentration of nifedipine in plasma blood.

Taking into account the experience of using nimodipine BMCC, it is impossible to exclude similar interactions with nifedipine: carbamazepine, phenobarbital can cause a decrease in the concentration of nifedipine in blood plasma and valproic acid - an increase in the concentration of nifedipine in blood plasma.

Method of administration and dosage:

Inside, after eating, without chewing and drinking enough liquid.

The dose of the drug is selected by the doctor individually, in accordance with the severity of the disease and the sensitivity of the patient to the drug. For patients with concomitant severe cerebrovascular diseases and elderly patients, the dose should be reduced.

Simultaneous food intake delays, but does not reduce the absorption of the active substance from the gastrointestinal tract.

Recommended dosage regimen for adults:

Chronic stable and vasospastic angina

The initial dose is 10 mg (1 table) 2-3 times a day. With an insufficiently pronounced clinical effect, the dose of the drug is gradually increased to 2 tablets (20 mg) 1-2 times a day. The maximum daily dose is 40 mg (4 tables).

Essential hypertension

The average daily dose is 10 mg (1 table) 2-3 times a day. With an insufficiently pronounced clinical effect, it is possible to gradually increase the dose of the drug to 20 mg (2 tables) 2 times a day. The maximum daily dose is 40 mg (4 tables).

With a 2-fold appointment, the minimum interval between doses of the drug should be at least 4 hours.

The duration of the course of treatment is determined by the attending physician.

Overdose:

Symptoms: headache, hyperemia of the facial skin, prolonged pronounced decrease in blood pressure, suppression of sinus node function, bradycardia / tachycardia, bradyarrhythmia. In case of severe poisoning - loss of consciousness, coma.

Treatment: symptomatic. In case of severe poisoning (collapse, sinus node depression), gastric lavage (if necessary, small intestine) is performed, activated charcoal is prescribed. The antidote is calcium preparations, an intravenous injection of 10% calcium chloride or calcium gluconate is indicated, followed by a transfer to a long-term infusion. With a marked decrease in blood pressure, slow intravenous administration of dopamine, dobutamine, adrenaline or norepinephrine is indicated. It is recommended to monitor the glucose content (the release of insulin may decrease) and electrolytes in the blood (K +, Ca2 +). With the development of heart failure - intravenous administration of strophanthin. In case of conduction disorders — atropine, isoprenaline or an artificial pacemaker.

Hemodialysis is ineffective, plasmapheresis is recommended.

Special instructions:

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

It is recommended to stop treatment with the drug gradually.

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

Simultaneous administration of beta-blockers should be carried out under careful medical supervision, as this may cause an excessive decrease in blood pressure, and in some cases — aggravation of symptoms of heart failure.

With severe heart failure, the drug is dosed with great caution.

The diagnostic criteria for prescribing the drug for vasospastic angina are: a classic clinical picture accompanied by an increase in the ST segment, the occurrence of ergon-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 a different voltage threshold or unstable angina, when ECG data indicate transient angiospasm).

For patients with severe obstructive cardiomyopathy, there is a risk of an increase in the frequency, severity and duration of angina attacks after taking nifedipine, in this case, withdrawal of the drug is necessary.

In patients with irreversible renal insufficiency who are on hemodialysis, have high blood pressure and a reduced total amount of blood, the drug should be used cautiously, since a sharp drop in blood pressure is possible. Patients with impaired liver function are carefully monitored, if necessary, the dose of the drug is reduced and / or other dosage forms of nifedipine are used.

If surgical intervention is necessary under general anesthesia, it is necessary to inform the anesthesiologist about the treatment of the patient with nifedipine.

During in vitro fertilization, in some cases, BMCC causes changes in the head of the sperm, which can lead to a violation of the functions of the sperm. In cases in which repeated in vitro fertilization failed for an unclear reason, the use of BMCC, including nifedipine, can be considered a possible cause of failure.

During treatment, it is possible to obtain a false positive result of a direct Coombs reaction and laboratory tests for antinuclear antibodies. In the spectrophotometric determination of vanillyl-almond acid in urine, nifedipine may be the cause of obtaining a false result, however, nifedipine does not affect the results of tests conducted using high-performance liquid chromatography.

With caution, simultaneous treatment with nifedipine, disopyramide and flecainamide should be carried out due to a possible increase in the inotropic effect.

Influence on the ability to drive a car and other mechanisms

During the treatment period, it is necessary to be careful when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.