KORINFAR UNO

Active material: Nifedipine
When ATH: C08CA05
CCF: Kalьcievыh channel blocker
ICD-10 codes (testimony): I10, i20, I20.1
When CSF: 01.03.02
Manufacturer: AWD.pharma GmbH & Co.KG (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

The modified-release tablet, coated (film) red-brown, round, lenticular, without smell.

Excipients: microcrystalline cellulose, lactose, gipromelloza 4000 mPa.s, magnesium stearate, colloidal silicon oxide anhydride.

The composition of the shell: gipromelloza 15 mPa.s, macrogol 6000, macrogol 400, iron oxide red (E172), Titanium dioxide (E171), talc.

10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pharmacological action

Selective calcium channel blocker, 1,4-dihydropyridine derivative. It has antianginal and hypotensive action. Reduces current extracellular calcium into kardimiotsitov and smooth muscle cells of the coronary and peripheral arteries, at high doses inhibits the release of calcium from intracellular stores. It reduces the number of functioning of calcium channels, without affecting the time of their activation, of inactivation and recovery. Separates the excitation and contraction in the myocardium (mediated by tropomyosin and troponin) and in vascular smooth muscle (mediated by calmodulin). At therapeutic doses, current normalizes transmembrane calcium ions, violations in a number of pathological conditions, especially with hypertension. It does not affect tone of veins. It increases coronary blood flow, It improves blood flow to ischemic areas of the myocardium without the development of the phenomenon “steal”, activates the functioning of the collaterals. Expanding the peripheral arteries, reduces peripheral vascular resistance, the tone of the myocardium, afterload. Almost no effect on the sinoatrial node and AV-, It has weak antiarrhythmic activity. It increases renal blood flow, causing moderate natriuresis. Otritsatelynoe hrono-, dromo- and inotropic effect overlaps reflex activation sympathoadrenal in response to peripheral vasodilatation.

Time of onset of clinical effect – 30 m, its duration – 12-24 no. Chronic administration (2-3 Months) develops tolerance to the drug.

Pharmacokinetics

Absorption

After oral administration nifedipine is highly absorbed from the gastrointestinal tract (more 90%). Bioavailability is 40-60% and rises simultaneously with the reception at meal. Dosage form a modified release tablet provides for gradual release of the active agent into the systemic circulation. FROM_max plasma levels achieved after 2.3-7.7 h and is 17-41.4 ng / ml.

Distribution

Penetrates the GEB and placental barrier, excreted in breast milk. The binding to plasma proteins – 90%. The cumulative effect is absent.

Metabolism and excretion

Podvegaetsya effect “first pass” through the liver. Completely metabolized in the liver. Excreted by the kidneys as inactive metabolites (70-80% the dose). 20% – the bile.

Pharmacokinetics in special clinical situations

In patients with hepatic insufficiency and decreased total clearance increases the half-life.

Testimony

- Stable angina (angina);

- variant angina (Prinzmetal angina);

- Arterial hypertension.

Dosage regimen

Tablets are taken morning while eating whole, not chewing and drinking plenty of fluids.

The recommended dose is 40 mg (1 tab.) 1 time / day.

Abolition of the drug should be gradual.

Side effect

Cardio-vascular system: tides, facial flushing, feeling the heat, tachycardia, arrhythmia, peripheral edema (ankles, stop, goleneй), excessive reduction of blood pressure, syncope, heart failure; some patients, especially at the beginning of treatment, may cause angina attacks, which requires discontinuation of the drug. Described isolated cases of myocardial infarction.

From the central and peripheral nervous system: headache, dizziness, generalized weakness, fatigue, drowsiness, paresthesia. Prolonged use of high doses – extrapyramidal (parkinsonian) infringement (ataxia, mask-like face, shuffling gait, stiffness of arms and legs, tremors of the hands and fingers, difficulty swallowing), depression.

From the digestive system: dry mouth, increased appetite, dyspepsia (nausea, diarrhea or constipation), giperplaziya right (completely disappear after drug withdrawal). With prolonged use of possible violations of liver function (intrahepatic cholestasis, increase in liver enzymes).

On the part of the musculoskeletal system: arthritis, myalgia; rarely – arthralgia, swelling of joints.

From the hematopoietic system: anemia, leukopenia, thrombocytopenia, trombotsitopenicheskaya purpura, agranulocytosis.

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

Allergic reactions: itch, hives, rash, exfoliative dermatitis, photodermatitis, autoimmune hepatitis, acute generalized allergic reaction – swelling of the mucous membranes, laryngeal edema, bronchospasm (until the development of dyspnea, threatening the life of the patient).

Other: blurred vision (incl. Transient blindness at the maximum plasma concentrations of nifedipine), gynecomastia (in elderly patients, completely disappear after drug withdrawal), galactorrhea, giperglikemiâ, pulmonary edema, weight gain.

Contraindications

- Cardiogenic shock;

- The acute phase of myocardial infarction (during the first 4 weeks);

- Unstable angina;

- Vыrazhennыy aortalnыy stenosis;

- Severe hypotension (systolic BP below 90 mmHg.);

- Concomitant use of rifampicin;

- Pregnancy;

- Lactation (breast-feeding);

- Up to 18 years (efficacy and safety have not been established);

- Hypersensitivity to nifedipine or other 1,4-dihydropyridine derivatives.

FROM caution use in patients with significant stenosis of the mitral valve, hypertrophic obstructive cardiomyopathy, bradycardia or tachycardia, SSS, in chronic heart failure, with mild to moderate hypotension, in severe violations of cerebral circulation, obstruction of the digestive tract, kidney and liver failure (especially in patients, hemodialysis, because of the high risk of excessive blood pressure lowering and unpredictable), the elderly.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breast-feeding).

Cautions

Patients should be warned of the need to regularly take the drug, regardless of the state of health.

Patients, hemodialysis, high blood pressure, and irreversible impairment of renal function and reduced the total amount of blood the drug should be used with caution, tk. possible sharp drop in blood pressure.

If abnormal liver function, patients require careful monitoring and, if necessary, – dose reduction or the use of other formulations of nifedipine.

In severe heart failure, dose selection should be cautious of nifedipine.

Co-administration of beta-blockers should be carried out under close medical supervision, because it can cause excessive blood pressure reduction, and in some cases – worsening symptoms of heart failure.

During treatment, the positive results are possible during the direct reaction of Coombs and laboratory tests for antinuclear antibodies.

It will be appreciated, that at the beginning of treatment may angina, especially after the recent abrupt withdrawal of beta-blockers (the past should be withdrawn gradually).

Diagnostic criteria for the appointment of the drug in vasospastic angina are: classical clinical picture, accompanied by ST-segment elevation, the occurrence of ergonovine-induced angina or coronary artery spasm, identification of coronary spasm during angiography or detection of a component without confirmation angiospastic (eg, at different threshold voltage or unstable angina, when ECG data indicate transient vasoconstriction).

Precautions should be prescribed concurrently with disopyramide and flekainamidom due to the possible increase in inotropic effect.

If the patient requires surgery under general anesthesia, you must inform the anesthesiologist about the nature of the therapy.

Caution must be exercised in elderly patients due to the high probability of age-related disorders of the kidney.

Against the background of the therapy should not drink alcohol.

Effects on ability to drive vehicles and management mechanisms

In the period of treatment should refrain from activities potentially hazardous activities, require high concentration and speed of psychomotor reactions.

Overdose

Symptoms: headache, facial flushing, long marked reduction of blood pressure, inhibition activity of the sinus node, bradycardia and / or tachycardia, ʙradiaritmija; in severe overdose – loss of consciousness, coma.

Treatment: washing the stomach and small intestine. An antidote is a calcium supplement, It is shown in / introduction 10% solution of calcium chloride or calcium gluconate, followed by continuous infusion. In marked decrease in blood pressure – slow in / introduction of dopamine, doʙutamina, epinephrine (adrenaline) or norepinephrine (noradrenaline). When violations of the conductivity – atropyn, isoprenaline or artificial pacemaker. It is recommended to control blood glucose (may decrease the release of insulin) electrolytes and (Potassium, Calcium). Hemodialysis is not effective.

Drug Interactions

The antihypertensive effect of nifedipine is enhanced by concomitant use of other antihypertensive agents, nitratami, cimetidine (to a lesser extent - Ranitidine), means for inhalation anesthesia, Diuretics.

It should be taken into account, Calcium channel blockers may increase the negative inotropic effect of amiodarone and quinidine.

In a joint application causes a decrease in the concentration of nifedipine in blood plasma quinidine, after the abolition of nifedipine may be a sharp increase in the concentration of quinidine.

With simultaneous application of nifedipine increases the concentration of digoxin and theophylline in the blood plasma (use of the combination requires monitoring clinical efficacy and maintenance of digoxin and theophylline in plasma).

Inductors of microsomal liver enzymes (incl. rifampicin) reduce the concentration of nifedipine.

In a joint application with nitrates nifedipine enhanced tachycardia.

The hypotensive effect of nifedipine is reduced while the use of sympathomimetics, NSAIDs, Estrogen, calcium supplementation.

Nifedipine can displace from its association with protein drugs, characterized by a high degree of binding (incl. indirect anticoagulants – coumarin and derivatives indandiona, anticonvulsants, NSAIDs, quinones, salicilaty, sulfinpirazon), thereby can increase their concentration in the blood plasma.

In a joint application nifedipine inhibits the metabolism of prazosin and other alpha-blockers, as a result may increase the hypotensive effect.

Nifedipine inhibits the excretion of vincristine from the body and may cause increased side effects of vincristine (if necessary, reduce the dose of vincristine).

When combined preparations of lithium may enhance the toxic effects (nausea, vomiting, diarrhea, ataksiyu, tremor, noise in ears).

When concomitant administration of cephalosporins (eg, cefixime) and increases the bioavailability of nifedipine to cephalosporin 70%.

Prokayn, quinidine and other drugs, causing prolongation of the QT interval, reinforce the negative inotropic effect and increase the risk of significant lengthening of the QT interval.

Diltiazem Nifedipine inhibits the metabolism in the body (use of the combination requires close monitoring and, if necessary, reduce the dose of nifedipine).

Grapefruit juice inhibits the metabolism in the body of nifedipine, and therefore its use is contraindicated with nifedipine.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in the dark, inaccessible to children at temperature not exceeding 30 ° C. Shelf life – 3 year.