Composition, form of production and packaging
Tablets of prolonged action, covered with a film membrane of yellow color, round, biconvex, with oblique margins; in the fracture, a homogeneous mass of yellow color.
1 tab.
nifedipine 10 mg
Excipients: lactose monohydrate, potato starch, microcrystalline cellulose, povidone K25, magnesium stearate.
Composition of the film coat: hypromellose, macrogol 6000, macrogol 35000, dye quinoline yellow (E104), titanium dioxide (E171), talc.
10 pieces. - blisters (3) - packs of cardboard.
50 pcs. - bottles of brown glass (1) - packs of cardboard.
100 pieces. - bottles of brown glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Selective blocker of slow calcium channels (BCCC), 1,4-dihydropyridine derivative. Has antianginal and hypotensive effect. Reduces the current of extracellular Ca 2+into the cardiomyocytes and smooth muscle cells of the coronary and peripheral arteries; in high doses, inhibits the release of Ca 2+ from intracellular stores.
In therapeutic doses normalizes the transmembrane current of Ca 2+ , 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 OPSS, myocardial tone, postnagruzku and the need for myocardium in oxygen. Virtually does not affect the sinoatrial node and AV node, has a weak 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 heart rate in response to peripheral vasodilation.
The time of onset of the clinical effect is 20 minutes and its duration is 4-6 hours.
At long reception (2-3 months) tolerance to action of a preparation develops.
PHARMACOKINETICS
Suction
Absorption is high (more than 90%). Bioavailability is 50-70%. Eating increases bioavailability. Has the effect of "first pass" through the liver. C max nifedipine in blood plasma after a single oral intake of 2 tablets (corresponding to 20 mg of nifedipine) is achieved after 1-3 hours and its value averages 28.3 ng / ml.
Distribution
Binding to plasma proteins (with albumins) is 95%.
Penetrates through the BBB and placental barrier, excreted in breast milk.
There is no cumulative effect.
Metabolism and excretion
It is completely metabolized in the liver.
T 1/2 is 2-5 hours. It is excreted by the kidneys in the form of an inactive metabolite (60-80% of the accepted dose), 20% - with bile.
Pharmacokinetics in special clinical cases
Chronic renal failure, hemodialysis and peritoneal dialysis do not affect the pharmacokinetics.
In patients with hepatic insufficiency, the total clearance decreases and T 1/2 increases .
INDICATIONS
- chronic stable angina (stress angina);
- Prinzmetal angina (variant angina);
- arterial hypertension.
DOSING MODE
Inside after eating, without chewing and washing down with a sufficient amount of 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 disease and in elderly patients, the dose of the drug should be reduced.
Simultaneous intake of food delays, but does not reduce the absorption of nifedipine from the gastrointestinal tract.
Chronic stable and vasospastic angina
The initial dose is 10 mg (1 tab.) 2-3 times / day. With an insufficiently pronounced clinical effect, the dose of the drug is gradually increased to 2 tab. (20 mg) 1-2 times / day. The maximum daily dose is 40 mg (4 tablets / day).
Essential hypertension
The average daily dose is 10 mg (1 tab.) 2-3 times / day.
With an insufficiently pronounced clinical effect, a gradual increase in the dose of the drug to 20 mg (2 tablets) is possible 2 times / day. The maximum daily dose is 40 mg (4 tablets / day).
When 2-fold appointment, the minimum interval between doses of the drug should be at least 4 hours.
The duration of treatment is determined by the attending physician.
SIDE EFFECT
Cardiovascular system: tachycardia, palpitations, arrhythmias, peripheral edema (ankles, feet, shins), excessive vasodilation (asymptomatic decrease in blood pressure, development or aggravation of heart failure, blood flushes to the skin of the face, hyperemia of the facial skin, a feeling of heat), a marked decrease in blood pressure (rarely), syncope. In some patients, especially at the beginning of treatment or with an increase in the dose, there may be angina attacks and in isolated cases - the development of myocardial infarction, which requires the withdrawal of the drug.
From the nervous system: headache, dizziness, general weakness, increased fatigue, drowsiness. With long-term use of the drug in high doses - paresthesia of limbs, tremor, extrapyramidal (parkinsonian) disorders (ataxia, "masky" face, shuffling gait, tremor of hands and fingers, difficulty swallowing), depression.
From the digestive system: dyspepsia (nausea, diarrhea or constipation), dry mouth, flatulence, increased appetite; rarely - gingival hyperplasia, completely disappearing after drug withdrawal; at long reception - disturbances of function of a liver (intrahepatic cholestasis, increase of activity of hepatic transaminases).
From the musculoskeletal system: arthritis, myalgia, puffiness of the joints, convulsions of the upper and lower extremities.
Allergic reactions: rarely - skin itching, hives, exanthema, autoimmune hepatitis, exfoliative dermatitis, photodermatitis, anaphylactic reactions.
On the part of the hematopoiesis system: anemia, leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis.
On the part of the urinary system: an increase in daily diuresis, impaired renal function (in patients with renal insufficiency).
Other: rarely - visual impairment (including transient blindness at the maximum concentration of nifedipine in blood plasma), gynecomastia (in elderly patients, completely disappearing after drug withdrawal), galactorrhea, hyperglycemia, pulmonary edema, bronchospasm, weight gain.
CONTRAINDICATIONS
- arterial hypotension (systolic blood pressure below 90 mm Hg);
- cardiogenic shock, collapse;
- chronic heart failure in the stage of decompensation;
- severe aortic stenosis;
- unstable angina;
- acute myocardial infarction (the first 4 weeks);
- joint use with rifampicin;
- I trimester of pregnancy;
- the period of lactation (breastfeeding);
- Hypersensitivity to nifedipine and other derivatives of 1,4-dihydropyridine or to other components of the drug.
With caution: stenosis of the mitral valve, hypertrophic obstructive cardiomyopathy, severe bradycardia or tachycardia, SSSU, malignant hypertension, hypovolemia, severe circulatory disorders, myocardial infarction with left ventricular failure, gastrointestinal obstruction, renal and hepatic insufficiency, hemodialysis (due to the risk of arterial hypotension), II and III trimesters of pregnancy, children and adolescents under 18 years (efficacy and safety not established), one-time menny beta-blockers, digoxin.
PREGNANCY AND LACTATION
The drug is contraindicated in the first trimester of pregnancy and during lactation.
With caution: should be prescribed in the II and III trimesters of pregnancy.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution: kidney failure
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution: liver failure.
APPLICATION FOR CHILDREN
With caution: age under 18 years (efficacy and safety not established).
SPECIAL INSTRUCTIONS
During the treatment it is necessary to refrain from taking ethanol. 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 under 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.
With severe heart failure, the drug is dosed with great care.
Diagnostic criteria for prescribing with vasospastic angina are: a classic clinical picture accompanied by an increase in the ST segment, the emergence of ergonovirus-induced angina pectoris or spasm of the coronary arteries, the detection of coronarospasm in angiography or the detection of an angiospastic component without confirmation (for example, with a different voltage threshold or unstable angina, when ECG data indicate a transient angiospasm).
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 with irreversible renal failure, on hemodialysis, having high blood pressure and reduced BCC, the drug should be used carefully, possibly a sharp drop in blood pressure. For patients with impaired liver function, careful monitoring is established; if necessary, the dose of the drug is reduced and / or used by other dosage forms of nifedipine.
If surgical intervention is necessary under anesthesia, the anesthetist should be informed of the patient's treatment with nifedipine.
In case of in vitro fertilization, in some cases BCCC caused changes in the head part of spermatozoa, which can lead to a disruption of the functions of spermatozoa.In cases in which repeated in vitro fertilization has not been performed for an unclear reason, the use of BCCC, including nifedipine, can be considered a possible cause of failure.
During treatment, it is possible to obtain a false positive result of Coombs' direct reaction and laboratory tests for antinuclear antibodies.
In the spectrophotometric determination of vanillyl-mandelic acid in urine, nifedipine may be the cause of a false-overestimated result, however, the results of HPLC tests show no effect on nifedipine.
With caution should be carried out simultaneous treatment with nifedipine, disopyramide and flecainide due to the possible enhancement of the inotropic effect.
Impact on the ability to drive vehicles and manage mechanisms
During the period of treatment, patients should be careful when driving vehicles and engage in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
OVERDOSE
Symptoms: headache, hyperemia of the facial skin, a long pronounced decrease in blood pressure, suppression of sinus node function, bradycardia / tachycardia, bradyarrhythmia. In severe poisoning - loss of consciousness, coma.
Treatment: symptomatic therapy. In severe poisoning (collapse, suppression of the sinus node), gastric lavage (if necessary, the small intestine) is carried out, and activated charcoal is administered. Antidote are calcium preparations, shown in / in the administration of 10% calcium chloride or calcium gluconate, followed by a transfer to a long infusion. With a marked decrease in blood pressure, a slow intravenous injection of dopamine, dobutamine, epinephrine, or norepinephrine is indicated. It is recommended to monitor the glucose content (insulin release may decrease) and electrolytes in the blood (K + , Ca 2+ ). With the development of heart failure - in / in the introduction of strophanthin. In conduction disorders - atropine, isoprenaline or an artificial pacemaker. Hemodialysis is not effective, plasmapheresis is recommended.
DRUG INTERACTION
With the simultaneous use of other antihypertensive drugs, as well as tricyclic antidepressants, nitrates, cimetidine, inhalational anesthetics, diuretics, the hypotensive effect of nifedipine may be enhanced.
BCCI can further enhance the negative inotropic effect of antiarrhythmics such as amiodarone and quinidine.
When combining nifedipine with nitrates, tachycardia increases.
Diltiazem inhibits the metabolism of nifedipine in the body, which may require a reduction in the dose of nifedipine with the simultaneous administration of these drugs.
Reduces the concentration of quinidine in the blood plasma.
Increases the concentration of digoxin and theophylline in the blood plasma.
Rifampicin accelerates the metabolism of nifedipine, joint use is not recommended.
At simultaneous appointment with cephalosporins (for example, cefixime) the concentration of cephalosporins in the blood can increase.
Sympathomimetics, NSAIDs (suppression of prostaglandin synthesis in the kidneys and retention of sodium and liquid ions in the body), estrogens (fluid retention in the body) reduce the hypotensive effect.
Nifedipine can displace drugs with a high degree of binding (including indirect anticoagulants - coumarin and indanedione derivatives, anticonvulsants, NSAIDs, quinines, salicylates, sulfinpyrazone) from the association with proteins, and as a result, their concentrations in the blood plasma may increase.
Nifedipine inhibits the metabolism of prazosin and other alpha-adrenoblockers, which can lead to an increase in the hypotensive effect.
If necessary, the dose of vincristine is reduced, because Nifedipine inhibits its elimination from the body, which can cause an increase in side effects.
Lithium preparations can enhance toxic effects (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
With the simultaneous administration of procainamide, quinidine and other drugs that cause prolongation of the QT interval, the risk of a significant prolongation of the QT interval increases.
Grapefruit juice inhibits the metabolism of nifedipine in the body, so it is contraindicated during treatment with nifedipine.
Nifedipine is metabolized by the CYP3A isoenzyme, so simultaneous use of drugs that inhibit this system can lead to interaction of the drug and nifedipine: for example, macrolides, antiviral drugs (eg, amprenavir, indinavir, nelfinavir, ritonavir or saquinavir), antifungal agents of the group azoles (ketoconazole, itraconazole or fluconazole) cause an increase in the concentration of nifedipine in the blood plasma.
Taking into account the experience of using BIMC nimodipine, it is impossible to exclude similar interactions with nifedipine: carbamazepine, phenobarbital may cause a decrease in the concentration of nifedipine in the blood plasma, and valproic acid - an increase in the concentration of nifedipine in the blood plasma.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
COR-RU-00002-DOK-PHARM
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, protected from light at a temperature of no higher than 25 В° C. Shelf life - 5 years.
