Translation of the instruction Mose

tablet NIFEDIPIN-DARNITSA, coated 10 mg

Instruction

On medical use of medicine

Ingredients:

Active ingredient: nifedipine;

1 tablet contains nifedipine 10 mg;

excipients: corn starch, lactose monohydrate, cellulose microcrystalline, povidone, magnesium stearate, sepifilm 752 white, macrogoal 6000, yellow decline of FCF (E 110).

Dosage form.

Tablet, coated.

Main physical and chemical properties: tablets, coated, orange color, round shape with a biconvex surface.

Pharmacotherapeutic group.

Selection blockers of calcium channels with primary action on vessels. dihydropyridine derivatives. nifedipine. code atkh s08s a05.

Pharmacological properties.

Pharmacodynamics.

Nifedipin — active ingredient of medicine — a selection blocker of calcium channels, derivative dihydropyridine. Has anti-anginal and antihypertensive effects. Slows down intake of calcium in cardiomyocytes and cells of smooth muscles of vessels. Reduces a tone of smooth muscles of vessels. Expands coronary and peripheral arteries, reduces the general peripheric resistance of vessels, arterial blood pressure and in insignificant degree — contractility of a myocardium, reduces an afterload and the need of a myocardium for oxygen. Improves coronary circulation. Does not suppress conductivity of a myocardium. At prolonged use, nifedipine can prevent formation of new atherosclerotic plaques in coronary vessels. In an initiation of treatment the tranzitorny reflex tachycardia and increase in warm emission which do not compensate the vazodilatation caused by medicine use can arise nifedipine. Nifedipine strengthens removal from an organism of sodium and liquid. At Reynaud's syndrome medicine can warn or weaken an angiospasm of extremities.

Pharmacokinetics.

nifedipine quickly and almost is completely soaked up by

After oral administration. The bioavailability owing to presistemny metabolism in a liver is 50%. The maximum concentration (T _max ) in blood plasma is reached in 1–3 hours after reception.

Nifedipine is metabolized by

in a wall of intestines and in a liver through the system of P450 3A4 cytochrome. Metabolites do not show pharmacological activity. Also about 5-15% are brought out of an organism in the form of metabolites mainly by kidneys — through intestines with bile. The insignificant amount of not changed substance (less than 0.1%) came to light in urine. Elimination half-life (T _1/2 ) nifedipine makes 2–5 hours of blood plasma.

Clinical characteristics.

Indication.

Arterial hypertension, coronary heart disease: chronic stable stenocardia, vasospastic stenocardia (stenocardia printsmetat).

Contraindication.

Hypersensitivity to nifedipine, to other derivatives of dihydropyridine or to other components of medicine; cardiogenic shock; aortal stenosis of heavy degree; unstable stenocardia; an acute myocardial infarction (for the first 4 weeks); ileostoma or kolostoma; use in a combination with rifampicin (because of impossibility to reach effective concentration of nifedipine in blood plasma); period of pregnancy and feeding by a breast.

Interaction with other medicines and other types of interactions.

Nifedipine is metabolized by

through the system of cytochrome r450 3a4 which is located in a mucous membrane of intestines and a liver. therefore the medicines inhibiting or inducing this system of enzymes (for example erythromycin, klaritromitsin, ciprofloxacin, norfloxacin, ketokonazol, itrakonazol, flukonazol, the means containing progestins, fluoxetine, indinavir, nelfinavir, ritonavir, amprenavir and sakvinavir), can change the first passing (after oral administration) or clearance of nifedipine.

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Though did not conduct researches of interaction of these in Vivo medicines, potentially at simultaneous use the increase in concentration of nifedipine in blood plasma is possible. Therefore it is necessary to control the level of arterial blood pressure and reduction of a dose of nifedipine can be required.

Antihypertensive effect of nifedipine can increase at use of other antihypertensive medicines and tricyclic antidepressants.

Medicines affecting efficiency of nifedipine

C hinupristinom/dalfopristiny, Cimetidinum, tsizapridy — owing to inhibition of P450 3A4 cytochrome the concentration of nifedipine in blood plasma increases; at simultaneous use of medicines it is recommended to carry out monitoring of arterial blood pressure and in case of need — a nifedipine dose decline.

With inhibitors of a system of P450 3A4 cytochrome, such as makrolidny antibiotics (for example ketokonazol), HIV protease inhibitors (for example ritonavir), azolny anti-mycotic means (for example ketokonazol), fluoxetine, nefazodon – clinical trials of interaction of these medicines and nifedipine were not carried out. It is known that medicines of this class inhibit in vitro the nifedipine metabolism mediated by P450 3A4 cytochrome therefore at simultaneous use it is impossible to exclude increase in concentration of the last in blood plasma and reduction in the rate of removal from an organism; it is recommended to carry out monitoring of arterial blood pressure and in case of need — a nifedipine dose decline.

Azithromycin having structural similarity to makrolidny antibiotics does not inhibit CYP3A4.

With rifampicin — owing to induction of P450 3A4 cytochrome the bioavailability and efficiency of nifedipine considerably decreases; simultaneous use of medicines is contraindicated.

With Phenytoinum — owing to induction of P450 3A4 cytochrome the bioavailability and efficiency of nifedipine decreases; at simultaneous use of medicines it is recommended to control the clinical response to therapy by nifedipine and in case of need to raise its dose; if raised a nifedipine dose during simultaneous use, after cancellation of Phenytoinum it is necessary to consider a question of the corresponding dose decline.

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With inductors of a system of P450 3A4 cytochrome, such as carbamazepine, phenobarbital, valproic acid — clinical trials of interaction of above-mentioned medicines and nifedipine it was not carried out. It is known that these medicines owing to induction of P450 3A4 cytochrome reduce concentration in blood plasma of structurally similar blocker of calcium channels of a nimodipin therefore at simultaneous use with nifedipine it is impossible to exclude increase in its concentration in blood plasma.

With Cimetidinum and ranitidine — owing to inhibition of P450 3A4 cytochrome Cimetidinum/ranitidine increases concentration of nifedipine in blood plasma and can enhance antihypertensive effect. Cimetidinum affects tsitokhromny CYP3A4 isoenzyme as inhibitor. Patients who already accept Cimetidinum should appoint nifedipine with care, and its dosage needs to be raised more gradually.

C tsizapridy — simultaneous use of a tsizaprid and nifedipine can lead to increase in concentration of nifedipine in blood plasma. Therefore constant control of arterial blood pressure is necessary and the nifedipine dose decline can be required.

With diltiazem – is weakened by disintegration and reduces clearance of nifedipine, at the same time increasing its concentration in blood plasma. Therefore it is necessary to apply with care nifedipine along with diltiazem, at the same time the nifedipine dose decline can be required.

With antihypertensives (diuretics, α- and β-adrenoblockers, APF inhibitors, antagonists of calcic receptors, antagonists of AT-1 of receptors, FDE-5 inhibitors, α-metildopy, magnesium sulfate) — strengthening of hypotensive effect is possible; at simultaneous use of nifedipine with β-adrenoblockers the careful monitoring of the patient as isolated cases of exacerbation of heart failure are known is necessary.

At simultaneous use of the glitseriltrinitrat and isosorbide of the prolonged action should take synergetic effect of nifedipine into account.

Accompanying intake of nifedipine and tricyclic antidepressants can lead

to increase in concentration of these medicines in blood plasma and to strengthening of antihypertensive effect of nifedipine.

fentanyl can cause arterial hypotension In patients who are treated by nifedipine. It is necessary to refrain from intake of nifedipine within not less than 36 hours before planned operation with use of anesthesia on the basis of fentanyl.

Nifedipin can lead

to toxic effect of magnesium sulfate that is the reason of neuromuscular blockade. The concomitant use of nifedipine and magnesium sulfate is not recommended because it is dangerous and can threaten the patient's life.

At the patients accepting anticoagulants on the basis of coumarin after addition of nifedipine observed increase in a prothrombin time. The importance of this interaction was not investigated fully.

Nifedipin can change

bronchial reactivity to metasincaline. Before the nonspecific bronkhoprovokatsionny test using metasincaline nifedipine needs to be cancelled (whenever possible).

With theophylline — needs to check expediency of use of theophylline with nifedipine as during a concomitant use of nifedipine with theophylline the concentration of theophylline in blood plasma can increase.

With digoxin — decrease in clearance of digoxin and increase in its concentration in blood plasma is possible; it is recommended to control the patient on existence of symptoms of overdose of digoxin and in case of need to correct a dose according to concentration of digoxin in blood plasma.

With Amiodaronum – the certain medicines relating to group of blockers of calcium channels can enhance negative inotropic effect of antiarrhytmic means, such as Amiodaronum. However information on interaction with nifedipine is absent.

With quinidine — it was reported about decrease in concentration of quinidine, and at nifedipine cancellation — about sharp increase in concentration of quinidine in blood plasma; it is recommended to control concentration of quinidine in blood plasma and in case of need to correct its dose; also there were messages about increase in concentration of nifedipine in blood plasma at their simultaneous use, however changes of pharmacokinetics of nifedipine were not noted. Considering on it, it is necessary to control carefully arterial blood pressure at inclusion of quinidine in the scheme of therapy by nifedipine. In case of need it is necessary to lower a nifedipine dose.

C takrolimusy — it was reported about increase in concentration of a takrolimus in blood plasma as a result of its metabolization through the system of P450 3A4 cytochrome. The published data indicate that in some cases the dose of a takrolimus at simultaneous use with nifedipine can be lowered. It is recommended to control concentration of a takrolimus in blood plasma and in case of need to correct its dose.

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At a concomitant use of Vincristinum observes weakening of removal of Vincristinum therefore side effects are possible, it is necessary to consider need of a dose decline; With cephalosporins (for example to a tsefiksim) — increase in bioavailability and levels of cephalosporin in blood plasma.

Other types of interactions

Grapefruit juice inhibits the system of P450 3A4 cytochrome. Consumption of grapefruit juice at use of nifedipine leads to increase in concentration of medicine in blood plasma and to increase in duration of effect of nifedipine owing to decrease in metabolism at the first passing or decrease in clearance. Thereof antihypertensive effect of medicine can amplify. After regular consumption of grapefruit juice this effect can last during at least 3 days after the last use of juice. Considering it, at therapy by nifedipine it is necessary to avoid consumption of grapefruits / grapefruit juice.

Use of medicine can lead

to obtaining the false increased results at spectrophotometric definition of concentration of vanililmindalny acid in urine (however at use of a method of highly effective liquid chromatography this effect is not observed).

Use of medicine can lead

to obtaining false positive results at X-ray analysis with use of baric contrast means (for example, defects of filling are interpreted as a polyp).

Feature of use.

Medicine can be applied in a combination with other antihypertensives. but it must be kept in mind a possibility of development of postural arterial hypotension.

recommends to control

At simultaneous use of medicine and β-adrenoblockers a condition of the patient as at the same time perhaps sharper falling of arterial blood pressure and weakening of warm activity.

Medicine should not be applied to patients with a bad attack of stable stenocardia.

. In this regard, nifedipine is recommended to be applied to treatment of patients with essential hypertensia or chronic stable stenocardia, in cases if treatment by other means does not approach.

Medicine should not be applied if communication between the previous use of nifedipine and ischemic pain is possible. Within 1–4 hours after the beginning of intake of nifedipine some patients complained of insignificant ischemic pain. And though confirmations of a syndrome of burglarizing were not received, it is necessary to stop treatment by nifedipine of patients in whom such symptoms were found. At patients with stenocardia the attacks can arise more often, and their duration and intensity can increase, especially in an initiation of treatment.

Nifedipin can slow down digoxin removal. The concomitant use of nifedipine with digoxin can lead to increase in concentration of digoxin and to emergence of side reactions at increase in concentration of medicines of group of cardiac glycosides.

Medicine to apply

with extra care to patients with the profound arterial hypotension (systolic pressure is lower than 90 mm Hg.), profound heart failure, heavy disturbances of cerebral circulation, diabetes, abnormal liver function. It is recommended to control a condition of the patient and in case of need to correct a nifedipine dose.

Medicine to apply

with care to the patients with chronic kidney disease who are on a hemodialysis on condition of malignant arterial hypertension or a hypovolemia as expansion of blood vessels can cause in them a considerable lowering of arterial pressure.

Medicine to apply

with care to patients who at the same time accept inhibitors of a system of P450 3A4 cytochrome as they can change the first passing or clearance of nifedipine.

To medicines which are weak or moderate inhibitors of a system of P450 3A4 cytochrome and can be led to increase in concentration of nifedipine in blood plasma, belong, for example:

• makrolidny antibiotics (for example erythromycin);
• protease anti-HIV inhibitors (for example ritonavir);
• azolny antifungal means (for example ketokonazol);
• antidepressants nefazodon and fluoxetine;
• hinupristin/dalfopristin;
• valproic acid;
• Cimetidinum.

recommends to control

arterial blood pressure and in case of need to correct a nifedipine dose.

Medicine to apply

with care to patients with the available strong narrowing of digestive tract because of possibility of obstructive symptoms. Emergence of obstructive symptoms at absence in the anamnesis of disturbances from digestive tract is described. Emergence of bezoar which can demand surgical intervention is possible.

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In isolated cases described obstructive symptoms at absence in the anamnesis of disturbances from digestive tract.

patients Cannot apply

with an ileal and intestinal vessel (ileostomy after a proktokolektomiya).

Excipients

Medicine contains lactose therefore to patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption it is not necessary to accept medicine.

Use during pregnancy or feeding by a breast.

Pregnancy.

Use of nifedipine is contraindicated to

during pregnancy.

Research on animals were shown by embriotoxity, a fetotoksichnost and teratogenecity of medicine and also negative impact on reproductive function. Nifedipine should not be applied to women who plan pregnancy in the nearest future.

Results of the corresponding and well controlled researches concerning safety of use of medicine to pregnant women are absent. From the available clinical data the specific prenatal risk was not established. Though it was reported about increase in frequency of cases of perinatal asphyxia, childbirth by Cesarean section and also premature births and a pre-natal growth inhibition. Finally it is not clear whether these cases are a consequence of presence of arterial hypertension, its therapy or specific effect of use of medicine. The available information is not enough to exclude serious collateral influence on a fruit or the newborn.

At intravenous use of blockers of calcium channels, including nifedipine, for decrease in patrimonial activity and/or at simultaneous use of agonists β to ₂ - adrenoceptors was reported about an acute fluid lungs (especially in case of polycarpous pregnancy).

careful monitoring of arterial blood pressure because of a possibility of its considerable decrease is necessary for

At use of nifedipine along with administration of magnesium of sulfate that can damage to mother and a fruit.

Feeding by a breast.

during use of medicine should stop feeding by a breast.

Nifedipin gets into breast milk, concentration of nifedipine in breast milk is almost comparable with concentration in blood plasma of mother. Influence of insignificant amounts of the absorbed nifedipine is unknown.

Fertility.

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In separate experiments of in vitro revealed interrelation between use of blockers of calcium channels, in particular nifedipine, and reversible biochemical changes of the spermatozoa worsening ability of the last to fertilization. If attempts of fertilization of in vitro are unsuccessful, in the absence of other explanations, blockers of calcium channels, in particular nifedipine, can be considered as the possible reason of this phenomenon.

Ability to influence speed of response at control of motor transport or other mechanisms.

Performing therapy using this medicine demands constant medical observation. at use of medicine the emergence of side reactions is possible; owing to various individual reactions of an organism to medicine influencing speed of response at control of motor transport or other mechanisms, performance of the actions demanding position of a body without support is broken. more these cautions concern, especially at the beginning of treatment, the period increase in a medicament dose, transition to other medicine or alcohol intake.

Route of administration and doses.

Medicine to apply

adult inside. to take a pill at the same time irrespective of meal, without chewing and washing down with enough liquid (except grapefruit juice). meal together with a tablet leads to delay, but not reduction of absorption.

Recommended interval between intake of medicine — 12 hours (but not less than 6 hours).

Drug dose and duration of a course of treatment is defined by

individually, with severity of a disease and reaction of the patient to treatment.

Depending on an individual clinical picture the recommended dose should be raised gradually.

Arterial hypertension.

Medicine to apply in a dose 20 mg 2 times a day.

Coronary heart disease.

Medicine to apply in a dose 20 mg 2 times a day. If necessary increase in a dose of nifedipine up to 60 mg/days is possible. It is necessary to raise a dose gradually.

Maximum daily dose of medicine should not exceed 80 mg.

Patients who at the same time apply inhibitors or inductors of CYP cytochrome 3A4. At simultaneous use with inhibitors or inductors of CYP cytochrome 3A4 the dose adjustment or cancellation of medicine can be required.

Patients with a liver failure need constant observation, the medicine dose decline can be required.

Because of possibility of a syndrome of a ricochet medicine should be cancelled gradually, especially in case of use of high doses and at long-term treatment.

Tablet should not be divided as in that case the protection against light guaranteed by a protective cover is not provided any more.

Children.

Medicine not to apply

to children as safety and efficiency of use of nifedipine is not established to children (aged up to 18 years).

Overdose.

Symptoms of acute intoxication: disturbance of consciousness up to development of a coma, a lowering of arterial pressure, tachycardia/bradycardia, a hyperglycemia, a metabolic acidosis, a hypoxia, the cardiogenic shock which is followed by a fluid lungs.

Treatment. First of all it is necessary to allocate measures for rendering emergency aid for removal of medicine from an organism and restoration of a stable hemodynamics. After oral administration it is recommended to empty completely a stomach, if necessary — in a combination with lavage of gastric and small intestine. It is recommended to consider need of use of activated carbon. In cases of intoxication caused by medicines of long release it is necessary to make efforts for fuller removal of medicine from an organism, including from a small intestine, for prevention of absorption of active ingredient. In spite of the fact that expedient the assumption of advantage of late use of activated carbon in case of overdose of medicines of the prolonged action is considered, it should be noted that proofs in confirmation of it do not exist.

At overdose treatment, poses a threat for life at adults, in an hour after reception of potentially toxic dose as an alternative it is necessary to consider need gastric lavage.

At reception of clinically significant amount of medicine with slow removal should consider need of use of one dose of depletive of osmotic action (for example, sorbite, lactulose and sulfate of magnesia) within four hours at simultaneous use of activated carbon.

should consider

At use of depletive that antagonists of calcium lead to decrease in a tone of muscles of intestines up to an intestines atony. As high extent of linking with proteins of blood plasma and rather small volume of distribution is characteristic of nifedipine, the hemodialysis is inefficient, however carrying out a plasma exchange is recommended.

in case of developing of bradycardia is recommended to apply β-sympathomimetics or atropine. At delay of the warm rhythm posing a threat for life the use of an artificial pacemaker is recommended. The arterial hypotension which arose owing to cardiogenic shock and a vazodilatation can be eliminated with calcium medicaments (or a gluconate to enter 10–20 ml of 10% of solution of Calcii chloridum intravenously slowly, then to repeat in case of need on condition of ECG monitoring). Thereof serumal levels of calcium can reach the upper bound of norm or to be slightly raised. If administration of calcium is insufficiently effective, reasonable use of such sympathomimetics as a dopamine, Dobutaminum, epinephrine or noradrenaline. To select doses of these medicines taking into account the reached medical effect. It is necessary to approach additional input of the fluid very carefully as at the same time the danger of an overload of heart increases. As high extent of linking with proteins of blood plasma and rather small volume of distribution is characteristic of nifedipine, the hemodialysis is inefficient, however carrying out a plasma exchange is recommended.

Patients without the expressed symptoms of intoxication have to be under observation not less than 4 hours after use of an overdose of medicine of short action and at least 12 hours after use of medicine of the prolonged action.

Side reactions.

Majority of side reactions arise because of vasodilating effect of nifedipine and, as a rule, disappear after the therapy termination by medicine.

from organs of sight: minor, temporary change of visual perception, disorder of vision, feeling of pain in eyes, excessive dacryagogue, amblyopia.

from the respiratory system, bodies of a thorax and mediastinum: nasal bleeding, congestion of a nose, dispny, a fluid lungs (in case of use to pregnant women as tokolitichesky means), cough, a spastic condition of bronchial muscles up to a life-threatening asthma which passes after the treatment termination.

from digestive tract: nausea, vomiting, dyspepsia, diarrhea, a constipation, a meteorism, a digestive tract discomfort/pain, feeling of overpopulation of a stomach, disturbance from a stomach, swelling, an eructation, lack of appetite, abdominal pain, intestinal impassability, an intestines ulcer, insufficiency of a gastroesophageal sphincter, a bezoar, dryness in a mouth, a hyperplasia of gums, a dysphagy.

from a liver and biliary tract: abnormal liver function, tranzitorny increase in activity of enzymes of a liver, jaundice, intra hepatic cholestasia, increase in level of a γ-glutamiltranspeptidaza.

from kidneys and an urinary system: a polyuria, a dysuria, patients with a renal failure have a deterioration in function of kidneys, increase in frequency of urination, increase in number of daily removal of urine, a nocturia.

from a metabolism, metabolism: a hyperglycemia (especially at patients with diabetes).

from nervous system: headache, migraine, dizziness / vertigo, tremor, steam/di/hypesthesia, hyperesthesia, sleep disorders, insomnia, drowsiness.

from mentality: feeling of uneasiness, change of mood, nervousness.

from a cardiovascular system: tachycardia, heart consciousness, arterial hypotension (symptomatic and orthostatic), swell, a vazodilatation, hyperaemia, collapse, a stethalgia (including typical attacks of stenocardia), a myocardial infarction, an erythremegalia, especially in an initiation of treatment, a loss of consciousness.

from blood and lymphatic system: change of indicators of a blood count, anemia, a leukopenia, thrombocytopenia (sometimes with manifestation of a purpura), a trombotichesky mikroangiopatiya, an agranulocytosis.

from the immune system: reactions of hypersensitivity, including: rashes, an itching, urticaria, a face edema, allergic swell / a Quincke's disease (including a laryngeal edema), anaphylactic/anaphylactoid reactions.

from skin and hypodermic cellulose: rashes, an itching, urticaria, a face edema, an erythema, Mitchell's disease, skin hypersensitivity reactions, such as itching, dieback, dropsies of cutaneous and mucous membranes, Eden or peripheral the Eden, not caused by heart failure or increase in body weight, photosensitivity, a photodermatitis, a purpura, exfoliative dermatitis, a toxic epidermal necrolysis (Lyell's disease).

from a musculoskeletal system and connective tissue: myalgia, an arthralgia, muscular spasms, swell joints.

from the reproductive system and function of mammary glands: erectile dysfunction, a gynecomastia (at elderly men).

General disturbances: the general weakness, an indisposition, increased fatigue, apathy, the increased sweating, a fever, nonspecific pain, at prolonged use is possible fever.

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At the patients with malignant arterial hypertension and a hypovolemia who are on a hemodialysis the considerable lowering of arterial pressure owing to a vazodilatation can be observed.

Expiration date.

2 years.

Storage conditions.

to Store

in original packing at a temperature not above 25 °C. to store out of children's reach.

Packing.

On 10 tablets in blister strip packaging; on 5 blister strip packagings in a pack.

Category of release.

According to the prescription.

Producer.

Chao's

"pharmaceutical "darnitsa".

Location of the producer and its address of the place of implementation of activity.

Ukraine, 02093, of cues, st. Boryspil, 13.