Pharmacological properties

Pharmacodynamics

Diklofenak-darnitsa contains sodium diclofenac — nonsteroid connection with the expressed antirheumatic, anti-inflammatory, analgeziruyushchy and febrifugal action. oppression of biosynthesis of prostaglandins is considered the main mechanism of effect of diclofenac. prostaglandins play an important role in genesis of inflammation, pain and fever.

In rheumatic diseases the anti-inflammatory and analgetic properties of medicine cause clinical effect which is characterized by considerable reduction of expressiveness of such symptoms and complaints as a rest pain and at the movement, morning constraint, puffiness of joints, also improvement of function of joints.

In vitro sodium diclofenac in concentration, equivalent subjects which are reached at treatment of patients does not oppress biosynthesis of proteoglycans of cartilaginous tissue.

At the posttraumatic and postoperative inflammatory phenomena diclofenac quickly relieves pain (as at rest, and at the movement), reduces inflammatory hypostasis and hypostasis of a postoperative wound.

Conducted clinical trials allowed to reveal considerable analgetic effect of medicine at a moderate and severe pain syndrome of not rheumatic genesis. Clinical trials also gave the chance to establish that diclofenac is capable to eliminate pain and to reduce expressiveness of blood loss at primary dysmenorrhea.

Diclofenac, besides, showed medical effect at migraine attacks.

Pharmacokinetics

Absorption. After intake active ingredient — diclofenac, is quickly and completely soaked up. Food reduces the absorption speed, however amount of active ingredient which is absorbed, does not change.

After single application of diclofenac inside in a dose of 50 mg of the C _max is reached approximately in 2 h and makes 1.5 mkg/ml (5 µmol/l). The amount of the absorbed active ingredient is linearly proportional to a dose.

Passing of a tablet through a stomach slows down if medicine to accept in time or after a meal (in comparison with reception to food) however amount of the absorbed diclofenac does not change. As about a half of a dose of diclofenac is metabolized during the first passing through a liver (effect of the first passing), AUC after oral or rectal administration makes about a half from the area in case of parenteral administration of an equivalent dose. At observance of the recommended interval of dosing of accumulation of medicine it is not observed.

are similar to

Concentration of medicine in blood plasma which are reached at children at ekvivalenty doses (body weight mg/kg) noted at adults.

absorption begins

After introduction of 75 mg of diclofenac by an injection immediately, and average C _max in blood plasma which make about 2.5 mkg/ml (8 µmol/l), is reached in 20 min. The volume of absorption can linearly depend on dose size.

In case 75 mg of diclofenac need to be entered by infusion during 2 h, average C _max in blood plasma makes about 1.9 mkg/ml (5.9 µmol/l). Shorter time of infusion causes higher rate of the C _max in blood plasma while longer infusions result in the concentration proportional to an infusion indicator in 3–4 h. After an injection in oil or reception of gastroresistant tablets, or application of suppositories concentration in blood plasma quickly decreases right after achievement of peak level.

after in oil or in/in introductions it is approximately twice more

AUC, than after oral or rectal administration as about a half of active substance is metabolized during the first passing through a liver (effect of the first passing) in case the medicament is administered in the oral or rectal way.

Pharmacokinetic properties do not change after repeated introduction. At observance of the recommended intervals of dosing of accumulation of medicine it is noted.

Distribution. 99.7% of diclofenac contact blood plasma proteins, mainly albumine (99.4%). The possible volume of distribution is 0.12-0.17 l/kg. Diclofenac gets into synovial fluid where reaches the C _max in 3–6 h. In 2 h after achievement of peak concentration in blood plasma the levels of active agent are already higher in synovial fluid, than in blood plasma, and remain high up to 12 h

Biotransformation. Biotransformation of diclofenac occurs partially by a glyukuronidation of an initial molecule, but mainly by single and repeated hydroxylation and a metoksilirovaniye that leads to formation of several phenolic metabolites (3’ - hydroxy, 4 ’-hydroxy, 5 hydroxies, 4’, 5-digidroksi- and 3 '-hydroxies-4 '-metoksi-diclofenac), the majority of which is converted into glyukuronidovy conjugates. Two of these phenolic metabolites biologically active, however to a lesser extent, than diclofenac.

Elimination. The general system clearance of diclofenac in blood plasma is 263±56 ml/min. (average value ± a standard deviation). Terminal the T _½ makes 1–2 h of blood plasma 4 metabolites, including 2 active, also have short T _½ from blood plasma. T _½ one of metabolites, 3 '-hydroxies-4 of '-metoksi-diclofenac, longer; however this metabolite is actually inactive.

About 60% of the accepted dose are removed by

with urine in the form of glyukuronidny conjugates of an initial molecule and metabolites, the majority of which also turns into glyukuronidny conjugates. Less than 1% are removed in the form of not changed substance. The remains of a dose are removed in the form of metabolites with bile.

Pharmacokinetics at different groups of patients. Significant differences in absorption, metabolism or removal of medicine depending on age of patients are noted.

accumulation of not changed active ingredient is impossible for

At patients with a renal failure, proceeding from kinetics of a single dose if to observe the usual scheme of application. At clearance of creatinine of 10 ml/min. the calculated stationary concentration in blood plasma of hydroxymetabolites are about 4 times higher, than at healthy faces. Thus, metabolites are finally removed with bile.

At patients with chronic hepatitis or the compensated cirrhosis kinetics and metabolism of diclofenac same, as well as at patients without liver diseases.

Indication

Tablet. inflammatory and degenerative forms of rheumatic diseases (the pseudorheumatism ankylosing a spondylitis, an osteoarthrosis, spondylarthrites).

Pain syndrome from a backbone.

Not joint rheumatism.

Bad attacks of gout.

Posttraumatic and postoperative pain syndrome which is followed by inflammation and hypostases, for example after dental and orthopedic interventions.

Gynecologic diseases which are followed by a pain syndrome and inflammation, for example primary dysmenorrhea or adnexitis.

As supportive application at a serious inflammatory illness of the ENT organs which are followed by feeling of pain, for example at a pharyngotonsillitis, otitis. According to the general therapeutic principles a basic disease it is necessary to treat means of basic therapy. Fever in itself is not the indication to use of medicine.

Solution for injections. Drug at introduction in oil is intended for treatment:

inflammatory and degenerative forms of rheumatism, pseudorheumatism, ankylosing spondylitis, osteoarthrosis, spondylarthritis, vertebralny pain syndrome, not articulate rheumatism;

bad attacks of gout;

renal and biliary colic;

pain and hypostasis after injuries and operations;

heavy attacks of migraine.

Drug at introduction in a look in/in infusions is intended to

for treatment or prevention of postoperative pain.

Use

Tablet. the mode of dosing is set individually taking into account indications and weight of a state. to accept diclofenac-darnitsa inside, tablets to swallow, without chewing, after a meal, washing down with enough water.

Medicine should be applied in minimal effective doses during the shortest span, considering problems of treatment at each patient separately.

Adult. The initial dose usually makes 100–150 mg/days. At not expressed symptoms and also at long therapy there is enough dose of 75-100 mg/days. To distribute a daily dose on 2–3 receptions. In order to avoid night pain or morning constraint the treatment by medicine can be added with purpose before going to bed of the rectal suppositories containing diclofenac. The daily dose should not exceed 150 mg.

At primary dysmenorrhea a daily dose should be selected individually, usually it makes 50–150 mg. The initial dose can be 50–100 mg, but in need of it it is possible to raise during several menstrual cycles to maximum which makes 200 mg/days. Use of medicine should be begun after emergence of the first painful symptoms and to continue several days depending on dynamics of regression of symptoms.

Children. Tablets in a dose of 25 mg can be applied at children from 8-year age (with body weight not less than 25 kg) up to 18 years on doctor's orders in a dose of 0.5-2 mg/kg of body weight depending on weight of symptoms: to divide this dose into 2–3 receptions.

For example, for the child with the body weight of 30 kg the daily dose can make 15–60 mg. Proceeding from this range, the child can appoint 2 tablets on 25 mg 2 times a day.

daily dose can be raised by

At treatment of a juvenile pseudorheumatism to 3 mg/kg of body weight — the maximum daily dose.

not to exceed the maximum daily dose — 150 mg.

Patients of advanced age. Though at patients of advanced age the pharmacokinetics of medicine does not worsen to any clinically significant degree, NPVP should be applied with extra care at persons who, as a rule, are more inclined to development of undesirable reactions. Especially or with a low indicator of body weight it is recommended to apply minimal effective doses to the weakened patients of senile age, also patients need to be examined regarding gastrointestinal bleedings at treatment of NPVP.

Solution for injections. Drug should be used in the lowest recommended doses during the shortest span, considering problems of treatment at each patient separately.

Drug Diklofenak-Darnitsa, solution for injections not to apply more than 2 days. In case of need treatment can be continued by the tablets Diklofenak-Darnitsa.

In oil injection. For the purpose of prevention of damage of nervous or other tissues to the place of an injection it is necessary to carry out the following rules.

Dose usually makes 75 mg (1 ampoule) a day which should be entered by a deep injection into the upper external sector of a big gluteus. In hard cases it is possible to raise a daily dose to 2 injections on 75 mg between which it is necessary to sustain an interval in several hours (on 1 injection in each buttock). As an alternative of 75 mg it is possible to combine with other dosage forms of the medicine Diklofenak-Darnitsa (for example tablets) to the general maximum total daily dose of 150 mg.

in the conditions of a migraine attack the clinical experience is limited to cases with initial application of 1 ampoule of 75 mg, it is necessary to enter a dose at once after application of diklofenaksoderzhashchy suppositories on 100 mg on the same day (in case of need). The general daily dose should not exceed 175 mg in the first day.

do not have

available data on use of medicine for treatment of attacks of migraine more, than 1 day.

In/in infusion. Diklofenak-Darnitsa, solution for injections, it is not necessary to enter in the form of a bolyusny injection.

Just before the beginning of infusion of Diklofenak-Darnitsa, depending on its necessary duration, 1 ampoule of medicine should be parted in 100–500 ml 0.9% of solution of sodium of chloride or 5% of solution of glucose, buferizirovanny with sodium bicarbonate solution for injections (0.5 ml of 8.4% of solution or 1 ml of 4.2% or the corresponding volume of other concentration) which was taken from just open container. It is possible to use only transparent solutions. If in solution there are crystals or a deposit, it cannot be applied to infusion.

two alternative modes of medicament dosing Diklofenak-Darnitsa, solution for injections Are recommended to

.

For treatment of moderate and heavy postoperative pain of 75 mg needs to be entered continuously of 30 min. to 2 h. In case of need treatment can be repeated in 4–6 h, but the dose should not exceed 150 mg/days

For prevention of postoperative pain through 15 min. — 1 h after surgical intervention it is necessary to enter a load dose of 25-50 mg, after that it is necessary to perform continuous infusion about 5 mg/h to the maximum daily dose of 150 mg.

Patients of advanced age. Though at patients of advanced age the pharmacokinetics of medicine does not worsen to any clinically significant degree, NPVP should be applied with care at such persons who, as a rule, are more inclined to development of undesirable reactions. In particular, the weakened patients of advanced age or with a low indicator of body weight are recommended to apply the lowest effective doses (see. Special INSTRUCTIONS); also patients need to be examined regarding gastrointestinal bleedings at treatment of NPVP.

Recommended maximum daily dose of the medicine Diklofenak-Darnitsa makes 150 mg.

Contraindication

Tablet. hypersensitivity to active ingredient or any other components of medicine.

Diklofenak-Darnitsa, as well as other NPVP, it is contraindicated to patients who in response to use of acetylsalicylic acid or other NPVP have attacks OH, urticaria or sharp rhinitis, polyps of a nose and other allergic symptoms.

III pregnancy trimester.

Acute ulcer of stomach or intestines; gastrointestinal bleeding or perforation.

Inflammatory bowel diseases (Crohn's disease or ulcer colitis).

Heavy liver failure (class C on Chaylda — I Drink, cirrhosis or ascites).

Heavy renal failure (clearance of creatinine of 30 ml/min.).

Stagnant heart failure (NYHA II–IV).

an ischemic heart disease at patients with stenocardia, the postponed myocardial infarction.

Cerebrovascular diseases at the patients who had a stroke or having episodes of the tranzitorny ischemic attacks.

Disease of peripheral arteries.

Treatment of postoperative pain after operation of coronary shunting (or uses of the cardiopulmonary bypass).

Bleeding or perforation of a GIT in the anamnesis which are connected with the previous treatment of NPVP.

Active form of a peptic ulcer / bleeding or a recurrent peptic ulcer / bleeding in the anamnesis (two or more separate episodes of the established ulcer or bleeding).

Solution for injections. The known hypersensitivity to active ingredient, metabisulphite or any other components of medicine.

As well as other NPVP, diclofenac it is also contraindicated to patients who have an application of an ibuprofen, acetylsalicylic acid or other NPVP provokes an attack OH, a Quincke's disease, a small tortoiseshell or sharp rhinitis.

Bleeding or perforation of a GIT in the anamnesis connected with the previous treatment of NPVP.

Active form of a peptic ulcer / bleeding or a recurrent peptic ulcer / bleeding in the anamnesis (two or more separate episodes of the established ulcer or bleeding).

Inflammatory bowel diseases (for example Crohn's disease or ulcer colitis).

Liver failure.

Renal failure.

Stagnant heart failure (NYHA II–IV).

an ischemic heart disease (stenocardia, the postponed myocardial infarction).

Cerebrovascular diseases at the patients who had a stroke or having episodes of the passing ischemic attacks.

Disease of peripheral arteries.

Treatment of perioperatsionny pain at aortocoronary shunting (or use of the cardiopulmonary bypass).

High risk of developing postoperative bleedings, not fibrillation, violations of a hemostasis, hemopoietic violations or cerebrovascular bleedings.

III pregnancy trimester.

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In this dosage form medicine is contraindicated to children.

are contraindicated to

In/in infusion at:

simultaneous application of NPVP or anticoagulant (including low doses of heparin);

hemorrhagic diathesis in the anamnesis or the confirmed/suspected cerebrovascular bleeding;

surgical interventions with high risk of bleeding;

OH in the anamnesis;

a moderate or heavy renal failure (creatinine level in blood plasma of 160 mmol/l);

a hypovolemia or dehydration of various genesis.

Side effects

Category of frequency of undesirable reactions, starting with the most frequent, is defined by

thus: very often (1/10); often (≥1/100, 1/10); infrequently (≥1/1000, 1/100); seldom (≥1/10,000, 1/1000); very seldom (1/10,000); frequency is unknown (it is impossible to estimate on the available data).

by

provided undesirable effects Below, including cases about which it was reported on condition of short-term or prolonged use of medicine.

from blood and lymphatic system: very seldom — thrombocytopenia, a leukopenia, anemia (including hemolytic anemia and aplastic anemia), the Agranulocytosis.

from the immune system: seldom — hypersensitivity, anaphylactic and anaphylactoid reactions (including arterial hypotension and shock); very seldom — a Quincke's disease (including a face edema).

from mentality: very seldom — a disorientation, a depression, insomnia, irritability, nightmares, mental disorders.

from nervous system: often — a headache, dizziness; seldom — drowsiness, fatigue; very seldom — paresthesia, violations of memory, a spasm, uneasiness, a tremor, aseptic meningitis, frustration of flavoring feelings, a stroke; frequency is unknown — confusion of consciousness, a hallucination, violation of sensitivity, a general malaise.

from an organ of sight: very seldom — a disorder of vision, misting of sight, a diplopia; frequency is unknown — an optic neuritis.

from an organ of hearing and a vestibular mechanism: often — vertigo; very seldom — a ring in ears, a hearing disorder.

from a cardiovascular system: very seldom — heart consciousness, a stethalgia, heart failure, a myocardial infarction, AG, arterial hypotension, a vasculitis.

from the respiratory system, bodies of a thorax and mediastinum: seldom — OH (including dispnoe); very seldom — a bronchospasm, a pneumonitis.

from a GIT: often — nausea, vomiting, diarrhea, dyspepsia, an abdominal pain, a meteorism, anorexia; seldom — gastritis, gastrointestinal bleedings (vomiting with blood impurity, a melena, diarrhea with blood impurity), ulcer of stomach and intestines, followed by bleeding or perforation (sometimes with a lethal outcome, especially at patients of advanced age); very seldom — colitis (including hemorrhagic colitis and exacerbation of ulcer colitis or Crohn's disease), a lock, stomatitis (including a stomacace), a glossitis, disorder of function of a gullet, a diafragmopodobny intestinal stenosis, pancreatitis.

from a liver and biliary tract: often — increase in level of Transaminases, is rare — hepatitis, jaundice, an abnormal liver function; very seldom — instant hepatitis, liver necrosis, a liver failure.

from skin and hypodermic cellulose: often — rashes; seldom — a small tortoiseshell; very seldom — rashes in the form of bubbles, eczema, an erythema, a multiformny erythema, Stephens's syndrome — Johnson, a Lyell's disease (toxic epidermal necrolysis), exfoliative dermatitis, a hair loss, reaction of photosensitivity, purple, including allergic, an itch.

from kidneys and an urinary system: very seldom — OPN, a hamaturia, a proteinuria, interstitial nephrite, a nephrotic syndrome, papillary necrosis of a kidney.

General violations: seldom — hypostases.

from the reproductive system and function of mammary glands: very seldom — impotence.

Diclofenac, especially in high doses (150 mg/days) and at prolonged use, can lead to increase in risk of emergence of arterial tromboembolic episodes (for example a myocardial infarction or a stroke).

General violations and violations in the injection site of medicine: a general malaise, reaction in the place of an injection, pain, hardening, hypostasis, necrosis in the place of an injection, abscess in the place of an injection.

Special instructions

General cautions concerning application npvp systemic action.

For reduction of risk of developing of a gastrointestinal ulcer, bleeding or perforation which can arise during any period of treatment of NPVP irrespective of their selectivity concerning TsOG-2 and even in the absence of symptoms harbingers or factors of predisposition in the anamnesis, it is necessary to apply minimal effective doses during the shortest period.

to Patients with violation from a digestive tract, an abnormal liver function or with suspicion of ulcer of stomach or intestines in the anamnesis this medicine it is necessary to apply only in case of the absolute indication and under careful control.

by

noted the increased risk of emergence of trombotichesky cardiovascular and cerebrovascular complications at use of certain selection TsOG-2 inhibitors. Now it is definitely not known whether such risk directly with COG-1/COG-2-selektivnostyyu of separate NPVP correlates.

can Appoint by

diclofenac to patients with considerable risk factors of the cardiovascular phenomena (for example AG, a lipidemia, diabetes, smoking) only after careful clinical assessment. As cardiovascular risks of diclofenac can increase with increase in a dose and duration of treatment, it needs to be applied during shorter span and in a minimal effective dose. It is necessary to reconsider periodically needs of the patient for use of diclofenac for relief of symptoms and the response to therapy. With care to apply at patients aged from 65 years.

Influence of NPVP on kidneys leads

to a delay of liquid and hypostases and/or AG therefore diclofenac should be applied with care at patients with violation from heart or other states at which there is a tendency to a liquid delay. With care to apply medicine at patients who at the same time apply diuretics or APF inhibitors or are subject to the increased risk of development of a hypovolemia.

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At application of NPVP, including diclofenac, it was reported about development of gastrointestinal bleeding, ulcer or perforation which can be lethal and can arise throughout treatment, with or without symptoms harbingers or heavy gastrointestinal frustration in the anamnesis. At patients of advanced age such complications have usually more serious consequences. In case of developing of gastrointestinal bleeding or an ulcer at patients who receive for treatment of Diklofenak-Darnitsa this medicine should be cancelled.

to

Very seldom in connection with application of NPVP it was reported about heavy reactions from skin (in certain cases — lethal), including exfoliative dermatitis, Stephens's syndrome — Johnson and a toxic epidermal necrolysis. The highest risk of emergence of such reactions at patients exists in an initiation of treatment, emergence of these reactions, as a rule, happens during the first month of treatment. Diklofenak-Darnitsa it is necessary to cancel at emergence of the first symptoms of rashes, damages of mucous membranes or any other signs of hypersensitivity.

System lupus erythematosus and the mixed diseases of connective tissue. At patients with a system lupus erythematosus and the mixed diseases of connective tissue the increased risk of developing aseptic meningitis can be observed.

As well as at use of all analgetics, at prolonged use of medicine for treatment of a headache the improvement or aggravation of symptoms is possible

(a headache because of excessive use of medicines). If the headache arises owing to excessive use of analgetics, it is not necessary to raise their dose, in such cases the treatment needs to be stopped. The headache owing to excessive use of medicines should be suspected at patients with frequent or daily attacks of a headache which arise, despite (or because of) regular use of analgetics.

As well as at application of other NPVP, allergic reactions (including anaphylactic/anaphylactoid reactions), even without preliminary use of diclofenac can seldom develop. As well as other NPVP, Diklofenak-Darnitsa thanks to the pharmakodinamichesky properties can mask signs and symptoms of an infection.

Caution

General. It is not necessary to apply at the same time Diklofenak-Darnitsa and other NPVP of systemic action, including selection TsOG-2 inhibitors as there are no confirmations concerning advantages of synergy action and also because of emergence of additional side effects.

Should apply with care medicine at patients of advanced age. In particular, physically weak patients of advanced age are recommended to appoint minimal effective doses or with insufficient body weight.

OH in the anamnesis. At patients with OH, seasonal allergic rhinitis, a rhinedema (for example nasal polyps), HOBL or persistent infections of a respiratory path (especially with the manifestations similar to symptoms of allergic rhinitis) at reception of NPVP more often than other patients, have such side effects as aggravation OH (so-called intolerance of analgetics or analgetic asthma), a Quincke's edema, urticaria. In this regard special measures (readiness for rendering emergency aid) are necessary for such patients. The above also concerns patients with allergic manifestations (for example rash, an itch, urticaria) at use of other medicines.

Influence on a digestive tract. As well as at application of other NPVP, careful medical control and extra care are necessary at prescription of medicine for patients with the symptoms indicating violations from a digestive tract or an ulcer, bleeding or perforation of a stomach or intestines in the anamnesis. The risk of developing of bleeding increases in a GIT at increase in a dose of NPVP and also at patients with an ulcer in the anamnesis, especially if there was a complication (bleeding or perforation), and at patients of advanced age. For reduction of risk of toxic impact on a digestive tract at such patients the treatment should be begun and supported in the lowest effective doses. For such patients and also for patients who need simultaneous use of the medicines containing the acetylsalicylic acid or other medicines increasing risk of harmful effects on a digestive tract it is necessary to consider the possibility of combination therapy using protective equipment (for example inhibitors of a proton pomp or mizoprostol). Patients with toxic influence on a digestive tract in the anamnesis, especially advanced age, have to report to the doctor about any unusual abdominal symptoms (especially about bleeding from a GIT). With care to appoint to the patients who are at the same time applying medicines which can increase risk of developing of an ulcer or bleeding (corticosteroids of systemic action, anticoagulants, antitrombotichesky medicines or selective serotonin reuptake inhibitors).

Influence on a liver. Patients with violation from a liver should provide constant medical observation as their state can worsen.

As well as at application of other NPVP, increase in level of one and more enzymes of a liver is possible

. It was observed very often at use of diclofenac, but very seldom was followed by manifestation of clinical symptoms. In most cases noted increase to limits. Increase in level of liver enzymes was followed by clinical manifestations of damage of a liver. This increase was, as a rule, reversible after medicine cancellation.

Should note

that Diklofenak-Darnitsa is recommended only for a short course of treatment (no more than 2 weeks). In case of prescribing of diclofenac to the long period a preventive measure is regular observation of function of a liver. Use of this medicine should be stopped if violation or deterioration in function of a liver is revealed if clinical signs or symptoms demonstrate development of a disease of a liver or there are other symptoms, for example, an eosinophilia, rash. Hepatitis can arise without prodromal symptoms.

to

Krom of increase in level of liver enzymes, it was seldom reported about heavy reactions from a liver, including jaundice and fulminantny hepatitis, necrosis of a liver and a liver failure which in certain cases were lethal.

With care to apply diclofenac at patients with a hepatic porphyria because of the probability of provoking of an attack.

Influence on kidneys. Prolonged use of high doses of NPVP often leads to developing of hypostases and AG.

Extra care should be observed to patients with violations from heart or kidneys, AG in the anamnesis, to elderly people, patients who at the same time apply the diuretics or medicines having considerable impact on function of kidneys and also to patients with significant reduction of volume of extracellular liquid, for example, before/after surgical interventions. When assigning in such cases of Diklofenaka-Darnitsa it is necessary to carry out monitoring of function of kidneys. After the therapy termination the condition of patients is usually normalized.

Influence on hematologic indicators. Diklofenak-Darnitsa it is recommended only for a short-term course of treatment. When prescribing this medicine to the long period it is recommended (as well as for other NPVP) to regularly control a gemogramma.

As well as other NPVP, diclofenac can temporarily inhibit aggregation of platelets therefore it is necessary to control carefully a condition of patients with violation of a hemostasis.

Diklofenak-Darnitsa contains lactose therefore it should not be applied at patients with rare hereditary forms of intolerance of a galactose, a lactose intolerance or a syndrome of glyukozo-galaktozny malabsorption.

during treatment should not take alcohol.

Use during pregnancy and feeding by a breast. Use of diclofenac for pregnant women is not studied. Researches on animals did not show any direct or indirect toxic impact on pregnancy, embryonic development, fetation, childbirth and/or post-natal development.

B I and the II trimester of pregnancy of Diklofenak-Darnitsa, a tablet enterosoluble, it is necessary to appoint only if the expected advantage for mother exceeds potential risk for a fruit and only in a minimal effective dose. As well as in case of application of other NPVP, medicine is contraindicated in the last trimester of pregnancy (oppression of sokratitelny ability of a uterus and premature closing of an arterial channel at a fruit are possible).

Inhibition of synthesis of prostaglandins can negatively affect pregnancy and/or development of an embryo/fruit. Data of epidemiological researches confirm the increased risk of abortions and/or risk of development of warm defects