Наклофен® WEDNESDAY

General characteristics. Structure:

Active ingredient: 100 mg of diclofenac of sodium.

Vspomogateln_e of substance: sucrose, cetyl alcohol, povidone, silicon dioxide colloid, anhydrous, magnesium stearate.

Cover: gipromelloza, dye ferrous oxide red (E172), titanium dioxide, macrogoal 6000, polysorbate 80, talc.

Non-steroidal anti-inflammatory drug with the expressed antiinflammatory, analgetic and febrifugal effect.

Pharmacological properties:

Pharmacodynamics. Diclofenac is non-steroidal anti-inflammatory drug, possessing analgeziruyushchy, antiinflammatory and febrifugal action.

The main mechanism of its action and side effects connected with it consist in not selective oppression of activity of enzyme of cyclooxygenase 1 and 2 (TsOG1 and TsOG2) that leads to disturbance of metabolism of arachidonic acid, decrease in synthesis of prostaglandins, prostacyclin and thromboxane. Synthesis of prostaglandins in kidneys, a mucous membrane of a stomach and synovial fluid decreases.

It is most effective at pains of inflammatory character. At rheumatic diseases antiinflammatory and analgeziruyushchy effect of diclofenac promotes considerable reduction of expressiveness of pain, morning constraint, a swelling of joints that improves a functional condition of a joint. At injuries, in the postoperative period diclofenac reduces pain and inflammatory hypostasis. As all non-steroidal anti-inflammatory drugs (NPVP), diclofenac has antiagregantny activity. In therapeutic doses diclofenac practically does not exert impact on a bleeding time. At prolonged treatment the analgeziruyushchy effect of diclofenac does not decrease.

Pharmacokinetics. As a result of the slowed-down drug release the maximum concentration (Cmax) in plasma is lower than that which is created at administration of medicine of short action; however it remains high after reception for a long time. Cmax - 0.5 mkg/ml, time necessary for achievement of the maximum concentration, (TCmax) - 5 h after reception of 100 mg of tablets of the prolonged action.

Concentration in plasma is in linear dependence on size of the entered dose.

Change of pharmacokinetics of diclofenac against the background of repeated introduction is not noted. Does not kumulirut at observance of the recommended interval between meals.

Bioavailability - 50%. Communication with proteins of plasma - more than 99% (the most part contacts albumine). Gets into breast milk, synovial fluid; Cmax in synovial fluid is observed on 2-4 h later, than in plasma. An elimination half-life (T1/2) from synovial fluid - 3-6 h (concentration of drug in synovial fluid in 4-6 h after its introduction are higher, than in plasma, and remain higher during 12 h).
50% of drug are exposed to metabolism during "the first passing" through a liver; the area under a curve "concentration – time" is twice less (AUC) after peroral administration of drug, than after parenteral administration of the same dose. Metabolism results from a repeated or single hydroxylation and a konjyugirovaniye with glucuronic acid. CYP2C9 isoenzyme also participates in drug metabolism. Pharmacological activity of metabolites is less, than diclofenac.

The system clearance makes 260 ml/min. of T1/2 of plasma - 1-2 h 60% of the entered dose are brought in the form of metabolites through kidneys; less than 1% are removed in not changed look, other part of a dose is removed in the form of metabolites with bile.

At patients with the expressed renal failure (clearance of creatinine less than 10 ml/min.) removal of metabolites with bile increases, at the same time increase in their concentration in blood is not observed.

At patients with chronic hepatitis or the compensated cirrhosis pharmacokinetic parameters do not change.

Indications to use:

• Inflammatory and degenerative diseases of a musculoskeletal system:
the pseudorheumatism, the psoriasis, juvenile chronic arthritis ankylosing a spondylarthritis (Bekhterev's Disease), gouty arthritis (at a bad attack it is more preferable to use high-speed dosage forms), arthritis at a disease of Reuters, rheumatic defeat of soft tissues, an osteoarthrosis of peripheral joints and a backbone, including with a radicular syndrome, a tendovaginitis, a periarthritis, a bursitis, a miositis, sinoviit).

• Pain syndrome of weak or moderate expressiveness: neuralgia, a mialgiya, a lumbar ishialgia, the posttraumatic pain syndrome which is followed   by an inflammation, postoperative pain, a headache, migraine (at a bad attack it is more preferable to use high-speed dosage forms), альгодисменорея, an adnexitis, a proctitis, a dentagra, renal and bilious colic.

• As a part of complex therapy of infectious and inflammatory diseases of an ear, a throat, a nose with the expressed pain syndrome (pharyngitis, tonsillitis, otitis).

• Feverish syndrome.

• Diclofenac is intended for symptomatic therapy and does not influence progressing of a disease.

Route of administration and doses:

Inside, it is necessary to swallow of tablets entirely, without chewing, washing down with enough water in time or after meal. 

Naklofen CP, tablets of the prolonged action, 100 mg it is necessary to use for long therapy.

The initial and supporting doses make 1 tablet a day.

If necessary Naklofen SR it is necessary to combine increase in a dose up to 150 mg a day with tablets or Naklofen's suppositories on 50 mg.

Features of use:

Naklofen SR it is necessary to apply with care: coronary heart disease, cerebrovascular diseases, дислипидемия / lipidemia, diabetes mellitus, diseases of peripheral arteries, smoking, clearance of creatinine less than 60 ml/min.; anamnestic data on development of a canker of digestive tract, existence of an infection of Helicobacter pylori, advanced age, long use of non-steroidal anti-inflammatory drugs (NPVP), frequent alcohol intake, heavy somatopathies, the induced porphyria, epilepsy, advanced age, a diverticulitis, general diseases of connecting fabric, considerable decrease in the volume of the circulating blood (VCB) (including after massive surgical intervention), elderly patients (it is appointed in lower doses) (including the receiving diuretics weakened patients and with low body weight), the accompanying therapy by the following drugs: anticoagulants (for example, warfarin), antiagregant (for example, acetylsalicylic acid, klopidogret), fibrinolitik, peroral glucocorticoids (for example, Prednisolonum), selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline). For decrease in risk of development of the undesirable phenomena from digestive tract it is necessary to use a minimal effective dose minimum possible course. Pregnancy I-II trimester.

Use of diclofenac for pregnant women is possible only when the expected advantage exceeds potential risk for a fruit. Diclofenac is not recommended to be used during the last trimester of pregnancy. In spite of the fact that diclofenac is found in breast milk in small amounts, its use during breastfeeding is not recommended.

During treatment reduction of speed of mental and motor reactions therefore it is necessary to abstain from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions is possible.

Side effects:

Often - 1-10%; sometimes - 0.1-1%; seldom - 0.01-0.1%; very seldom - less than 0.01%, including separate cases.

From the alimentary system: often - epigastric pain, abdominal spasms, nausea, vomiting, diarrhea, dyspepsia, a meteorism, anorexia, increase in activity of aminotransferases; seldom - gastritis, a proctitis, bleeding from the digestive tract (DT) (vomiting with blood, a melena, diarrhea with blood impurity), GIT ulcers (with or without bleeding or perforation), hepatitis, jaundice, an abnormal liver function; very seldom - stomatitis, a glossitis, dryness of mucous membranes (including a mouth), injuries of a gullet, diafragmopodobny strictures of intestines (nonspecific hemorrhagic colitis, an exacerbation of ulcer colitis or a disease Krone), a lock, pancreatitis, fulminant hepatitis).

From a nervous system: often - a headache, dizziness; seldom - drowsiness; very seldom - sensitivity disturbance, including paresthesias, dysmnesias, a tremor, spasms, alarm, cerebrovascular disturbances, aseptic meningitis, a disorientation, a depression, sleeplessness, night "nightmares", irritability, excitement, mental disturbances.

From sense bodys: often - вертиго; very seldom - a vision disorder (sight misting, a diplopia), a hearing disorder, a sonitus, disturbance of flavoring feelings.

From an urinary system: very seldom - an acute renal failure, a hamaturia, a proteinuria, intersticial nephrite, a nephrotic syndrome, a papillary necrosis, hypostases.

From bodies of a hemopoiesis: very seldom - thrombocytopenia, a leukopenia, an eosinophilia, hemolitic and aplastic anemia, an agranulocytosis.

Allergic reactions: anaphylactic/anaphylactoid reactions, including the expressed lowering of arterial pressure (ABP) and shock; very seldom - a Quincke's disease (including persons), in some cases a vasculitis.

From cardiovascular system: very seldom - heartbeat, tachycardia, premature ventricular contraction, a stethalgia, increase in the ABP, a vasculitis, heart failure, a myocardial infarction.

From respiratory system: seldom – cough, bronchial asthma (including an asthma); very seldom – a pneumonitis, throat hypostasis.

From integuments: often - skin rash; seldom - a small tortoiseshell; very seldom -  violent rashes, eczema, including multiformny and Stephens-Johnson's syndrome, a Lyell's disease, exfoliative dermatitis, an itch, a hair loss, a photosensitization, a purpura, including allergic.

Interaction with other medicines:

Increases concentration in plasma of digoxin, a methotrexate, drugs of lithium and cyclosporine.

Reduces effect of diuretics, against the background of kaliysberegayushchy diuretics the risk of development of a hyperpotassemia amplifies; against the background of anticoagulants, antiagregantny and thrombolytic medicines (an alteplaza, Streptokinasa, an urokinase) the risk of development of bleedings increases (more often than a GIT).

Reduces effect of hypotensive and somnolent medicines.

Increases probability of emergence of side effects of other NPVP and glucocorticosteroids (bleeding from a GIT), toxicity of a methotrexate and nephrotoxicity of cyclosporine.

Acetylsalicylic acid reduces concentration of diclofenac in blood. Simultaneous use with paracetamol increases risk of development of nefrotoksichny effects of diclofenac.

Hypoglycemic means – it can be observed hypo - or a hyperglycemia. At this combination of means control of concentration of glucose in blood is necessary.

Tsefamandol, цефоперазон, цефотетан, valproic acid and пликамицин increase the frequency of development of a prothrombinopenia.

Cyclosporine and drugs of gold increase influence of diclofenac on synthesis of prostaglandins in kidneys that is shown by increase in nephrotoxicity.
Selective serotonin reuptake inhibitors increase risk of development of bleedings from a GIT.

Co-administration with ethanol, colchicine, corticotropin and drugs of a St. John's Wort increases risk of development of bleedings in a GIT.

 

The medicines causing a photosensitization increase the sensibilizing effect of diclofenac to ultra-violet radiation.

The medicines blocking canalicular secretion increase concentration in diclofenac plasma, thereby, increasing its toxicity.

Antibacterial medicines from group of a hinolon - risk of development of spasms.

Contraindications:

• Hypersensitivity to diclofenac; a full or incomplete combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms and intolerance of acetylsalicylic acid and other NPVP (including in the anamnesis).
• The period after performing aortocoronary shunting.
• Erosive and ulcer changes of a mucous membrane of a stomach or 12-perstny gut, active gastrointestinal bleeding.
• Inflammatory diseases of intestines, in an aggravation phase (The Nonspecific Ulcer Colitis (NUC), the Disease Krone).
• Cerebrovascular bleeding or other bleedings and disturbances of a hemostasis.
• The expressed liver failure or an active disease of a liver.
• The expressed renal failure (clearance of creatinine less than 30 ml/min.),  including the confirmed hyperpotassemia, the progressing disease of kidneys.
• Dekompensirovanny heart failure.
• Oppression of a marrowy hemopoiesis.
• III trimester of pregnancy, breastfeeding period.
• Children's age (up to 18 years).

Overdose:

Symptoms: vomiting, nausea, abdominal pains, bleeding from a GIT, diarrhea, a headache, dizziness, a sonitus, a hyperexcitability, the hyperventilation phenomena with the increased convulsive readiness, spasms, at considerable overdose – an acute renal failure, a hepatotoxic action. 

Treatment: a gastric lavage, absorbent carbon, the symptomatic therapy  directed to elimination of increase in the ABP, a renal failure, spasms, irritations of a GIT, respiratory depression. The artificial diuresis, a hemodialysis are ineffective (considerable communication with proteins and intensive metabolism).

Storage conditions:

To store in the dry place, at a temperature not higher than 25 degrees of S. Hranit in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action, film coated on 100 mg. On 10 tablets in the blister. On 2 blisters in a pack cardboard together with the application instruction.