Наклофен®

General characteristics. Structure:

Active ingredient: 50 mg of diclofenac of sodium

Excipients: fat firm.

Non-steroidal anti-inflammatory drug with the expressed antiinflammatory and analgeziruyushchy effect.

Pharmacological properties:

Pharmacodynamics. Diclofenac is the non-steroidal anti-inflammatory drug (NPVP) 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, puffiness of joints that improves a functional condition of joints. At injuries, in the postoperative period diclofenac reduces pain and inflammatory hypostasis. As all 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. Absorption. Diclofenac is quickly soaked up after rectal administration. The maximum serumal concentration (Cmax) are reached (TCmax) in 1 hour. At a rectal way of introduction meal does not influence absorbability of diclofenac.

Distribution. 99% of the absorbed diclofenac contact proteins of plasma, generally albumine. Diclofenac actively gets into synovial fluid where reaches 60 - 70% of serumal concentration. In 3-6 hours after use of concentration of active agent and metabolites in synovial fluid is higher, than in serum. Diclofenac from synovial fluid is removed more slowly, than from blood serum.

Metabolism and removal. The elimination half-life (T ½) diclofenac makes 1 - 2 hour.

Diclofenac is almost completely metabolized in a liver, is preferential by a hydroxylation and a metoksilirovaniye.  The fermental P450 CYP2C9 system takes part in metabolism of drug. Pharmacological activity of metabolites is lower, than diclofenac. T ½ of plasma – 2 hours. About 70% of the entered dose are removed in the form of pharmacological inactive metabolites by 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 (the clearance of creatinine (CC) 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, and also at elderly patients pharmacokinetic parameters of diclofenac do not change.

Indications to use:

Diseases at which achievement of bystry antiinflammatory or analgetic effect is required:

• inflammatory diseases of a musculoskeletal system (pseudorheumatism, seronegative spondylarthritis, juvenile chronic arthritis, arthritises of other etiology);
• degenerative diseases of a musculoskeletal system (osteoarthritis);
• microcrystallic arthritises (gouty arthritis, pseudo-gouty arthritis);
• rheumatic defeat of soft tissues;
• periarthritis, bursitis, miositis, tendinitis, synovitis;
• other inflammatory diseases of skeletal and muscular system which are followed by a pain syndrome.

As the analgetic Naklofen is used at injuries of soft tissues, in stomatology, after surgical interventions, at heavy migrenozny attacks, primary algodismenorea, an adnexitis, and also at renal or bilious colic.

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

Route of administration and doses:

Rektalno. At bad portability patients of peroral forms of diclofenac Naklofen it is possible to appoint rektalno in the form of suppositories in the corresponding doses. At a combination of several dosage forms (in addition to oral administration of drug) it is necessary to consider that the daily dose of diclofenac should not exceed 150 mg. The adult the initial dose makes 100 - 150 mg a day (on 1 suppository 2-3 times a day), depending on disease severity. To teenagers aged from 15 years is also more senior about 1 suppository no more than 2 times a day is recommended. The maintenance dose usually makes 100 mg a day (on 1 suppository 2 times a day). It is necessary to use a minimal effective dose minimum possible course.

Features of use:

Naklofen suppositories rectal should be applied with care: coronary heart disease (CHD), cerebrovascular diseases, дислипидемия / lipidemia, diabetes mellitus, diseases of peripheral arteries, smoking, KK 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 NPVP, frequent alcohol intake, heavy somatopathies, pregnancy the I-II trimester, the accompanying therapy by the following drugs: anticoagulants (for example, warfarin), antiagregant (for example, acetylsalicylic acid, klopidogret), fibrinolitik, peroral glucocorticosteroids (for example, Prednisolonum), selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline).

Use of diclofenac for pregnant women is possible only when the expected advantage for mother exceeds potential risk for a fruit. Diclofenac should not 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:

Classification of frequency of development of side effects (WHO):
very often   > 1/10
often             from> 1/100 to <1/10
infrequently          from> 1/1000 to <1/100
seldom             from> 1/10000 to <1/1000
very seldom  from <1/10000, including separate messages.

From the alimentary system: often - epigastric pain, nausea, vomiting, diarrhea, dyspepsia, a meteorism, anorexia, increase in activity of aminotransferases; seldom - gastritis, a proctitis, an exacerbation of hemorrhoids, 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. When using suppositories perhaps local irritation and an inflammation.

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, 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.

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).

From cardiovascular system: very seldom - heartbeat, 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 (a thicket - a GIT).

Reduces effect of hypotensive and somnolent medicines.

Increases probability of emergence of side effects of other NPVP and glucocorticosteroids (GKS) (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.

At a concomitant use with 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 hinolon increase 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 (The Nonspecific Ulcer Colitis (NUC), the Disease Krone) in an aggravation phase.
• Rectal bleedings, hemorrhoids, injury or inflammation of a rectum.
• Cerebrovascular bleeding.
• Hemophilia and other disturbances of coagulability.
• The expressed liver failure or an active disease of a liver.
• The expressed renal failure (KK 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 15 years).

Overdose:

At use of suppositories the overdose is improbable.  
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: the symptomatic therapy directed to elimination of increase in the arterial pressure (AP), a renal failure, spasms, irritations of a GIT, respiratory depression. The artificial diuresis and a hemodialysis are ineffective (considerable communication with proteins and intensive metabolism).

Storage conditions:

List B. At a temperature not higher than 25 degrees of S. Hranit in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Suppositories rectal on 50 mg. On 5 suppositories in a strip. 2 strips place in a pack cardboard together with the application instruction.