Composition:
per 1 capsule of the drug:
Active ingredients: diclofenac sodium - 50 mg, pyridoxine hydrochloride - 50 mg, thiamine hydrochloride - 50 mg, cyanocobalamin - 0.25 mg.
Excipients:
lysine hydrochloride - 110.75 mg, microcrystalline cellulose - 150 mg, anhydrous colloidal silicon dioxide - 4.0 mg, magnesium stearate - 5.0 mg.
The composition of the hard gelatin capsule No. 0:
case - titanium dioxide - 0.944 mg, red iron oxide - 0.177 mg, crimson dye [Ponso 4R] - 0.0527 mg, diamond black dye - 0.0034 mg, purified water - 8.555 mg, gelatin - 49.265 mg; cap - titanium dioxide - 0.74 mg, yellow iron oxide - 0.0925 mg, crimson dye [Ponceau 4R] - 0.0006 mg, purified water - 5.365 mg, gelatin - 30.8025 mg
Special conditions:
During the period of treatment with the drug, a systematic monitoring of the pattern of peripheral blood, liver and kidney function, and examination of feces for occult blood should be carried out.
Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when prescribing to patients with heart failure, as well as in the treatment of elderly patients taking diuretics, and patients who, for whatever reason, have a decrease in the volume of circulating blood (i.e. hours after extensive surgery). If diclofenac is prescribed in such cases, it is recommended that kidney function be monitored as a precaution.
If, after the use of the drug, an increase in the activity of “hepatic” transaminases is observed, or clinical symptoms of hepatotoxicity are noted (including nausea, fatigue, drowsiness, diarrhea, skin itching, jaundice), treatment should be stopped and should not be repeated in the future.
Diclofenac (like other non-steroidal anti-inflammatory drugs) can cause hyperkalemia.
Due to the negative effect on fertility, women who wish to become pregnant are not recommended to use the drug. In patients with infertility (including those undergoing examination), it is recommended to cancel the drug.
The effect of a medicinal product for medical use on the ability to drive vehicles, mechanisms
During the treatment period, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
Drug interaction:
With simultaneous use with Clodifen Neuro:
- the effect of diuretics decreases, while the use of potassium-sparing diuretics increases the risk of hyperkalemia;
- increased plasma concentration of digoxin, methotrexate, lithium and cyclosporin;
- the effects of antihypertensive and hypnotics are reduced;
- the risk of bleeding (usually gastrointestinal bleeding) increases during therapy with anticoagulants and thrombolytic agents (alteplase, streptokinase, urokinase);
- the likelihood of unwanted reactions of other non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticosteroids (gastrointestinal bleeding), the toxicity of methotrexate and the nephrotoxicity of cyclosporine are increased;
- the effect of hypoglycemic agents decreases;
- the antiparkinsonian effectiveness of levodopa decreases;
- cefamandol, cefoperazone, cefotetan, valproic acid increase the incidence of hypoprothrombinemia;
- ethanol, colchicine, corticotropin, serotonin reuptake inhibitors and St. John's wort preparations increase the risk of gastrointestinal bleeding;
- diclofenac enhances the action of drugs that cause photosensitivity.
Concomitant use with paracetamol increases the risk of nephrotoxic effects of diclofenac.
Acetylsalicylic acid reduces the concentration of diclofenac in the blood.
Cyclosporin and gold preparations increase the effect of diclofenac on the synthesis of prostaglandins in the kidneys, which increases the risk of nephrotoxicity.
Drugs that block tubular secretion increase the plasma concentration of diclofenac, thereby increasing its toxicity.
Ethanol dramatically reduces the absorption of thiamine (blood levels may decrease by 30%).
Long-term anticonvulsant treatment can lead to thiamine deficiency.
The use of colchicine and biguanides reduces the absorption of cyanocobalamin.
While taking the drug, it is not recommended to take multivitamin complexes, which include B vitamins.
Pharmacodynamics:
Clodifen Neuro is a combination of diclofenac with B vitamins. Diclofenac has a pronounced anti-inflammatory, analgesic and moderate antipyretic effect.
Pharmacodynamics:
The mechanism of action of diclofenac is associated with inhibition of the activity of cyclooxygenase, the main enzyme in the metabolism of arachidonic acid, which is a precursor of prostaglandins, which play a major role in the pathogenesis of inflammation, pain, and fever.
Thiamine (vitamin B1) in the human body as a result of phosphorylation processes turns into cocarboxylase, which is a coenzyme of many enzyme reactions. Vitamin B1 plays an important role in carbohydrate, protein and fat metabolism. Actively involved in the processes of nervous excitation in synapses.
Pyridoxine (vitamin B6) is necessary for the normal functioning of the central and peripheral nervous system. In phosphorylated form it is a coenzyme in the metabolism of amino acids (decarboxylation, transamination). It acts as a coenzyme of the most important enzymes that act in nerve tissues.
Cyanocobalamin (vitamin B12) is necessary for the normal blood formation and maturation of red blood cells, and is also involved in a number of biochemical reactions that ensure the vital activity of the body - in the transfer of methyl groups, in the synthesis of nucleic acids, protein, in the exchange of amino acids, carbohydrates, lipids.
Pharmokinetics:
Suction and distribution.
The absorption of diclofenac is fast and complete, food slows down the absorption rate by 1-4 hours and reduces the maximum concentration by 40%. After oral administration of 50 mg, the maximum concentration (Cmax) of 1.4 μg / ml is reached after 2-3 hours. The plasma concentration is linearly dependent on the dose administered.
Changes in the pharmacokinetics of diclofenac against the background of repeated administration are not observed, do not cumulate.
Bioavailability is 50%. The binding of diclofenac to plasma proteins is more than 99% (most of it binds to albumin). Penetrates into the synovial fluid; the maximum concentration in the synovial fluid is observed 2-4 hours later than in plasma. The half-life from the synovial fluid is 3-6 hours (the concentration of the active substance in the synovial fluid 4-6 hours after administration of the drug is higher than in plasma, and remains higher for another 12 hours).
Thiamine and pyridoxine are absorbed in the upper small intestine. The absorption of cyanocobalamin depends to a large extent on the presence of an internal factor in the body (in the stomach and upper part of the small intestine), in the future, the delivery of vitamin in the tissue is determined by the transport protein transcobalamin.
The vitamins that make up Clodifen Neuro are water-soluble, which eliminates the possibility of their cumulation in the body.
Metabolism. Diclofenac metabolism occurs in the liver, 50% of the active substance is metabolized during the "first passage" through the liver. Metabolism occurs as a result of repeated or single hydroxylation and conjugation with glucuronic acid. The enzyme system of cytochrome P450, the CYP2C9 isoenzyme, takes part in the metabolism of the drug. The pharmacological activity of metabolites is lower than diclofenac. The systemic clearance is 350 ml / min, the distribution volume is 550 ml / kg.
Thiamine and pyridoxine are metabolized in the liver. The degree of absorption depends on the dose, with an overdose, the excretion of thiamine and pyridoxine through the intestine significantly increases. Cyanocobalamin metabolism occurs in the liver.
Breeding.
The half-life of diclofenac from plasma is 2 hours. 65% of the administered dose is excreted in the form of metabolites by the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted in the form of metabolites with bile. In patients with severe renal failure (creatinine clearance less than 10 ml / min), excretion of metabolites with bile increases, while there is no increase in their concentration in the blood.
In patients with chronic hepatitis or compensated liver cirrhosis, the pharmacokinetic parameters of diclofenac do not change. Diclofenac passes into breast milk.
Thiamine and pyridoxine are excreted by the kidneys (about 8-10% - unchanged).
Cyanocobalamin is excreted mainly with bile, the degree of excretion by the kidneys is variable - from 6 to 30%.
Indications:
- pain with inflammations of a non-rheumatic nature (after injuries, surgical and dental interventions; with gynecological diseases - primary algodismenorrhea, adnexitis; with inflammatory diseases of the ENT organs - pharyngitis, tonsillitis, otitis media);
- inflammatory and degenerative diseases of the joints and spine (chronic polyarthritis, osteoarthrosis, spondylarthrosis);
- neuritis and neuralgia (cervical syndrome, lumbago, sciatica);
- acute gouty arthritis.
Contraindications:
- Hypersensitivity to the components of the drug (including other NSAIDs);
- peptic ulcer of the stomach and duodenum in the acute phase;
gastrointestinal bleeding;
- intracranial bleeding;
- a complete or incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including history);
- blood formation disorders;
- severe liver failure;
- active liver disease;
- severe renal failure (creatinine clearance less than 30 ml / min);
- progressive kidney disease;
- severe heart failure;
- the period after coronary artery bypass grafting;
- chronic heart failure IV functional class according to NYHA.
- confirmed hyperkalemia;
- hemostatic disorders (including hemophilia);
- inflammatory bowel disease in the acute phase;
- pregnancy and lactation;
- age up to 18 years (effectiveness and safety have not been established).
Carefully:
Peptic ulcer of the stomach and duodenum, ulcerative colitis, Crohn's disease in remission; a history of liver disease; hepatic porphyria; chronic liver failure; chronic heart failure (I-III functional class according to NYHA); arterial hypertension; a significant decrease in the volume of circulating blood (including after extensive surgery); elderly patients (including those receiving diuretics, debilitated patients with low body weight); bronchial asthma; concomitant use of glucocorticosteroids (including prednisone), anticoagulants (including warfarin), antiplatelet agents (including ASA, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine sertraline); cardiac ischemia; cerebrovascular disease; dyslipidemia / hyperlipidemia; diabetes; peripheral artery disease; smoking; chronic renal failure (creatinine clearance 30 - 60 ml / min); the presence of Helicobacter pylori infection; prolonged use of NSAIDs; alcoholism; severe somatic diseases.
Use during pregnancy and during breastfeeding
The use of the drug during pregnancy and during breastfeeding is contraindicated.
Overdose:
Symptoms: vomiting, bleeding from the gastrointestinal tract (GIT), epigastric pain, diarrhea, dizziness, tinnitus, lethargy, cramps; rarely - increased blood pressure, acute renal failure, hepatotoxic effect, respiratory depression, coma.
Treatment: gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating the increase in blood pressure, impaired renal function, seizures, gastrointestinal irritation, respiratory depression. Forced diuresis, hemodialysis are ineffective (due to a significant connection with proteins and intense metabolism).
Side effects:
The frequency of adverse reactions is presented in accordance with the WHO classification: often - 1-10%; infrequently - 0.1-1%; rarely - 0.01-0.1%; very rarely - less than 0.001%, including individual messages.
From the digestive system: often - abdominal pain, bloating, diarrhea, nausea, constipation, flatulence, increased activity of liver enzymes, peptic ulcer with possible complications (bleeding, perforation), gastrointestinal bleeding; rarely - vomiting, jaundice, melena, blood in the stool, damage to the esophagus, aphthous stomatitis, dry mucous membranes (including the mouth), hepatitis (possibly fulminant), liver necrosis, cirrhosis, hepatorenal syndrome, changes in appetite, pancreatitis, cholecystopancreatitis , pricks.
From the hemopoietic organs: rarely - anemia (including hemolytic and aplastic anemia), leukopenia, thrombocytopenia, eosinophilia, agranulocytosis, thrombocytopenic purpura.
From the side of the central nervous system: often - headache, dizziness; rarely - sleep disturbance, drowsiness, depression, irritability, aseptic meningitis (more often in patients with systemic lupus erythematosus and other systemic diseases of the connective tissue), cramps, general weakness, disorientation, nightmares, a feeling of fear.
From the sensory organs: often - tinnitus; rarely - blurred vision, diplopia, taste disorder, reversible or irreversible hearing loss, scotoma.
From the respiratory system: rarely - cough, bronchospasm, laryngeal edema, pneumonia.
On the part of the cardiovascular system: rarely - increased blood pressure, heart failure, extrasystole, chest pain, myocardial infarction.
From the urinary system: often - fluid retention; rarely - nephrotic syndrome, proteinuria, oliguria, hematuria, interstitial nephritis, papillary necrosis, acute renal failure, azotemia.
Dermatological reactions: often - itchy skin, skin rash; rarely - alopecia, urticaria, eczema, toxic dermatitis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), increased photosensitivity, small-scale hemorrhages, bullous rashes.
Allergic reactions: rarely - anaphylactoid reactions, anaphylactic shock, swelling of the lips and tongue, allergic vasculitis.
Other: rarely - worsening of the course of infectious processes.
Ways of application:
To reduce the risk of adverse events from the gastrointestinal tract, the minimum effective dose should be used with the minimum possible short course.
The drug should be taken orally during meals, without chewing and drinking plenty of fluids.
The drug is prescribed 1 capsule 3 times a day at the beginning of treatment, as a maintenance dose, 1 capsule 1-2 times a day. The duration of therapy is determined by the doctor and depends on the nature and severity of the disease.
