Clodifen neuro capsules, No. 30

• pain syndrome in inflammations of a non-rheumatic nature (after injuries, surgical and dental interventions; in gynecological diseases - primary algomenorrhea, adnexitis; in inflammatory diseases of the ENT organs - pharyngitis, tonsillitis, otitis media);

• inflammatory and degenerative diseases of the joints and spine (chronic polyarthritis, osteoarthritis, spondyloarthrosis);

• neuritis and neuralgia (cervical syndrome, lumbago, sciatica);

• acute gouty arthritis.

To reduce the risk of developing adverse events from the gastrointestinal tract, the minimum effective dose should be used in the smallest possible short course.

The drug should be taken orally with meals, without chewing and drinking plenty of liquid.

The drug is prescribed 1 capsule 3 times / day at the beginning of treatment, as a maintenance dose, 1 capsule 1-2 times / day. The duration of therapy is determined by the doctor and depends on the nature and severity of the disease.

Hard gelatin capsules, size No. 0, opaque, body from pinkish-red to brick-red, yellow cap; the contents of the capsules are a mixture of almost white to light pink powder with white agglomerates and particles.

1 caps.

diclofenac sodium 50 mg

pyridoxine hydrochloride (vit. B6) 50 mg

thiamine hydrochloride (vit. B1) 50 mg

cyanocobalamin (vit. B12) 0.25 mg

Excipients: lysine hydrochloride - 110.75 mg, microcrystalline cellulose - 150 mg, colloidal anhydrous silicon dioxide - 4 mg, magnesium stearate - 5 mg.

• 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;

• 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);

• hematopoietic disorders;

• severe liver failure;

• active liver disease;

• severe renal failure (CC less than 30 ml / min);

• progressive kidney disease;

• severe heart failure;

• period after coronary artery bypass grafting;

• chronic heart failure IV functional class according to NYHA;

• confirmed hyperkalemia;

• disorders of hemostasis (including hemophilia);

• inflammatory bowel disease in the acute phase;

• pregnancy;

• lactation period;

• age up to 18 years (efficacy and safety have not been established).

• Carefully

  Peptic ulcer and duodenal ulcer, ulcerative colitis, Crohn's disease in remission; history of liver disease; hepatic porphyria; chronic liver failure; chronic heart failure (NYHA functional class I-III); arterial hypertension; a significant decrease in the BCC (including after extensive surgical intervention); elderly patients (including those receiving diuretics, debilitated patients and those with low body weight); bronchial asthma; simultaneous administration of corticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); Ischemic heart disease; cerebrovascular diseases; dyslipidemia / hyperlipidemia; diabetes;peripheral arterial disease; smoking; chronic renal failure (CC 30-60 ml / min); presence of Helicobacter pylori infection; long-term use of NSAIDs; alcoholism; severe somatic diseases.

pharmachologic effect

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 of 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, is converted into cocarboxylase, which is a coenzyme of many enzymatic reactions. Vitamin B1 plays an important role in carbohydrate, protein and fat metabolism. It actively participates in the processes of conduction of nervous excitement in synapses.

Pyridoxine (vitamin B6) is essential 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). Acts as a coenzyme of the most important enzymes acting in nerve tissues.

Cyanocobalamin (vitamin B12) is necessary for normal hematopoiesis and erythrocyte maturation, and also participates 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.

Pharmacokinetics

Absorption 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 Cmax - 1.4 ?g / ml is achieved after 2-3 hours. Plasma concentration is linearly dependent on the size of the administered dose.

Changes in the pharmacokinetics of diclofenac against the background of repeated administration are not observed, does not cumulate.

Bioavailability is 50%. The binding of diclofenac to plasma proteins is more than 99% (most of it binds to albumin). Penetrates into synovial fluid; the maximum concentration in the synovial fluid is observed 2-4 hours later than in the plasma. T1 / 2 from synovial fluid 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 intrinsic factor in the body (in the stomach and upper part of the small intestine); further delivery of the vitamin to the tissue is determined by the transport protein transcobalamin.

The vitamins that make up Clodifen Neuro are water-soluble, which excludes the possibility of their accumulation in the body.

Metabolism. Diclofenac metabolism occurs in the liver, 50% of the active substance is metabolized during the 'first pass' through the liver. Metabolism occurs as a result of multiple or single hydroxylation and conjugation with glucuronic acid. The enzyme system of cytochrome P450, the isoenzyme CYP2C9, takes part in the metabolism of the drug. The pharmacological activity of metabolites is lower than that of diclofenac. Systemic clearance is 350 ml / min, Vd - 550 ml / kg.

Thiamine and pyridoxine are metabolized in the liver. The degree of absorption depends on the dose; in case of an overdose, the excretion of thiamine and pyridoxine through the intestine is significantly increased. Cyanocobalamin metabolism occurs in the liver.

Withdrawal

T1 / 2 of diclofenac from plasma - 2 hours. 65% of the administered dose is excreted as metabolites by the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted as metabolites in the bile. In patients with severe renal failure (creatinine clearance less than 10 ml / min), the excretion of metabolites in the bile increases, while an increase in their concentration in the blood is not observed.

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 in the bile, the degree of excretion by the kidneys is variable - from 6 to 30%.

Side effect

The incidence 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, the appearance of blood in the stool, damage to the esophagus, aphthous stomatitis, dry mucous membranes (including the mouth), hepatitis (possibly fulminant course), liver necrosis, cirrhosis, hepatorenal syndrome, changes in appetite, pancreatitis , cholecystopancreatitis, colitis.

From the side of hematopoiesis: 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), convulsions, general weakness, disorientation, nightmares, a feeling of fear.

From the senses: often - tinnitus; rarely - blurred vision, diplopia, taste disturbance, reversible or irreversible hearing loss, scotoma.

From the respiratory system: rarely - cough, bronchospasm, laryngeal edema, pneumonia.

From the side 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 - itching, skin rash; rarely - alopecia, urticaria, eczema, toxic dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), increased photosensitivity, small punctate hemorrhages, bullous rashes.

Allergic reactions: rarely - anaphylactoid reactions, anaphylactic shock, swelling of the lips and tongue, allergic vasculitis.

Others: rarely - worsening of the course of infectious processes.

Application during pregnancy and lactation

The use of the drug during pregnancy and during breastfeeding is contraindicated.

Due to the negative effect on fertility, the drug is not recommended for women wishing to become pregnant.

In patients with infertility (including those undergoing examination), it is recommended to cancel the drug.

Application for violations of liver function

Contraindications: severe renal failure (CC less than 30 ml / min); progressive kidney disease.

Application for impaired renal function

Contraindications: severe hepatic impairment; active liver disease.

special instructions

During the period of drug treatment, systematic monitoring of the peripheral blood picture, liver and kidney function, and fecal occult blood tests should be carried out.

Due to the important role of prostaglandins in maintaining renal blood flow, special care should be taken when prescribing patients with heart failure, as well as when treating elderly patients taking diuretics, and patients who, for any reason, have a decrease in BCC (incl. after extensive surgery). If diclofenac is prescribed in such cases, it is recommended to monitor renal function as a precautionary measure.

If, after using the drug, an increase in the activity of 'hepatic' transaminases is observed, or clinical symptoms of hepatotoxicity are noted (including nausea, fatigue, drowsiness, diarrhea, pruritus, jaundice), treatment should be discontinued and should not be repeated later.

Diclofenac (like other NSAIDs) can cause hyperkalemia.

Influence on the ability to drive vehicles and mechanisms

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms: vomiting, bleeding from the gastrointestinal tract, epigastric pain, diarrhea, dizziness, tinnitus, lethargy, convulsions; rarely - increased blood pressure, acute renal failure, hepatotoxic effect, respiratory depression, coma.

Treatment: gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating increased blood pressure, renal dysfunction, seizures, gastrointestinal irritation, respiratory depression. Forced diuresis, hemodialysis are ineffective (due to the significant connection with proteins and intensive metabolism).

Drug interactions

With simultaneous use with Clodifen Neuro:

• the effect of diuretics decreases, against the background of the use of potassium-sparing diuretics, the risk of hyperkalemia increases;

• the concentration in plasma of digoxin, methotrexate, lithium preparations and cyclosporin increases;

• the effects of antihypertensive and hypnotics are reduced;

• the risk of bleeding (more often gastrointestinal bleeding) increases during therapy with anticoagulants and thrombolytic agents (alteplase, streptokinase, urokinase);

• the likelihood of adverse reactions of other NSAIDs and corticosteroids (gastrointestinal bleeding), the toxicity of methotrexate and the nephrotoxicity of cyclosporine increases;

• the effect of hypoglycemic agents decreases;

• the antiparkinsonian efficacy of levodopa decreases;

• cefamandol, cefoperazone, cefotetan, valproic acid increase the incidence of hypoprothrombinemia;

• ethanol, colchicine, corticotropin, serotonin reuptake inhibitors and St. John's wort drugs increase the risk of gastrointestinal bleeding;

• diclofenac enhances the effect of drugs that cause photosensitization.

Concomitant use with paracetamol increases the risk of developing nephrotoxic effects of diclofenac.

Acetylsalicylic acid reduces the concentration of diclofenac in the blood.

Cyclosporine 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 can decrease by 30%).

Long-term treatment with anticonvulsants 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 containing B vitamins.