The composition and form of issue:
Capsules, 1 capsule contains:
diclofenac sodium 50 mg
thiamine hydrochloride 50 mg
pyridoxine hydrochloride 50 mg
cyanocobalamin 0, 25 mg
excipients: povidone, methacrylic acid and ethylacrylate copolymer (Eudragit NE30D), trimetilatsetat, talc, silicone antispamimage agent SE2 MC, gelatin, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172)
in packing contour cell 10 PCs per cartons 3 packages.
Description pharmaceutical form:
Hard gelatin capsules №1 with body pinkish-yellow color and a brown cap containing a mixture of the white granules (sodium diclofenac) and pink powder (thiamine hydrochloride, pyridoxine hydrochloride and cyanocobalamin).
Absorption of diclofenac — quick and full, the food slows the absorption rate for 1-4 h and reduces maximum concentration of 40%. After oral administration of 50 mg C Max — 1, 4 µg/ml is reached within 2-3 h. plasma Concentration is in linear dependence on the dose administered.
Changes in the pharmacokinetics of diclofenac amid repeated introduction is not marked, not accumulates.
Bioavailability of 50%. The plasma protein binding is more than 99% (the majority is bound to albumin). Penetrates into synovial fluid Cmax in synovial fluid is observed in 2-4 hours later than in plasma. T1/2 of the synovial fluid is 3-6 h (the concentration of active substance in the synovial fluid after 4-6 hours after administration of the drug higher than in plasma and remained higher for another 12 hours). The relationship of drug concentration in synovial fluid with clinical efficacy is unclear. Metabolism: 50% of the active substance is metabolized during “first pass” through the liver. Metabolism occurs as a result of repeated or single hydroxylation and conjugation with glucuronic acid. In the metabolism of the drug involved enzyme system P450 CYP2C9. The pharmacological activity of metabolites below, than diclofenac.
Systemic clearance is 350 ml/min, the volume of 550 ml/kg. T1/2 of plasma, 2 h 65% of the administered dose was excreted as metabolites by the kidneys less than 1% in an unmodified form, the rest of the dose as metabolites in the bile. In patients with severe renal insufficiency (Cl creatinine less than 10 ml/min) increases the excretion of metabolites in bile, with increase of their concentration in blood is not observed.
In patients with chronic hepatitis or compensated cirrhosis pharmacokinetic parameters of diclofenac are not changed.
Diclofenac passes into breast milk.
Vitamins that are included Neurodiscovery are water soluble, which eliminates the possibility of cumulation in the body. Thiamine and pyridoxine are absorbed in the upper part of the small intestine, metabolised in the liver and excreted by the kidneys (about 8-10% — unaltered). The degree of absorption depends on the dose, the overdose is significantly increased excretion of thiamine and pyridoxine in the intestine. The absorption of cyanocobalamin to a large extent depends on the availability of the body’s internal factor (in the stomach and upper part of the small intestine), further delivery of the vitamin in the tissue is determined by the transport protein transcobalamin. After metabolism in the liver cyanocobalamin are excreted mainly with bile, the degree of excretion by the kidneys is variable — from 6 to 30%.
Description pharmacological action:
Diclofenac has anti-inflammatory, analgesic, antiplatelet and antipyretic effects. Non-selectively inhibiting COX-1 and -2, violates the metabolism of arachidonic acid, reduces the amount of prostaglandins in inflammation. In rheumatic diseases anti-inflammatory and analgesic effect of diclofenac contributes to a significant decrease in severity of pain, morning stiffness, swelling of joints that improves a functional condition of the joint. In trauma, postoperative diclofenac reduces pain and inflammatory swelling.
Thiamine (vitamin B1) in the human body as a result of the process of phosphorylation turns into kokarboksilazu, which is kofermentom many enzyme reactions. Vitamin b 1 plays an important role in carbohydrate, protein and fat metabolism. Actively involved in the processes of nervous excitation in the synapses.
Pyridoxine (vitamin B6) is necessary for normal functioning of the Central and peripheral nervous system. In fosfaurilirovanna form is kofermentom in amino acid metabolism (decarboxylation, transamination, etc.). Acts as a cofactor of important enzymes active in nerve tissues. Involved in the biosynthesis of many neurotransmitters — such as dopamine, serotonin, norepinephrine, epinephrine, histamine and GABA.
Cyanocobalamin (vitamin B12) is necessary for normal hematopoiesis and maturation of erythrocytes, and is involved in several biochemical reactions, providing the support body in the transfer of methyl groups in the synthesis of nucleic acids, protein, metabolism of amino acids, carbohydrates, lipids. Has a beneficial effect on the processes in the nervous system (the synthesis of nucleic acids and lipid composition of cerebrosides and phospholipids). Coenzyme form of cyanocobalamin — methylcobalamin and adenosylcobalamin is required for the replication and growth of cells.
A combination of b vitamins potentiates the analgesic effect of diclofenac.
Application of pregnancy and breast-feeding:
Contraindicated in pregnancy. At the time of treatment should stop breastfeeding.
Tract: often (1%) — abdominal pain, sensation of bloating, diarrhea, nausea, constipation, flatulence, elevated liver enzymes, peptic ulcer with possible complications (bleeding, perforation), gastrointestinal bleeding is rare (1%) — vomiting, jaundice, melena, appearance of blood in the stool, lesions of the esophagus, aphthous stomatitis, dry mucous membranes (including the mouth), hepatitis (possibly lightning), liver necrosis, cirrhosis, hepatorenal syndrome, appetite change, pancreatitis, holetsistopankreatit, colitis.
Nervous system: often (1%) — headache, dizziness rare (1%) — sleep disturbance, drowsiness, depression, irritability, aseptic meningitis (usually in patients with systemic lupus erythematosus and other systemic diseases of connective tissue), convulsions, weakness, disorientation, nightmares, feeling of fear.
Special senses: frequent (1%) — tinnitus rare (1%) — blurred vision, diplopia, taste disturbance, and reversible or irreversible hearing loss, scotoma.
Skin: frequent (1%) — pruritus, skin rashes rare (1%) — alopecia, urticaria, eczema, toxic dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), increased photosensitivity, petechial hemorrhages.
Genitourinary system: (1%) — fluid retention (1%) — nephrotic syndrome, proteinuria, oliguria, hematuria, interstitial nephritis, papillary necrosis, acute renal failure, azotemia.
Organs of hematopoiesis and the immune system: (1%) — anemia (including hemolytic and aplastic anemia), leukopenia, thrombocytopenia, eosinophilia, agranulocytosis, thrombocytopenic purpura, worsening of infectious processes (including development of necrotizing fasciitis).
Respiratory system: rare(1%) — cough, bronchospasm, laryngeal edema, pneumonitis.
Cardiovascular system: rarely(1%) — increase in blood pressure congestive heart failure, arrythmia, chest pain, myocardial infarction.
Allergic reactions: rare(1%) — anaphylactoid reactions, anaphylactic shock (usually develops rapidly), swelling of the lips and tongue, allergic vasculitis.
Increases concentration in plasma digoxin, methotrexate, lithium preparations and cyclosporine.
Reduces effect of diuretics, against kalisberegath dioretikov increases risk giperkaliemii against the background of anticoagulants, thrombolytic drugs (alteplase, streptokinase, urokinase) — the risk of bleeding (often from the gastrointestinal tract).
Reduces the effects of hypotensive and hypnotic drugs.
Increases the likelihood of side effects of other NSAIDs and corticosteroids (bleeding in the digestive tract), toxicity of methotrexate and nephrotoxicity of cyclosporine.
Acetylsalicylic acid reduces the concentration of diclofenac in the blood.
Simultaneous use with paracetamol increases the risk of nephrotoxic effects of diclofenac.
Reduces the effect of hypoglycemic agents.
Cefamandole, cefoperazone, cefotetan, valproic acid and plicamycin increase the frequency of gipoprotrombinemii.
Cyclosporine and gold drugs increase the effect of diclofenac on the synthesis of PG in the kidney, which increases the nephrotoxicity.
Coadministration with ethanol, colchicine, corticotropin, inhibitors of serotonin reuptake and St. John’s wort preparations increases the risk of bleeding in the digestive tract.
Diclofenac enhances the effect of drugs that cause photosensitivity.
Drugs that block tubular secretion, increase in plasma concentration of diclofenac, thereby increasing its toxicity.
Martikovich reduces the antiparkinsonian efficacy of levodopa.
Ethanol dramatically reduces the absorption of thiamine (level in the blood may be reduced by 30%). The use of colchicine and biguanide reduces the absorption of cyanocobalamin.
Method of application and dose:
Inside, during a meal, without chewing, drinking plenty of fluid.
Usually appoint 1 KAPS. 1-3 times a day.
Martikovich adults appoint 1 caps.: at the beginning of treatment 3 times a day, as maintenance dose — 1-2 times a day. The duration of therapy depends on the nature and severity of the disease.
Symptoms: vomiting, dizziness, headache, shortness of breath, dizziness, children — myoclonic seizures, nausea, abdominal pain, bleeding, impaired liver and kidneys.
Treatment: gastric lavage, administration of activated charcoal, symptomatic therapy, forced diuresis.
Hemodialysis is ineffective.
During the period of drug treatment should be systematic monitoring picture peripheral blood, liver, kidneys, examination of feces for presence of blood.
Patients receiving the drug should refrain from activities, require increased attention and rapid mental and motor reactions, alcohol consumption.
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