Pharmacological properties

Pharmacodynamics. neurodiklovit — a combination of diclofenac and neurotropic vitamins v1, v6 and v12. as well as others npvp, diclofenac oppresses enzyme tsog, the turning arachidonic acid in prostaglandins. diclofenac oppresses also enzyme a lipoxygenase. analgeziruyushchy, anti-inflammatory and febrifugal effect of diclofenac is caused by oppression of synthesis of prostaglandins.

Vitamins of group B perform function of coenzymes in a metabolism, including in neurology that positively affects analgesic effect of diclofenac of sodium.

Pharmacokinetics. After intake, diclofenac is well and completely soaked up from a GIT. The bioavailability does not depend on meal. The C _max in blood plasma is reached in 1–2 h after reception (on an empty stomach quicker, than after meal). The vitamins which are contained in medicament are soaked up in intestines thanks to active and passive mechanisms. Distribution and removal are similar to the vitamins coming to an organism with food. After oral administration of diclofenac in blood plasma reveal a half of the concentration of medicine noted after parenteral application of the same dose. Therapeutic concentration in blood plasma makes about 0.7-2.0 mg/l. Nearly 99% of diclofenac contact proteins of blood plasma, mainly albumine.

with kidneys in the form of active metabolites, in not changed look 1% of diclofenac is removed. About 30% of a dose of medicine are removed in the form of metabolites through bile, with a stake. T _½ diclofenac makes about 2 h of blood plasma. The general system clearance of diclofenac is about 250 ml/min. of blood plasma

Renal failure does not cause accumulation of active agent owing to increase in bilious excretion. Absorption, metabolism and removal of medicine do not depend on age.

Indication

Inflammatory and degenerative forms of rheumatic diseases:

• chronic polyarthritis;
• ankylosing spondylitis (Bekhterev's disease);
• arthrosis;
• spondylarthritis;
• sharp gouty arthritis;
• extraarticular rheumatism of soft tissues;
• neuritis and neuralgia, such as cervical syndrome, lumbago, ischialgia.

Use

Capsule whole, washing down with enough liquid, at meal time.

Depending on disease severity the recommended dose makes 1–3 capsules a day that is equivalent to 50-150 mg of diclofenac respectively.

Adult. For initial therapy the dose of medicine makes 2–3 capsules a day. A maintenance dose — 1 capsule 1–2 times a day. The maximum daily dose should not exceed 3 capsules.

Children are aged more senior than 14 years. The maximum daily dose — on 1 capsule 2 times a day.

Duration of treatment is defined by the doctor.

Patients of advanced age. Though the pharmacokinetics of diclofenac does not depend on age, patients of advanced age should select a dose with care.

Contraindication

Hypersensitivity to medicine components; ulcer of stomach or duodenum; porphyria, hemorrhagic diathesis, blood formation violation; Crohn's disease, ulcer colitis; heavy heart failure. heavy renal and liver failure; gastrointestinal bleeding or perforation; erythremia, hyperglobulia, thrombembolia; allergic diseases.

Drug is contraindicated to patients who have asthma attacks, skin reactions or sharp rhinitises are provoked by intake of acetylsalicylic acid or other medicines inhibiting synthesis of prostaglandins.

Side effects

Co of the party of a cardiovascular system: heart failure, ag, hypostases, tachycardia, heart consciousness, stethalgia, myocardial infarction, vasculitis.

from blood: blood formation violation (leukopenia, thrombocytopenia, aplastic anemia, panmyelopathia, purple, Agranulocytosis, hemolytic anemia).

from nervous system: a headache, nausea, drowsiness, spasms, dizziness, paresthesias, memory violation, uneasiness, a tremor, aseptic meningitis, violation of taste, violation of cerebral circulation, violation of feeling at touch.

Disorder of vision: a disorder of vision (illegibility of the image, doubling in eyes).

Hearing disorder: sonitus, hearing disorder.

from a GIT: pain in the field of epigastrium, the anorexia, a hiccups, nausea, indigestions, gastrointestinal bleeding, gastrointestinal ulcers which are followed by severe bleedings, perforation and anemia, vomiting, diarrhea, dyspepsia, a meteorism, gastritises, colitis (including hemorrhagic colitis and exacerbation of ulcer colitis or Crohn's disease), a lock, stomatitis, a glossitis, disorders of a gullet, increase in acidity of gastric juice, diafragmopodobny strictures of intestines, pancreatitis.

from kidneys and urinary tract: renal failure, nephrotic syndrome, hamaturia, sharp renal failure, interstitial nephrite, papillary necrosis, proteinuria.

from skin and hypodermic fabrics: rash, reddening, itch, alopecia, erythema of different types, exfoliative dermatitis, photosensitization.

from the immune system: allergic reactions, such as bronchospasm, small tortoiseshell, anaphylactic/anaphylactoid reactions, Stephens's syndrome — Johnson, a Lyell's disease, a Quincke's disease.

from a gepatobiliarny system: hepatitis, including lightning hepatitis, jaundice, increase in level of Transaminases, seldom sharp.

Mental disorders: insomnia, condition of superexcitation, irritability, disorientation, depression, nightmares, psychotic frustration, indisposition.

General violations: a delay of sodium and water in an organism, peripheral hypostases, the increased sweating, asthma, a pneumonitis.

Risk of emergence of side effects can be reduced by

by application of minimum effective dose within a short period of time, a symptom, necessary for control.

With care should use medicament to patients with asthma, hay fever, swelling of a mucous membrane of a nose (nasal polyps) or chronic infectious diseases of airways.

Appropriate observation and consultation are demanded by patients with the raised ABP in the anamnesis and/or heart failure as at treatment of NPVP it was reported about a delay of liquid and hypostases.

to Patients with insufficiently controlled AG, heart failure, an ischemic heart disease in the anamnesis, peripheral arterial vascular and/or cerebrovascular diseases diclofenac is appointed after careful assessment. Similar factors should be considered also before administration of medicament if the patient is inclined to cardiovascular diseases (for example AG, a lipidemia, diabetes, smoking).

Clinical trials and epidemiological data show that diclofenac use, especially in high doses (150 mg/days) and during the long period can be followed by slight increase of risk of arterial trombotichesky complications (myocardial infarction or an attack).

During long-term treatment by Neurodiklovit is recommended to control indicators of peripheral blood, function of a liver and kidneys.

Patients with a peptic ulcer of a stomach and duodenum or dispeptic symptoms in the anamnesis, with diseases of a liver, kidneys, heart failure or AG demand careful medical control.

gastrointestinal ulcers, bleedings and perforation (sometimes with a lethal outcome) which can note during treatment, against the background of precautionary symptoms, or at their absence, or in the presence of the serious gastrointestinal phenomena in the anamnesis are characteristic

all NPVP. In general such phenomena are most dangerous to patients of advanced age. In some cases, when at the patients applying diclofenac these complications develop, medicine should be cancelled.

to

Due to the application of NPVP, including diclofenac, it was very seldom reported about heavy, even with a lethal outcome skin reactions, including exfoliative dermatitis, Stephens's syndrome — Johnson and a toxic epidermal necrolysis. The high risk of these reactions was revealed at the beginning of therapy, and development of these reactions is noted in most cases in the first month of treatment. It is necessary to cancel medicine at the first manifestations of skin rash and ulcers of a mucous membrane or any other manifestations of hypersensitivity.

Diclofenac thanks to the pharmakodinamichesky properties can mask the symptoms characteristic of infectious and inflammatory diseases.

At introduction of _{12 vitamin B} clinical picture and also laboratory analyses at a funicular myelosis or pernicious anemia can lose the specificity.

Intake of alcohol and black tea reduces thiamine absorption. Consumption of the drinks containing sulfites (for example wine), increases thiamine degradation.

to Patients with new growths, except for the cases which are followed by megaloblastny anemia and deficiency of _{12 vitamin B} , should not use drug.

Drug is not used at stenocardia.

Ability to influence speed of response at control of vehicles or work with mechanisms. Though negative impact on ability to steer vehicles and to work with mechanisms is not revealed, it is impossible to exclude the fact that the reactivity can worsen owing to undesirable influence of diclofenac on central nervous system (dizziness, fatigue).

Use during pregnancy and feeding by a breast. In view of lack of clinical data the simultaneous use of _{1 vitamins B} , In ₆ and In ₁₂ is not recommended during pregnancy or feeding by a breast.

Children. It is not recommended to children aged up to 14 years.

Interaction

Combined purpose of the neurodiklovit and other medicines can cause increase or decrease in efficiency:

increase:

• level of lithium and digoxin in blood plasma;
• risk of gastrointestinal bleedings at the accompanying therapy by glucocorticoids;
• expressiveness of side effect of other NPVP;
• efficiency of kaliysberegayushchy diuretics (control of level of potassium);
• efficiency of medicines, inhibiting aggregation of platelets;
• level and toxicity of a methotrexate. It is necessary to avoid purpose of NPVP less than for 24 h to or after treatment by a methotrexate;

decrease:

• efficiency of diclofenac furosemide and other loopback diuretics;
• efficiency of diclofenac antihypertensive drugs;
• concentration of diclofenac and acetylsalicylic acid in blood plasma;
• absorption of _{12 vitamin B} at the combined application with colchicine, GRAZED, Neomycinum and anti-diabetic means of type of a biguanidin.

Contraindicated simultaneous application with a levodopa as _{6 vitamin B} can reduce expressiveness of protivoparkinsonichesky action of a levodopa.

As well as other NPVP, at simultaneous application with diuretics or antihypertensive medicines (for example blockers of β-adrenoceptors and blockers of calcium channels, APF inhibitors) their antihypertensive effect can reduce. Therefore it is necessary to appoint a combination of such medicines with care, and patients (especially advanced age) should control the ABP periodically. Patients should use enough water, and at the beginning and after completion of the accompanying therapy it is necessary to control periodically function of kidneys, in particular at use of diuretics and APF inhibitors owing to the increased risk of emergence of nephrotoxicity. Simultaneous application of system NPVP and selective serotonin reuptake inhibitors can increase risk of gastrointestinal bleeding.

Perhaps simultaneous use of diclofenac and antidiabetic medicines, at the same time the efficiency of the last does not change. However separate messages about development in such cases both a hypoglycemia, and a hyperglycemia are known that caused need of change of a dose of glucose-lowering medicaments during use of diclofenac. For this reason it is recommended to control during therapy glucose level in blood. Simultaneous use of diclofenac and a kolestipol or Colestyraminum reduces diclofenac absorption approximately by 30 and 60% respectively. The medicaments should be taken at an interval of several hours. The means stimulating enzymes, for example rifampicin, carbamazepine, Phenytoinum, a St. John's wort (Hypericum perforatum) and others are theoretically capable to reduce concentration of diclofenac in blood plasma. Influence of NPVP on synthesis of prostaglandins in kidneys can increase nephrotoxicity of cyclosporine. There are separate messages about development of spasms in patients, the receiving at the same time derivative hinolon and NPVP.

5-fluorouratsily as the last competitively inhibits phosphorylation of thiamine in thiamine pyrophosphate.

Antacids reduce thiamine absorption. The loopback diuretics, for example furosemide braking a canalicular reabsorption at long therapy can cause increase in excretion of thiamine and, thus, reduce thiamine level.

Concomitant use with antagonists of a pyridoxine (for example an isoniazid, gidralazin, Penicillaminum or Cycloserinum), oral contraceptives can increase the need for _{6 vitamin B} .

Overdose

Symptoms of overdose of diclofenac and intoxication — increase in frequency of side effects from a GIT and central nervous system. symptomatic therapy.

.

_{1 Vitamin B} : has wide therapeutic range. After oral administration no symptoms are revealed. At reception of very high doses (10 g) note kurarepodobny effect, suppressing conductivity of nervous impulses.

_{6 Vitamin B} : shows very much hypotoxicity. Long reception (more than 6-12 months) in doses of 50 mg of _{6 vitamin B} can daily lead to peripheral touch neuropathy. Excessive use of _{6 vitamin B} in doses of 1 g/days within several months can result in neurotoxic effects. Neuropathies with an ataxy and disorders of sensitivity, cerebral spasms with changes on EEG and also in some cases hypochromia anemia and seborrheal dermatitis were described after introduction of 2 g/days

_{12 Vitamin B} : after parenteral administration (in rare instances — after oral administration) above the recommended doses allergic reactions, eczematic skin violations and a benign form of an acne were observed. At prolonged use in high doses the violation of activity of enzymes of a liver, pain in heart, hypercoagulation is possible.

Storage conditions

B the dry, protected from light place at a temperature up to 25 °C.