Катадолон®

General characteristics. Structure:

Active agent: flupirtina maleate of 100 mg
Excipients: hydrophosphate calcium dihydrate, коповидон, magnesium stearate, silicon dioxide colloid;
Cover: gelatin, the water purified dye ferrous oxide red (E172), titanium dioxide, sodium lauryl sulfate.

Description: opaque solid gelatin capsules (a body - red-brown color, a lid - red-brown color) the size 2.
Contents of capsules: powder from white till light yellow or grayish-yellow or light green color.

Pharmacological properties:

Pharmacodynamics. Flupirtin is the representative of a class of medicines of the selection activators of neyronalny potassium channels ("Selective Neuronal Potassium Channel Opener" - SNEPCO). On the pharmacological effects drug represents not opioid analgetic of the central action which is not causing dependence and accustoming, besides, has myorelaxation and neuroprotective effect.
Activation of potentsialnezavisimy potassium channels which leads to stabilization of membrane potential of neuron is the cornerstone of action of a flupirtin. Influence on current of potassium ions it is mediated by impact of drug on system of regulatory G-protein. The anesthetizing action is based as on indirect antagonism in relation to NMDA (N-metil-D-aspartat) - receptors, and by means of modulation of the mechanisms of pain connected with influence on GAMK-ergichesky systems.
In therapeutic concentration флупиртин does not communicate with alfa1-, alfa2-adrenoceptors, serotoninovy 5HT1, 5HT2-receptors, dofaminergichesky, benzodiazepine, opiate, central muskarinergichesky or nikotinergichesky receptors.
The central action of a flupirtin is based on 3 main effects:
The anesthetizing action
 Flupirtin activates (opens) potentsialnezavisimy potassium channels that leads to stabilization of membrane potential of a nervous cell. At the same time there is a braking of activity of NMDA receptors and, as a result, blockade of neyronalny ion channels of calcium, decrease in intracellular current of calcium ions. Owing to the developing suppression of excitement of neuron in response to nociceptive incentives, inhibition of nociceptive activation, the analgesic effect is implemented. At the same time there is a braking of increase of the neyronalny answer to repeated painful incentives. Such action prevents strengthening of pain and its transition to a chronic form, and at already available chronic pain syndrome leads to decrease in its intensity. Also modulating influence of a flupirtin on perception of pain through the descending noradrenergichesky system is established.
Myorelaxation action
 Anti-spastic action on muscles is connected with the blocking of transfer of excitement on motor-neurons and interneuronels leading to removal of muscular tension. This action of a flupirtin is shown at many chronic diseases which are followed by painful muscular spasms (skeletal and muscular neck and spin pains, arthropathies, tenzionny headaches, fibromyalgia).
Neuroprotective action
 Neuroprotective properties of drug cause protection of nervous structures against toxic action of high concentration of ions of intracellular calcium that is connected with its ability to cause blockade of neyronalny ion calcium channels and to reduce intracellular current of calcium ions.

Pharmacokinetics. After intake drug quickly and almost completely (90%) is soaked up in digestive tract. To 75% of the accepted dose it is metabolized in a liver with formation of metabolites of M1 and Sq.m. Active M1 metabolite (2-amino-Z-atsetamino-6-[4 fluorine] - benzylaminopyridine) it is formed as a result of hydrolysis of urethane structure (1 phase of reaction) and the subsequent acetylation (the 2nd phase of reaction) provides on average 25% of the anesthetizing activity of a flupirtin. Other metabolite of Sq.m - is not biologically active, is formed as a result of oxidation reaction (1 phase) p-ftorbenzila with the subsequent conjugation (the 2nd phase) of p-fluobenzoic acid with glycine.
The drug elimination half-life makes about 7 hours of a blood plasma (10 hours for the main substance and a metabolite of M1) that is sufficient for ensuring analgesic effect.
Concentration of active ingredient in a blood plasma is proportional to a dose.
At elderly people (65 years are more senior) in comparison with young patients increase in an elimination half-life of drug (to 14 h is observed at a single dose and to 18,6 h at reception within 12 days), and the maximum concentration of drug in a blood plasma is respectively 2 - 2,5 times higher.
Mostly it is removed by kidneys (69%): 27% - in not changed look, 28% - in the form of a metabolite of M1 (acetyl metabolite), 12% - in the form of the Sq.m metabolite (steam-ftorgippurovaya acid); 1/3 entered doses are removed in the form of metabolites of the obscure structure. A small part of a dose is brought out of an organism with bile and a stake.

Indications to use:

Acute and chronic pain at the following states:
• muscular spasms (skeletal and muscular neck and spin pains, arthropathies, fibromyalgia),
• headaches,
• malignant new growths,
• dysmenorrhea,
• posttraumatic pain,
• a pain syndrome at traumatologic/orthopedic operations and interventions.

Route of administration and doses:

Inside, without chewing and washing down with a small amount of liquid (100 ml).
Adult: On 1 capsule 3-4 times a day with equal intervals between receptions. At the expressed pains - on 2 capsules 3 times a day. The maximum daily dose - 600 mg (6 capsules).
Doses select depending on intensity of pain and individual sensitivity of the patient to drug.
The patient 65 years are more senior: in an initiation of treatment on 1 capsule in the morning and in the evening. The dose can be increased to 300 mg depending on intensity of pain and portability of drug.
At patients with the expressed symptoms of a renal failure or at a hypoalbuminemia the daily dose should not exceed 300 mg (3 capsules).
At patients with reduced function of a liver the daily dose should not exceed 200 mg (2 capsules).
In need of purpose of higher doses of drug for patients establish careful observation.
Duration of therapy is defined by the attending physician and depends on dynamics of a pain syndrome and portability. At prolonged use it is necessary to control activity of liver enzymes for the purpose of identification of early symptoms of a hepatotoxic.

Features of use:

At patients with reduced function of a liver or kidneys it is necessary to control activity of liver enzymes and content of creatinine in urine.
At patients 65 years are more senior or with the expressed symptoms of a renal and/or liver failure or a hypoalbuminemia it is necessary to carry out dose adjustment.
At treatment of a flupirtin false positive reactions of the test with diagnostic strips for bilirubin, urobilinigen and protein in urine are possible.
Similar reaction is possible at quantitative determination of level of bilirubin in a blood plasma.
At use of drug in high doses coloring of urine in green color in some cases can be noted that is not a clinical sign of any pathology.

Influence on ability to manage motor transport and work with mechanisms
 Considering that Katadolon® can weaken attention and slow down speed of response, during treatment it is recommended to abstain from driving by transport and occupations potentially dangerous types of activity.

Side effects:

Most often (> 10% of cases): fatigue/weakness (at 15% of patients), especially in an initiation of treatment.
Often (from 1% to 10%): dizziness, heartburn, nausea, vomiting, a lock, a digestive disturbance, a meteorism, an abdominal pain, dryness in a mouth, appetite loss, a depression, sleep disorders, perspiration, concern, nervousness, a tremor, a headache, diarrhea.
Seldom (from 0,1% to 1%): confusion of consciousness, a vision disorder and allergic reactions (rash, urticaria and an itch, sometimes with fervescence).
Very seldom (less than 0,01%): passing increase in activity of "hepatic" transaminases (at a dose decline or drug withdrawal is returned to normal indicators), acute or chronic medicinal hepatitis (with jaundice or without, with elements of a cholestasia or without them).
Side effects generally depend on a drug dose (except for allergic reactions). In many cases they disappear in itself in process of carrying out or after the end of treatment.

Interaction with other medicines:

Strengthens effect of alcohol, sedatives and muscle relaxants.
Because флупиртин contacts proteins, it is necessary to consider a possibility of interaction it with other at the same time accepted medicines, (for example, acetylsalicylic acid, benzylpenicillin, digoxin, Glibenclamidum, propranolol, a clonidine, warfarin and diazepam) which can be forced out flupirtiny of communication with proteins that can lead to strengthening of their activity. Especially this effect can be expressed at a concomitant use of warfarin or diazepam with flupirtiny.
At co-administration of a flupirtin and derivatives of coumarin it is regularly recommended to control a prothrombin ratio timely to correct a coumarin dose. There are no data on interaction with other anticoagulants or antiagregant (acetylsalicylic acid, etc.).
At simultaneous use of a flupirtin with drugs which are metabolized in a liver regular control of level of "hepatic" enzymes is required. It is necessary to avoid the combined use of a flupirtin and the medicines containing paracetamol and carbamazepine.

Contraindications:

Hypersensitivity to active ingredient or any other component of drug, a liver disease in the anamnesis, a cholestasia, the expressed myasthenia, alcoholism, pregnancy, the feeding period a breast, children's age up to 18 years.
With care: abnormal liver functions and/or kidneys, age are more senior than 65 years, a hypoalbuminemia.

Overdose:

Symptoms: nausea, tachycardia, a condition of prostration, tearfulness, confusion of consciousness, dryness in a mouth.
Treatment: symptomatic (gastric lavage, artificial diuresis, administration of absorbent carbon and electrolytes). There is no specific antidote.

Storage conditions:

At a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to use drug after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Capsules on 100 mg.
On 10 capsules in the blister from PVC / aluminum foil.
On 1, 3, 5 blisters place in a cardboard pack together with the application instruction.