Catadolon forte - instructions for use, dose, side effects, contraindications

active ingredient flupirtine maleate 400 mg; auxiliaries: methyl methacrylate and ethyl acrylate copolymer [2: 1] 22,50 mg, talc 22,50 mg, calcium hydrogen phosphate dihydrate 38.00 mg, microcrystalline cellulose 59.74 'mg, croscarmellose sodium 34.95 mg, hypromellose 8.00 mg, iron dye oxide yellow (E 172) 6.25 mg, silicon dioxide colloidal anhydrous 2.06 mg, magnesium stearate 6.00 mg.

Description:

oblong biconvex tablets, even on one side and with a risk on the other side, light yellow or yellow with light and dark impregnations.

Pharmacotherapeutic group:analgesic non-narcotic agent.

ATX: & nbsp

N.02.B.G.07 Flupirtine

Pharmacodynamics:

Flupirtine is a representative of the drugs "Selective Neuronal Potassium Channel Opener" (SNEPCO) and refers to non-narcotic analgesics of the central action, not causing addiction and dependence.

Flupirtine activates G-protein-associated neuronal K + internal rectification channels. The yield of K + ions causes stabilization of the resting potential and a decrease in the excitability of neuronal membranes. As a result, indirect inhibition of NMDA (N-methyl-D-aspartate) receptors occurs, since NMDA receptor blockade with Mg2 + remains until it comes cell membrane depolarization (indirect antagonistic effect on NMDA receptors).

With therapeutically significant concentrations flupirtine does not communicate with alpha1, alpha2-, 5HT1 (5-hydroxytryptophan) -, 5HT2-serotonin, dopamine, benzodiazepine, opioid, central m- and n-cholinergic receptors.

Such a central effect of flupirtine leads to the implementation of three main effects.

Analgesic effect

Because of the selective discovery potential-dependent K + channels of neurons with the accompanying yield of K + The resting potential of the neuron is stabilized.

The neuron becomes less irritable. Indirect antagonism of flupirtine in respect NMDA-receptor protects neurons from the input of Ca2 + ions. Thus, image, softens sensitizing effect of increasing intracellular concentration of Ca2 + ions. Therefore, when a neuron is excited transmission inhibition occurs ascending nociceptive impulses.

Miorelaksiruyuschy effect

Pharmaceutical effects described for analgesic effect, functionally reinforced by the absorption ions Ca2 + mitochondria, which occurs at therapeutically significant concentrations. Miorelaxing the effect arises as a result of the concomitant inhibition of the transfer of impulses to motor neurons and the corresponding effects of interstitial neurons. Thus, this effect is manifested mainly in relation to local muscle spasms, and not in relation to the whole musculature as a whole.

The effect of the processes of chronicification The processes of chronicization should be considered as processes of neuronal conduction, conditional plasticity of neuron functions.Through the induction of intracellular processes, the elasticity of the functions of neurons creates the conditions for the realization of mechanisms such as "inflation", under which the response to each subsequent impulse increases. The launch of such changes is largely responsible for NMDA receptors (gene expression). Indirect blockade of these receptors under the influence of flupirtine leads to suppression of these effects. Thus, unfavorable conditions are created for clinically significant chronic pain, and in the case of previous chronic pain for "erasing" the pain memory by stabilizing the membrane potential, which leads to a decrease in the pain threshold of sensitivity.

Pharmacokinetics:

After oral administration, approximately 90% of flupirtine is absorbed from the gastrointestinal tract (GI tract), and after rectal administration about 70% of the administered dose is absorbed.

About 3/4 of the accepted dose of flupirtine is metabolized in the liver. Metabolite Ml (2-amino-3-acetamino-6- (4-fluoro) -benzylaminopyridine) is formed by metabolism as a result of hydrolysis of the urethane structure (reaction of phase I) and acetylation of the obtained amine (phase II reaction).The analgesic effect of this metabolite is about a quarter of the analgesic effect of flupirtine, therefore it is also involved in the therapeutic effect of flupirtine.

Another metabolite is formed by oxidative cleavage (phase I reaction) of residual fluorobenzyl, followed by coupling (phase II reaction) of the fluorobenzoic acid obtained with glycine. This metabolite (M2) does not have biological activity. To date, there has been no research aimed at finding the isoenzyme, which is responsible for the oxidative (less significant) pathway of metabolism.

It is assumed that flupirtine has a negligible potential of drug interaction.

Most of the accepted dose of flupirtine (69%) is excreted by the kidneys. This part is characterized by the following: 27% - unchanged, 28% - metabolite Ml (acetyl metabolite), 12% - metabolite M2 (para-fluorohypuric acid); The remaining third consists of several small metabolites, the structure of which has not yet been studied.

A small part of the dose of flupirtine is excreted in the urine and feces.

The half-life (T1 / 2) is about 15 hours; when eating, T1 / 2 is reduced.The main metabolite is output somewhat slower (T1 / 2 about 20 hours and 16 hours, respectively).

After taking flupirtine in doses of 50 to 300 mg of its concentration in the blood plasma have dose-dependent characteristics. In elderly patients (over 65 years of age) after repeated administration of the drug Catadolon® forte, one tablet of prolonged action per day for 7 days against a background of increased distribution values, an increase in the area under the concentration-time curve was observed from 0 to 24 hours (AUCo- 24): 22.9 μg / ml * h compared to 16.8 μg / ml * h for a control group consisting of younger patients; In addition, in older patients, the T1 / 2 elongation was observed (23.72 h compared to 15.94 h). In addition, in patients with impaired renal function (creatinine clearance (CK) less than 30 ml / min), compared with patients in the control group was observed

an increase in AUC0-24: 23.11 μg / ml * h compared to 16.8 μg / ml * h, as well as an elongation of T1 / 2 (20.01 h compared to 15.94 h).

The pharmacokinetics of the drug Catadolon forte is determined by the characteristics of its drug Forms: a rapidly releasing fraction of flupirtine (100 mg) and a slowly releasing fraction of flupirtine (300 mg).With a single application of the drug, the maximum concentration (Cmax) of flupirtine 0.8 μg / ml (0.4-1.5 μg / ml) was achieved after 2.4 hours, and with repeated administration (400 mg daily for 7 days) after 1.9 hours, with Stach being 1.0 μg / ml (0.6-2.4 μg / ml). Under the influence of food, there is a slight increase in absorption (AUCo-oo 14.1 μg / ml * h compared to 10.7 μg / ml * h), and an increase in C max (1.0 μg / ml compared to 0.8 μg / ml), and the time to reach the maximum concentrations.

Indications:

Treatment of acute pain of mild to moderate severity in adults.

Contraindications:

Hypersensitivity to the active ingredient or any other component of the drug.

Patients with a risk of developing hepatic encephalopathy and patients with cholestasis, since. can develop encephalopathy or aggravate the course of already existing encephalopathy or ataxia.

Patients with myasthenia gravis gravis in connection with the miorelaksiruyuschim action flupirtina. Patients with concomitant liver disease or alcoholism. The simultaneous use of flupirtine with other drugs that may cause repatoxic effect.

Patients with newly healed or existing ringing in the ears, because patients have a high risk of increasing the activity of "liver" enzymes.

Children under 18 years.

Carefully:

Renal failure, hypoalbuminemia, elderly age over 65 years.

Pregnancy and lactation:HThere is insufficient data on the use of flupirtine in pregnancy. In experimental studies on animals flupirtine showed reproductive toxicity, but not teratogenicity. The potential risk to humans is unknown. The preparation Catadolon® forte should not be used during pregnancy, except when the benefit to the mother exceeds the potential risk to the fetus.

According to the studies, flupirtine in an insignificant amount is absorbed into breast milk. In this regard, Catadolon® forte can not be used during breastfeeding, except when there is an extreme need for taking the drug. If you need to use the drug Kadadolon forte during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, without chewing the pill and washing down sufficient liquid (preferably water).

400 mg (1 tablet) 1 time per day to reduce pain for the shortest possible time.This dose is the total daily dose. If this dose can not have a sufficient analgesic effect, you can use capsadol ® with a larger daily dose.

The dose is selected depending on the intensity of pain and individual tolerance of the drug. Use the lowest effective dose for the shortest possible time. Duration of treatment should not exceed 2 weeks.

Elderly patients over 65 years of age: the initial dose of 200 mg (1/2 tablet) once a day. With good tolerability, the dose can be increased to 400 mg (1 tablet) 1 time per day. The maximum daily dose is 400 mg.

In patients with renal disease insufficiency: should be control the concentration of creatinine in the blood plasma.

In patients with mild and moderate renal failure: correction of the dose is not required. When severe renal failure the initial dose of 200 mg (1/2 tablets) once a day. With good tolerability, the dose can be increased to 400 mg (1 tablet) 1 time per day. If it is necessary to use the drug in a higher dose, such patients should be under the supervision of a doctor. Patients with hypoalbuminemia: there is no data on the efficacy and safety of the use of the drug Kadadolon forte, prolonged-release tablets 400 mg, in patients with hypoalbuminemia. Patients with hypoalbuminemia should use the preparation Kadadolon®, capsules 100 mg.

Side effects:

Undesirable reactions are classified in frequency as follows: very often (> 1/10); often (> 1/100, but <1/10); infrequently (> 1/1000, but <1/100); rarely (> 1/10000, but <1/1000); rarely (1/10000); frequency is unknown (impossible based on available data).

From the hepatobiliary system:

very often - increased activity "hepatic" transaminases; frequency unknown - hepatitis, hepatic failure.

From the immune system: infrequently -hypersensitivity to the drug, allergic reactions (in separate cases accompanied by increased body temperature, skin rash, hives, skin itching).

FROMabout the side of metabolism: often - lack of appetite.

From the nervous system: often - sleep disturbance, depression, anxiety /nervousness, dizziness, tremor, headache; infrequently confused consciousness.

From the side of the organ of vision: infrequently - impaired vision.

From the gastrointestinal side tract: often - dyspepsia, nausea, vomiting, pain in the stomach, constipation, pain in the abdomen, dryness of the oral mucosa, flatulence, diarrhea.

From the skin and subcutaneous tissues: often - sweating.

Other: very often fatigue / weakness (in 15% of patients), especially at the beginning of treatment. Side effects mainly depend on the dose of the drug (with the exception of allergic reactions). In many cases, they disappear by themselves as they take place or after the end of treatment.

Overdose:

There are reports of isolated cases overdose with suicidal intentions. In this case, the dose of 5 g flupirtine caused the following symptoms: nausea, tachycardia, condition prostration, tearfulness, confusion consciousness, deafness of consciousness, dryness the mucous membrane of the mouth.

After vomiting or applying forced diuresis, reception of activated carbon and the introduction of electrolytes well-being

was restored within 6-12 hours. There were no reports of life-threatening conditions.

In case of overdose or signs of intoxication, one should bear in mind the possibility of the occurrence of disorders from the central nervous system,as well as manifestations of hepatotoxicity by the type of enhancement of metabolic disorders in the liver. It should be symptomatic treatment. The specific antidote is unknown.

Interaction:

Strengthens the effect of alcohol, sedatives and muscle relaxants.

Due to flupirtine has a high degree of connection with proteins, it can change the degree of binding with the proteins of other concomitantly used drugs. As a result of the in vitro study of the interaction of flupirtine with warfarin, diazepam, acetylsalicylic acid, benzylpenicillin, digoxin, glibenclamide, propranolol, clonidine, it was found that only verapamil and diazepam are displaced by flupirtine from the bond with plasma proteins, which can lead to an increase in their activity.

With simultaneous application of flupirtine and indirect anticoagulants - coumarin derivatives (warfarin) it is recommended to regularly monitor prothrombin time in order to timely adjust the dose of indirect anticoagulants. There are no data on the interaction with other anticoagulant and antiplatelet agents (acetylsalicylic acid and etc.).

With the simultaneous use of flupirtine with drugs that are metabolized in the liver, regular monitoring of the activity of "hepatic" enzymes is required. Combined use of flupirtine and medications containing paracetamol and carbamazepine.

Special instructions:

The preparation Catadolon® forte should be used if treatment with other analgesics (for example, non-steroid anti-inflammatory drugs (NSAIDs) or light opioid drugs) is contraindicated.

In patients with impaired renal function, the concentration of creatinine in the blood plasma should be monitored.

Patients over 65 years of age or with signs of severe renal disease Dose correction is required. During treatment with the Catadolon® fort, once a week, the liver function should be monitored, since with flupirtin therapy possibly increased activity "hepatic" transaminases, development hepatitis and liver failure.

If the results of a liver test deviate from the norm or manifest themselves clinical symptoms that indicate to liver damage, it follows that discontinue use of the drug Catadolon® forte.

Patients should be warned that during treatment with Catadolon® forte it is necessary to pay attention to any symptoms of liver damage (eg, lack of appetite, nausea, Vomiting, stomach pain, fatigue, dark urine, jaundice, itching). When such symptoms should stop taking preparation of Cataladol® forte and in urgentorder to see a doctor.

In the treatment of flupirtin, false positive reactions of the test with diagnostic strips for bilirubin, urobilinogen and protein in the urine are possible. A similar reaction is possible with a quantitative determination of the concentration of bilirubin in the blood plasma.

When using the drug in high doses, in some cases, the color of urine can be marked in green, which is not a clinical sign of any pathology.

Effect on the ability to drive transp. cf. and fur:

When using the drug Catadolon forte, you should refrain from driving vehicles and controlling mechanisms, due to the fact that patients can develop drowsiness and dizziness, which can affect the concentration of attention and the speed of psychomotor reactions.It is especially important to remember this when using alcohol at the same time.

Form release / dosage:

Long-acting tablets 400 mg.

Packaging:

For 7 tablets in a blister of PVC / aluminum foil. 1 blister together with instructions for use in a cardboard box.

For 14 tablets in a blister of PVC / aluminum foil. 1, 3 or 6 blisters together with instructions for use in a cardboard box.

For 10 tablets in a blister of PVC / aluminum foil. 2 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001320

Date of registration:02.12.2011

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Operations Poland, Sp. z o.o. Poland

Information update date: & nbsp22.10.2015

Illustrated instructions

Instructions

Catadolon® forte (Katadolon® forte)