Catadolone - instructions for use, doses, side effects, contraindications

Flupirtine is the representative of the "Selective Neuronal Potassium Channel Opener" (SNEPCO) and refers to the non-opioid analgesics of the central action.

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, comes indirect inhibition of NMDA receptors (N-methyl-D-aspartate), since NMDA receptor blockade with Mg2 + ions persists until cell membrane depolarization occurs (indirect antagonistic action on NMDA receptors).

When therapeutically significant concentrations flupirtine does not bind to alpha1, and alpha2-, 5HT1 (5-hydroxytryptophan), 5HT2-serotonin, dopamine, benzodiazepine, opioid, central m-and n-choline receptors. Such a central action of flupirtine leads to the realization of three main effects.

Analgesic effect Due to the selective opening of potential-dependent K + channels of neurons with the concomitant release of K + ions, the resting potential of the neuron is stabilized. The neuron becomes less irritable. The indirect antagonism of flupirtine against NMDA receptors protects neurons from the entry of Ca2 + ions. Thus, the sensitizing effect of increasing the intracellular concentration of Ca ions softens.

Consequently, when the neuron is excited, inhibition of the transfer of ascending nociceptive impulses occurs.

The miorelaxing effect The pharmacological effects described for the analgesic effect are functionally supported by the increased absorption of ions by mitochondria, which occurs when therapeutically significant concentrations. The miorelaksiruyuschee effect arises as a result of 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 Chronical Processes chronicle should be

considered as processes of neural 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, to "erase" the pain memory by stabilizing the membrane potential, which leads to a decrease in pain sensitivity.

Pharmacokinetics:

After oral administration flupirtine quickly and almost completely (90%) is absorbed in the gastrointestinal tract (GIT). Up to 75% of the dose is metabolized in the liver with the formation of metabolites Ml and M2.

The active metabolite Ml (2-amino-3-acetamino-6- [4-fluoro] -benzylaminopyridine) is formed as a result of hydrolysis of the urethane structure (1 phase of the reaction) and subsequent acetylation (phase 2 of the reaction) and provides an average of 25% of the analgesic activity of flupirtine . Another metabolite of M2 is not biologically active, it is formed as a result of the oxidation reaction (1 phase) of p-fluorobenzyl followed by conjugation (2 phase) of p-fluorobenzoic acid with glycine. Studies on which isoenzyme is predominantly involved in the oxidative pathway of degradation have not been carried out.It should be expected that flupirtine will have only a small ability to interaction.

The half-life (T1 / 2) of flupirtine from the blood plasma is about 7 hours (10 hours for the main substance and metabolite Ml), which is sufficient to provide an analgesic effect.

The concentration of flupirtine in the blood plasma is proportional to the dose.

In elderly people (over 65 years) compared with young patients, there is an increase in Tf flupirtine (up to 14 hours with a single admission and up to 18.6 hours with admission for 12 days), and a maximum concentration of flupirtine in the blood plasma, respectively, in 2- 2,5 times higher.

Mostly excreted by the kidneys (69%): 27% - unchanged, 28% - in the form of metabolite Ml (acetyl-metabolite), 12% - in the form of metabolite M2 (para-fluorohypuric acid); 1/3 of the administered dose is excreted as metabolites of an unexplained structure. A small part of the dose is excreted from the body with bile and feces.

Indications:

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

Contraindications:

Increased sensitivity to the active ingredient or any other component of the preparation.

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 in connection with the miorelaksiruyuschim action flupirtina.

Patients with concomitant liver disease or alcoholism.

The simultaneous use of flupirtine with other drugs that can have a hepatotoxic 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 old

Carefully:Renal failure, hypoalbuminemia, elderly age over 65 years

Pregnancy and lactation:

There 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 drug Catadolon® can not be used in 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® can not be used during breastfeeding, except when there is an extreme need for taking the drug. If necessary

Dosing and Administration:

Inside, without chewing the capsule and squeezed enough amount of liquid

(preferably water). If possible, the drug is taken while in an upright position.

In exceptional cases, the capsule of the drug Catadolon® can be opened and taken inside / through the probe only the contents of the capsule. When ingestion of the contents of the capsule, it is recommended to neutralize its bitter taste by eating food, for example, a banana.

Apply 100 mg (1 capsule) 3-4 times a day, if possible, with equal intervals between doses. At the expressed pains - on 200 mg (2 capsules) 3 times a day. The maximum daily dose of 600 mg / day (6 capsules).

The dose is selected depending on the intensity pain and individual drug tolerance. 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: at the beginning of treatment apply 100 mg (1 capsule) 2 times a day in the morning and in the evening.

In patients with renal insufficiency: the concentration of creatinine in the blood plasma should be monitored. The maximum daily dose should not exceed 300 mg / day (3 capsules).

In patients with mild and moderate renal failure: dose adjustment is not required.

In patients with severe renal failure or from

hypoalbuminemia: the maximum daily dose should not exceed 300 mg / day (3 capsules). If it is necessary to use the drug in a higher dose, patients should be under the supervision of a doctor.

Side effects:

Undesirable reactions are classified according to 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); very rarely (1/10000); frequency is unknown (can not be estimated from available data).

From the hepatobiliary system: very often - increased activity of "liver" transaminases; frequency unknown - hepatitis, hepatic insufficiency.

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

From 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 tract: often - dyspepsia, nausea, vomiting, pain in the stomach, constipation, abdominal pain, 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, prostration, tearfulness, confusion, deafness of consciousness, dry mucous shell of the oral cavity.

After vomiting or using forced diuresis, reception of activated carbon and the introduction of electrolytes, the well-being was restored within 6-12 hours. Life-threatening conditions were not reported.

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 the manifestation 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 it binds to proteins, it should be taken into account that it can interact with other concomitant medications (eg, acetylsalicylic acid, benzylpenicillin, digoxin, glibenclamide, propranolol, clonidine, warfarin and diazepam), which can be displaced by flupirtine from binding to proteins, which can lead to strengthening their activity. Especially, this effect can be expressed by simultaneous administration of warfarin or diazepam with flupirtine.

With the simultaneous administration of flupirtine and coumarin derivatives, it is recommended that the prothrombin index be regularly monitored in order to timely adjust the dose coumarin. There are no data on interaction with other anticoagulants or antiplatelet agents (acetylsalicylic acid and etc.).

At simultaneous application of flupirtine with drugs, which

metabolized in the liver, requires regular monitoring of the level of "liver" enzymes. Combined use of flupirtine and medications containing paracetamol and carbamazepine.

Special instructions:

The drug Catadolon® should be used if treatment with other analgesics (for example, non-steroidal 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 severe signs of renal failure or hypoalbuminemia require dose adjustment.

During treatment with Catadolon®, once a week, the liver function should be monitored,as with the therapy with flupirtin may increase the activity of "liver" transaminases, the development of hepatitis and liver failure.

If the results of a liver test deviate from the norm or manifest clinical symptoms that indicate on liver damage, it should be stopped use of the drug Kadadolon®.

Patients should be warned that during treatment with Catadolon® It is necessary to pay attention to any symptoms of liver damage (eg, lack of appetite, nausea, vomiting, pain in the stomach, fatigue, dark urine, jaundice, itching). When these symptoms develop should stop taking the drug Catadolon® and urgently apply to the doctor.

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

When applying 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 Kadadolon *, 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:

Capsules of 100 mg.

Packaging:

For 10 capsules in a blister of PVC / aluminum foil.

For 1, 3, 5 blisters are placed in a cardboard box together with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years. Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N015611 / 01

Date of registration:14.01.2013

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: & nbsp21.10.2015

Illustrated instructions

Instructions

Catadolon® (Katadolon®)