Instruction for use: Katadolon

Active substance Flupirtine

ATX code N02BG07 Flupirtine

Pharmacological groups

Other non-narcotic analgesics, including non-steroidal and other anti-inflammatory drugs

Nosological classification (ICD-10)

R52.0 Acute pain

Acute pain syndrome, Acute pain syndrome with osteoarthritis, Acute pain syndrome of traumatic origin, Severe pain of a neurogenic nature, Severe pain, Pain syndrome at delivery

R52.2 Other constant pain

Pain syndrome, rheumatic origin, Pain at vertebral lesions, Pain in the chamber, Pain for burns, Pain syndrome weak or moderate, Perioperative pain,Moderate to severe pain, Moderately or weakly expressed pain syndrome, Moderate to severe pain, Ear pain of otitis, Neuropathic pain, neuropathic pain

Composition

Capsules 1 caps.

active substance:

flupirtine maleate 100 mg

auxiliary substances: calcium hydrophosphate dihydrate - 212 mg; copovidone - 4 mg; magnesium stearate - 3.5 mg; silicon dioxide colloidal - 0.5 mg

capsule shell: gelatin - 52.9704 mg; purified water 8.82 mg; iron dye red oxide (E172) - 0.945 mg; titanium dioxide - 0.2079 mg; sodium lauryl sulfate - 0.0567 mg

Description of dosage form

Capsules: opaque hard gelatinous (body and lid - red-brown color), size 2.

Contents of capsules: powder from white to light yellow or grayish-yellow, or light green color.

pharmachologic effect

Pharmacological action - miorelaksiruyuschee, analgesic central.

Pharmacodynamics

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

Flupirtine activates G-protein-associated neural K + channels of internal rectification. 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 receptors (N-methyl-D-aspartate) occurs, since NMDA receptor blockade with Mg2 + ions persists until the cell membrane depolarization occurs (indirect NMDA receptor antagonism).

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

Such a central action of flupirtine leads to the realization of three main effects.

Analgesic effect

Due to the selective opening of the 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 Ca2 + ions is mitigated.

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

Miorelaxing effect

The pharmacological effects described for the analgesic effect are functionally supported by increased absorption of Ca2 + ions by mitochondria, which occurs at 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 the chronification processes

Chronicification processes should be considered as processes of neuronal conduction, due to the plasticity of the functions of neurons. Through the induction of intracellular processes, the elasticity of the functions of the neurons creates the conditions for the realization of mechanisms such as "inflation", under which the response to each subsequent impulse increases. NMDA receptors (gene expression) are responsible for the launch of such changes. 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 ingestion flupirtine quickly and almost completely (90%) is absorbed into the digestive tract. Up to 75% of the dose is metabolized in the liver with the formation of metabolites M1 and M2. The active metabolite M1 (2-amino-3-acetamino-6- (4-fluoro) -benzylaminopyridine) is formed as a result of hydrolysis of the urethane structure (1st reaction phase) and subsequent acetylation (reaction 2-stage) and provides an average of 25 % analgesic activity of flupirtine. Another metabolite, M2, is not biologically active, is formed as a result of the oxidation reaction (1st phase) of p-fluorobenzyl followed by conjugation (2nd 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 capacity for interaction.

T1 / 2 flupirtine from the blood plasma is about 7 hours (10 hours for the main substance and metabolite M1), 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 T1 / 2 flupirtine (up to 14 hours with a single dose and up to 18.6 hours with admission for 12 days) and Cmax flupirtine in blood plasma, respectively, in 2- 2,5 times higher.

Mostly excreted by the kidneys (69%): 27% - unchanged, 28% - in the form of metabolite M1 (acetyl-metabolite), 12% - in the form of metabolite M2 (p-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

hypersensitivity to the active substance or any other component of the drug;

risk of development of hepatic encephalopathy and cholestasis, as. can develop encephalopathy or aggravate the course of already existing encephalopathy or ataxia;

myasthenia gravis in connection with the miorelaksiruyuschim action flupirtina;

concomitant liver disease or alcoholism;

simultaneous application of flupirtine with other drugs that can have hepatotoxic effects;

recently healed or existing ringing in the ears, due to the high risk of increased hepatic enzyme activity;

children's age till 18 years.

With caution: kidney failure; hypoalbuminemia; old age (patients older than 65 years).

pregnancy and lactation

There is insufficient data on the use of flupirtine in pregnancy. In experimental animal studies, flupirtin showed reproductive toxicity, but not teratogenicity. The potential risk to humans is unknown. The drug Katadolon® can not be used in pregnancy, except when the benefit to the mother exceeds the potential risk to the fetus.

According to the research, flupirtine penetrates into breast milk in a small amount. In this regard, Katadolon® 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® during lactation, breastfeeding should be stopped.

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 - an increase in the activity of hepatic transaminases; frequency unknown - hepatitis, hepatic insufficiency.

On the part of the immune system: infrequently - hypersensitivity to the drug, allergic reactions (in some cases accompanied by fever, skin rash, urticaria, 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.

Interaction

Strengthens the effect of alcohol, sedatives and muscle relaxants. Due to the fact that flupirtine binds to proteins, it should be considered the possibility of its interaction with other concomitant drugs (for example, acetylsalicylic acid, benzylpenicillin, digoxin, glibenclamide, propranolol, clonidine, warfarin and diazepam), which can be displaced by flupirtine from binding to proteins, which can lead to an increase in 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 correct the dose of coumarin in a timely manner. There are no data on the interaction with other anticoagulants or antiplatelet agents (including acetylsalicylic acid). With the simultaneous use of flupirtine with drugs that are metabolized in the liver, regular monitoring of the level of liver enzymes is required. Combined use of flupirtine and drugs containing paracetamol and carbamazepine should be avoided.

Dosing and Administration

Inside, not liquid and squeezed a small amount of liquid (preferably water). If possible, the drug is taken while in an upright position.

In exceptional cases, the capsule of the drug Katadolon® 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 caps.) 3-4 times a day, if possible with equal intervals between doses. At the expressed pains - on 200 mg (2 caps.) 3 times a day. The maximum daily dose is 600 mg (6 caps.).

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: at the beginning of treatment, apply 100 mg (1 caps.) 2 times a day in the morning and in the evening.

Patients with severe renal failure or hypoalbuminemia: the concentration of creatinine in the blood plasma should be monitored. The maximum daily dose should not exceed 300 mg (3 caps.). If it is necessary to use the drug in a higher dose, patients should be under the supervision of a doctor.

Patients with mild and moderate renal insufficiency: should monitor the concentration of creatinine in the blood plasma, dose adjustment is not required.

Overdose

There are reports of single cases of overdose with suicidal intentions. At the same time taking a dose of 5 g of flupirtine caused the following symptoms: nausea, tachycardia, prostration, tearfulness, confusion, stunned consciousness, dryness of the oral mucosa.

After vomiting or using forced diuresis, reception of activated carbon and the introduction of electrolytes, the state of health was restored within 6-12 hours. No life-threatening conditions were reported.

In case of overdose or signs of intoxication, one should bear in mind the possibility of 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.

Treatment: symptomatic. The specific antidote of the drug is unknown.

special instructions

The preparation Katadolon® should be used if treatment with other analgesics (for example, 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 Katadolon®, once a week, the liver function should be monitored, when flupirtin is used, an increase in hepatic transaminase activity, hepatitis and hepatic insufficiency may occur. If the results of the liver test deviate from the norm or if there are clinical symptoms that indicate liver damage, then the use of the Katadolon® drug should be discontinued. Patients should be cautioned that during treatment with the Katadolon® drug, attention should be paid to any symptoms of liver damage (eg, lack of appetite, nausea, vomiting, stomach pain, fatigue, dark urine, jaundice, pruritus). If these symptoms occur, stop taking the Katadolon® and consult a doctor as a matter of urgency.

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

Influence on the ability to drive vehicles and work with machinery. When using the drug Kadadolon®, you should refrain from driving vehicles and controlling mechanisms, because patients may 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 of issue

Capsules, 100 mg. In a blister of PVC / aluminum foil, 10 pcs. 1, 3 or 5 blisters in a cardboard bundle.

Conditions of leave from pharmacies

On prescription.

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 after the expiry date printed on the package.