Composition, form of production and packaging
The long-acting tablets are oblong, biconcave, even on one side and with a risk on the other side, light yellow or yellow with light and dark impregnations.
1 tab.
flupirtine maleate 400 mg
Auxiliary substances: copolymer of methyl methacrylate and ethyl acrylate [2: 1] - 22.5 mg, talc - 22.5 mg, calcium hydrophosphate dihydrate 38 mg, microcrystalline cellulose 59.74 mg, croscarmellose sodium 34.95 mg, hypromellose 8 mg, iron oxide yellow oxide E172) - 6.25 mg, silicon dioxide colloidal anhydrous - 2.06 mg, magnesium stearate - 6 mg.
7 pcs. - blisters made of PVC / aluminum foil (1) - packs of cardboard.
10 pieces. - blisters from PVC / aluminum foil (2) - packs cardboard.
14 pcs. - blisters made of PVC / aluminum foil (1) - packs of cardboard.
14 pcs. - blisters of PVC / aluminum foil (3) - packs of cardboard.
14 pcs. - blisters of PVC / aluminum foil (6) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Selective activator of neuronal potassium channels. According to its pharmacological effects, the drug is a non-narcotic analgesic of central action that does not cause addiction and dependence.
Flupirtine activates G-protein-associated neuronal potassium 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 occurs, since the NMDA receptor blockade with Mg 2+ ionspersists until the cell membrane depolarization occurs (indirect antagonistic action on NMDA receptors).
In therapeutically significant concentrations, flupirtine does not bind to? 1 - and? 2- adrenoreceptors, 5HT 1 (5-hydroxytryptophan) -, 5HT 2 -serotonin receptors, 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 potential-dependent potassium 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 Ca 2+ ions . Thus, the sensitizing effect of increasing the intracellular concentration of Ca 2+ ions is mitigated.
Consequently, when the neuron is excited, inhibition of the transfer of ascending nociceptive impulses occurs.
Miorelaxing effect
The pharmaceutical effects described for the analgesic effect are functionally supported by the 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 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 for "erasing" the pain memory by stabilizing the membrane potential, which leads to a decrease in the pain threshold of sensitivity.
PHARMACOKINETICS
Suction
After oral administration, approximately 90% of flupirtine is absorbed from the gastrointestinal tract, and after rectal administration about 70% of the dose is absorbed.
After taking flupirtine in doses of 50 to 300 mg, its concentration in the blood plasma is dose-dependent.
The pharmacokinetics of the preparation Catadolon В® forte is due to the peculiarities of its dosage form: the rapidly released flupirtine fraction (100 mg) and the slowly released flupirtin fraction (300 mg). With a single application of the drug C max flupirtine 0.8 Ојg / ml (0.4-1.5 Ојg / ml) was achieved after 2.4 hours, and with repeated administration (400 mg daily for 7 days) after 1.9 hours, with C max being 1 Ојg / ml (0.6-2.4
μg / ml). Under the influence of food, a slight increase in absorption occurs (AUC 0- 14.1 μg / ml-h compared to 10.7 μg / ml-h), as well as an increase in C max (1 μg / ml compared to 0.8 μg / ml), with T mах increased (3.2 h compared to 2.4 h).
Metabolism
About 3/4 of the dose of flupirtine is metabolized in the liver. Metabolite M1 (2-amino-3-acetamino-6- (4-fluoro) -benzylaminopyridine) forms 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 an insignificant potential for drug interaction.
Excretion
Most of the accepted dose of flupirtine (69%) is excreted by the kidneys. This part is characterized by the following: 27% - unchanged, 28% - metabolite M1 (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.
T 1/2 is about 15 hours; when eating, T 1/2 decreases. The main metabolite is output somewhat slower (T 1/2 about 20 h and 16 h, respectively).
Pharmacokinetics in special clinical cases
In elderly patients (over 65 years) after repeated administration of the drug Catadolon ® forte on 1 tablet of prolonged action per day for 7 days against a background of increased values ​​of the distribution, an increase in AUC was observed of 0-24 : 22.9 μg / ml · h compared to 16.8 μg / ml? h for a control group consisting of younger patients; In addition, an increase in T 1/2 was observed in older patients (23.72 h compared to 15.94 h).
In patients with impaired renal function (CK <30 mL / min), compared to patients in the control group, there was an increase in AUC of 0-24 : 23.11 Ојg / mL-h compared to 16.8 Ојg / mL-h, as well as an increase in T 1 / 2 (20.01 h compared with 15.94 h).
INDICATIONS
- Treatment of acute pain of mild to moderate severity in adults.
DOSING MODE
The drug is taken orally, without chewing the tablet and squeezed with a sufficient amount of liquid (preferably water).
To reduce pain for the shortest period of time prescribed 400 mg (1 tab.) 1 time / day. This dose is the total daily dose. If this dose is not effective, then Catadolon В®can be used in the form of capsules in a larger daily dose.
The dose is selected depending on the intensity of pain and individual tolerance of the drug. Use the minimum effective dose for the shortest possible time. Duration of treatment should not exceed 2 weeks.
Patients older than 65 years: the initial dose of 200 mg (1/2 tab.) 1 time / day. With good tolerability, the dose can be increased to 400 mg (1 tab.) 1 time / day. The maximum daily dose is 400 mg.
In patients with renal insufficiency , the concentration of creatinine in the blood plasma should be monitored. In patients with mild to moderate renal insufficiency,dose adjustment is not required. In case of severe renal insufficiency, the initial dose is 200 mg (1/2 tab.) 1 time / day. With good tolerability, the dose can be increased to 400 mg (1 tab.) 1 time / 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 В® forte, prolonged-release tablets 400 mg, in this category of patients. In such cases, you should use Katalolon В® in the form of capsules 100 mg.
SIDE EFFECT
Determination of the frequency of adverse reactions: very often (> 1/10); often (> 1/100, but <1/10); infrequently (> 1/1000, but <1/100); rarely (> 1/10 000, but <1/1000); very rarely (1/10 000); 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.
From the digestive system: often - dyspepsia, nausea, vomiting, pain in the stomach, constipation, abdominal pain, dryness of the oral mucosa, flatulence, diarrhea.
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 - confusion.
From the side of the organ of vision: infrequently - impaired vision.
From the skin and subcutaneous tissues: often - sweating.
Other: very often fatigue / weakness (in 15% of patients), especially at the beginning of treatment.
Adverse reactions 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.
CONTRAINDICATIONS
- hypersensitivity to the components of the drug;
- Patients with a risk of developing hepatic encephalopathy and patients with cholestasis, can develop encephalopathy or aggravate the course of already existing encephalopathy or ataxia;
- Patients with myastenia gravis due to the miorelaksiruyuschim action flupirtina;
- patients with concomitant liver disease or alcoholism;
- simultaneous use of flupirtine with other drugs that can have hepatotoxic effects;
patients with newly healed or existing ringing in the ears; patients have a high risk of increased activity of "hepatic" enzymes;
- Children and adolescence under 18 years.
With caution: renal failure, hypoalbuminemia, elderly patients over 65 years of age.
PREGNANCY AND LACTATION
Data on the use of flupirtine in pregnancy is not enough. Catadolon В® forte should not be used during pregnancy, except when the benefit to the mother exceeds the potential risk to the fetus.
In experimental animal studies, the reproductive toxicity of flupirtine is shown, but not teratogenicity. The potential risk to humans is unknown.
According to the studies, flupirtine in small amounts is excreted in breast milk. In this regard, Catadolon В® forte should not be used during breastfeeding, except when there is an extreme need for taking the drug. If the use of the drug Catadolon В® forte is necessary during lactation, breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in violations of kidney function.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in liver diseases, incl. accompanied by cholestasis and a high risk of developing hepatic encephalopathy.
APPLICATION FOR CHILDREN
Contraindicated in children and adolescents under 18 years.
APPLICATION IN ELDERLY PATIENTS
Contraindicated in patients older than 65 years.
SPECIAL INSTRUCTIONS
Catadolon В® forte 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.
In patients older than 65 years old or with symptoms of severe renal insufficiency, dose adjustment is required.
During treatment with Catadolon В® fort fort once a week, it is necessary to monitor the liver function status, as with flupirtin it is possible to increase the activity of hepatic transaminases, the development of hepatitis and hepatic insufficiency. If the liver test results differ from the norm or if there are clinical symptoms that indicate liver damage, then the use of the drug Catadolon В® forte should be discontinued.
Patients should be cautioned that during treatment with the Catadolon В® Fort, any symptoms of liver damage (eg, lack of appetite, nausea, vomiting, stomach pain, fatigue, dark urine, jaundice, pruritus) should be taken into account. If these symptoms occur, stop taking the drug Catadolon В® forte and seek medical advice immediately.
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.
Impact on the ability to drive vehicles and manage mechanisms
When using the drug Catadolon В® Fort, patients should refrain from driving vehicles and controlling mechanisms, due to the risk of developing 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.
OVERDOSE
Symptoms: There are reports of single cases of overdose with suicidal intentions. When flupirtine was taken in a dose of 5 g, nausea, tachycardia, prostration, tearfulness, confusion, stunned consciousness, dryness of the oral mucosa were observed. 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: after vomiting or use of 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. It should be symptomatic treatment. The specific antidote is unknown.
DRUG INTERACTION
Strengthens the action of ethanol, sedatives and muscle relaxants.
Due to the fact that flupirtine has a high degree of binding to proteins, it can change the degree of binding to 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 binding to 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 correct the dose of indirect anticoagulants. There are no data on the interaction with other anticoagulant and antiplatelet agents (including acetylsalicylic acid).
With the simultaneous use of flupirtine with drugs that are metabolized in the liver, regular monitoring of hepatic enzyme activity is required. Combined use of flupirtine and drugs containing paracetamol and carbamazepine should be avoided.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
KTDL-RU-00076-DOC-06092017
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, protected from light at a temperature of no higher than 25 В° C. Shelf life - 3 years.
