Ardalon

Ardalon

Flupirtine

Capsules

Acute pain of mild to moderate severity in adults (treatment).

Inside, do not chew the capsule and drink enough liquid (preferably water). If possible, the drug is taken while in an upright position.

In exceptional cases, the capsule of the drug Neurodolon can be opened and taken orally/injected through the probe only the contents of the capsule, when ingesting the contents of the capsule, it is recommended to neutralize its bitter taste with food, such as a banana.

Apply 100 mg (1 capsule) 3-4 times a day with equal intervals between doses. For severe pain — 200 mg (2 caps.) 3 times a day. The maximum daily dose is 600 mg/day (6 capsules).

The doses are selected depending on the intensity of the pain and the individual tolerability of the drug. The minimum effective dose should be used for the shortest possible period of time. The duration of treatment should not exceed 2 weeks.

Patients over 65 years of age: at the beginning of treatment-100 mg (1 capsule) 2 times a day in the morning and in the evening. The dose can be increased to 300 mg depending on the intensity of the pain and the tolerability of the drug.

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 to moderate renal insufficiency no dose adjustment is required.

In patients with severe renal insufficiency or with 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.

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

patients at risk of developing hepatic encephalopathy and patients with cholestasis, because encephalopathy may develop or the course of existing encephalopathy or ataxia may worsen,

patients with myasthenia gravis gravis due to the muscle relaxant effect of flupirtin,

patients with concomitant liver disease or alcoholism,

concomitant use of flupirtin with other drugs that may have a hepatotoxic effect,

patients with recently cured or existing tinnitus, because these patients patients have a high risk of liver enzyme activity,

children under 18 years of age.

With caution: renal failure, hypoalbuminemia, elderly over 65 years of age.

Who classification in the incidence of side effects: very often — ≥1/10 appointments (≥10%), often from ≥1/100 to <1/10 appointments (≥1 and <10%), infrequently — dated ≥1/1000 to <1/100 appointments (≥0.1 and <1%) , and from ≥1/10000 to <1/1000 appointments (≥0.01 and <0.1% of), very rarely — <1/10000 appointments (<0,01%), frequency unknown (cannot be estimated on the basis of available data).

From the side of the hepatobiliary system: very often — increased activity of hepatic transaminases, the frequency is unknown-hepatitis, liver failure.

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

On the part of the visual organ: infrequently-visual impairment.

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 on their own as the treatment is carried out or after the end of treatment.

Symptoms: (after taking flupirtin in a dose of 5 g) nausea, tachycardia, prostration, tearfulness, stupor, confusion, deafness of consciousness, dryness of the oral mucosa. In the case of overdose or signs of intoxication, it should be borne in mind the possibility of violations of the central nervous system, as well as manifestations of hepatotoxicity by the type of increased metabolic disorders in the liver.

There are reports of isolated cases of overdose with suicidal intentions.

Treatment: induction of vomiting or the use of forced diuresis, the appointment of activated carbon and the introduction of electrolytes. In this case, the state of health was restored within 6-12 hours. No life-threatening conditions were reported. Conduct symptomatic treatment. The specific antidote is unknown.

Flupirtin is a representative of selective activators of neuronal potassium channels (Selective Neuronal Potassium Channel Opener — SNEPCO) and refers to non-opioid analgesics of central action. Flupirtin activates G-protein-bound neuronal cells. -channels for internal rectification. The release of ions To it causes the stabilization of the resting potential and a decrease in the excitability of the neuronal membranes. As a result, indirect inhibition of NMDA receptors (N-methyl-B-aspartate) occurs, since the blockade of NMDA receptors by Mg ions² it persists until depolarization of the cell membrane occurs (indirect antagonistic effect on NMDA receptors).

At therapeutically significant concentrations, flupirtin does not bind to alpha₁- , alpha₂-, 5NT₁- (5-hydroxytryptophan)-, 5NT₂- serotonin, opioid, central m-and n-cholinergic receptors.

This central action of flupirtin leads to the realization of three main effects.

Analgesic effect. Due to the selective opening of potential-dependent K channels of neurons with a concomitant release of ions To - the resting potential of the neuron is stabilized. The neuron becomes less excitable.

Indirect anatagonism of flupirtin against MNDA receptors protects neurons from the entry of Ca ions² . Thus, the sensitizing effect of increasing the intracellular concentration of Ca ions is mitigated² . Consequently, when the neuron is excited, the transmission of ascending nociceptive impulses is inhibited.

Muscle relaxant effect. The pharmacological effects described for the analgesic effect are functionally supported by increased absorption of Ca ions² mitochondria, which occurs at therapeutically significant concentrations. The muscle relaxant effect occurs as a result of concomitant inhibition of the transmission of impulses to motor neurons and the corresponding effects of insertion neurons. Thus, this effect manifests itself mainly in relation to local muscle spasms, and not the entire musculature as a whole.

The effect of the process of chronification. The process of chronification should be seen as processes of neuronal conduction, due to the plasticity of neuronal functions through induction of intracellular processes elasticity functions of neurons creates the conditions for the implementation of the mechanisms of inflation at which the gain response for each subsequent pulse. NMDA receptors (gene expression) are largely responsible for triggering such changes.). Indirect blockade of these receptors under the action of flupirtin leads to the suppression of these effects. Thus, unfavorable conditions are created for clinically significant chronization of pain, and in the case of previously present chronic pain-for erasing pain memory by stabilizing the membrane potential, which leads to a decrease in pain sensitivity

After oral administration, flupirtin is rapidly and almost completely (90%) absorbed into the gastrointestinal tract. Up to 75% of the dose is metabolized in the liver to form metabolites.₁ and M₂. The active metabolite M₁ (2-amino-3-acetamino-6-(4-fluoro)-benzylaminopurine) formed by the hydrolysis of the urethane structure (1-phase reaction) and subsequent acetylation (2nd phase reaction) and provides an average of 25% of anaesthetic activity flupirtine.

Another metabolite — M₂ - it is not biologically active, it is formed as a result of the oxidation reaction (phase 1) of p-fluorobenzyl followed by conjugation (phase 2) of p-fluorobenzoic acid with glycine. Studies on which isoenzyme is predominantly involved in the oxidative degradation pathway have not been conducted. It should be expected that flupirtin will have only a minor ability to interact.

T_1/2 flupirtin from the blood plasma is about 7 h (10 h - for the main substance and metabolite M₁), which is sufficient to provide an analgesic effect.

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

In elderly patients (over 65 years of age), compared with young patients, there is an increase in T_1/2 (up to 14 hours for a single dose and up to 18.6 hours for a 12-day dose) and C_max the level of the drug in the blood plasma is 2-2. 5 times higher,respectively.

Most of it is excreted by the kidneys (69%): 27% - in unchanged form, 28% - in the form of the metabolite M₁ (acetyl-metabolite), 12% - as a metabolite of M₂ (persipura acid), 1/3 of the administered dose was excreted as metabolites outstanding structure. A small portion of the dose is excreted from the body with bile and feces.

• Non-narcotic analgesic agent [Other non-narcotic analgesics, including non-steroidal and other anti-inflammatory drugs]

Increases the effect of alcohol, sedatives and muscle relaxants.

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

With the simultaneous use of flupirtin and indirect anticoagulants-coumarin derivatives-it is recommended to regularly monitor the PV in order to adjust the dose of indirect anticoagulants in a timely manner. There are no data on interaction with other anticoagulant or antiplatelet agents (including acetylsalicylic acid).

With the simultaneous use of flupirtin with drugs that are metabolized in the liver, regular monitoring of the activity of liver enzymes is required. The combined use of flupirtin and drugs containing paracetamol and carbamazepine should be avoided.