Nolodactak - instructions for use, dose, side effects, contraindications

active substance: flupirtine maleate in terms of 100% of the substance - 100 mg;
Excipients: calcium hydrophosphate dihydrate - 186 mg; copovidone - 6 mg; sodium carboxymethyl starch - 4.5 mg; silicon dioxide colloidal - 1.5 mg; magnesium stearate - 2 mg.

Composition of hard gelatin capsule: gelatin - 74.4572 mg; titanium dioxide - 0.76 mg; ferric oxide red oxide - 0.532 mg; ferric oxide black oxide - 0.152 mg; ferric oxide yellow oxide - 0.0988 mg.

Description:

Hard gelatin capsules number 1 brown.

The contents of the capsules are white to white powder with a gray or yellowish hue of color.

Pharmacotherapeutic group:analgesic non-narcotic agent.

ATX: & nbsp

N.02.B.G.07 Flupirtine

Pharmacodynamics:

Flupirtine is a representative of the class of drugs "selective activators of neuronal potassium channels"("Selective Neuronal Potassium Channel Opener" - SNEPCO) and refers to non-opioid analgesics of central action that are not addictive and addictive. In addition, it has a miorelaksiruyuschee effect.

Flupirtine activates G-protein-associated neuronal potassium channels of internal rectification. The yield of potassium 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, as NMDA receptors blockade with magnesium ions until cell membrane depolarization occurs (indirect antagonistic action on NMDA receptors).

In therapeutic concentrations flupirtine does not bind to alpha1, alpha2-adrenoreceptors, serotonin 5HT1, 5HT2 receptors, dopamine, benzodiazepine, opiate, central m-and n-cholinergic receptors.

The central effect of flupirtine is based on 3 main effects:

Analgesic action

Flupirtine activates the potential of non-dependent potassium channels, which leads to stabilization of the membrane potential of the nerve cell. This inhibits the activity of NMDA receptors and, as a consequence, blockade of neuronal ionic calcium channels, a decrease in the intracellular current of calcium ions.Due to the developing inhibition of neuron excitation in response to nociceptive stimuli (inhibition of nociceptive activation), an analgesic effect is realized. This inhibits the growth of the neuronal response to repeated pain stimuli, which prevents the increase of pain and its transition to a chronic form, and with the existing chronic pain syndrome leads to a decrease in its intensity. The modulating effect of flupirtine on the perception of pain through the descending noradrenergic system was also established.

Miorelaksiruyuschee action

Antispastic action on muscles is associated with blocking the transmission of excitation to motoneurons and intermediate neurons, leading to the removal of muscle tension. This action flupirtina manifests itself in many chronic diseases, accompanied by painful muscle spasms (musculoskeletal pain in the neck and back, arthropathy, tension headaches, fibromyalgia).

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, 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 M1 and M2. The active metabolite M1 (2-amino-3-acetamino-6- [4-fluoro] -bipzylaminopyridine) is formed as a result of hydrolysis of the urethane structure (phase I reaction) and subsequent acetylation (phase II reaction), provides an average of 25% of flupirtine analgesic activity .The other M2-ns metabolite is biologically active, formed as a result of the oxidation reaction (phase I reaction) of p-fluorobenzyl, followed by conjugation (phase II reaction) 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.

The half-life period (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 when taken in accordance with the indicated dosing regimen.

The concentration of the active substance 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 (up to 14 hours with a single admission and up to 18.6 hours with admission for 12 days), and the maximum concentration (Cmax) in the plasma blood, respectively, 2-2.5 times higher.

Write mainly kidneys (69%): 27% - unchanged, 28% - as a metabolite M1 (acetyl metabolite), 12% - in the form M2 metabolite (para-ftorgippurovaya 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 in the intestine.

Indications:Treatment of acute pain of mild to moderate intensity in adults.

Contraindications:

- Hypersensitivity to the active substance 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 due to the muscle relaxant effect of flupirtine.

- Patients with concomitant liver disease or alcoholism.

- The simultaneous use of flupirtine with other drugs that can have a hepatotoxic effect.

- Patients with a 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; 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 Nolodatak® 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 a small amount penetrates into breast milk. In this regard, the preparation Nolodatak® can not be used during breastfeeding except when taking the drug there is an urgent need. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, the capsule should be swallowed whole, not liquid and drink with a small amount of liquid (100 ml). If possible, keep the upper body vertically, namely, take the drug in a sitting or standing position. In exceptional cases, capsules can be opened and dissolved in water, it is recommended to add food additive to the contents to neutralize the extremely bitter taste of the drug.

1 capsule 3-4 times a day with equal intervals between doses.At the expressed pains - on 2 capsules 3 times a day. The maximum daily dose is 600 mg (6 capsules).

Doses are selected depending on the intensity of pain and the individual sensitivity of the patient to the drug.

The duration of therapy is determined by the attending physician and depends on the dynamics of the pain syndrome and tolerability. With prolonged use, the activity of "liver" transaminases should be monitored in order to identify early symptoms of hepatotoxicity. Duration of treatment should not exceed 2 weeks.
Use in special patient groups

Patients over 65 years of age: at the beginning of treatment 1 capsule in the morning and in the evening. The dose may be increased to 300 mg, depending on the intensity of pain and the tolerability of the drug.

In patients with reduced liver function The daily dose of ns should exceed 200 mg (2 capsules).

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

Patients with mild and moderate renal insufficiency: correction of the dose is not required.

Patients with severe renal failure or 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:

The following undesirable phenomena are distributed according to the incidence of side effects that develop when taking the drug and are classified according to the recommendations of the World Health Organization (WHO): very often (≥ 10%); often (≥ 1%, <10%); infrequently (≥ 0.1%, <1%); rarely (≥ 0.01%, <0.1%); very rarely (<0.01%, including individual messages); the frequency is not established - according to the available data, it is not possible to establish the frequency of occurrence.

From the liver and bile ducts: 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 fever, skin rashes, 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 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 have been 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 appearance 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 (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 an increase in the binding of proteins to the protein. 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 to monitor prothrombin time on a regular basis to timely correct the dose of coumarin.There are no data on interaction with other anticoagulants or antiplatelet agents (acetylsalicylic acid and etc.).

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

Special instructions:

The drug Nolodatac® should be used if treatment with other analgesics (for example, non-steroidal anti-inflammatory drugs (NSAIDs) or opioid preparations) is contraindicated.

In patients with tinnitus, including recently healed, the risk of increased activity of "hepatic" transaminases with flupirtine is increased, and therefore, the drug is contraindicated in such patients.

In patients with reduced renal function, creatinine levels in the blood plasma should be monitored.

In patients over 65 years of age or with severe signs of renal failure or hypoalbuminemia, dose adjustment should be performed (see the section "Dosing and Administration").

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

If the results of a liver test deviate from the norm or if there are clinical symptoms that indicate liver damage, the drug should be discontinued.

Patients should be warned that during treatment with Nolodate®, 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 medication and consult the 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.

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

When using the drug 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 100 mg.

Packaging:

10 capsules per contour cell packaging made of polyvinylchloride film and aluminum foil.

1, 3 or 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002822

Date of registration:14.01.2015

Expiration Date:14.01.2020

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp23.09.2016

Illustrated instructions

Instructions

Nolodatex® (Nolodatak)