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

Excipients: calcium hydrophosphate dihydrate - 219.05 mg; Copovidone - 1.00 mg; silicon dioxide colloidal - 1,70 mg; magnesium stearate - 3.25 mg; composition of the capsule: body - gelatin up to 100%, titanium dioxide (E 171) 2.1118%, cap - gelatin up to 100%, titanium dioxide (E 171) 2.1118%.

Description:

Hard gelatin capsules No. 2 with a white body and a white lid. The contents of the capsules are a powder of almost white color.

Pharmacotherapeutic group:analgesic non-narcotic remedy

ATX: & nbsp

N.02.B.G.07 Flupirtine

Pharmacodynamics:

Flupirtine is a representative of a class of medicines for selective activators of neuronal potassium channels and refers to non-opioid analgesics of central action that are not addictive and addictive.

Flupirtine activates the Gprotein neuronal K⁺ channels of internal rectification. The yield of ions K⁺ causes stabilization of the resting potential and a decrease in the excitability of neuronal membranes. As a result, indirect inhibition of receptors NMDA (N-metil-D-aspartat), since the blockade of receptors NMDA ions Mg²⁺ remains until the cell membrane depolarization occurs (an indirect antagonistic effect on the NMDA-receptors).

In therapeutic doses flupirtine does not bind to alpha and alpha₂- adrenergic receptors, serotonin (5NT₁, 5NT₂), dopamine, benzodiazepine, opioid receptors and central m- and n-choline receptors.

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

Analgesic action flupirtine is associated with the activation of potential-independent potassium channels, which leads to stabilization of the membrane potential of the nerve cell. This inhibits the activity NMDA-receptors and, as a consequence, blockade of neuronal ion channels of calcium and decrease in intracellular current of calcium cations. The analgesic effect is manifested due to the developing suppression of neuron excitation in response to nociceptive stimuli and inhibition of nociceptive activation.This leads to inhibition of 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 already developed chronic pain syndrome leads to a decrease in its intensity.

Miorelaksiruyuschee action flupirtine is associated with the blocking of excitation transfer 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). Flupirtine eliminates the muscle tone associated with pain, while not affecting the state of other muscles.

Effect on Chronification Processes. Since the functions of neurons are characterized by plasticity, development of chronification processes, that is, processes of neuronal conduction, associated with the induction of intracellular processes, is possible. At the same time, the response to each subsequent pulse is amplified, and NMDA receptors participate in the regulation of the expression of the involved genes.Therefore, the indirect inhibition of these receptors in the administration of flupirtine helps suppress the effects of chronic processes. Thus, for clinically significant development of chronic pain syndrome under the influence of flupirtine, unfavorable conditions are created, and in the case of already observed chronic pain, the stabilization of the membrane potential leads to a decrease in pain sensitivity and "erasure" of pain memory.

Also for flupirtine a specific neuroprotective effect is associated with its ability to cause blockade of neuronal ionic calcium channels, which causes the protection of nervous structures from the toxic effect of high concentrations of intracellular calcium cations.

Pharmacokinetics:

After ingestion flupirtine quickly and almost completely (90%) is absorbed in the gastrointestinal tract. Time to reach the maximum concentration of flupirtine in plasma (T_mOh) on the average is about 2.2 hours. Up to 75% of the accepted 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 the hydrolysis of the urethane structure(phase I reaction) and subsequent acetylation (phase II reaction) and provides about 25% of the analgesic activity of flupirtine.

Another metabolite M2 (para-fluorohypuric acid) is not biologically active, is formed as a result of oxidation reaction (phase I reaction) of p-fluorobenzyl, followed by conjugation (phase II reaction) of p-fluorobenzoic acid with glycine.

The half-life (T_1/2) flupirtine from plasma is about 7 hours (approximately 10 hours for the active substance and metabolite Ml), which is sufficient to provide an analgesic effect when taking the drug in accordance with the indicated dosing regimen.

The concentration of the active substance in the blood plasma is proportional to the dose taken.

In the elderly (over 65) in comparison with young patients, an increase in the half-life of the drug (up to 14 hours with a single dose and up to 18.6 hours with admission for 12 days) is observed, with the maximum concentration (C_max) flupirtine in the blood plasma, respectively, 2-2.5 times higher.

A significant portion of flupirtine (67%) is excreted by the kidneys: 27% - in an unchanged form, 28% - in the form of a metabolite Ml (acetylated), 12% - in the form of metabolite M2. 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 intensity in adults.

Contraindications:

Hypersensitivity to the active ingredient or any other component of the drug.

Patients at risk of developing hepatic encephalopathy and patients with cholestasis (as encephalopathy may develop or aggravate the course of already existing encephalopathy or ataxia).

Patients with myasthenia gravis gravis (as flupirtine has a muscle relaxant effect).

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 (since patients have a high risk of increasing the activity of "liver" enzymes).

Children under 18 years.

Carefully:

Renal failure; age over 65; hypoalbuminemia.

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. A potential risk to a person is not known. The preparation Flugesik® can not be used in pregnancy, except when the intended benefit to the mother exceeds the potential risk to the fetus.

Flupirtine and the products of its metabolism can penetrate into breast milk, therefore the preparation Flugesik® can not be used during breastfeeding. If it is necessary to prescribe the drug during breastfeeding, breastfeeding should be stopped for the period of treatment.

Dosing and Administration:

Inside, not chewing and squeezed a small amount of liquid (100 ml).

At the same time (if it is possible), keep the trunk vertically (that is, take Flugesik® in the position of the body while sitting or standing).

In exceptional cases, capsules for ingestion may be opened and their contents dissolved in water. It is recommended that you take food or a food supplement to alleviate the very bitter taste of flupirtine.

For 100 mg (1 capsule) 3-4 times a day with equal intervals between doses. At the expressed pains - on 200 mg (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. Use the lowest effective dose for the shortest possible time. Duration of treatment should not exceed 2 weeks.

Duration of therapy determined by the attending physician and depends on the dynamics of the pain syndrome and tolerability of the drug, but should not exceed 2 weeks.

Patients over 65 years of age: at the beginning of treatment for 100 mg (1 capsule) morning and evening. The dose can be increased to 300 mg (3 capsules) depending on the intensity of pain and drug tolerance.

In patients with renal insufficiency during treatment should monitor the concentration of creatinine in the plasma.

Patients with renal insufficiency light and moderate degree: correction of the dose of Flugesik® is not required.

Patients with severe renal failure or with hypoalbuminemia: the daily dose should not exceed 300 mg (3 capsules).If you need to use the drug in a daily dose of more than 300 mg, patients should be under the supervision of a doctor.

Side effects:

Classification of the incidence of adverse events is given in accordance with WHO recommendations: oFrequently: (≥ 1/10); hasto: (≥ 1/100 - <1/10); Mr.Frequently: (≥ 1/1000 - <1/100); RTerribly: (≥ 1/10000 - <1/1000); aboutrarely: (<1/10000, including individual cases); hThe frequency is unknown (can not be estimated from the available data).

From the liver and biliary tract: very often - an increase in the activity of "hepatic" transaminases; frequency is 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 nervous system: often - sleep disturbance, depression, anxiety, dizziness, tremor, headache; infrequently - drowsiness, confusion.

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.

Disorders related to metabolism: often - a decrease (up to absence) of appetite.

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 during or after the end of treatment.

Overdose:

There are reports of single cases of an overdose of flupirtine with suicidal intentions. In this case, taking 5 g of flupirtine caused the following symptoms: prostration, tachycardia, tearfulness, confusion, nausea, "stunnedness", stupor, dryness of the oral mucosa. In this case, 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; life-threatening conditions were not observed.

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: gastric lavage, forced diuresis, the introduction of activated carbon and electrolytes.

The specific antidote for an overdose of flupirtine is unknown.

Interaction:

Flupirtine enhances the effect of alcohol, sedatives and muscle relaxants.

Due to flupirtine it is necessary to take into account the possibility of its interaction with other concurrent 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 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 (in order to timely adjust the dose of coumarin derivatives). Data on the interaction with other anticoagulant or antiplatelet agents (acetylsalicylic acid and others).

With the simultaneous use of flupirtine with drugs that are metabolized in the liver, regular monitoring of the activity of "liver" enzymes (transaminase, etc.) is required.

Combined use of flupirtine and medications containing paracetamol and carbamazepine.

Special instructions:

The preparation Flugesik® should be used in case the treatment with other analgesics (for example, non-steroidal anti-inflammatory drugs or opioids) is contraindicated.

In patients with reduced renal function, the activity of creatinine in the 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").

In patients suffering from tinnitus (including recently healed), when taking flupirtine, the risk of increasing the activity of "liver" enzymes increases, and therefore the use of Flugesik® is contraindicated in such patients.

During treatment with Flugesik® once a week, the liver function status should be monitored, since it is possible to increase the activity of "liver" enzymes (transaminase, etc.), the development of hepatitis and liver failure.If the results of the liver test show a deviation from the norm or if there are clinical signs indicating liver damage, stop taking the medication. At the same time, 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 flupirtine is used in high doses, urine may be colored in green in some cases, which is not a clinical sign of any pathology.

When prescribing Flugesik®, patients should be warned that during treatment, attention should be paid to any symptoms of liver damage (eg: lack of appetite, nausea, vomiting, stomachache, fatigue, dark urine).

If these symptoms appear, stop taking the medication and seek medical attention immediately.

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

Given that flupirtine can cause dizziness, confusion, visual impairment, which can weaken attention and slow down the speed of psychomotor reactions,during treatment it is recommended to refrain from driving and working with potentially dangerous mechanisms. This indication is especially important when using alcohol at the same time.

Form release / dosage:

Capsules, 100 mg.

Packaging:

10 capsules per blister of aluminum foil and PVC film.

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

Storage conditions:

In the 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 after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003516

Date of registration:22.03.2016

Expiration Date:22.03.2021

The owner of the registration certificate:Lupine Co., Ltd.Lupine Co., Ltd. India

Manufacturer: & nbsp

LUPIN, Ltd. India

Representation: & nbspLUPIN LIMITEDLUPIN LIMITED

Information update date: & nbsp07.08.2016

Illustrated instructions

Instructions

Flugesic® (Flugesic®)