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

Pharmacodynamics:A non-opioid analgesic of central action, a selective activator of neuronal K + -channels. Due to indirect antagonism to NMDA receptors, which activate the descending mechanisms of pain modulation and GABAergic processes, it has analgesic, miorelaxing and neuroprotectiveIn therapeutic concentrations, it is not associated with alpha1 and alpha2-adrenocorticalectors, 5HT1- and 5HT2-serotonindopamine, benzodiazepineopioid as well as central cholinergic receptors. In therapeutic doses, activates the potentialOther K + channels, which leads to stabilization of the membrane potential of the nerve cell. This inhibits the activity of NMDA receptors (N-methyl-D-aspartat-receptors) and as a consequence of the blockade of neuronal Ca2 + -channels, reduction of intracellular Ca2 + current, inhibition of neuronal excitation in response to nociceptive stimuli (analgesia). As a result of these processes is constrained by the formation of nociceptive (pain) sensitivity and the phenomenon of "wind up" ( "inflation" - the growth of the neuronal response to repeated painful stimuli), which prevents the increase in pain, moving her to a chronic form, and with already existing chronic pain leads to a decrease in its intensity. It has also been established that the modulating effect of flupirtine on the percept (perception) of pain is carried out through the descending noradrenergicth system. Muscle relaxant action involves blocking excitation transfer to motoneurons and intermediate neurons, leading to a weakening of muscular tension. Neuroprotectivee properties of the drug are responsible for protecting neural structures from the toxic effect of high concentrations of intracellular Ca2 +, which is associated with its ability to induce a blockade of neuronal Ca2 + -channels and to reduce current intracellular Ca2 +.

Pharmacokinetics:After oral administration, quickly and almost completely (up to 90%) is absorbed into the digestive tract.Metabolised in the liver (up to 75% of the dose) to form the active metabolite M1 (2-amino-3-acetonemino-6- [4-fluoro] -benzylaminopyridein), formed as a result of hydrolysis of the urethane structure and subsequent acetylation. M1 provides an average of 25% of the analgesic activity of flupirtine. Another metabolite (M2) - pharmacologically inactive, is formed as a result of the reaction of oxidation of parafluorobenzyl, followed by conjugation of parafluorobenzeneth acid with glycine. The half-life is 7 hours (10 hours for the active substance and metabolite Ml). The concentration of flupirtine in the blood plasma is proportional to the dose. In elderly people (over 65 years) there is an increase in the half-life of up to 14 hours with a single admission and up to 18.6 hours with admission for 12 days and a maximum concentration of 2-2.5 times, respectively. It is excreted mainly by 69% of the kidneys: 27% in unchanged form, 28% in the form of Ml, 12% in the form of M2, and 1/3 in the form of several metabolites with an unclear structure. A small part is excreted with bile.

Indications:Pain syndrome (acute and chronic): muscle spasm, malignant neoplasms, algodismenorea, headache, post traumaticpain, traumatologynon-orthopedice operations and interventions.

ICD-10

XIV.N80-N98.N94.4 Primary dysmenorrhea

XVIII.R25-R29.R25.2 Cramp and spasm

XVIII.R50-R69.R51 Headache

XVIII.R50-R69.R52.0 Acute pain

XVIII.R50-R69.R52.2 Another constant pain

Contraindications:Hypersensitivityliver failure with encephalopathy, cholestasis, severe myasthenia gravis, alcoholism, pregnancy, lactation, age under 18 years.

Carefully:Renal / hepaticinsufficiency, hypoalbuminemia, age over 65 years.

Pregnancy and lactation:

Category of recommendations for FDA is not defined. Qualitative and well-controlled studies on humans have not been conducted. Do not apply!

There is no information on the penetration into breast milk. Do not apply!

Dosing and Administration:

Inside, not liquid and squeezed a small amount of liquid (100 ml). For 100 mg 3-4 times a day with an equal interval between doses. At the expressed pains - 200 mg 3 times a day. The maximum daily dose is 600 mg.

Patients older than 65 years: at the beginning of treatment, 100 mg 2 times a day (morning and evening). The dose may be increased to 300 mg, depending on the intensity of pain and the tolerability of the drug.

With severe renal failure or hypoalbuminemia, the daily dose should not exceed 300 mg, with severe hepatic insufficiency - 200 mg.

If it is necessary to prescribe higher doses of the drug, the patients are carefully monitored.

The duration of therapy depends on the dynamics of pain syndrome and tolerability.

Side effects:

Dizziness, heartburn, nausea, vomiting, constipation or diarrhea, flatulence, abdominal pain, dry mouth, anorexia, depression, sleep disorders, sweating, anxiety, nervousness, tremor, headache.

Confusion, visual impairment and allergic reactions (hyperthermia, hives and itching), drug dependence (moderate risk).

Increased activity of transaminases (after drug cancellation return to normal), hepatitis (acute or chronic, with or without jaundice, with or without cholestasis).

Overdose:

Symptoms: nausea, tachycardia, prostration, tearfulness, confusion, dryness of the oral mucosa.

Treatment: gastric lavage, forced diuresis, Activated carbon and electrolytes. There is no specific antidote, treatment is symptomatic.

Interaction:

Warfarin, diazepam - displacing them flupirtin from the connection with proteins, the risk of overdose.

Carbamazepine, paracetamol - Do not apply at the same time.

Miorelaxants - potentiation of inhibitory effect on neuromuscular conduction.

Sedatives, ethanol - Increased oppressive effect on the central nervous system.

Special instructions:

In renal / hepatic insufficiency during the treatment period, it is necessary to monitor the activity of liver enzymes, the concentration of creatinine in the urine.

During the treatment period, 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 clinically significant.

Influence on the ability to drive vehicles and work with mechanisms.

Given that flupirtine can weaken attention and slow down the response of the body, it is recommended during the treatment to abstain from driving the vehicle and engage in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Instructions

Flupirtine (Flupirtinum)