Melperon сандоз

General characteristics. Structure:

Pharmacological properties:

Pharmacodynamics. Active ingredient of drug Melperon SANDOZ — мелперон — concerns to group of phenyl propyl ketones, has antipsychotic activity, characteristic of drugs of this group, which fluctuates from insignificant to moderate. As results of pilot studies testify, phenyl propyl ketones block dopamine receptors and thus reduce expressiveness of effects of a neurotransmitter of a dopamine. In the researches in vitro it was established that extent of linkng of a melperon with D2 receptors is nearly 200 times less, than a haloperidol. Along with dofaminergichesky properties мелперон also has the expressed antiserotoninergichesky effect. Both the central, and peripheral anticholinergic and antihistaminic effects of a melperon hard give in to assessment.
At reception of a melperon the dozozavisimy affective relaxation with a tendency to drowsiness reduction is noted. The antipsychotic effect is shown only at administration of drug in high doses.
Except the specified main effects typical for neuroleptics with low activity, мелперон can also cause muscle relaxation and have antiarrhytmic effect.
Contrary to other neuroleptics, мелперон in therapeutic doses does not raise a threshold of convulsive readiness of brain structures. It was proved that slight increase of this threshold is possible at introduction of a melperon of a hydrochloride in average therapeutic doses.
Influence of a melperon on extrapyramidal motor functions insignificant.

Pharmacokinetics. After oral administration мелперон it is quickly and completely soaked up in blood and is exposed to intensive metabolism of the first passing. Cmax in a blood plasma is defined by 1–1,5 h.
With increase in a dose note nonlinear increase in Cmax of drug in a blood plasma that it is connected with features of metabolism in a liver.
Extent of linkng with proteins of a blood plasma makes 50% (18% – a seralbumin).
Meal does not influence absorption of drug and level of its concentration in blood.
Melperon quickly and almost is completely metabolized in a liver. 5–10% of active agent are allocated with kidneys in an invariable look. Т½ after one-time oral administration — 4–6 h. At repeated introduction Т½ increases to 6–8 h.
Unlike other derivatives of phenyl propyl ketone, metabolism of a melperon does not change under the influence of inductors of liver enzymes, such as phenobarbital, Phenytoinum, carbamazepine.

Indications to use:

Dyssomnia, condition of confusion of consciousness, psychomotor excitement, agitation, especially:
• at mentally sick patients of advanced age;
• at patients with neurosises, psychoses, an oligophrenia, dementia caused by organic lesions of a brain (if tranquilizers cannot be applied in connection with intolerance or risk of development of dependence);
• at alcoholics.

Route of administration and doses:

The dose Melperona SANDOZ should be korrigirovat taking into account individual portability, age and body weight of the patient, and also type and weight of a clinical picture of a disease. The basic principle by which at the same time the doctor has to be guided is the greatest possible dose decline and reduction of duration of treatment.
For obtaining weak sedative and preferential anxiolytic effect which is followed by improvement of mood drug is used at adults and children 12 years in a dose of 20-75 mg/days are aged more senior. For achievement of more expressed sedation it is necessary to accept drug in a high dose in the evening.
For patients with agitation and confusion of consciousness the initial dose of drug makes 50–100 mg/days. In case of need it can be raised for several days to 200 mg/days. At some serious conditions of agitation and confusion of consciousness associated with aggression, and also illusory and hallucinogenic states, the daily dose of drug can be raised to maximum which makes 400 mg.
The daily dose of drug should be divided into several receptions.
For example, at use Melperon SANDOZ in the form of solution, it is necessary to accept a daily dose of 200 mg (40 ml) on 20 ml 2 times a day; the dose of 300 mg (60 ml) is distributed on 3 receptions on 20 ml; the dose of 375 mg (75 ml) of drug is accepted by 3 times on 20 ml and 1 time — on 15 ml.
The necessary amount of solution can be measured by means of a measured glass with a marking.
Melperon SANDOZ, tablets, accept with a small amount of liquid after food.
It is better to accept higher dose of a melperon before going to bed (especially in need of receiving sedation). Not to accept drug with coffee, tea or milk.
Drug use duration Melperon SANDOZ usually is not limited. The necessary antipsychotic effect can sometimes not be shown for 2–3 weeks of therapy. Further depending on individual reaction of the patient the dose can be reduced.
At simultaneous use of drugs of lithium of a dose of both medicines it is necessary to lower whenever possible.

Features of use:

Drug should be used with extra care at:
• heart diseases (even at initial stages);
• nefarmakogenny symptoms of a disease of Parkinson;
• the expressed hypotension or orthostatic dysregulation;
• quantitative changes from peripheral blood (a leukopenia, thrombocytopenia);
• prolaktinzavisimy tumors, for example tumors of a mammary gland.

Precautionary measures for patients of risk group
Melperon shows anticonvulsant properties, however in clinical conditions does not reduce a threshold of convulsive readiness of a brain therefore it can be applied at patients with epileptic attacks in the anamnesis only in a complex with anticonvulsant drugs.
Patients of advanced age should carry out treatment with care in connection with higher sensitivity to drug. Reception in low doses suffices often.
At administration of drug in high doses, and also depending on individual reaction of an organism disturbances in the form of involuntary movements (extrapyramidal frustration) are possible that can be shown in the form of early dyskinesia, symptoms of a disease of Parkinson, and also an akathisia (hyperkinesia). Early dyskinesia and symptoms of a disease of Parkinson are controlled by a dose decline of drug and/or administration of anticholinergic antiparkinsonichesky drugs. After cancellation of a neuroleptic these symptoms completely disappear. Treatment of an akathisia more difficult. At the first stage the drug dose can be lowered if it is not enough, apply therapy by sedatives, Biperidinum, somnolent drugs or blockers of β-adrenoceptors..........
It was in some cases reported about developing of the late dyskinesia connected using a melperon along with other medicines which are potentially capable to cause it.
The risk of emergence of late diskineziya and especially their irreversibility, increases depending on duration of therapy and a dose of neuroleptics. Patients of advanced age, especially women are more inclined to their development, however late dyskinesia can also develop even after short-term treatment, and also at administration of drug in low doses. Treatment by neuroleptics in an initiation of treatment can mask symptoms of late diskineziya which are shown after drug withdrawal.
Prior to treatment melperony it is necessary to carry out the analysis of indicators of peripheral blood (including the developed blood count and quantity of thrombocytes). At a deviation of the received values from norm treatment melperony should be carried out only at constant control of indicators of blood.
At patients with a cardiopathy monitoring of an ECG is necessary (through equal intervals), considering the message on possibility of arrhythmia.
The patient needs to be informed on inadmissibility of self-treatment by analgetics at display of fever, an ulitis and stomatitis, pharyngitis, quinsy, and also at flu symptoms, especially at their emergence for the first 3 months after an initiation of treatment drug.
At renal failures, a liver or circulatory system in the anamnesis мелперон it is necessary to apply with care with regular monitoring of the corresponding functions.
Emergence of high temperature of a body and muscle tension can demonstrate emergence of a malignant antipsychotic syndrome which is often incorrectly diagnosed as katatonichny schizophrenia. As in this case repeated introduction of neuroleptics is potentially dangerous, differential diagnosis is of particular importance (the medical anamnesis, the rigidity test, fever, and also increase in activity of a creatine kinase in blood serum or urine).
Melperon SANDOZ, tablets, contain lactose therefore to patients with the most rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption it is not necessary to use drug.
Melperon SANDOZ, solution oral. 5 ml of drug contain 0,56 g of sorbite of which 0,14 g of fructose are formed that about 0,05 exchange carbohydrate units are equivalent.
Sorbite can have easy laxative effect.
Use during pregnancy and feeding by a breast. Experience of use of a melperon during pregnancy is limited therefore drug is not recommended to be used during this period. Feeding by a breast during treatment by drug needs to be stopped.
Children. Drug is not used at children aged up to 12 years.
Ability to influence speed of response at control of vehicles or other mechanisms. During treatment it is necessary to refrain from control of vehicles or work with other mechanisms as emergence of side reactions from TsNS and mentality is possible.

Side effects:

Drug in therapeutic doses usually does not influence or influences slightly functions of breath, blood circulation, digestion, an urination and function of a liver.
From cardiovascular system: very seldom – hypotension, orthostatic dysregulation, reflex increase in ChSS, arrhythmia, lengthening of an interval of Q-T on an ECG; in some cases noted ventricular tachycardia like torsade de pointes. Treatment melperony in such cases should be stopped.
From TsNS: fatigue (in an initiation of treatment), the headache, the involuntary movements (extrapyramidal frustration), can be shown in the form of early dyskinesia (a spastic bite of language, a spasm of muscles of a throat, a wryneck, neck muscle tension, a spasm of maxillary muscles), Parkinson's syndrome (trembling, rigidity), an akathisia (hyperkinesia). Temporary communication between developing of early dyskinesia and reception of a melperon was sometimes traced. However in all these cases along with melperony or before its reception there were other medicines which are capable to cause similar side effect.
From a GIT: a xerostomia (dryness in a mouth), a lock, nausea, vomiting, diarrhea, lack of appetite.
From gepatobiliarny system: seldom – the taking place increase in activity of liver enzymes, deterioration in outflow of bile (an intra hepatic cholestasia), jaundice.
From skin: seldom — allergic reactions on skin (dieback).
From blood and lymphatic system: seldom – a leukopenia, thrombocytopenia, a pancytopenia; very seldom – an agranulocytosis.
From reproductive system: development of a dysmenorrhea, galactorrhoea, gynecomastia, sexual dysfunction is in some cases possible.
Other: very seldom, especially at treatment by neuroleptics in high doses, potentially lethal malignant antipsychotic syndrome can be shown (with body temperature above 40 °C, muscle tension, a vegetative decompensation with tachycardia and hypertensia, oppression of consciousness to coma), at the same time it is necessary to cancel drug immediately. It is necessary to take the emergency medical measures.
Do not exclude emergence of such symptoms as disturbance of thermal control, accommodation, an urination, decrease in sense of smell in connection with a nose congestion, increase in intraocular pressure, increase in body weight.
At reception of a melperon there is a risk of development of a vein thrombosis of the lower extremities and a basin that it is necessary to consider at an immobilization, a bed rest and/or tendency to it. Emergence of the expressed hyponatremia is not excluded.
Propylparaben (E216) and methylparaben (E218) can cause the hypersensitivity reactions (delayed including).

Interaction with other medicines:

The concomitant use of alcohol and melperon can lead to a potentsiirovaniye of effect of alcohol.
The combined use with the drugs suppressing TsNS (hypnotic drugs, analgetics, other psychotropic drugs, antihistaminic medicines) can lead to increase in sedation or respiratory depression. Administration of drug in a combination with tricyclic antidepressants can lead to reciprocal increase in effect.
The effect of anti-hypertensive medicines can be increased at the combined reception with melperony.
Simultaneous use with antagonists of a dopamine (for example a levodopa) can lead to decrease in effect of an agonist of a dopamine.
The combined use of neuroleptics and other antagonists of a dopamine (for example Metoclopramidum) can lead to increase in expressiveness of extrapyramidal motor effects.
At simultaneous use of a melperon with medicines of anticholinergic action (for example with atropine) strengthening of anticholinergic effects is possible. It can be shown in the form of a dysopia (vision disorder), increases in intraocular pressure, a xerostomia (dryness in a mouth), increases in ChSS, a lock, disturbance of an urination, salivation, difficulty of the speech, partial amnesia and decrease in sweating. Expressiveness of effect of a melperon can decrease owing to decrease in its absorption in a GIT.
Phenyl propyl ketones can form complexes with coffee, tea and milk which are badly dissolved and thereof absorption of drug is complicated.
Though at reception of a melperon note rather small and short-term increase in concentration of prolactin, effect of inhibitors of prolactin, such as гонадорелин, it can be weakened. Similar interaction with melperony was not revealed, but it is impossible to exclude it.
In spite of the fact that interactions of a melperon with following medicines still did not note, they cannot be excluded in connection with existence at a melperon of α-adrenergic effect.
Stimulators of amphetamine type can reduce antipsychotic action of a melperon.
Epinephrinum — developing of paradoxical hypotension, tachycardia is possible.
At simultaneous use with melperony reduction of expressiveness of effect of Phenylephrinum is possible.
The concomitant use of a melperon and dopamine can lead to antagonistic action on a peripheral vazodilatation (for example a renal artery) or, in case of a high dose of a dopamine, vasoconstriction.

Contraindications:

Hypersensitivity to a melperon, other phenyl propyl ketones or any of drug components; the acute intoxication and comas caused by alcohol, opiates, hypnotic drugs and other psychotropic drugs which reduce activity of TsNS (neuroleptics, antidepressants, lithium salts), a heavy liver failure, a malignant antipsychotic syndrome in the anamnesis, inborn intolerance of fructose.

Overdose:

 Due to the big range of therapeutic doses of a melperon intoxication is revealed only at its considerable overdose. In case of overdose noted not all listed below symptoms, but it is impossible to exclude any of them connected with effect of drug.
Intoxication symptoms: drowsiness up to coma, sometimes excitement and delirious confusion of consciousness; anticholinergic effects (sight opacification, glaucoma, disturbance of a vermicular movement of intestines, urination delay); cardiovascular (hypotension, tachycardia/bradycardia, ventricular tachyarrhythmia, heart failure and circulatory unefficiency); hyperthermia or hypothermia; heavy extrapyramidal frustration (acute diskinetichesky or dystonic symptoms, glossopalatine syndrome, vision disorder, spasms of a throat or throat); separate disturbances of respiratory function (cyanosis, respiratory depression, apnoea, aspiration, pneumonia).
Treatment. Therapy symptomatic is also based on the general principles of treatment of intoxication, but has certain features owing to bystry absorption of drug. The gastric lavage is effective only in case of early establishment of the diagnosis; the artificial diuresis or dialysis are ineffective; at heavy extrapyramidal symptoms apply antiparkinsonichesky means, for example Biperidinum in/in; the spasm of muscles of a throat can be prevented an intubation or use of a muscular relaxant of short action; at hypotension for prevention of paradoxical increase in pressure it is necessary to use drugs, similar to Norepinephrinum and not to appoint drugs, similar to Epinephrinum; agonists of blockers of β-adrenoceptors are not appointed (cause a vazodilatation); anticholinergic symptoms can be eliminated by means of administration of physostigmine of salicylate (1–2 mg in/in; perhaps repeated introduction), however the standard mode of dosing is not recommended, considering emergence of serious side reactions.

Storage conditions:

Period of validity 3 years. To store in the place, unavailable to children, at a temperature not above 25 °C. After opening of a bottle solution keeps the properties within 8 weeks. Drug should not be used after the termination of above-mentioned term.

Issue conditions:

According to the recipe

Packaging:

Tablets п / captivity. cover of 10 mg blister, No. 20
Tablets п / captivity. cover of 25 mg blister, No. 20
Tablets п / captivity. cover of 50 mg blister, No. 20
Tablets п / captivity. cover of 100 mg blister, No. 20
Solution of oral 5 mg/ml фл. 200 ml, with мерн. glass, No. 1

Solution of oral 5 mg/ml фл. 300 ml, with мерн. glass, No. 1