Melperon hexal

Melperone hexal is an antipsychotic, belongs to the group of butyrophenone derivatives.

The active ingredient of the drug is the substance melperone (under the guise of hydrochloride), which is included in the category of butyrophenones. This component has a neuroleptic effect characteristic of butyrophenones, which varies from weak to moderate. According to animal tests, butyrophenones block the action of dopamine endings, thereby weakening the intensity of the influence of the dopamine neurotransmitter.

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Indications Melperone hexal

It is used for the following disorders:

• insomnia, confusion, psychosis and agitation of a psychomotor nature (especially in people with mental disorders and the elderly);
• dementia (associated with organic lesions of the central nervous system);
• hypophrenia;
• neuroses (if it is impossible to use tranquilizers due to hypersensitivity or the risk of addiction);
• alcoholism.

Release form

The medicinal element is released in tablets - 20 pieces inside a blister pack, 2 packs inside a pack.

Pharmacodynamics

In vitro testing has shown that melperone has a lower synthesis rate with D2-terminals than with haloperidol (almost 200 times). In addition to dopaminergic activity, the drug exhibits a strong antiserotonergic effect.

The central and peripheral antihistamine and anticholinergic effects of the drug are difficult to assess.

The antipsychotic effect develops only with the administration of large doses of the drug.

In addition to the effects described above, which are usually observed in neuroleptics with weak activity, melperone is capable of exerting a muscle relaxant effect and an antiarrhythmic effect.

The drug differs from other neuroleptics in that when administered in therapeutic doses, it does not have a negative effect on the brain's seizure threshold. The corresponding tests have shown that a slight increase in this threshold can be observed when using the drug in average medicinal doses.

The effect of melperone on extrapyramidal motor activity is rather weak.

Pharmacokinetics

When taken orally, melperone is completely and rapidly absorbed into the blood and then participates in intensive metabolic processes during the first intrahepatic passage. Plasma Cmax values are recorded after 60-90 minutes from the moment of oral administration.

Increasing the dosage results in a non-linear increase in plasma Cmax levels, which occurs due to the peculiarities of intrahepatic metabolism.

The level of synthesis with intraplasmic protein is 50% (of which 18% is with serum albumin).

Food intake does not change the intensity of drug absorption or its blood levels.

The drug undergoes intrahepatic metabolism almost completely and at high speed. In animal tests, a number of metabolic components were found in the urine.

5-10% of the active ingredient is excreted unchanged through the kidneys. The half-life of a single dose is approximately 4-6 hours. After repeated administration, this figure increases to approximately 6-8 hours.

Dosing and administration

The dose of Melperon Hexal should be selected taking into account the person's weight and age, as well as his/her personal tolerance, and in addition the intensity and type of the disease. In this case, the doctor is most important to be guided by the possibility of maximally reducing the dose and duration of therapy.

The daily dose should be divided into several doses. A single dose should be taken with food (especially if a sedative effect is required), before bedtime. It is forbidden to use with tea, coffee or milk.

To obtain a mild sedative and enhanced anxiolytic effect, which improves mood, a daily dose of 20-75 mg is often used. To achieve a stronger sedative effect, the maximum dosage can be used (in the evening).

Persons with confusion and agitation should initially take 0.05-0.1 g of the drug per day. If necessary, the dose can be increased to 0.2 g over several days. In some cases with severe disorders, in which aggressiveness, hallucinations and illusions are observed, the maximum dose of 0.4 g can be administered.

There are often no restrictions on the term of use of the drug. The required antipsychotic effect may not develop for 2-3 weeks of treatment. Then, taking into account the patient's personal reaction, the dose can be reduced.

Combined use with lithium substances requires a reduction in the dosage of both medications.

Use Melperone hexal during pregnancy

Melperon Hexal should not be used during pregnancy because there is too little information available regarding its safety for a newborn baby.

Due to the lack of information regarding the volume of the active component excreted in breast milk, if there is a need to use the drug during lactation, breastfeeding should be discontinued during therapy.

Contraindications

Main contraindications:

• severe intolerance to melperone, other butyrphenones or other components of the drug;
• acute poisoning or coma caused by taking opiates, alcohol, sleeping pills and other psychotropic drugs that weaken the central nervous system (including antidepressants and neuroleptics, as well as lithium salts);
• severe liver failure.

Side effects Melperone hexal

Therapeutic doses of drugs often have no effect (or have a weak effect) on the processes of blood circulation, respiration, urination, digestion of food and liver function.

At the initial stage of therapy, fatigue or (occasionally) orthostatic dysregulation/decrease in blood pressure, or a reflex increase in heart rate may develop. People with cardiopathy should have their ECG readings regularly monitored, because they sometimes develop arrhythmia.

The use of large doses of Melperon Hexal, taking into account the individual reaction of the body, can lead to a disorder of involuntary movements (the appearance of extrapyramidal disorders). Among the signs are early dyskinesia (spasm of the pharyngeal muscles, having a spastic form of tongue bite, torticollis, oculogyric crisis, spasm affecting the muscles of the jaw, and rigidity of the neck muscles) and manifestations of shaking palsy (rigidity or tremor) and akathisia (the appearance of hyperkinesia).

The development of the early stage of dyskinesia and signs of shaking palsy is controlled by reducing the dose of the drug or introducing anticholinergic antiparkinsonian drugs. Cancellation of the neuroleptic completely eliminates these signs. But akathisia is more difficult to cure. First, you can try to reduce the dose of the drug, and if there is no result, prescribe treatment with the introduction of bipyridene, sedative or hypnotic drugs or substances that block the action of β-adrenergic receptors.

Sometimes a temporary connection is noted between the appearance of an early type of dyskinesia and the use of melperone. But in all such cases, other medications were used together with this drug or before its administration, which can provoke such a side symptom. Therapy for it has not yet been developed.

Rarely, intrahepatic cholestasis or jaundice occurs, and the action of intrahepatic enzymes is temporarily increased.

When administering butyrophenones, epidermal signs of allergy (exanthema) have been observed occasionally.

Sometimes the use of melperone leads to the appearance of disorders associated with the blood system - pancytopenia, leukopenia or thrombocytopenia. Agranulocytosis is observed sporadically.

Rarely, especially when administering highly active neuroleptics in large doses, potentially fatal NMS (with temperature readings above 40°C, suppression of consciousness reaching coma, rigidity, as well as decompensation of a vegetative nature with increased blood pressure and tachycardia) may develop, requiring immediate discontinuation of the drug. As in the case of intoxication, such adverse effects require emergency medical care.

Galactorrhea, weight loss, dysmenorrhea and sexual dysfunction are occasionally observed.

It is also possible to develop thermoregulatory or accommodation disorders, headaches, olfactory disorders (due to nasal congestion), xerostomia, constipation, vomiting with nausea, and in addition, loss of appetite, urinary disorders and an increase in the level of intraocular pressure.

As with other sedative psychotropic drugs, the use of the drug increases the risk of developing venous thrombosis in the pelvic and leg areas - this factor should be taken into account in cases of bed rest, prolonged immobility or a predisposition to this disorder.

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Overdose

Due to the wide range of therapeutic dosages of melperone, poisoning is detected only in cases of significant overdose. Not all of the manifestations listed below have been observed in cases of intoxication, but none of them can be ruled out.

Signs of poisoning:

• drowsiness, which can develop into a coma, and sometimes there is also confusion of a delirious nature and agitation;
• anticholinergic symptoms (glaucoma, urinary retention, blurred vision or intestinal motility disorders);
• cardiovascular disorders (bradycardia or tachycardia, insufficiency of blood flow processes, decreased blood pressure, ventricular tachyarrhythmia or heart failure);
• hypo- or hyperthermia;
• severe stages of extrapyramidal disorders (optic spasms, acute dystonic or dyskinetic manifestations, spasms affecting the larynx or pharynx, as well as damage to the glossopharyngeal nerve);
• isolated lesions associated with respiratory activity (aspiration, cyanosis, pneumonia, respiratory arrest or suppression).

Standard symptomatic actions are carried out, which are often used in cases of poisoning; but in this case there are some peculiarities, because the drug is quickly absorbed. Gastric lavage can only be performed if poisoning is detected early. Dialysis with forced diuresis will be ineffective.

In cases of severe extrapyramidal disorders, antiparkinsonian drugs are used (for example, an intravenous injection of biperiden).

To prevent spasm of the pharyngeal muscles, intubation is performed or a muscle relaxant with a short type of action is administered.

In case of a decrease in blood pressure, in order to prevent its paradoxical increase, it is necessary to use drugs similar to norepinephrine (or noradrenaline), but it is forbidden to use substances similar to epinephrine (or adrenaline). It is forbidden to use β-adrenergic receptor agonists, because they lead to vasodilation.

Cholinolytic symptoms are eliminated with physostigmine salicylate (administration of 1-2 mg with the possibility of repeating the application). The standard dosage scheme cannot be used, because it can provoke severe side effects.

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Interactions with other drugs

Taking the medicine with alcoholic beverages may increase the alcohol's effects.

Administration in combination with medications that suppress the central nervous system (painkillers, hypnotics, antihistamines or other psychotropics) may result in increased sedative effects or respiratory depression.

Use with tricyclics may cause a reciprocal increase in activity.

The effect of antihypertensive drugs may be enhanced when combined with Melperon hexal.

Combination with dopamine antagonists (for example, levodopa) causes a decrease in the therapeutic activity of the dopamine agonist.

The use of neuroleptics simultaneously with other dopamine antagonists (for example, metoclopramide) can provoke a potentiation of the intensity of motor extrapyramidal signs.

The combined use of melperone and drugs with an anticholinergic effect (for example, with atropine) causes a potentiation of this effect. Symptoms include dysopia, xerostomia, increased IOP or heart rate, urinary disorders, constipation, hypersalivation, partial memory loss, speech problems, and hypohidrosis. The intensity of the drug's effect may be weakened due to a decrease in its absorption in the gastrointestinal tract.

Butyrophenones can form poorly soluble combinations with tea, coffee or milk, which makes it difficult for the drug to be absorbed.

Although the use of Melperone Hexal causes only a rather weak and short-term increase in prolactin levels, the effect of prolactin inhibitors (eg, gonadorelin) may be reduced. Such an interaction has not yet been noted, but its development cannot be completely ruled out.

Although the development of drug interactions with the medications listed below has not been previously recorded, they cannot be completely ruled out because melperone has α-adrenergic activity.

Amphetamine-type stimulants: a weakening of the antipsychotic effect of melperone and the stimulant activity of amphetamine is noted.

Epinephrine (or adrenaline) leads to tachycardia or a paradoxical decrease in blood pressure.

Combination with phenylephrine causes a decrease in the effect of this drug.

The use of dopamine causes vasodilation of peripheral vessels (e.g., renal arteries). The introduction of large doses of dopamine causes vasoconstriction under the action of melperone. The use of melperone can have an antagonistic effect on vasodilation of peripheral vessels (e.g., renal arteries) or, with a large dose of dopamine, vasoconstriction.

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Storage conditions

Melperon hexal should be stored in a place inaccessible to small children. Temperature values - no more than 25 ° C.

Shelf life

Melperone hexal can be used for a period of 3 years from the date of sale of the drug.

Application for children

The medication should not be prescribed to persons under 12 years of age.

Analogues

Analogues of the drug are the substances Halomond, Halopril with Haloperdol and Senorm.