Neuleptyl, 10 mg capsules 50 pcs

Neuleptyl is a neuroleptic of phenothiazine piperidine derivatives. It has a moderate antipsychotic and sedative effect without a stimulant component. It has adrenolytic, antispasmodic, parasympatholytic, antiemetic, hypothermic effects. It potentiates the activity of narcotic and non-narcotic-hanalgesics and sleeping pills.

It has a clear sedative effect, reduces aggressiveness, excitability and disinhibition. It has a hypnotic effect.

Because of its selective normalizing effect on behavior, Neuleptyl has been called a “behavioral adjuster.”

Pharmacokinetics

It is well absorbed from the gastrointestinal tract. After oral administration, plasma concentrations are lower than those after intravenous administration (first-pass effect through the liver) and vary widely.

The binding to plasma proteins is 90%. Intensely penetrates into tissues, as it easily passes through histohematic barriers, including the blood-encephalic barrier. It penetrates into breast milk.

Metabolized in the liver by hydroxylation and conjugation, has a “first pass” effect through the liver, is subject to hepatic recirculation.

T1/2 – 30 h. Elimination of metabolic products is longer. It is excreted by the kidneys, with bile and feces.

Indications

Active ingredient

Composition

Active ingredient:

Periciazine – 10 mg.

Auxiliary substances:

calcium hydrophosphate dihydrate,

magnesium stearate,

titanium dioxide (E 171),

gelatin.

How to take, the dosage

Neulectil, 10 mg capsules, is intended for oral administration in adult patients. In children, Neulectil 4% oral solution should be used.

The dosing regimen varies considerably depending on the indication and condition of the patient. Doses of the drug should be selected individually. If the patient’s condition allows, treatment should begin with low doses, which may then be gradually increased. The lowest effective dose should always be used.

The daily dose should be divided into 2 or 3 doses and most of the dose should always be taken in the evening. In adults, the daily dose can range from 30 mg to 100 mg. The maximum daily dose is 200 mg.

The treatment of acute and chronic psychotic disorders: the initial daily dose is 70 mg (divided into 2-3 doses). The daily dose may be increased by 20 mg per week until optimal effect is achieved (on average, up to 100 mg per day). In exceptional cases, the daily dose may be increased to 200 mg.

Correction of behavioral disorders: the initial daily dose is 10-30 mg.

Treatment of elderly patients: doses are reduced 2-4 times.

Interaction

Contraindicated combinations: with dopaminergic agonists (levodopa, amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, pyribedil, pramipexole, quinagolide, ropinirole) in patients without Parkinson’s disease – mutual antagonism between dopaminergic agonists and pericyazine. Dopaminergic agonists should not be used to treat neuroleptic-induced extrapyramidal disorders (reduction or loss of neuroleptic activity), in which case anticholinergic antiparkinsonian agents are more indicated.

Unrecommended combinations: With dopaminergic agonists (levodopa, amantadine, apomorphine, bromocriptine, cabergoline, entacapone, lisuride, pergolide, pyribedil, pramipexole, quinagolide, ropinirole) in patients with Parkinson’s disease – mutual antagonism between dopaminergic agonists and pericyazine. Dopaminergic agonists can exacerbate psychotic disorders. If patients with Parkinson’s disease receiving dopaminergic agonists require neuroleptic treatment, they should be withdrawn by gradually reducing their doses (abrupt withdrawal of dopaminergic agonists may increase the risk of malignant neuroleptic syndrome). When using pericyzine in conjunction with levodopa, the lowest effective doses of both drugs should be used. With alcohol – potentiation of the sedative effect caused by pericyazine. With amphetamine, clonidine, guanethidine – the effect of these drugs is reduced when taken concomitantly with neuroleptics. With sultopride – increased risk of ventricular arrhythmias, particularly ventricular fibrillation .

Combinations of drugs for which caution is required: with drugs that can prolong the OT interval (Class IA and III antiarrhythmics, moxifloxacin, erythromycin, methadone, mefloquine, sertindol, tricyclic antidepressants, lithium salts and cisalride, etc.) – increased risk of arrhythmias. With thiazide diuretics – increased risk of arrhythmias, due to the possibility of electrolyte disorders (hylokalemia, hylomagnesemia). With hypotensive agents, especially alpha-adrenoblockers – increased hypotensive effect and risk of orthostatic hypotension (additive effect). For clonidine and guanethidine see section “Interaction with other medicinal agents”, subsection “Unrecommended drug combinations”. With other drugs with CNS depressant effect: morphine derivatives (analgesics, cough suppressants), barbiturates, benzodiazepines, non-benzodiazepine anxiolytics, hypnotics, neuroleptics, antidepressants with sedative effect (amitriptyline, doxepin, mianserine, mirtazapine, trimipramine), histamine H1 receptor blockers with sedative effect, central hypotensive agents, baclofen, thalidomide, pizotifen – the risk of additional CNS depression, respiratory depression. With tricyclic antidepressants, MAO inhibitors, maprotiline – increased risk of malignant neuroleptic syndrome, possible increase and duration of sedative and anticholinergic effects. With atropine and other cholinolytics, as well as with drugs with cholinolytic action (imipramine antidepressants, anticholinergic antiparkinsonian drugs, disopyramide) – possibility of cumulation of adverse effects associated with cholinolytic action, such as urinary retention, constipation, dry mouth, heat stroke, etc. – as well as reducing the antipsychotic effect of neuroleptics. With beta-adrenoblockers – risk of hypotension, especially orthostatic (additive effect), and risk of irreversible retinopathy, arrhythmias and tardive dyskinesia. With hepatotoxic drugs – increased risk of hepatotoxic effects. With lithium salts – reduced absorption in the gastrointestinal tract, increased rate of lithium excretion, increased severity of extrapyramidal disorders; and the early signs of lithium intoxication (nausea and vomiting) may be masked by the antiemetic effect of phenothiazines. With alpha- and beta-adreno stimulants (epinephrine, ephedrine) – reduction of their effects, possible paradoxical reduction of blood pressure. With antithyroid drugs – increased risk of agranulocytosis. With apomorphine – reduction of the vomiting effect of apomorphine, increasing its depressing effect on the CNS. With hypoglycemic drugs – when combined with neuroleptics, hypoglycemic effect may decrease, which may require increasing their doses.

Combinations of medicinal products in administration of which there is interaction that should be taken into account: with antacids (salts, oxides and hydroxides of magnesium, aluminum and calcium) – decrease of absorption of pericyazine in the gastrointestinal tract. If possible, the interval between intake of antacids and pericyazine should be at least two hours. With bromocriptine – increased plasma prolactin concentration when taking pericyazine interferes with the effects of bromocriptine. With agents for appetite reduction (with the exception of fenfluramine ) – reduction of their effect.

Special Instructions

When taking pericyazine, it is recommended to monitor the peripheral blood regularly, especially in case of fever or infection (possibility of leukopenia and agranulocytosis). If significant changes in peripheral blood are detected (leukocytosis, granulocytopenia), treatment with pericyazine should be discontinued.

Malignant neuroleptic syndrome – If unexplained increase in body temperature, treatment with pericyazine should be stopped, because it may be a manifestation of malignant neuroleptic syndrome, early manifestations of which may also be the appearance of autonomic disorders (such as increased sweating, unstable pulse and blood pressure).

Because of the drug’s ability to lower the seizure threshold, patients with epilepsy should be closely monitored clinically and, if possible, electroencephalographically when taking pericyazine.

Except in special cases, pericyazine should not be used in patients with Parkinson’s disease. Phenothiazine derivatives neuroleptics are capable of dose-dependently prolonging the QT interval, which is known to increase the risk of severe ventricular arrhythmias, including life-threatening bidirectional pirouette-type ventricular tachycardia. Their risk increases in the presence of bradycardia, hypokalemia and prolongation of the QT interval (congenital or acquired under the influence of drugs that increase the QT interval duration). Before prescribing therapy with neuroleptics, if the patient’s condition allows, it is necessary to exclude the presence of factors predisposing to the development of these severe arrhythmias (bradycardia less than 55 beats per minute, hypokalemia, hypomagnesemia, intraventricular conduction delay and congenital prolonged QT interval or prolonged QT interval when using other QT interval prolonging drugs). These risk factors should also be monitored during treatment with the drug.

If abdominal distention and abdominal pain occur with pericyazine, necessary tests should be performed to rule out obstruction, because this side effect requires immediate action. Particular close monitoring of patients and special caution are required when prescribing pericyzine and other neuroleptics to elderly patients, patients with cardiovascular disease, patients with hepatic and renal impairment, elderly patients with dementia and patients who have risk factors for stroke.

In randomized clinical trials comparing some atypical neuroleptics to placebo conducted in elderly patients with dementia, there was a threefold increased risk of cerebrovascular events. The mechanism of this risk is not known. We cannot rule out an increase in this risk with other neuroleptics or in other patient populations, so pericyzine should be prescribed with caution in patients with risk factors for stroke.

In elderly patients with psychosis associated with dementia, an increased risk of death has been observed with antipsychotic treatment. An analysis of 17 placebo-controlled trials (mean duration greater than 10 weeks) showed that most patients treated with atypical antipsychotics had a 1.6-1.7-fold greater risk of death than patients treated with placebo. Although the causes of death in clinical trials with atypical antipsychotics varied, most causes of death were either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia ) in nature. Observational studies have confirmed that like treatment with atypical antipsychotics, treatment with conventional antipsychotics can also increase mortality. The extent to which the increase in mortality may be due to the antipsychotic medication, rather than to certain patient characteristics, is not clear.

There have been cases of venous thromboembolism, sometimes fatal, with the use of antipsychotic drugs. Therefore, pericyazine should be used with caution in patients with risk factors for thromboembolism.

Because of the possibility of withdrawal syndrome when abruptly stopping treatment with high doses of pericyazine, the drug should be withdrawn gradually when used in high doses.

Because of the possibility of photosensitization, patients receiving pericyazine should be advised to avoid direct sunlight.

Because of the fact that in persons frequently treated with phenothiazines, in very rare cases it is possible to develop skin contact sensitization to phenothiazines, direct contact of the drug with the skin should be avoided.

At the time of treatment, alcohol and preparations containing alcohol should not be taken as this potentiates the sedative effect and leads to a decrease in reaction, which may be dangerous for persons driving vehicles and mechanisms. Patients, especially those who are drivers of vehicles or persons working with other mechanisms, should be informed about the possibility of drowsiness.

Contraindications

Absolute:

The drug should be used with caution in patients with diseases of the cardiovascular system, renal and/or hepatic insufficiency, in elderly patients (excessive sedative and hypotensive effects may develop).

Side effects

Neulectil® is usually well tolerated, however, in some cases the following adverse reactions may be observed, the occurrence of which may or may not depend on the dose taken and in the latter case may be due to increased individual sensitivity of the patient.
Central nervous system
Sedation or somnolence, more pronounced at the beginning of treatment and usually disappearing after a few days.
Apathy, anxiety, mood changes.
In some cases paradoxical effects are possible: insomnia, agitation, sleep inversion, increased aggressiveness and increased psychotic symptoms.
Extrapyramidal disorders (more common when using the drug in high doses):

Overdose

Symptoms: CNS depression progressing from somnolence to coma with areflexia. In patients with initial manifestations of intoxication or moderate intoxication, restlessness, confusion, agitation, agitated or derelict state may be observed. Other manifestations of overdose include decreased blood pressure, tachycardia, ventricular arrhythmias, changes in ECS collapse, hypothermia, pupil constriction, tremor, muscle twitching, muscle spasm or rigidity, seizures, dystonic movements, muscle hypotonia, difficulty swallowing, respiratory depression, apnea, cyanosis. Polyuria leading to dehydration and severe extrapyramidal dyskinesias are also possible.

The treatment: should be symptomatic and should be carried out in a specialized department, where monitoring of respiratory and cardiovascular functions can be organized and continued until the phenomena of overdose are completely eliminated. If after drug intake less than 6 hours have passed, gastric lavage or aspiration of its contents should be carried out. Vomiting is contraindicated due to the risk of aspiration of the vomit on the background of lethargy and/or extrapyramidal disorders. Activated charcoal may be used. There is no specific antidote. Treatment should be aimed at maintaining vital body functions.

In case of decreased blood pressure, the patient should be transferred to the horizontal position with elevated legs. Intravenous infusion of fluids is indicated. If fluid administration is insufficient to relieve hypotension, norepinephrine, dopamine or phenylephrine may be given. Administration of epinephrine is contraindicated, In hypothermia, you can wait for its independent resolution, except when the body temperature decreases to the level at which cardiac arrhythmias can develop (i.e. up to 29.4 ° C).

The ventricular or supraventricular tachyarrhythmias usually respond to restoration of normal body temperature and elimination of hemodynamic and metabolic disturbances. If life-threatening rhythm abnormalities persist, antiarrhythmic drugs may need to be administered. Lidocaine and, if possible, long-acting antiarrhythmic agents should be avoided. CNS and respiratory depression may require transfer of the patient to artificial lung ventilation and antibiotic therapy to prevent pulmonary infections. Severe dystonic reactions usually respond to intramuscular or intravenous administration of procyclidine (5-10 mg) or orphenadrine (20-40 mg). Seizures may be managed with intravenous diazepam. In extrapyramidal disorders, anticholinergic antiparkinsonian agents are used intramuscularly.