Haloperidol

General characteristics. Structure:

Active ingredient: 1,5 mg or 5,0 mg of a haloperidol.

Excipients: lactoses monohydrate, potato starch, silicon dioxide colloid A-300 or A-380 brand, talc, magnesium stearate.

Antipsychotic (the having braking effect on the central nervous system and in usual doses not causing somnolent effect) means with the expressed antipsychotic effect.

Pharmacological properties:

Pharmacodynamics. Antipsychotic means (neuroleptic) derivative of phenyl propyl ketone. Has the expressed antipsychotic effect caused by blockade of depolarization or reduction of extent of excitement of dopamine neurons (decrease in release) and blockade postsynaptic dopamine D2 receptors in mesolimbic and mesocortical structures of a brain.

Has the moderate sedative effect caused by blockade of α-adrenoceptors of a reticular formation of a trunk of a brain; the expressed antiemetic action caused by blockade dopamine D2 receptors of a trigger zone of the emetic center; hypothermal action and the galactorrhoea caused by blockade of dopamine receptors of a hypothalamus.

Long reception is followed by change of the endocrine status, in a front share of a hypophysis products of prolactin raise and products of gonadotropic hormones decrease.

Blockade of dopamine receptors in dopamine ways of black and striped substance promotes development of extrapyramidal motor reactions; blockade of dopamine receptors in tuberoinfundibulyarny system causes reduction of release of STG.

Practically has no holinoblokiruyushchy effect.

Eliminates permanent changes of the personality, nonsense, hallucinations, manias, increases interest in surrounding. It is effective at patients, resistant to other neuroleptics. Has some activating effect. At hyperactive children eliminates an excess physical activity, behavioural frustration (impulsiveness, the complicated concentration of attention, aggression).

Unlike a haloperidol haloperidol деканоат it is characterized by the prolonged action.

Pharmacokinetics. At intake it is absorbed from a GIT for 60%. Cmax in plasma at intake is reached in 3-6 h, at introduction in oil - in 10-20 min., at introduction of a haloperidol in oil of a dekanoat - 3-9 days. Is exposed to effect of "the first passing" through a liver.

Linkng with proteins makes 92%. Vd at equilibrium concentration - 18 l/kg. It is actively metabolized in a liver with the participation of isoenzymes of CYP2D6, CYP3A3, CYP3A5, CYP3A7. Is CYP2D6 isoenzyme inhibitor. There are no active metabolites.

Easily gets through gistogematichesky barriers, including GEB. It is allocated with breast milk

T1/2 at intake is 24 h, at introduction in oil - 21 h, at in introduction - 14 h. A haloperidol деканоат it is removed during 3 weeks.

It is removed by kidneys - 40% and with bile through intestines - 15%.

Indications to use:

Acute and chronic psychotic frustration (including schizophrenia, maniac-depressive, epileptic, alcoholic psychoses), psychomotor initiation of various genesis, nonsense and hallucinations of various genesis, a trochee of Gentington, an oligophrenia, the agitated depression, disorders of behavior at advanced and children's age (including hyperreactivity at children and children's autism), psychosomatic disturbances, Turett's disease, stutter, is long vomiting and a hiccups, prevention and treatment of nausea and vomiting, remaining and steady against therapy, when carrying out chemotherapy.

Route of administration and doses:

At intake for adults an initial dose - on 0.5-5 mg of 2-3 times/days, for patients of advanced age - on 0.5-2 mg of 2-3 times/days. Further, depending on reaction of the patient to treatment, a dose gradually increase in most cases up to 5-10 mg/days. High doses (more than 40 mg/days) apply in rare instances, within a short period of time and in the absence of associated diseases. For children - 25-75 mkg/kg/days in 2-3 receptions.

At introduction in oil by the adult the initial single dose makes 1-10 mg, an interval between repeated injections - 1-8 h; at use of depot form the dose makes 50-300 mg of 1 times in 4 weeks.

For in/in introductions a single dose - 0.5-50 mg, the frequency of introduction and a dose at repeated introduction depend on indications and a clinical situation.

Maximum doses: at intake for adults - 100 mg/days; in oil - 100 mg/days, at use of depot form - 300 mg/month.

Features of use:

Parenteral use for children is not recommended.

With care apply at cardiovascular diseases with the decompensation phenomena, disturbances of conductivity of a myocardium, increase in an interval of QT or risk of increase in an interval of QT (including a hypopotassemia, simultaneous use with drugs which can increase QT interval); at epilepsy; to closed-angle glaucoma; liver and/or renal failure; at a thyrotoxicosis; pulmonary and cordial and respiratory insufficiency (including at HOBL and acute infectious diseases); at a prostate hyperplasia with an ischuria; at an alcoholism; along with anticoagulants.

In case of development of late dyskinesia it is necessary to lower gradually a dose of a haloperidol and to appoint other drug.

There are messages on a possibility of emergence against the background of therapy by a haloperidol of symptoms of not diabetes mellitus, an exacerbation of glaucoma, a tendency (at prolonged treatment) to development of a limfomonotsitoz.

Patients of advanced age usually need a smaller initial dose and more gradual selection of a dose. The high probability of development of extrapyramidal disturbances is characteristic of this contingent of patients. For identification of precursory symptoms of late dyskinesia careful observation of the patient is recommended.

Against the background of treatment by neuroleptics development of ZNS is possible at any time, but most often it arises soon after the beginning of therapy or after transfer of the patient from one neuroleptic on another, during the combined treatment with other psychotropic drug or after increase in a dose.

During treatment not to allow alcohol intake.

Influence on ability to driving of motor transport and to control of mechanisms

During use of a haloperidol it is necessary to abstain from occupations potentially dangerous types of activity requiring special attention and high speed of psychomotor reactions.

The haloperidol is contraindicated at pregnancy and in the period of a lactation. In pilot studies in some cases teratogenic and fetotoksichesky action is revealed. The haloperidol is allocated with breast milk. It is shown that concentration of a haloperidol in breast milk are sufficient to cause sedation and disturbance of motive functions in the baby.

With care apply at a renal and liver failure.

Side effects:

From TsNS: a headache, sleeplessness, a condition of concern, feeling of alarm and fear, euphoria, excitement, drowsiness (especially in an initiation of treatment), an akathisia, a depression or euphoria, a lethargy, an epilepsy attack, development of paradoxical reaction (an exacerbation of psychosis, hallucination); at prolonged treatment - extrapyramidal frustration (including late dyskinesia, late dystonia and ZNS).

From cardiovascular system: at use in high doses - arterial hypotension, tachycardia, arrhythmia, changes of an ECG (increase in an interval of QT, signs of trembling and ventricular fibrillation).

From the alimentary system: at use in high doses - a loss of appetite, dryness in a mouth, a hypoptyalism, nausea, vomiting, a lock or diarrhea, abnormal liver functions up to development of jaundice.

From system of a hemopoiesis: seldom - an easy and temporary leukopenia, a leukocytosis, an agranulocytosis, an insignificant erythropenia and a tendency to a monocytosis.

From endocrine system: a gynecomastia, pains in chest glands, a giperprolaktinemiya, disturbances of a menstrual cycle, decrease in a potentiality, increase in a libido, a priapism.

From a metabolism: hyper - and a hypoglycemia, a hyponatremia; the increased sweating, peripheral hypostases, increase in body weight.

From an organ of sight: visual acuity disturbances, cataract, retinopathy, accommodation disturbances.

Allergic reactions: seldom - skin rash, a bronchospasm, a laryngospasm, a hyper pyrexia.

Dermatological reactions: makulo-papular and akneobrazny changes of skin; seldom - a photosensitization, an alopecia.

The effects caused by cholinergic action: dryness in a mouth, a hypoptyalism, an ischuria, a lock.

Interaction with other medicines:

At simultaneous use with the medicines exerting the oppressing impact on TsNS with ethanol strengthening of a depression of TsNS, respiratory depression and hypotensive action is possible.

At simultaneous use of the drugs causing extrapyramidal reactions increase in frequency and weight of extrapyramidal effects is possible.

At simultaneous use of the medicines having anticholinergic activity strengthening of anticholinergic effects is possible.

At simultaneous use with anticonvulsants change of a look and/or frequency of epileptiform attacks, and also decrease in concentration of a haloperidol in a blood plasma is possible; with tricyclic antidepressants (including with desipramine) - metabolism of tricyclic antidepressants decreases, the risk of development of spasms increases.

At simultaneous use the haloperidol exponentiates action of anti-hypertensive means.

At simultaneous use with beta adrenoblockers (including with propranolol) the expressed arterial hypotension is possible. At simultaneous use of a haloperidol and propranolol the case of heavy arterial hypotension and a cardiac standstill is described.

At simultaneous use reduction of effect of indirect anticoagulants is observed.

At simultaneous use with salts of lithium development of more expressed extrapyramidal symptoms in connection with strengthening of blockade of dopamine receptors is possible, and at use in high doses irreversible intoxication and heavy encephalopathy is possible.

At simultaneous use with venlafaksiny increase in concentration of a haloperidol in a blood plasma is possible; with guanetidiny - reduction of hypotensive action of a guanetidin is possible; with an isoniazid - there are messages on increase in concentration of an isoniazid in a blood plasma; with imipenemy - there are messages on tranzitorny arterial hypertension.

At simultaneous use with indometacin drowsiness, confusion of consciousness are possible.

At simultaneous use with carbamazepine which is the inductor of microsomal enzymes of a liver increase in speed of metabolism of a haloperidol is possible. The haloperidol can increase concentration of carbamazepine in a blood plasma. Manifestation of symptoms of a neurotoxicity is possible.

At simultaneous use decrease in therapeutic action of a levodopa, pergolid owing to blockade by a haloperidol of dopamine receptors is possible.

At simultaneous use from metildopy sedative action, a depression, dementia, confusion of consciousness, dizziness are possible; with morphine - development of a myoclonus is possible; with rifampicin, Phenytoinum, phenobarbital - reduction of concentration of a haloperidol in a blood plasma is possible.

At simultaneous use with fluvoksaminy there are limited messages on possible increase in concentration of a haloperidol in a blood plasma that is followed by toxic action.

At simultaneous use with fluoxetine development of extrapyramidal symptoms and dystonia is possible; with quinidine - increase in concentration of a haloperidol in a blood plasma; with tsizapridy - lengthening of an interval of QT on an ECG.

At simultaneous use with Epinephrinum "perversion" of pressor action of Epinephrinum is possible, and as a result of it is development of heavy arterial hypotension and tachycardia.

Contraindications:

TsNS diseases which are followed by symptoms of extrapyramidal frustration, a depression, hysteria, a coma of various etiology; the heavy toxic oppression of TsNS caused by medicines. Pregnancy, lactation. Children's age up to 3 years. Hypersensitivity to a haloperidol and other derivatives of phenyl propyl ketone.

Overdose:

In case of overdose the possibility of overdose as a result of reception of several drugs has to be considered.

Symptoms: drowsiness, sedation, consciousness oppression, tachycardia, decrease in the ABP, extrapyramidal frustration, in rare instances — lengthening of an interval of QT.

Treatment: it is necessary to provide free passability of respiratory tracts for ensuring adequate ventilation and oxygenation, a gastric lavage (after an intubation if the unconscious patient) and purpose of absorbent carbon in a combination to purgatives. The symptomatic therapy directed to maintenance of the vital functions of an organism. For timely diagnosing of possible disturbances of a heart rhythm it is necessary to begin monitoring of an ECG as soon as possible. Careful medical observation and monitoring of an ECG will see to total disappearance of symptoms of intoxication. The specific antidote is absent. Decrease in the ABP and a collapse should be eliminated in/in infusions of liquid and/or sympathomimetic drugs. In case of development of acute extrapyramidal symptoms it is necessary to appoint m-holinoblokatory (trigeksifenidit).

Storage conditions:

List B. To store in dry, protected from light and the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

10 pieces - strip packagings planimetric (aluminia/PVC) - packs cardboard.
50 pieces - banks of light-protective glass - a pack cardboard.