Haloperidol

General characteristics. Structure:

Active agent of a haloperidol of 1,5 mg or 5 mg;

excipients — a hypro rod (hydroxypropyl cellulose, brand Klutsel), potato starch, lactose (sugar milk), magnesium stearate, cellulose microcrystallic.

Description: tablets of color, white or white with slightly yellowish shade, a ploskotsilindrichesky form with a facet.

Pharmacological properties:

Antipsychotic means (neuroleptic) derivative of phenyl propyl ketone. Possesses the expressed antipsychotic action, sedation, (in small doses has the activating effect) and the expressed antiemetic action. Causes extrapyramidal frustration, has practically no holinoblokiruyushchy effect.

Sedative action is caused by blockade of alpha adrenoceptors of a reticular formation of a trunk of a brain; antiemetic action — blockade dopamine D2 receptors of a trigger zone of the emetic center; hypothermal action and a galactorrhoea — 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 increase and decrease — gonadotropic hormones.

Pharmacokinetics. Absorption at intake — 60%. Time of achievement of the maximum concentration at oral administration — 3 h. Distribution volume — 18 l/kg, communication with proteins of plasma — 92%. Easily passes through gistogematichesky barriers, including the blood-brain barrier (BBB).

It is metabolized in a liver, has effect of "the first passing" through a liver. Isoenzymes of CYP2D6, CYP3A3, CYP3A5, CYP3A7 take part in metabolism of drug. Is CYP2D6 inhibitor. There are no active metabolites. An elimination half-life (T1/2) at oral administration — 24 h (12–37 h).

It is removed with bile and urine: after intake with bile 15%, with urine — 40% are removed (including 1% — in not changed look). Gets into breast milk.

Indications to use:

• The acute and chronic psychoses which are followed by excitement, hallucinatory and crazy frustration, maniacal states, psychosomatic frustration.

• Disorders of behavior, change of the personality (paranoid, schizoid, and others), Gilles de la Turett's syndrome, both at children's age, and at adults.

• Tics, chorea of Gentington.

• It is long the vomiting, remaining and steady against therapy, including connected with antineoplastic therapy and a hiccups.

Route of administration and doses:

Inside, in time or after food, washing down full (240 ml) with a glass of water or milk, an initial dose for adults — 0.5–5 mg 2–3 times a day. If necessary the dose is gradually increased before achievement of desirable therapeutic effect (on average — to 10–15 mg, at chronic forms of schizophrenia — to 20–60 mg). The maximum dose — 100 mg/days. Treatment duration — 2–3 months. Reduce a dose slowly, maintenance doses — 5–10 mg/days.

To the elderly or weakened patients in an initiation of treatment appoint inside, 0.5–2 mg 2–3 times a day.

Children are 3–12 years old (or with a body weight of 15-40 kg) at psychotic frustration — inside, 0.05 mg/kg/days in 2–3 divided doses; if necessary taking into account portability the dose is increased by 0.5 mg of 1 times within 5–7 days to the general dose of 0.15 mg/kg/days. At not psychotic behavior disorders, Turett's diseases — inside, at the beginning of 0:05 mg/kg/days in 2–3 divided doses, then increase a dose by 0.5 mg of 1 times in 5–7 days to 0.075 mg/kg/days. At children's autism — inside, 0.025–0.05 mg/kg/days.

In the absence of effect within 1 month treatment is not recommended to be continued.

Features of use:

During therapy by the patient it is regularly necessary to exercise control of an ECG, a blood count, "hepatic" tests.

At development of late dyskinesia the gradual dose decline (is recommended up to full drug withdrawal).

It is necessary to be careful during the performing of hard physical activity, acceptance of a hot bathtub (development of heatstroke owing to suppression of the central and peripheral thermal control in a hypothalamus is possible).

During treatment it is not necessary to accept "anti-cold" OTC medicines (possibly strengthening of anticholinergic effects and risk of emergence of heatstroke).

It is necessary to protect open sites of skin from excess sunlight owing to the increased risk of a photosensitization.

Treatment is stopped gradually in order to avoid emergence of a syndrome of "cancellation".

Antiemetic action can mask signs of medicinal toxicity and complicate diagnosis of states which first symptom is nausea.

It is noted that doses for children of 6 mg/days cause additional improvement at behavior disorders and tics.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From a nervous system: headache, dizziness, sleeplessness or drowsiness (various degree of manifestation), condition of concern, alarm, psychomotor excitement, fear, akathisia, euphoria, depression, epileptic seizures, in rare instances exacerbation of psychosis, including hallucination; extrapyramidal frustration; at prolonged treatment — late dyskinesia (smacking and wrinkling of lips, inflation of cheeks, the bystry and worm-shaped movements of language, the uncontrollable chewing movements, the uncontrollable movements of hands and legs), late dystonia (the speeded-up blinking or spasms a century, an unusual look or position of a body, the uncontrollable bent movements of a neck, a trunk, hands and legs) and a malignant antipsychotic syndrome (a hyperthermia, muscular rigidity, the complicated or hurried breathing, tachycardia, arrhythmia, decrease or increase in arterial pressure, the increased sweating, an urine incontience, convulsive frustration, consciousness oppression).

From cardiovascular system: when using in high doses — a lowering of arterial pressure, orthostatic hypotension, arrhythmias, tachycardia, changes on an electrocardiography (ECG) (lengthening of an interval of Q-T, 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, diarrhea or locks, an abnormal liver function, up to development of jaundice.

From bodies of a hemopoiesis: seldom — a temporary leukopenia or a leukocytosis, an agranulocytosis, an erythropenia and a tendency to a monocytosis.

From urinogenital system: an ischuria (at a prostate hyperplasia), peripheral hypostases, pains in chest glands, a gynecomastia, a giperprolaktinemiya, disturbance of a menstrual cycle, decrease in a potentiality, increase in a libido, a priapism.

From sense bodys: cataract, retinopathy, sight illegibility.

Allergic reactions: makulopapulezny and akneobrazny changes of skin, a photosensitization, it is rare — a bronchospasm, a laryngospasm.

Laboratory indicators: a hyponatremia, hyper - or a hypoglycemia.

Others: alopecia, increase in body weight.

Interaction with other medicines:

Increases expressiveness of the oppressing influence on the central nervous system of ethanol, tricyclic antidepressants, opioid analgetics, barbiturates and somnolent medicines, means for the general anesthesia.

Strengthens action of peripheral m-holinoblokatorov and the majority of antihypertensives (reduces action of a guanetidin owing to replacement it from alpha and adrenergic neurons and suppression of its capture by these neurons).

Slows down metabolism of tricyclic antidepressants and inhibitors of monoaminoxidases (MAO), at the same time their sedation and toxicity increases (mutually).

At simultaneous use with bupropiony reduces an epileptic threshold and increases risk of developing of big epileptic seizures.

Reduces effect of anticonvulsants (decrease in a convulsive threshold a haloperidol).

Weakens vasoconstrictive action of a dopamine, Phenylephrinum, Norepinephrinum, ephedrine and Epinephrinum (blockade of alpha adrenoceptors a haloperidol that can lead to a perversion of action of Epinephrinum and to paradoxical decrease in the ABP).

Reduces effect of protivoparkinsonichesky means (antagonistic influence on dofaminergichesky structures of the central nervous system).

Changes (can raise or reduce) effect of anticoagulants.

Reduces action of Bromocriptinum (correction of a dose can be required).

At use from metildopy increases risk of development of mental disturbances (including a disorientation in space, delay and difficulty of processes of thinking).

Amphetamines reduce antipsychotic action of a haloperidol which in turn reduces their psychogogic effect (blockade by a haloperidol of alpha adrenoceptors).

Anticholinergic, antihistaminic (the I generations) and protivoparkinsonichesky medicines can strengthen

m-holinoblokiruyushchee influence of a haloperidol also reduce its antipsychotic action (dose adjustment can be required).

Long purpose of carbamazepine, barbiturates, etc. inductors of a microsomal oxidation reduces concentration of a haloperidol in plasma.

In combination with drugs of an ion of lithium (Li+) (especially in high doses) development of encephalopathy (can cause irreversible neurointoxication) and strengthening of extrapyramidal symptomatology is possible.

At a concomitant use with fluoxetine the risk of development of side effects from TsNS increases, especially extrapyramidal reactions.

Contraindications:

Hypersensitivity, heavy oppression of function of the central nervous system (CNS) against the background of intoxication xenobiotics, a coma of various genesis, TsNS diseases which are followed by pyramidal or extrapyramidal symptomatology (including Parkinson's disease), pregnancy, the lactation period, children's age (up to 3 years).

Patients with rare hereditary diseases, such as intolerance of a galactose, deficit of lactase or glyukozo-galaktozny malabsorption, should not accept drug.

With care
Dekompensirovanny diseases of cardiovascular system (including stenocardia, disturbances of endocardiac conductivity, lengthening of an interval of Q-T or predisposition to it is a hypopotassemia, simultaneous use of other medicines which can cause lengthening of an interval of Q-T), epilepsy and convulsive states in the anamnesis, closed-angle glaucoma, a liver and/or renal failure, a hyperthyroidism (with the thyrotoxicosis phenomena), pulmonary and cordial and respiratory insufficiency (including at a chronic obstructive pulmonary disease and acute infectious diseases), prostate hyperplasia with an ischuria, alcoholism.

Overdose:

Symptoms: consciousness oppression, muscle tension, a tremor, drowsiness, a lowering of arterial pressure, sometimes — increase in arterial pressure. In hard cases — coma, respiratory depression, shock.

Treatment: at intake — a gastric lavage, absorbent carbon. At respiratory depression — artificial ventilation of the lungs. For blood circulation improvement intravenously enter plasma or solution of albumine, Norepinephrinum. Epinephrinum in these cases is strictly forbidden to be applied! Reduction of extrapyramidal symptoms — the central holinoblokator and protivoparkinsonichesky medicines. Dialysis is inefficient.

Storage conditions:

List B. To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 3 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets on 1,5 mg and 5 mg.

On 10, 20 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 3, 5 blister strip packagings on 10 tablets or on 1, 2, 3 blister strip packagings on 20 or 30 tablets together with the application instruction place in a pack from a cardboard.