Haloperidol

General characteristics. Structure:

Active agents:  haloperidol of 1,5 mg and 5 mg.

Auxiliary ingradiyenta:  starch, lactose (sugar milk),  gelatin, talc,  magnesium stearate – before receiving  a tablet weighing 120 mg and 300 mg.

Description. Tablets of color, white or white with slightly yellowish shade, ploskotsilindrichesky, with a facet (for tablets with a dosage of 1,5 mg), with risky and a facet (for tablets with a dosage of 5 mg).

Pharmacological properties:

Antipsychotic means (neuroleptic) derivative of phenyl propyl ketone. Possesses the expressed antipsychotic action, blocks postsynaptic dopamine receptors in mesolimbic and mesocortical structures of a brain. High antipsychotic activity is combined with moderate  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.

Haloperidol деканоат in comparison with a haloperidol has longer action. Eliminates permanent changes of the personality, nonsense, hallucinations, manias, increases interest in surrounding. It is effective at patients, resistant to other antipsychotic HP. Has some activating effect. At hyperactive children eliminates an excess physical activity, behavioural frustration (impulsiveness, the complicated concentration of attention, aggression).

The therapeutic effect of the prolonged form can proceed to 6 weeks.

Pharmacokinetics. Absorption at intake - 60%. TCmax at oral administration is 3 h.  Distribution volume – 18 l/kg,  communication with proteins of plasma - 92%. Easily passes through gistogematichesky barriers, including GEB. 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. T ½  at oral administration are 24 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:

Psychoses (maniac-depressive, epileptic, against the background of schizophrenia, alcoholic, medicinal, including "steroid"), psychomotor initiation    of various genesis, nonsense and hallucinations (paranoid states, acute psychosis),    Turett's disease, an oligophrenia, the agitated depression, a chorea  of Gentington, is long a hiccups, nausea and vomiting, remaining and steady against therapy, at chemotherapy,  stutter, a behavior disorder at advanced and children's age (including a hyperactivity at  children, children's autism), psychosomatic disturbances.

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 - 1,5-5 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 1,5-2,5 mg 2-3    times a day (depending on a condition of the patient). 

To children from 3 to 12 years: 25-75 mkg/kg a day in 2-3 receptions.

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 for elektrokardioagrammy, 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.

Before purpose of the prolonged form it is necessary to transfer at first the patient from any other neuroleptic on a haloperidol (prevention of unexpected hypersensitivity to a haloperidol).

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

During reception of a haloperidol driving of vehicles,        service of mechanisms and other types of the works demanding the increased concentration of attention is forbidden. 

Side effects:

From a nervous system: a headache, sleeplessness or drowsiness (especially in  an initiation of treatment), a condition of concern, uneasiness, excitement, fears, an akathisia, euphoria or a depression, a lethargy, epilepsy attacks, development of paradoxical reaction  – an exacerbation of psychosis and hallucination; at prolonged treatment – extrapyramidal frustration, in t. h 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 (the complicated or hurried breathing, tachycardia, arrhythmia, a hyperthermia, increase or a lowering of arterial pressure, the increased sweating, an urine incontience, muscular rigidity, epileptic seizures, a loss of consciousness).

From CCC: when using in high doses –  a lowering of arterial pressure, orthostatic hypotension, arrhythmias, tachycardia, changes on an 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 central nervous a sistemuetanola, tricyclic antidepressants, opioid analgetics, barbiturates and HP hypnotic drugs, 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 adrenergic neurons and suppression of its capture by these neurons).

Slows down metabolism of tricyclic antidepressants and an ingibitorovmonoamioksidaza, 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 a paradoxical lowering of arterial pressure).

Reduces effect of protivoparkinsonichesky means (antagonistic influence on dofaminergichesky structures of TsNS).

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 своюочередь reduces their psychogogic effect (blockade by a haloperidol of alpha adrenoceptors).

Anticholinergic, antihistaminic (1 generations) and protivoparkinsonichesky medicines can strengthen m-holinoblokiruyushchee influence of a haloperidol and 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 the drugs 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  the central nervous system increases, especially extrapyramidal reactions.

At simultaneous use with the drugs causing extrapyramidal reactions increases the frequency and weight of extrapyramidal frustration.

The use of strong tea or coffee (especially in large numbers) reduces action of a haloperidol.

Contraindications:

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

Overdose:

Symptoms: muscle tension, tremor, drowsiness, decrease, and sometimes increase in arterial pressure. In hard cases – coma, respiratory depression, shock.

Treatment: at intake – a gastric lavage, absorbent carbon. At respiratory depression – IVL. For improvement of blood circulation in/in 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. In the dry, protected from light place  to Store in the place, unavailable to children. Period of validity 2 years. After validity period not to use drug.

Issue conditions:

According to the recipe

Packaging:

Tablets of 1,5 mg and 5 mg.

On 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. 

On 50 tablets in bank from polymeric materials. 

5 blister strip packagings or to 1 bank together with the application instruction place in a pack from a cardboard.