International name:
Haloperidol ( Haloperidol ) Synonyms : Halofen , Aloperidin , Haldol , Halidol, Haloperidin , Haloperin , Halophen , Halopidol , Serenace , Seranase , Haloper , Novo Peridol , Senorm
Group affiliation:
Neuroleptic (antipsychotic)
Description of the active substance (INN): 4- (para Chlorophenyl ) – 1 [3′- (para – fluorobenzoyl ) -propyl] – piperidinol-4, or 4- [4- (para- chlorophenyl ) -4-hydroxypiperidino] -4 ‘-fluorobutyrophenone.
Dosage form: tablets for oral administration of 0.0005 g; 0.001 g; 0.0015 g; 0.002 g; 0.0025 g; 0.005 g and 0.01; solution for injection 0.5%; oral solution in the form of drops containing 0.002 g of the active substance in 1 ml (10 drops contain 1 mg of haloperidol); solution of haloperidol decanoate , the injection of which provides a therapeutic effect lasting about 4 weeks .
Pharmachologic effect:
Antipsychotic agent (neuroleptic), butyrophenone derivative . Due to the blockade of depolarization or a decrease in the degree of excitation of dopamine neurons and the blockade of postsynaptic dopamine D2 receptors in the mesolimbic and mesocortical structures of the brain, it has a pronounced antipsychotic effect.
Due to the blockade of α – adrenergic receptors of the reticular formation of the brain stem, it has a moderate sedative effect. Thus, it eliminates delirium, manic states, hallucinations, persistent personality changes. It also has a pronounced antiemetic effect (due to the blockade of dopamine D2 receptors in the trigger zone of the vomiting center). Influences autonomic functions (reduces the tone of hollow organs, motility and secretion of the gastrointestinal tract, eliminates spasms of blood vessels) in diseases accompanied by excitement, anxiety, fear of death. Effective in patients resistant to other antipsychotics. Unlike chlorpromazine, it does not cause lethargy and apathy in patients, on the contrary, it has an activating effect. In hyperactive children, it eliminates excessive motor activity, behavioral disorders (impulsivity, aggressiveness, difficulty concentrating).
Indications:
Acute and chronic psychotic disorders (including schizophrenia, manic-depressive, epileptic, alcoholic psychoses), psychomotor agitation of various origins (mania, dementia, mental retardation, schizophrenia, chronic alcoholism), delusions and hallucinations (paranoid states, acute psychosis ), oligophrenia, agitated depression, Tourette’s disease , Hettington ‘s chorea , behavioral disorders in children (including hyperreactivity and childhood autism) and the elderly, stuttering, psychosomatic disorders.
It is also used for intractable vomiting (including during chemotherapy for the prevention and treatment of nausea and vomiting), long-term and treatment-resistant hiccups.
In small doses (up to 10 mg) it is indicated in the treatment of reactive states and neuroses.
In the case of alcoholic delirium with visual hallucinations under the influence of haloperidol, psychomotor agitation quickly decreases, hallucinations disappear.
It can be used in combination with hypnotics, analgesics and other neurotropic drugs in preparation for surgery.
It is also known about the effectiveness of haloperidol for the relief of pain, agitation, nausea and vomiting in acute coronary insufficiency (often together with analgesics).
Contraindications:
Hypersensitivity to the drug (including other butyrophenone derivatives , sesame oil), for intramuscular and intravenous injections – children under 3 years of age, CNS diseases accompanied by pyramidal and extrapyramidal symptoms (including Parkinson’s disease), depression , coma of various origins, hysteria, severe depression of the central nervous system function against the background of intoxication with xenobiotics.
Haloperidol is categorically contraindicated during pregnancy and lactation . Experimentally proven toxic effect on the fetus, a violation of its development. It has also been established that haloperidol is excreted in breast milk (in this case, a sedative effect and impaired motor functions are found in a child during breastfeeding).
In the case of the development of tardive dyskinesia (the occurrence of phenomena such as protruding tongue, smacking lips, puffing out the cheeks, sucking, chewing, swallowing movements, grimacing, respiratory failure, rolling eyes, obsessive stereotypical movements of the limbs, head), it is necessary to gradually reduce the dose of haloperidol and prescribe another a drug.
With great caution, haloperidol is prescribed for diseases of the cardiovascular system with decompensation phenomena, conduction disorders of the heart muscle (including angina pectoris, prolongation of the QT interval on the ECG or a predisposition to it, hypokalemia , simultaneous use of other drugs that can cause an interval prolongation QT) and kidney function.
Limited use of haloperidol for epilepsy, liver and / or kidney failure, thyrotoxicosis, pulmonary heart and respiratory failure (including chronic obstructive pulmonary disease and acute infectious diseases), prostatic hyperplasia with urinary retention, alcoholism, angle-closure glaucoma.
There are reports of the possibility of the appearance of symptoms of diabetes insipidus during haloperidol therapy, a tendency (with long-term treatment) to the development of lymphomonocytosis .
Elderly patients usually require a lower initial dose and a more gradual dose adjustment due to the high likelihood of developing extrapyramidal disorders. Careful monitoring of the patient is important. During the period of treatment with haloperidol, it is necessary to refrain from drinking alcohol, and you should also refrain from engaging in potentially hazardous activities that require increased attention and a high speed of psychomotor reactions (including driving vehicles).
Side effects:
From the side of the central nervous system: headache, insomnia or drowsiness (especially at the beginning of treatment), anxiety, anxiety, fear, agitation, euphoria or depression, restlessness, epileptic attacks, paradoxical reaction (exacerbation of psychosis, hallucinations). With long-term treatment, extrapyramidal disorders may occur: tardive dyskinesia (smacking and wrinkling of the lips, pouting of the cheeks, fast and worm-like movements of the tongue, uncontrolled chewing movements, uncontrolled movements of the limbs); tardive dystonia (increased blinking, eyelid spasms, unusual facial expressions, grimacing, unusual body position, uncontrolled twisting movements of the neck, torso, arms and legs); neuroleptic malignant syndrome (difficult or rapid breathing, rapid heartbeat, heart rhythm disturbance, fever, increase or decrease in blood pressure, increased sweating, urinary incontinence, muscle rigidity, epileptic seizures, loss of consciousness).
From the side of the cardiovascular system: when using high doses – a decrease in blood pressure, orthostatic hypotension, cardiac arrhythmias, increased heart rate, ECG changes (prolongation of the QT interval, signs of flutter and ventricular fibrillation).
From the gastrointestinal tract: when using high doses – dry mouth, difficulty salivation, loss of appetite, nausea, vomiting, constipation or diarrhea, impaired liver function up to jaundice.
From the endocrine system: gynecomastia, pain in the mammary glands, increased levels of prolactin in the blood, menstrual disorders, decreased potency, increased libido, priapism.
From the genitourinary system: urinary retention (with prostatic hyperplasia), peripheral edema.
From the side of metabolism: an increase or decrease in blood glucose, a decrease in sodium in the blood, sweating, weight gain.
On the part of the hematopoietic system: rarely – mild and temporary leukopenia, leukocytosis, agranulocytosis, slight erythropenia , a tendency to monocytosis .
On the part of the organs of vision: cataract, retinopathy, blurred vision, disturbances of accommodation.
Allergic reactions: rarely – skin rash, bronchospasm, larynx. Dermatological reactions: maculo -papular and acne -like skin changes; rarely – photosensitivity, alopecia.
Overdose:
Symptoms: severe extrapyramidal disorders (tardive dyskinesia, tardive dystonia, neuroleptic syndrome), drop in blood pressure, drowsiness, lethargy, in severe cases – coma, respiratory depression, shock. Treatment: There is no specific antidote. In case of an overdose caused by ingestion of the drug, it is necessary to perform a gastric lavage, followed by the appointment of activated charcoal. With respiratory depression – taking measures for artificial ventilation of the lungs, with a pronounced decrease in blood pressure – the introduction of plasma-substituting fluids, plasma, norepinephrine (but not adrenaline!), to reduce the severity of extrapyramidal disorders – central anticholinergics and antiparkinsonian drugs.
Dosage and administration:
Haloperidol is taken orally, during or after a meal, with a full (240 ml) glass of water or milk, the initial dose for adults is 0.5-5 mg 2-3 times a day. If necessary, the dose is gradually increased until the desired therapeutic effect is achieved (on average, up to 10-15 mg, in chronic forms of schizophrenia, up to 20-60 mg). The maximum dose is 100 mg / day . Duration of treatment – 2-3 months. Reduce the dose slowly, maintenance doses – 5-10 mg / day . Elderly or debilitated patients at the beginning of treatment are prescribed orally, 0.5-2 mg 2-3 times a day. Children 3-12 years old (or weighing 15-40 kg) with psychotic disorders – inside, 0.05 mg / kg / day in 2-3 divided doses; if necessary, taking into account tolerance, the dose is increased by 0.5 mg 1 time for 5-7 days to a total dose of 0.15 mg / kg / day . With non -psychotic behavioral disorders, Tourette’s disease – inside, first 0.05 mg / kg / day in 2-3 divided doses, then the dose is increased by 0.5 mg 1 time in 5-7 days to 0.075 mg / kg / day . In childhood autism – inside, 0.025-0.05 mg / kg / day . If there is no effect within 1 month. treatment is not recommended to continue.
Haloperidol drops are taken with meals, dosed with a teaspoon, added to drinks or food, or on a piece of sugar (except for diabetics).
Adults and adolescents at the beginning of treatment usually take 0.5-1.5 mg of haloperidol 2-3 times a day (initial daily dose of 0.5-5 mg). Then the dose is gradually increased by 0.5-2 mg per day (in resistant cases by 2-4 mg per day) until the desired therapeutic effect is achieved. With the relief of acute symptoms in stationary conditions, the initial daily doses can be increased to 15 mg of haloperidol, in therapeutically resistant cases and higher.
On average, the therapeutic dose is usually 10-15 mg / day , in chronic forms of schizophrenia – 20-40 mg / day , in resistant cases – up to 50-60 mg / day . Maintenance doses (without exacerbation) on an outpatient basis can range from 0.5 to 5.0 mg / day .
In acute conditions and in cases where oral administration is not possible, intramuscular or intravenous injections are used. With “indomitable” vomiting – 1.5-2 mg 2 times a day. The average single dose for intramuscular injection is 2-5 mg, the interval between injections is 4-8 hours. In acute psychosis, 5-10 mg intravenously or intramuscularly. The specified dose can be administered repeatedly 1-2 times with an interval of 30-40 minutes until the desired effect is obtained. The maximum daily dose is 100 mg. In acute alcoholic psychosis – intravenously 5-10 mg; in case of inefficiency, an additional infusion is carried out at a dose of 10-20 mg at a rate of not more than 10 mg / min. Solution for injection containing haloperidol decanoate , strictly intramuscularly, 25 mg every 15-30 days, if necessary, it is possible to increase the dose to 100-150 mg (the interval between doses and the dose is adjusted at intervals of at least 1 month ).
Doses for children of 6 mg/ day have been shown to produce additional improvement in behavioral disturbances and tics.
Special instructions:
During therapy, patients should regularly monitor the ECG, blood tests, “liver” tests. Intramuscular and intravenous administration of haloperidol should be carried out under the close supervision of a physician (especially in elderly patients and children), when a therapeutic effect is achieved, it should be switched to oral administration. With the development of tardive dyskinesia, a gradual dose reduction is recommended (up to the complete withdrawal of the drug). Care must be taken when performing heavy physical work, taking a hot bath (heat stroke may develop due to suppression of central and peripheral thermoregulation in the hypothalamus). Exposed skin should be protected from excessive solar radiation due to an increased risk of photosensitivity.
During treatment, you should not take “anti-cold” OTC drugs (possibly increased anticholinergic effects and the risk of heat stroke).
Treatment is stopped gradually in order to avoid the occurrence of the “withdrawal” syndrome. Antiemetic activity can blur the picture of drug toxicity and make it difficult to diagnose conditions whose first symptom is nausea. When a concentrated solution of haloperidol for oral administration is mixed with coffee, tea or lithium citrate syrup, free haloperidol may precipitate.
Before prescribing a prolonged form, the patient should first be transferred from any other antipsychotic to haloperidol (prevention of unexpected hypersensitivity to haloperidol).
Interaction:
Increases the severity of the inhibitory effect on the central nervous system of ethanol, tricyclic antidepressants, opioid analgesics, barbiturates and hypnotics, drugs for general anesthesia, it is possible to increase respiratory depression and hypotensive action.
With the simultaneous use of drugs that cause extrapyramidal reactions, it is possible to increase the frequency and severity of extrapyramidal effects.
Enhances the effect of peripheral m – anticholinergics and most antihypertensive drugs (reduces the effect of guanethidine due to its displacement from alpha-adrenergic neurons and suppression of its uptake by these neurons). With simultaneous use with venlafaxine , an increase in the concentration of haloperidol in the blood plasma is possible; with isoniazid – there are reports of an increase in the concentration of isoniazid in the blood plasma; with imipenem – there are reports of transient arterial hypertension. With simultaneous use with beta-blockers (including propranolol ), a strong decrease in blood pressure is possible. With the simultaneous use of haloperidol and propranolol , a case of severe arterial hypotension and cardiac arrest has been described.
Weakens the vasoconstrictor effect of dopamine, phenylephrine , norepinephrine, ephedrine and epinephrine (blockade of alpha – adrenergic receptors by haloperidol, which can lead to a perversion of the action of epinephrine and to a paradoxical decrease in blood pressure).
With simultaneous use with epinephrine, a “perversion” of the pressor action of epinephrine is possible, and as a result of this, the development of severe arterial hypotension and tachycardia.
With simultaneous use with anticonvulsants, it is possible to change the type and / or frequency of epileptiform seizures, as well as a decrease in the concentration of haloperidol in the blood plasma, reduces the effect of anticonvulsants (reduction of the convulsive threshold with haloperidol). It inhibits the metabolism of tricyclic antidepressants and MAO inhibitors, while increasing (mutually) their sedative effect and toxicity, seizures may develop.
Reduces the effect of antiparkinsonian drugs (antagonistic effect on the dopaminergic structures of the central nervous system), which in turn can enhance the m – anticholinergic effect of haloperidol and reduce its antipsychotic effect (dose adjustment may be required).
When used with methyldopa , it increases the risk of developing mental disorders (including disorientation in space, confusion, slowing down and difficulty in thinking processes, sedation, depression, dementia, dizziness).
With simultaneous use, it is possible to reduce the therapeutic effect of levodopa , pergolide due to blockade of dopamine receptors by haloperidol.
When used with carbamazepine (which is an inducer of microsomal liver enzymes), it is possible to increase the rate of metabolism of haloperidol. Haloperidol may increase plasma concentrations of carbamazepine . Possible manifestation of symptoms of neurotoxicity . Changes (may increase or decrease) the effect of anticoagulants.
Amphetamines reduce the antipsychotic effect of haloperidol, which in turn reduces their psychostimulant effect (blockade of alpha- adrenergic receptors by haloperidol ); when used with morphine, myoclonus may develop . Long-term administration of barbiturates reduces the plasma concentration of haloperidol.
With simultaneous use with fluvoxamine , there have been cases of an increase in the concentration of haloperidol in the blood plasma, which is accompanied by a toxic effect.
With simultaneous use with fluoxetine, extrapyramidal symptoms and dystonia may develop; with quinidine – an increase in the concentration of haloperidol in the blood plasma; with cisapride – prolongation of the QT interval on the ECG.
Anticholinergic, antihistamine (I generation) and antiparkinsonian drugs can increase the m- anticholinergic effect of haloperidol and reduce its antipsychotic effect (dose adjustment may be required).
With simultaneous use with indomethacin, drowsiness and confusion are possible.
With simultaneous use with lithium salts, more pronounced extrapyramidal symptoms may develop due to increased blockade of dopamine receptors, and when used in high doses, irreversible intoxication and severe encephalopathy are possible. The use of strong tea or coffee (especially in large quantities) reduces the effect of haloperidol.