Haloperidol (Tablets, Solution) Instructions for Use

ATC Code

N05AD01 (Haloperidol)

Active Substance

Haloperidol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Psychotropic agents, antipsychotic agents, butyrophenone derivatives

Pharmacological Action

Antipsychotic agent (neuroleptic), a butyrophenone derivative. It exerts a pronounced antipsychotic effect due to the blockade of depolarization or a reduction in the degree of excitation of dopamine neurons (reduced release) and blockade of postsynaptic dopamine D₂ receptors in the mesolimbic and mesocortical structures of the brain.

It has a moderate sedative effect due to the blockade of α-adrenergic receptors in the brainstem reticular formation; a pronounced antiemetic effect due to the blockade of dopamine D₂ receptors in the trigger zone of the vomiting center; a hypothermic effect and galactorrhea due to the blockade of dopamine receptors in the hypothalamus.

Long-term use is accompanied by changes in endocrine status: in the anterior pituitary lobe, prolactin production increases and the production of gonadotropic hormones decreases.

Blockade of dopamine receptors in the dopamine pathways of the substantia nigra contributes to the development of extrapyramidal motor reactions; blockade of dopamine receptors in the tuberoinfundibular system causes a decrease in the release of growth hormone.

It has practically no anticholinergic action.

It eliminates persistent personality changes, delusions, hallucinations, manias, and enhances interest in the environment. It is effective in patients resistant to other neuroleptics. It has some activating effect. In hyperactive children, it eliminates excessive motor activity, behavioral disorders (impulsivity, difficulty concentrating, aggressiveness).

Unlike haloperidol, haloperidol decanoate is characterized by a prolonged action.

Pharmacokinetics

When taken orally, it is absorbed from the gastrointestinal tract by 60%. C_max in plasma when taken orally is reached in 3-6 hours, with intramuscular administration – in 10-20 minutes, with intramuscular administration of haloperidol decanoate – in 3-9 days. It undergoes the first-pass effect through the liver.

Protein binding is 92%. V_d at equilibrium concentration is 18 L/kg. It is actively metabolized in the liver with the participation of isoenzymes CYP2D6, CYP3A3, CYP3A5, CYP3A7. It is an inhibitor of the CYP2D6 isoenzyme. There are no active metabolites.

It easily penetrates histohematic barriers, including the blood-brain barrier. It is excreted in breast milk.

T_1/2 when taken orally is 24 hours, with intramuscular administration – 21 hours, with intravenous administration – 14 hours. Haloperidol decanoate is eliminated within 3 weeks.

It is excreted by the kidneys – 40% and with bile through the intestine – 15%.

Indications

Acute and chronic psychotic disorders (including schizophrenia, manic-depressive, epileptic, alcoholic psychoses), psychomotor agitation of various origins, delusions and hallucinations of various origins, Huntington’s chorea, intellectual disability, agitated depression, behavioral disorders in the elderly and childhood (including hyperactivity in children and childhood autism), psychosomatic disorders, Tourette’s disease, stuttering, persistent and therapy-resistant vomiting and hiccups, prevention and treatment of nausea and vomiting during chemotherapy.

ICD codes

Dosage Regimen

Tablets, Solution

When taken orally for adults, the initial dose is 0.5-5 mg 2-3 times/day, for elderly patients – 0.5-2 mg 2-3 times/day. Further, depending on the patient’s response to treatment, the dose is gradually increased in most cases to 5-10 mg/day. High doses (more than 40 mg/day) are used in rare cases, for a short time and in the absence of concomitant diseases. For children – 25-75 mcg/kg/day in 2-3 divided doses.

For intramuscular administration in adults, the initial single dose is 1-10 mg, the interval between repeated injections is 1-8 hours; when using the depot form, the dose is 50-300 mg once every 4 weeks.

For intravenous administration, the single dose is 0.5-50 mg, the frequency of administration and the dose for repeated administration depend on the indications and clinical situation.

Maximum doses when taken orally for adults – 100 mg/day; intramuscularly – 100 mg/day, when using the depot form – 300 mg/month.

Adverse Reactions

From the central nervous system headache, insomnia, restlessness, anxiety and fear, euphoria, agitation, drowsiness (especially at the beginning of treatment), akathisia, depression or euphoria, lethargy, epileptic seizure, development of a paradoxical reaction (exacerbation of psychosis, hallucinations); with long-term treatment – extrapyramidal disorders (including tardive dyskinesia, tardive dystonia and neuroleptic malignant syndrome).

From the cardiovascular system when used in high doses – arterial hypotension, tachycardia, arrhythmia, ECG changes (prolongation of the QT interval, signs of ventricular flutter and fibrillation).

From the digestive system when used in high doses – decreased appetite, dry mouth, hyposalivation, nausea, vomiting, constipation or diarrhea, impaired liver function up to the development of jaundice.

From the hematopoietic system rarely – mild and temporary leukopenia, leukocytosis, agranulocytosis, slight erythropenia and a tendency to monocytosis.

From the endocrine system gynecomastia, breast pain, hyperprolactinemia, menstrual cycle disorders, decreased potency, increased libido, priapism.

From metabolism hyper- and hypoglycemia, hyponatremia; increased sweating, peripheral edema, weight gain.

From the organ of vision visual acuity disorders, cataract, retinopathy, accommodation disorders.

Allergic reactions rarely – skin rash, bronchospasm, laryngospasm, hyperpyrexia.

Dermatological reactions maculopapular and acneiform skin changes; rarely – photosensitivity, alopecia.

Effects due to cholinergic action dry mouth, hyposalivation, urinary retention, constipation.

Contraindications

Diseases of the central nervous system accompanied by symptoms of extrapyramidal disorders, depression, hysteria, coma of various etiologies; severe toxic depression of the central nervous system caused by drugs. Pregnancy, lactation. Children under 3 years of age. Hypersensitivity to haloperidol and other butyrophenone derivatives.

Use in Pregnancy and Lactation

Haloperidol is contraindicated during pregnancy and lactation.

In experimental studies, teratogenic and fetotoxic effects were detected in a number of cases. Haloperidol is excreted in breast milk. It has been shown that the concentrations of haloperidol in breast milk are sufficient to cause a sedative effect and impaired motor functions in the breastfed infant.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

Contraindicated in children under 3 years of age. Parenteral administration is not recommended in children.

Geriatric Use

Elderly patients usually require a lower initial dose and a more gradual dose titration. This category of patients is characterized by a greater likelihood of developing extrapyramidal disorders. Careful monitoring of the patient is recommended to detect early signs of tardive dyskinesia.

Special Precautions

Parenteral administration is not recommended in children.

Use with caution in cardiovascular diseases with signs of decompensation, myocardial conduction disorders, QT interval prolongation or risk of QT interval prolongation (including hypokalemia, simultaneous use with drugs that can prolong the QT interval); in epilepsy; angle-closure glaucoma; hepatic and/or renal insufficiency; in thyrotoxicosis; cardiopulmonary and respiratory insufficiency (including COPD and acute infectious diseases); in prostatic hyperplasia with urinary retention; in chronic alcoholism; simultaneously with anticoagulants.

In case of tardive dyskinesia development, it is necessary to gradually reduce the dose of haloperidol and prescribe another drug.

There are reports of the possibility of diabetes insipidus symptoms, exacerbation of glaucoma, and a tendency (with long-term treatment) to develop lymphomonocytosis during therapy with haloperidol.

Elderly patients usually require a lower initial dose and a more gradual dose titration. This category of patients is characterized by a greater likelihood of developing extrapyramidal disorders. Careful monitoring of the patient is recommended to detect early signs of tardive dyskinesia.

During treatment with neuroleptics, the development of neuroleptic malignant syndrome is possible at any time, but it occurs most often shortly after the start of therapy or after switching a patient from one neuroleptic agent to another, during combined treatment with another psychotropic drug, or after a dose increase.

Do not consume alcohol during treatment.

Effect on the ability to drive vehicles and operate machinery

During the use of haloperidol, one should refrain from engaging in potentially hazardous activities that require increased attention and high speed of psychomotor reactions.

Drug Interactions

With simultaneous use with drugs that have a depressant effect on the central nervous system, with ethanol, an increase in central nervous system depression, respiratory depression and hypotensive action is possible.

With simultaneous use of drugs that cause extrapyramidal reactions, an increase in the frequency and severity of extrapyramidal effects is possible.

With simultaneous use of drugs with anticholinergic activity, an increase in anticholinergic effects is possible.

With simultaneous use with anticonvulsants, a change in the type and/or frequency of epileptiform seizures is possible, as well as a decrease in the concentration of haloperidol in blood plasma; with tricyclic antidepressants (including desipramine) – the metabolism of tricyclic antidepressants decreases, the risk of seizures increases.

With simultaneous use, Haloperidol potentiates the effect of antihypertensive agents.

With simultaneous use with beta-blockers (including propranolol), severe arterial hypotension is possible. A case of severe arterial hypotension and cardiac arrest has been described with the simultaneous use of haloperidol and propranolol.

With simultaneous use, a decrease in the effect of indirect anticoagulants is observed.

With simultaneous use with lithium salts, the development of more pronounced extrapyramidal symptoms is possible due to the enhancement of dopamine receptor blockade, and when used in high doses, irreversible intoxication and severe encephalopathy are possible.

With simultaneous use with venlafaxine, an increase in the concentration of haloperidol in blood plasma is possible; with guanethidine – a decrease in the hypotensive effect of guanethidine is possible; with isoniazid – there are reports of an increase in the concentration of isoniazid in blood plasma; with imipenem – there are reports of transient arterial hypertension.

With simultaneous use with indomethacin, drowsiness and confusion are possible.

With simultaneous use with carbamazepine, which is an inducer of liver microsomal enzymes, an increase in the rate of metabolism of haloperidol is possible. Haloperidol may increase the concentration of carbamazepine in blood plasma. Manifestation of neurotoxicity symptoms is possible.

With simultaneous use, a decrease in the therapeutic effect of levodopa, pergolide is possible due to the blockade of dopamine receptors by haloperidol.

With simultaneous use with methyldopa, sedative effect, depression, dementia, confusion, dizziness are possible; with morphine – the development of myoclonus is possible; with rifampicin, phenytoin, phenobarbital – a decrease in the concentration of haloperidol in blood plasma is possible.

With simultaneous use with fluvoxamine, there are limited reports of a possible increase in the concentration of haloperidol in blood plasma, which is accompanied by a toxic effect.

With simultaneous use with fluoxetine, the development of extrapyramidal symptoms and dystonia is possible; with quinidine – an increase in the concentration of haloperidol in blood plasma; with cisapride – prolongation of the QT interval on the ECG.

With simultaneous use with epinephrine, a “perversion” of the pressor action of epinephrine is possible, and as a result – the development of severe arterial hypotension and tachycardia.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.