|Systematic (IUPAC) name|
|Oral, intramuscular injection, intravenous therapy, depot (as decanoate ester)|
|Biological half-life||14–26 hours (IV), 20.7 hours (IM), 14–37 hours (oral)|
|Excretion||Biliary (hence in faeces) and in urine|
|CAS Registry Number|
|Molecular mass||375.9 g/mol|
Haloperidol, marketed under the
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- Kornhuber, Johannes; Schultz, Andreas; Wiltfang, Jens; Meineke, Ingolf; Gleiter, Christoph H.; Zöchling, Robert; Boissl, Karl-Werner; Leblhuber, Friedrich; Riederer, Peter (1999). "Persistence of Haloperidol in Human Brain Tissue". The American Journal of Psychiatry 156 (6): 885–90.
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- "Veterinary:Avian at Lloyd Center Pharmacy".
Haloperidol is also used on many different kinds of animals. It appears to be particularly successful when given to birds, e.g., a parrot that will otherwise continuously pluck its feathers out.
It is sold under the tradenames Aloperidin, Bioperidolo, Brotopon, Dozic, Duraperidol (Germany), Einalon S, Eukystol, Haldol (common tradename in the US and UK), Halosten, Keselan, Linton, Peluces, Serenace and Sigaperidol.
Haloperidol is heavily protein bound in human plasma, with a free fraction of only 7.5 to 11.6%. It is also extensively metabolized in the liver with only about 1% of the administered dose excreted unchanged in the urine. The greatest proportion of the hepatic clearance is by glucuronidation, followed by reduction and CYP-mediated oxidation, primarily by CYP3A4.
Distribution and metabolism
The concentration of haloperidol in brain tissue is about 20-fold higher compared to blood levels. It is slowly eliminated from brain tissue, which may explain the slow disappearance of side effects when the medication is stopped.
Plasma levels of four to 25 micrograms per liter are required for therapeutic action. The determination of plasma levels can be used to calculate dose adjustments and to check compliance, particularly in long-term patients. Plasma levels in excess of the therapeutic range may lead to a higher incidence of side effects or even pose the risk of haloperidol intoxication.
The bioavailability is 100% in intravenous (IV) injection, and the very rapid onset of action is seen within seconds. The T1/2 is 14.1 to 26.2 hours. The apparent volume of distribution is between 9.5 to 21.7 L/kg. The duration of action is four to six hours. If haloperidol is given as a slow IV infusion, the onset of action is slowed, and the duration of action is prolonged.
The drug is well and rapidly absorbed with a high bioavailability when injected intramuscularly. The Tmax is 20 minutes in healthy individuals and 33.8 minutes in patients with schizophrenia. The mean T1/2 is 20.7 hours. The decanoate injectable formulation is for intramuscular administration only and is not intended to be used intravenously. The plasma concentrations of haloperidol decanoate reach a peak at about six days after the injection, falling thereafter, with an approximate half-life of three weeks.
The bioavailability of oral haloperidol ranges from 60–70%. However, there is a wide variance in reported mean Tmax and T1/2 in different studies, ranging from 1.7 to 6.1 hours and 14.5 to 36.7 hours respectively.
- Dopamine D1 (Silent antagonist) – Unknown efficiency
- Dopamine D5 (Silent antagonist) – Unknown efficiency
- Dopamine D2 (inverse agonist) – 1.55nM
- Dopamine D3 (Inverse agonist) – 0.74nM
- Dopamine D4 (inverse agonist) – 5–9nM
- Sigma 1(Irreversible inactivation by HPP+) – 3nM
- Sigma 2 agonist: 54nM
- 5HT1A receptor agonist – 1927nM
- 5HT2A (Silent antagonist) – 53nM
- 5HT2C (Silent antagonist) – 10,000nM
- 5HT6 (Silent antagonist) – 3666nM
- 5HT7 (Irreversible silent antagonist) – 377.2nM
- Histamine H1 (Silent antagonist) – 1800nM
- Muscarinic M1 (Silent antagonist) – 10,000nM
- Alpha Adrenergic 1a (Silent antagonist) – 12nM
- Alpha Adrenergic 2a (Silent antagonist) – 1130nM
- Alpha Adrenergic 2b (Silent antagonist) – 480nM
- Alpha Adrenergic 2c (Silent antagonist) – 550nM
- NR1\NR2B Subunit containing NMDA receptor antagonist (Ifenprodil site): IC50 – 2,000 nM
Haloperidol acts on these receptors: (Ki)
Haloperidol is a typical butyrophenone type antipsychotic that exhibits high affinity dopamine D2 receptor antagonism and slow receptor dissociation kinetics. It has effects similar to the phenothiazines. The drug binds preferentially to D2 and Alpha 1 receptors at low dose (ED50 = 0.13 and 0.42 mg/kg, respectively), and 5-HT2 receptors at a higher dose (ED50 = 2.6 mg/kg). Given that antagonism of D2 receptors is more beneficial on the positive symptoms of schizophrenia and 5-HT2 receptors on the negative symptoms, this characteristic underlies haloperidol's greater effect on delusions, hallucinations and other manifestations of psychosis. Haloperidol's negligible affinity for histamine H1 receptors and muscarinic M1 acetylcholine receptors yields an antipsychotic with a lower incidence of sedation, weight gain, and orthostatic hypotension though having higher rates of treatment emergent extrapyramidal symptoms.
In general, the prognosis of overdose is good, and lasting damage is not known, provided the person has survived the initial phase. An overdose of haloperidol can be fatal.
Treatment is merely symptomatic and involves intensive care with stabilization of vital functions. In early detected cases of oral overdose, induction of emesis, gastric lavage, and the use of activated charcoal can all be tried. Epinephrine is avoided for treatment of hypotension and shock, because its action might be reversed. In the case of a severe overdose, antidotes such as bromocryptine or ropinirole may be used to treat the extrapyramidal effects caused by haloperidol, acting as dopamine receptor agonists. ECG and vital signs should be monitored especially for QT prolongation and severe arrhythmias should be treated with antiarrhythmic measures.
- Severe extrapyramidal side effects with muscle rigidity and tremors, akathisia, etc.
- Hypotension or hypertension
- Anticholinergic side effects (dry mouth, constipation, paralytic ileus, difficulties in urinating, decreased perspiration)
- Coma in severe cases, accompanied by respiratory depression and massive hypotension, shock
- Rarely, serious ventricular arrhythmia (torsades de pointes), with or without prolonged QT-time
- Epileptic seizures
Symptoms are usually due to side effects. Most often encountered are:
Experimental evidence from animal studies indicates the doses needed for acute poisoning are quite high in relation to therapeutic doses. Overdoses with depot injections are uncommon, because only certified personnel are legally permitted to administer them to patients.
- Other central depressants (alcohol, tranquilizers, narcotics): actions and side effects of these drugs (sedation, respiratory depression) are increased. In particular, the doses of concomitantly used opioids for chronic pain can be reduced by 50%.
- Methyldopa: increased risk of extrapyramidal side effects and other unwanted central effects
- Levodopa: decreased action of levodopa
- Tricyclic antidepressants: metabolism and elimination of tricyclics significantly decreased, increased toxicity noted (anticholinergic and cardiovascular side effects, lowering of seizure threshold)
- Lithium: rare cases of the following symptoms have been noted: encephalopathy, early and late extrapyramidal side effects, other neurologic symptoms, and coma.
- Guanethidine: antihypertensive action antagonized
- Epinephrine: action antagonized, paradoxical decrease in blood pressure may result
- Amphetamine and methylphenidate: counteracts increased action of norepinephrine and dopamine in patients with narcolepsy or ADD/ADHD
- Amiodarone: Q-Tc interval prolongation (potentially dangerous change in heart rhythm).
- Other drugs metabolized by the CYP3A4 enzyme system: inducers such as carbamazepine, phenobarbital, and rifampicin decrease plasma levels and inhibitors such as quinidine, buspirone, and fluoxetine increase plasma levels 
- Pre-existing Parkinson's disease or dementia with Lewy bodies
- Patients at special risk for the development of QT prolongation (hypokalemia, concomitant use of other drugs causing QT prolongation)
- Compromised liver function, as haloperidol is metabolized and eliminated mainly by the liver
- In patients with hyperthyreosis, the action of haloperidol is intensified and side effects are more likely.
- IV injections: risk of hypotension or orthostatic collapse
- Patients with a history of leukopenia: a complete blood count should be monitored frequently during the first few months of therapy and discontinuation of the drug should be considered at the first sign of a clinically significant decline in white blood cells.
- Elderly patients with dementia-related psychosis: analysis of 17 trials showed the risk of death in this group of patients was 1.6 to 1.7 times that of placebo-treated patients. Most of the causes of death were either cardiovascular or infectious in nature. It is not clear to what extent this observation is attributed to antipsychotic drugs rather than the characteristics of the patients. The drug bears a boxed warning about this risk.
- Pre-existing coma, acute stroke
- Severe intoxication with alcohol or other central depressant drugs
- Known allergy against haloperidol or other butyrophenones or other drug ingredients
- Known heart disease, when combined will tend towards cardiac arrest
- Acute hepatic failure
- Liver function test abnormal
- Anaphylactic reaction
- Psychotic disorder
- Confusional state
- Torsades de pointes
- Ventricular fibrillation
- Ventricular tachycardia
- Laryngeal oedema
- Leukocytoclastic vasculitis
- Dermatitis exfoliative
- Photosensitivity reaction
- Urinary retention
- Sudden death
- Face oedema
- Injection site abscess
- Pulmonary embolism
- Tardive dyskinesia
- Neuroleptic malignant syndrome
- Rare (<1% incidence)
- Prolonged QT interval
- Orthostatic hypotension
- Increased respiratory rate
- Visual disturbances
- Unknown frequency
- Extrapyramidal side effects such as: (As haloperidol is a high-potency typical antipsychotic, it tends to produce significant extrapyramidal side effects. According to a recent meta-analysis of the comparative efficacy and tolerability of 15 antipsychotic drugs it was the most prone of the 15 for causing extrapyramidal side effects.)
Anticholinergic side effects such as: (These adverse effects are more common than with lower-potency typical antipsychotics, such as chlorpromazine and thioridazine.)
- Dry mouth
- Blurred vision
- Somnolence (which is not a particularly prominent side effect, as is supported by the results of the aforementioned meta-analysis.)
- Common (>1% incidence)
Sources for the following lists of adverse effects
Topical formulations of haloperidol should not be used as treatment for nausea because research does not indicate this therapy is more effective than alternatives.
The decanoate ester of haloperidol (haloperidol decanoate, trade names Haldol decanoate, Halomonth, Neoperidole) has a much longer duration of action, so is often used in people known to be noncompliant with oral medication. A dose is given by intramuscular injection once every two to four weeks. The IUPAC name of haloperidol decanoate is 4-(4-chlorophenyl)-1-1[4-(4-fluorophenyl)-4-oxobutyl]-4 piperidinyl decanoate.
- Depot forms are also available; these are injected deeply intramuscularly at regular intervals. The depot forms are not suitable for initial treatment, but are suitable for patients who have demonstrated inconsistency with oral dosages.
Other forms of therapy (psychotherapy, occupational therapy/ergotherapy, or social rehabilitation) should be instituted properly. PET imaging studies have suggested low doses are preferable. Clinical response was associated with at least 65% occupancy of D2 receptors, while greater than 72% was likely to cause hyperprolactinaemia and over 78% associated with extrapyramidal side effects. Doses of haloperidol greater than 5 mg increased the risk of side effects without improving efficacy. Patients responded with doses under even 2 mg in first-episode psychosis. For maintenance treatment of schizophrenia, an international consensus conference recommended a reduction dosage by about 20% every 6 months until a minimal maintenance dose is established.
During long-term treatment of chronic psychiatric disorders, the daily dose should be reduced to the lowest level needed for maintenance of remission. Sometimes, it may be indicated to terminate haloperidol treatment gradually. In addition, during long-term use, routine monitoring including measurement of BMI, blood pressure, fasting blood sugar, and lipids, is recommended due to the risk of side effects.
Haloperidol, when given to lactating women, is found in significant amounts in their milk. Breastfed children sometimes show extrapyramidal symptoms. If the use of haloperidol during lactation seems indicated, the benefit for the mother should clearly outweigh the risk for the child, or breastfeeding should be stopped.
Data from animal experiments indicate haloperidol is not teratogenic, but is embryotoxic in high doses. In humans, no controlled studies exist. Reports in pregnant women revealed possible damage to the fetus, although most of the women were exposed to multiple drugs during pregnancy. In addition, reports indicate neonates exposed to antipsychotic drugs are at risk for extrapyramidal and/or withdrawal symptoms following delivery, such as agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. Following accepted general principles, haloperidol should be given during pregnancy only if the benefit to the mother clearly outweighs the potential fetal risk.
Pregnancy and lactation
A multiple-year study suggested this drug and other neuroleptic antipsychotic drugs commonly given to Alzheimer's patients with mild behavioural problems often make their condition worse and its withdrawal was even beneficial for some cognitive and functional measures.
Haloperidol was considered indispensable for treating psychiatric emergency situations, although the newer atypical drugs have gained greater role in a number of situations as outlined in a series of consensus reviews published between 2001 and 2005.
- Acute psychosis, such as drug-induced psychosis caused by LSD, psilocybin, amphetamines, ketamine, and phencyclidine, and psychosis associated with high fever or metabolic disease
- Hyperactivity, aggression
- Hyperactive delirium (to control the agitation component of delirium)
- Otherwise uncontrollable, severe behavioral disorders in children and adolescents
- Agitation and confusion associated with cerebral sclerosis
- Adjunctive treatment of alcohol and opioid withdrawal
- Treatment of severe nausea and emesis in postoperative and palliative care, especially for palliating adverse effects of radiation therapy and chemotherapy in oncology
- Treatment of neurological disorders, such as tic disorders such as Tourette syndrome, and chorea
- Therapeutic trial in personality disorders, such as borderline personality disorder
- Treatment of intractable hiccups
- Alcohol-induced psychosis
- Hallucinations in alcohol withdrawal
Haloperidol is used in the control of the symptoms of:
Medical uses 1
- Pregnancy and lactation 1.1
- Other considerations 1.2
Adverse effects 2
- Contraindications 2.1
- Special cautions 2.2
- Interactions 2.3
- Symptoms 3.1
- Treatment 3.2
- Prognosis 3.3
- Pharmacology 4
- Oral 5.1
- Intramuscular injections 5.2
- Intravenous injections 5.3
- Therapeutic concentrations 5.4
- Distribution and metabolism 5.5
- Brand names 6.1
- Veterinary use 7
- References 8
- External links 9
 It is the most commonly used typical antipsychotic. The cost in the United States is around 250 US dollars. The yearly cost of the typical dose of haloperidol is about 20 to 800 pounds (30 to 1,250 US dollars) in the United Kingdom..health system, the most important medications needed in a basic WHO Model List of Essential Medicines It is on the .meperidine It was made from .Paul Janssen Haloperidol was discovered in 1958 by .Parkinson's disease It should not be used in people with  When taken during pregnancy it may result in problems in the infant. it results in an increased risk of death.dementia may occur. In older people with psychosis due to QT-interval prolongation and Neuroleptic malignant syndrome which may be permanent. tardive dyskinesia Haloperidol may result in a movement disorder known as