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Pronunciation |
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(ha
loe PER i
dole) |
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U.S. Brand
Names |
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Haldol®; Haldol®
Decanoate |
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Generic
Available |
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Yes |
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Synonyms |
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Haloperidol Decanoate; Haloperidol Lactate |
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Pharmacological Index |
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Antipsychotic Agent, Butyrophenone |
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Use |
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Treatment of psychoses; control of tics and vocal utterances of Tourette's
disorder in children and adults; severe behavioral problems in children
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Pregnancy Risk
Factor |
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C |
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Contraindications |
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Hypersensitivity to haloperidol or any component; Parkinson's disease; severe
CNS depression, bone marrow suppression, severe cardiac or hepatic disease;
coma |
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Warnings/Precautions |
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Hypotension may occur, particularly with parenteral administration. Decanoate
form should never be administered I.V. Avoid in thyrotoxicosis. May be sedating,
use with caution in disorders where CNS depression is a feature. Caution in
patients with hemodynamic instability, predisposition to seizures, subcortical
brain damage, renal or respiratory disease. Esophageal dysmotility and
aspiration have been associated with antipsychotic use - use with caution in
patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast
cancer or other prolactin-dependent tumors (may elevate prolactin levels). May
alter temperature regulation or mask toxicity of other drugs due to antiemetic
effects. May alter cardiac conduction - life-threatening arrhythmias have
occurred with therapeutic doses of antipsychotics. Adverse effects of decanoate
may be prolonged. May cause orthostatic hypotension - use with caution in
patients at risk of this effect or those who would tolerate transient
hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other
medications which may predispose). Some tablets contain tartrazine.
May cause extrapyramidal reactions, including pseudoparkinsonism, acute
dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions
is high relative to other neuroleptics). May be associated with neuroleptic
malignant syndrome (NMS) or pigmentary retinopathy. |
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Adverse
Reactions |
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Cardiovascular: Hypotension, hypertension, tachycardia, arrhythmias, abnormal
T waves with prolonged ventricular repolarization
Central nervous system: Restlessness, anxiety, extrapyramidal reactions,
dystonic reactions, pseudoparkinsonian signs and symptoms, tardive dyskinesia,
neuroleptic malignant syndrome (NMS), altered central temperature regulation,
akathisia, tardive dystonia, insomnia, euphoria, agitation, drowsiness,
depression, lethargy, headache, confusion, vertigo, seizures
Dermatologic: Hyperpigmentation, pruritus, rash, contact dermatitis,
alopecia, photosensitivity (rare)
Endocrine & metabolic: Amenorrhea, galactorrhea, gynecomastia, sexual
dysfunction, lactation, breast engorgement, mastalgia, menstrual irregularities,
hyperglycemia, hypoglycemia, hyponatremia
Gastrointestinal: Nausea, vomiting, anorexia, constipation, diarrhea,
hypersalivation, dyspepsia, xerostomia
Genitourinary: Urinary retention, priapism
Hematologic: Cholestatic jaundice, obstructive jaundice
Ocular: Blurred vision
Respiratory: Laryngospasm, bronchospasm
Miscellaneous: Heat stroke, diaphoresis |
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Overdosage/Toxicology |
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Symptoms of overdose include deep sleep, dystonia, agitation, dysrhythmias,
extrapyramidal symptoms
Following initiation of essential overdose management, toxic symptom
treatment and supportive treatment should be initiated. Critical cardiac
arrhythmias often respond to I.V. lidocaine, while other antiarrhythmics can be
used. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic reactions)
requiring management with benztropine mesylate I.V. 1-2 mg (adult) may be
effective. These agents are generally effective within 2-5 minutes.
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Drug
Interactions |
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CYP1A2 enzyme substrate, CYP2D6 enzyme substrate (minor); CYP2D6 enzyme
inhibitor CYP2C8 and 3A3/4 enzyme substrate; CYP1A2, 2C, and 3A3/4 inducer
Benztropine (and other anticholinergics) may inhibit the therapeutic response
to haloperidol and excess anticholinergic effects may occur
Chloroquine may increase haloperidol concentrations
Cigarette smoking may enhance the hepatic metabolism of haloperidol. Larger
doses may be required compared to a nonsmoker.
Concurrent use of haloperidol with an antihypertensive may produce additive
hypotensive effects
Concurrent use with TCA may produce increased toxicity or altered therapeutic
response
Haloperidol may inhibit the antiparkinsonian effect of levodopa; avoid this
combination
Haloperidol plus lithium may rarely produce neurotoxicity
Barbiturates may reduce haloperidol concentrations
Propranolol may increase haloperidol concentrations
Sulfadoxine-pyrimethamine may increase haloperidol concentrations
Haloperidol and CNS depressants (ethanol, narcotics) may produce additive CNS
depressant effects
Haloperidol and trazodone may produce additive hypotensive effects
Carbamazepine appears to stimulate the metabolism of haloperidol. Monitor for
reduced efficacy
Fluoxetine and paroxetine may inhibit the metabolism of haloperidol resulting
in EPS; monitor for EPS
Haloperidol in combination with indomethacin may result in drowsiness,
tiredness, and confusion; monitor for adverse effects
Quinidine appears to increase haloperidol concentrations; monitor for EPS
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Stability |
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Protect oral dosage forms from light
Haloperidol lactate injection should be stored at controlled room temperature
and protected from light, freezing and temperatures
>40°C; exposure to light may cause discoloration and
the development of a grayish-red precipitate over several weeks
Haloperidol lactate may be administered IVPB or I.V. infusion in
D5W solutions; NS solutions should not be used due to reports of
decreased stability and incompatibility
Standardized dose: 0.5-100 mg/50-100 mL D5W
Stability of standardized solutions is 38 days at room temperature
(24°C) |
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Mechanism of
Action |
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Blocks postsynaptic mesolimbic dopaminergic D1 and D2
receptors in the brain; depresses the release of hypothalamic and hypophyseal
hormones; believed to depress the reticular activating system thus affecting
basal metabolism, body temperature, wakefulness, vasomotor tone, and
emesis |
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Pharmacodynamics/Kinetics |
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Onset of sedation: I.V.: Within 1 hour
Duration of action: ~3 weeks for decanoate form
Distribution: Crosses the placenta; appears in breast milk
Protein binding: 90%
Metabolism: In the liver to inactive compounds
Bioavailability: Oral: 60%
Half-life: 20 hours
Time to peak serum concentration: 20 minutes
Elimination: 33% to 40% excreted in urine within 5 days; an additional 15%
excreted in feces |
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Usual Dosage |
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Children: 3-12 years (15-40 kg): Oral:
Initial: 0.05 mg/kg/day or 0.25-0.5 mg/day given in 2-3 divided doses;
increase by 0.25-0.5 mg every 5-7 days; maximum: 0.15 mg/kg/day
Usual maintenance:
Agitation or hyperkinesia: 0.01-0.03 mg/kg/day once daily
Nonpsychotic disorders: 0.05-0.075 mg/kg/day in 2-3 divided doses
Psychotic disorders: 0.05-0.15 mg/kg/day in 2-3 divided doses
Children 6-12 years: I.M. (as lactate): 1-3 mg/dose every 4-8 hours to a
maximum of 0.15 mg/kg/day; change over to oral therapy as soon as able
Adults:
Oral: 0.5-5 mg 2-3 times/day; usual maximum: 30 mg/day
I.M. (as lactate): 2-5 mg every 4-8 hours as needed
I.M. (as decanoate): Initial: 10-20 times the daily oral dose administered at
4-week intervals
Maintenance dose: 10-15 times initial oral dose; used to stabilize
psychiatric symptoms
Sedation in the Intensive Care Unit:
I.M./IVP/IVPB: May repeat bolus doses after 30 minutes until calm achieved
then administer 50% of the maximum dose every 6 hours
Mild agitation: 0.5-2 mg
Moderate agitation: 2.5-5 mg
Severe agitation: 10-20 mg
Oral: Agitation: 5-10 mg
Continuous intravenous infusion (100 mg/100 mL D5W): Rates of 1-40
mg/hour have been used
Rapid tranquilization of agitated patient (administer every 30-60 minutes):
Oral: 10 mg
I.M.: 5 mg
Average total dose for tranquilization: 30-60 mg
Elderly (nonpsychotic patients, dementia behavior):
Initial: Oral: 0.25-0.5 mg 1-2 times/day; increase dose at 4- to 7-day
intervals by 0.25-0.5 mg/day; increase dosing intervals (twice daily, 3
times/day, etc) as necessary to control response or side effects
Hemodialysis/peritoneal dialysis: Supplemental dose is not necessary
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Dietary
Considerations |
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Alcohol: Additive CNS effect, avoid use |
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Monitoring
Parameters |
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Monitor orthostatic blood pressures 3-5 days after initiation of therapy or a
dose increase; observe for tremor and abnormal movement or posturing
(extrapyramidal symptoms) |
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Reference Range |
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Therapeutic: 5-15 ng/mL (SI: 10-30 nmol/L) (psychotic disorders - less for
Tourette's and mania)
Toxic: >42 ng/mL (SI: >84 nmol/L) |
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Test
Interactions |
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cholesterol
(S) |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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Manufacturer's information states that haloperidol may block vasopressor
activity of epinephrine. This has not been observed during use of epinephrine as
a vasoconstrictor in local anesthesia. |
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Dental Health:
Effects on Dental Treatment |
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Orthostatic hypotension and nasal congestion possible in dental patients.
Since the drug is a dopamine antagonist, extrapyramidal symptoms of the TMJ a
possibility. |
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Patient
Information |
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Use exactly as directed (do not increase dose or frequency); may cause
physical and/or psychological dependence. It may take 2-3 weeks to achieve
desired results; do not discontinue without consulting prescriber. Dilute oral
concentration with water or juice. Do not take within 2 hours of any antacid.
Store away from light. Avoid excess alcohol or caffeine and other prescription
or OTC medications not approved by prescriber. Maintain adequate hydration (2-3
L/day of fluids unless instructed to restrict fluid intake). Avoid skin contact
with medication; may cause contact dermatitis (wash immediately with warm, soapy
water). You may experience excess drowsiness, restlessness, dizziness, or
blurred vision (use caution driving or when engaging in tasks requiring
alertness until response to drug is known); nausea, vomiting (small frequent
meals, frequent mouth care, chewing gum, or sucking lozenges may help);
constipation (increased exercise, fluids, or dietary fruit and fiber may help);
postural hypotension (use caution climbing stairs or when changing position from
lying or sitting to standing); urinary retention (void before taking
medication); decreased perspiration (avoid strenuous exercise in hot
environments). Report persistent CNS effects (eg, trembling fingers, altered
gait or balance, excessive sedation, seizures, unusual movements, anxiety,
abnormal thoughts, confusion, personality changes); chest pain, palpitations,
rapid heartbeat, severe dizziness; unresolved urinary retention or changes in
urinary pattern; vision changes; skin rash or yellowing of skin; difficulty
breathing; or worsening of condition. Pregnancy/breast-feeding
precautions: Inform prescriber if you are or intend to be pregnant.
Breast-feeding is not recommended. |
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Nursing
Implications |
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Avoid skin contact with oral suspension or solution; may cause contact
dermatitis |
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Dosage Forms |
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Concentrate, oral, as lactate: 2 mg/mL (5 mL, 10 mL, 15 mL, 120 mL, 240 mL)
Injection, as decanoate: 50 mg/mL (1 mL, 5 mL); 100 mg/mL (1 mL, 5 mL)
Injection, as lactate: 5 mg/mL (1 mL, 2 mL, 2.5 mL, 10 mL)
Tablet: 0.5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg |
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References |
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Aunsholt NA,
"Prolonged Q-T Interval and Hypokalemia Caused by Haloperidol," Acta
Psychiatr Scand, 1989, 79(4):411-2.
Bauer M,
"Concurrent Agranulocytosis and Acute Hepatitis Resulting From Combination of Classic Neuroleptics and Subsequent Successful Clozapine Treatment,"
Pharmacopsychiatry, 1995, 28(1):29-31.
Cole RM, Robinson F, Harvey L, et al,
"Successful Control of Intractable Nausea and Vomiting Requiring Combined Ondansetron and Haloperidol in a Patient With Advanced Cancer,"
J Pain Symptom Manage, 1994, 9(1):48-50.
Di Salvo TG and O'Gara PT,
"Torsade de Pointes Caused by High-Dose Intravenous Haloperidol in Cardiac Patients,"
Clin Cardiol, 1995, 18(5):285-90.
Doenecke AL and Heuermann RC,
"Treatment of Haloperidol Abuse With Diphenhydramine," Am J Psychiatry,
1980, 137(4):487-8.
Fisher H,
"A New Approach to Emergency Department Therapy of Migraine Headache With Intravenous Haloperidol: A Case Series,"
J Emerg Med, 1995, 13(1):119-22.
Harada H, Igarashi M, Sugae S, et al,
"A Schizophrenic Patient Who Developed Extreme Hypothermia After an Increase in the Dose of Haloperidol: A Case Report,"
Jpn J Psychiatry Neurol, 1994, 48(3):595-8.
Kubota T, Ishikura T, and Jibiki I,
"Alopecia Areata Associated With Haloperidol," Jpn J Psychiatry Neurol,
1994, 48(3):579-81.
Mahutte CK, Nakasato SK, and Light RW,
"Haloperidol and Sudden Death Due to Pulmonary Edema," Arch Intern Med,
1982, 142(10):1951-2.
Peabody CA, Warner MD, Whiteford HA, et al,
"Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.
Plotkin DA, Plotkin D, and Okun R,
"Haloperidol in the Treatment of Nausea and Vomiting Due to Cytotoxic Drug Administration,"
Curr Ther Res Clin Exp,1973, 15(9):599-602.
Riker RR, Fraser GL, and Cox PM,
"Continuous Infusion of Haloperidol Controls Agitation in Critically Ill Patients,"
Crit Care Med, 1994, 22(3):433-40.
Risse SC and Barnes R,
"Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr
Soc, 1986, 34(5):368-76.
Saltz BL, Woerner MG, Kane JM, et al,
"Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA,
1991, 266(17):2402-6.
Schwartz M, Weller B, Erdreich M, et al,
"Rabbit Syndrome and Tardive Dyskinesia: Two Complications of Chronic Neuroleptic Treatment,"
J Clin Psychiatry, 1995, 56(5):212.
Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm
Pract, 1984, 6:403-16.
Serrano AC, "Haloperidol - Its Use in Children," J Clin Psychiatry,
1981, 42(4):154-6.
Silvey L, Carpenter JT Jr, Wheeler RH, et al,
"A Randomized Comparison of Haloperidol Plus Dexamethasone Versus Prochlorperazine Plus Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Breast Cancer,"
J Clin Oncol, 1988, 6(9):1397-400.
Spencer EK, Kafantaris V, Padron-Gayol MV, et al,
"Haloperidol in Schizophrenic Children: Early Findings From a Study in Progress,"
Psychopharmacol Bull, 1992, 28(2):183-6.
Wilt JL, Minnema AM, Johnson RF, et al,
"Torsade de Pointes Associated With the Use of Intravenous Haloperidol," Ann
Intern Med, 1993, 119(5):391-4. |
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