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Special Alerts
Antipsychotics (Conventional and Atypical): Association With an Increased Risk of Mortality in Elderly Patients Treated for Dementia-Related Psychosis - June 2008
The Food and Drug Administration (FDA) is notifying healthcare professionals that conventional antipsychotics (eg, haloperidol, fluphenazine) will now carry a similar boxed warning as atypical antipsychotics (eg, risperidone, aripiprazole) concerning an increased risk of mortality in elderly patients treated for dementia-related psychosis. Atypical antipsychotics received the boxed warning in April 2005 after study data from seven placebo-controlled trials indicated an increased risk of death in patients treated with certain atypicals for dementia-related behavioral disorders.
The FDA requirement to extend the warning to conventional antipsychotics was prompted by two recently published observational studies. Both studies revealed an increased risk of mortality in elderly patients treated with these medications. One of the two studies was a retrospective cohort study which examined 37,241 patients, ?65 years of age, treated with antipsychotics. Of these patients, 12,882 received a conventional antipsychotic compared to 24,359 patients who received an atypical antipsychotic. All-cause mortality within the first 180 days of use was compared between the two groups. The results showed that the risk of death in patients who received a conventional-type antipsychotic was comparable to (and may be greater than) the risk of death in patients receiving an atypical. The second study was also a retrospective cohort study; it involved 27,259 matched pairs of patients, ?66 years of age, diagnosed with dementia. Risk of death was compared in patients who received an atypical antipsychotic versus no antipsychotic, and in patients who received a conventional antipsychotic versus an atypical antipsychotic. An increased risk of death was observed in the groups receiving an atypical antipsychotic compared to no antipsychotic and also in patients receiving a conventional antipsychotic compared to patients receiving an atypical antipsychotic. This effect was seen at 30 days and persisted at 180 days, and was seen in both community-dwelling and long-term care facility patients.
The FDA believes that considering all the available evidence, conventional antipsychotics at least share a similar increased risk of death that has been observed with the use of atypical antipsychotics in elderly patients with dementia-related psychosis. The FDA is reminding practitioners that antipsychotic medications are not approved for the treatment of dementia-related psychosis. Elderly patients treated with antipsychotics, conventional or atypical, are at an increased risk of death. Practitioners prescribing antipsychotics to elderly patients for this purpose should inform the patient and their caregivers of this risk prior to prescribing.
Additional information may be found at http://www.fda.gov/medwatch/safety/2008/safety08.htm#Antipsychotics
References:
Gill SS, Bronskill SE, Normand SL, et al, “Antipsychotic Drug Use and Mortality in Older Adults With Dementia,” Ann Intern Med, 2007, 146(11):775-86.
Schneeweiss S, Setoguchi S, Brookhart A, et al, “Risk of Death Associated With the Use of Conventional Versus Atypical Antipsychotic Drugs Among Elderly Patients,” CMAJ, 2007, 176(5): 627-32.
Haloperidol: Risk of QT Prolongation and Torsade de Pointes ? September, 2007
The Food and Drug Administration (FDA), in conjunction with Johnson and Johnson, is informing healthcare professionals of updated prescribing information for haloperidol (Haldol®). The labeling updates note an increased risk of QT prolongation, torsade de pointes (TdP), and sudden death associated with haloperidol use. Incidence appears greater with intravenous administration and with doses higher than recommended. Haloperidol injection is approved for intramuscular use only; however, the FDA is aware of the relatively common off-label clinical practice of intravenous administration using haloperidol lactate injection (haloperidol decanoate should never be administered intravenously). The FDA cites at least 28 case reports of QT prolongation and TdP, including fatalities, occurring with intravenous haloperidol. Case-control studies indicate a dose-response between intravenous haloperidol and TdP.
In light of the potential for adverse cardiac conduction effects, caution or avoidance of haloperidol is advised in patients with predisposing risk factors including electrolyte abnormalities (eg, hypokalemia, hypomagnesemia), hypothyroidism, familial long QT syndrome, concomitant medications which may augment QT prolongation, or any underlying cardiac abnormality which may also potentiate risk. In addition, ECG monitoring is recommended with off-label intravenous use of haloperidol.
For more information, refer to the following FDA website http://www.fda.gov/medwatch/safety/2007/safety07.htm#Haloperidol
Medication Safety Issues
Sound-alike/look-alike issues:
Haloperidol may be confused Halotestin®
Haldol® may be confused with Halcion®, Halenol®, Halog®, Halotestin®, Stadol®
Pronunciation
(ha loe PER i dole)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of schizophrenia; control of tics and vocal utterances of Tourette's disorder in children and adults; severe behavioral problems in children
Use: Unlabeled/Investigational
Treatment of non-schizophrenia psychosis; may be used for the emergency sedation of severely-agitated or delirious patients; adjunctive treatment of ethanol dependence; antiemetic; psychosis/agitation related to Alzheimer's dementia
Pregnancy Risk Factor
C
Lactation
Enters breast milk/not recommended (AAP rates “of concern”)
Breast-Feeding Considerations
Decline in developmental scores may be seen in nursing infants.
Contraindications
Hypersensitivity to haloperidol or any component of the formulation; Parkinson's disease; severe CNS depression; bone marrow suppression; severe cardiac or hepatic disease; coma
Warnings/Precautions
Concerns related to adverse effects:
• Altered cardiac conduction: May alter cardiac conduction and prolong QT interval; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics, but risk may be increased with doses exceeding recommendations and/or intravenous administration (unlabeled route). Use with caution or avoid use in patients with electrolyte abnormalities (eg, hypokalemia, hypomagnesemia), hypothyroidism, familial long QT syndrome, concomitant medications which may augment QT prolongation, or any underlying cardiac abnormality which may also potentiate risk. Monitor ECG closely for dose-related QT effects. Adverse effects of decanoate may be prolonged.
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. Relative to other neuroleptics, haloperidol has a low potency of cholinergic blockade.
• Blood dyscrasias: Myelosuppression (eg, leukopenia, agranulocytosis) has been observed with antipsychotic use; check blood counts periodically and discontinue at first signs of blood dyscrasias; use is contraindicated in patients with bone marrow suppression.
• Esophageal dysmotility/aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; use with caution in patients at risk of pneumonia (ie, Alzheimer's disease).
• Extrapyramidal symptoms: May cause extrapyramidal symptoms, including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is high relative to other neuroleptics).
• Neuroleptic malignant syndrome (NMS): Use may be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability (risk may be increased in patients with Parkinson's disease or Lewy body dementia).
• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
• Pigmentary retinopathy: May be associated with pigmentary retinopathy.
• Sedation: May be sedating, use with caution in disorders where CNS depression is a feature; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease.
• Glaucoma: Use with caution in patients with narrow-angle glaucoma; condition may be exacerbated by cholinergic blockade. Screening is recommended.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; condition may be exacerbated by cholinergic blockade.
• Parkinson's disease: Use with caution in patients with Parkinson's disease; they may be more sensitive to adverse effects.
• Prolactin-dependent tumors: Use with caution in patients with breast cancer or other prolactin-dependent tumors; elevates prolactin levels.
• Renal impairment: Use with caution in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
• Thyroid dysfunction: Avoid in thyrotoxicosis.
Concurrent drug therapy issues:
• Antiemetic effects: May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reye's syndrome, brain tumor) due to antiemetic effects.
Dosage form specific issues:
• Tartrazine: Some tablets contain tartrazine.
Other warnings/precautions:
• Parenteral administration: Hypotension may occur, particularly with parenteral administration. Risk of QT prolongation, torsade de pointes, and sudden death appear to be increased with intravenous administration, particularly at higher doses. Although the short-acting form (lactate) is used clinically intravenously, the I.V. use of the injection is not an FDA-approved route of administration; the decanoate form should never be administered intravenously.
Adverse Reactions
Frequency not defined.
Cardiovascular: Abnormal T waves with prolonged ventricular repolarization, arrhythmia, hyper-/hypotension, QT prolongation, sudden death, tachycardia, torsade de pointes
Central nervous system: Agitation, akathisia, altered central temperature regulation, anxiety, confusion, depression, drowsiness, dystonic reactions, euphoria, extrapyramidal reactions, headache, insomnia, lethargy, neuroleptic malignant syndrome (NMS), pseudoparkinsonian signs and symptoms, restlessness, seizure, tardive dyskinesia, tardive dystonia, vertigo
Dermatologic: Alopecia, contact dermatitis, hyperpigmentation, photosensitivity (rare), pruritus, rash
Endocrine & metabolic: Amenorrhea, breast engorgement, galactorrhea, gynecomastia, hyper-/hypoglycemia, hyponatremia, lactation, mastalgia, menstrual irregularities, sexual dysfunction
Gastrointestinal: Anorexia, constipation, diarrhea, dyspepsia, hypersalivation, nausea, vomiting, xerostomia
Genitourinary: Priapism, urinary retention
Hematologic: Cholestatic jaundice, obstructive jaundice
Ocular: Blurred vision
Respiratory: Bronchospasm, laryngospasm
Miscellaneous: Diaphoresis, heat stroke
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), 2D6 (major), 3A4 (major); Inhibits CYP2D6 (moderate), 3A4 (moderate)
Drug Interactions
Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotics. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: Antipsychotics may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Anti-Parkinson 's Agents (Dopamine Agonist): Antipsychotics (Typical) may diminish the therapeutic effect of Anti-Parkinson 's Agents (Dopamine Agonist). Risk D: Consider therapy modification
Carbamazepine: May increase the metabolism of Haloperidol. Risk D: Consider therapy modification
ChlorproMAZINE: Haloperidol may enhance the QTc-prolonging effect of ChlorproMAZINE. ChlorproMAZINE may decrease the metabolism of Haloperidol. Risk D: Consider therapy modification
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: A lower starting dose of eplerenone (25 mg once daily) is recommended in patients with hypertension who are also taking drugs that are moderate inhibitors of CYP3A4. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Lithium formulations: May enhance the neurotoxic effect of Antipsychotics. Lithium formulations may decrease the serum concentration of Antipsychotics. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Maraviroc: CYP3A4 Inhibitors may increase the serum concentration of Maraviroc. Risk D: Consider therapy modification
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
Quinidine: May increase the serum concentration of Haloperidol. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Haloperidol. Risk C: Monitor therapy
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Thioridazine: CYP2D6 Inhibitors may decrease the metabolism of Thioridazine. Risk X: Avoid combination
Tramadol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Tramadol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Protect oral dosage forms from light. Haloperidol lactate injection should be stored at controlled room temperature; do not freeze or expose to temperatures >40°C. Protect from light; exposure to light may cause discoloration and the development of a grayish-red precipitate over several weeks. Stability of standardized solutions is 38 days at room temperature (24°C).
Reconstitution
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.
Compatibility
Stable in D5W; variable stability (consult detailed reference) in D51/4NS, LR, 1/2NS, NS.
Y-site administration: Compatible: Amifostine, amsacrine, aztreonam, cimetidine, cisatracurium, cladribine, dobutamine, docetaxel, dopamine, doxorubicin liposome, etoposide phosphate, famotidine, filgrastim, fludarabine, gatifloxacin, gemcitabine, granisetron, lidocaine, linezolid, lorazepam, melphalan, midazolam, nitroglycerin, norepinephrine ondansetron, paclitaxel, phenylephrine, propofol, remifentanil, sufentanil, tacrolimus, teniposide, theophylline, thiotepa, vinorelbine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, cefepime, fluconazole, foscarnet, heparin, piperacillin/tazobactam, sargramostim. Variable (consult detailed reference): Sodium nitroprusside.
Compatibility in syringe: Compatible: Hydromorphone, sufentanil. Incompatible: Diphenhydramine, heparin, hydroxyzine, ketorolac. Variable (consult detailed reference): Benztropine, cyclizine, diamorphine, morphine.
Mechanism of Action
Haloperidol is a butyrophenone antipsychotic which 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
Pharmacodynamics/Kinetics
Onset of action: Sedation: I.M., I.V.: 30-60 minutes
Duration: Decanoate: 2-4 weeks
Distribution: Vd: 8-18 L/kg; crosses placenta; enters breast milk
Protein binding: 90%
Metabolism: Hepatic to inactive compounds
Bioavailability: Oral: 60%
Half-life elimination: 18 hours; Decanoate: ?1 day
Time to peak, serum: Oral: 2-6 hours; I.M.: 20 minutes; Decanoate: 7 days
Excretion: Urine (33% to 40% as metabolites) within 5 days; feces (15%)
Clearance: 550 ± 133 mL/minute
Dosage
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: Sedation/psychotic disorders: 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:
Psychosis:
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
Delirium in the intensive care unit (unlabeled use, unlabeled route):
I.V.: 2-10 mg; may repeat bolus doses every 20-30 minutes until calm achieved then administer 25% of the maximum dose every 6 hours; monitor ECG and QTc interval
Intermittent I.V.: 0.03-0.15 mg/kg every 30 minutes to 6 hours
Oral: Agitation: 5-10 mg
Continuous intravenous infusion (100 mg/100 mL D5W): Rates of 3-25 mg/hour have been used
Rapid tranquilization of severely-agitated patient (unlabeled use): Administer every 30-60 minutes:
Oral: 5-10 mg
I.M. (as lactate): 5 mg
Average total dose (oral or I.M.) for tranquilization: 10-20 mg
Elderly: Nonpsychotic patient, dementia behavior (unlabeled use): 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
Administration: Oral
Dilute the oral concentrate with water or juice before administration. Note: Avoid skin contact with oral medication; may cause contact dermatitis.
Administration: I.M.
The decanoate injectable formulation should be administered I.M. only; do not give decanoate I.V.
Administration: I.V.
Decanoate: Do not administer I.V.
Lactate: Although not an FDA-approved route of administration, Haldol® has been administered by this route in many acute care settings.
Administration: I.V. Detail
The response to I.V. Haldol® may be delayed by several minutes.
pH: 3.0-3.6
Monitoring Parameters
Vital signs; lipid profile, fasting blood glucose/Hgb A1c; BMI; mental status, abnormal involuntary movement scale (AIMS), extrapyramidal symptoms (EPS); ECG (with off-label intravenous administration)
Reference Range
Therapeutic: 5-20 ng/mL (SI: 10-40 nmol/L) (psychotic disorders - less for Tourette's and mania)
Toxic: >42 ng/mL (SI: >84 nmol/L)
Patient Education
Use exactly as directed; do not increase dose or frequency. 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 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 or vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, fruit, or 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); or 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; respiratory difficulty; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
Geriatric Considerations
Many elderly patients receive antipsychotic medications for inappropriate nonpsychotic behavior. Before initiating antipsychotic medication, the clinician should investigate any possible reversible cause; any stress or stress from any disease can cause acute “confusion” or worsening of baseline nonpsychotic behavior. Most commonly acute changes in behavior are due to increases in drug dose or addition of new drug to regimen; fluid electrolyte loss; infections; and changes in environment.
Any changes in disease status in any organ system can result in behavior changes.
In the treatment of agitated, demented, elderly patients, authors of meta-analysis of controlled trials of the response to the traditional antipsychotics (phenothiazines, butyrophenones) in controlling agitation have concluded that the use of neuroleptics results in a response rate of 18%. Clearly neuroleptic therapy for behavior control should be limited with frequent attempts to withdraw the agent given for behavior control.
Clinical studies of haloperidol did not include sufficient numbers of subjects ?65 years of age to determine whether they respond differently from younger subjects. Other reported clinical experience has not consistently identified differences between the elderly and younger patients. However, the prevalence of tardive dyskinesia appears to be highest among the elderly, especially elderly women. Also, the pharmacokinetics of haloperidol in geriatric patients generally warrants the use of lower doses.
Anesthesia and Critical Care Concerns/Other Considerations
Delirium in the ICU Patient: Set goals for control of delirium. Haloperidol has not been studied in well-controlled trials enrolling ICU patients with acute delirium or agitation. The FDA and Johnson and Johnson have recently (September, 2007) informed healthcare providers about an increased risk of QT prolongation, torsade de pointes (TdP), and sudden death associated with haloperidol use, particularly high dose, intravenous administration (unlabeled use). Case-control studies indicate a dose-response between intravenous haloperidol and TdP. Even when used at recommended doses, cardiac arrhythmias have occurred. Caution or avoidance of haloperidol is advised in patients with predisposing risk factors including electrolyte abnormalities (eg, hypokalemia, hypomagnesemia), hypothyroidism, familial long QT syndrome, concomitant medications which may augment QT prolongation, or any underlying cardiac abnormality which may also potentiate risk. In addition, ECG monitoring is recommended with off-label intravenous use of haloperidol.
Haloperidol may cause extrapyramidal symptoms. It is the most frequently implicated antipsychotic associated with neuroleptic malignant syndrome.
Cardiovascular Considerations
Hypotension may occur, particularly with parenteral administration. Tachycardic arrhythmias and QT interval prolongation may also occur. When used at recommended doses, cardiac arrhythmias have occurred.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). Orthostatic hypotension, and nasal congestion are possible; since the drug is a dopamine antagonist, extrapyramidal symptoms of the TMJ are a possibility.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
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. Haloperidol is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, levonordefrin [Neo-Cobefrin®]) be used with caution.
Mental Health: Comment
Haloperidol is a high-potency antipsychotic. Older antipsychotic medications (chlorpromazine, haloperidol), which do not meet specific criteria for “atypical” antipsychotics, are often referred to as typical antipsychotics. They are associated with the troubling side effect, EPS. However, it is commonly believed that in order for a drug to treat psychosis, it must block dopamine is some manner.
Common side effects include sedation and neuroleptic effect (reduced initiative, interest in the environment, and display of emotion or affect). All typical antipsychotics are considered to be equally effective if given in equipotent doses. An inverse relationship exists between intrinsic antimuscarinic activity and propensity to cause extrapyramidal side effects. If dystonia or pseudoparkinsonism occurs, antiparkinsonian agents should be considered. If akathisia occurs, beta-blockers (eg, propranolol), benzodiazepines, or antiparkinsonian agents should be considered. Tardive dyskinesia (TD) secondary to typical antipsychotics has an estimated incidence of 3% to 5% per year for the first 5 years of treatment. After this time period, the incidence is estimated to be 2% to 3% per year. Prevalence rates are ?15% to 20%. Female gender and age constitute risk factors for TD. Indeed, prevalence rates have been reported to be as high as 70% in elderly females. No specific treatment exists for TD, however, patients are often initiated on/switched to an atypical antipsychotic because of their lower incidence to cause TD and hopes of suppression.
Typical antipsychotics are usually only indicated for schizophrenia, but are generally effective for mania and psychosis and/or behavioral syndromes secondary to other mental conditions. Nonpsychiatric uses include Tourette's syndrome, Huntington's disease, and occasionally, intractable hiccups, pruritus, nausea, and vomiting.
These drugs are thought to exert their antipsychotic activity by blocking dopamine D2 receptors in the mesolimbic dopaminergic pathway. Side effects are often related to their ability to antagonize dopamine receptors in the nigrostriatal and tuberoinfundibular pathways.
Long-acting dosage form is useful in patients nonadherent to treatment.
Coadministration of two or more antipsychotics does not generally improve clinical response and may increase the potential for adverse effects.
Nursing: Physical Assessment/Monitoring
Assess other medications patient is taking for effectiveness and interactions (especially drugs metabolized by P450 enzymes). Review ophthalmic screening. Monitor therapeutic effectiveness and adverse reactions at beginning of therapy and periodically with long-term use. With I.M. or I.V. use, monitor for hypotension and cardiac irregularities. Initiate at lower doses and taper dosage slowly when discontinuing. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Note: Strength expressed as base.
Injection, oil, as decanoate: 50 mg/mL (1 mL, 5 mL); 100 mg/mL (1 mL, 5 mL)
Haldol® Decanoate: 50 mg/mL (1 mL; 5 mL [DSC]); 100 mg/mL (1 mL; 5 mL [DSC]) [contains benzyl alcohol, sesame oil]
Injection, solution, as lactate: 5 mg/mL (1 mL, 10 mL)
Haldol®: 5 mg/mL (1 mL)
Solution, oral concentrate, as lactate: 2 mg/mL (15 mL, 120 mL)
Tablet: 0.5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg
Pricing: U.S. (www.drugstore.com)
Solution (Haldol Decanoate)
100 mg/mL (5): $378.99
Solution (Haloperidol Decanoate)
100 mg/mL (5): $184.99
Tablets (Haloperidol)
0.5 mg (90): $17.00
1 mg (90): $19.99
2 mg (90): $18.99
5 mg (90): $25.99
10 mg (60): $72.26
20 mg (60): $124.07
References
“American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,” Pediatrics, 2001, 108(3):776-89.
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