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haloperidol (Haldol, Halperon, Aloperidol, Halomonth)

Tradenames: Haldol, Halperon. Indications: 1) symptomatic management of psychotic disorders 2) management of sedation/agitation/delirium in the ICU* 3) management of nausea/vomiting in cancer patients 4) management of intractable hiccups 5) management of Gilles de la Tourette's syndrome 6) PCP-induced psychosis 7) cough not responsive to other therapies 8) symptomatic relief of dyspnea 9) psychosis & agitation in the elderly [11] * haloperidol 1.0-3.8 mg QD for 3-11 days associated with very-small dose-dependent improvement in survival of critically-ill patients with delirium (RR=0.91-0.95 at 28 days, 0.96-0.98 at 90 days) [14] * no better than placebo for treatment of delirium in ICU patients [15] Contraindications: 1) narrow-angle glaucoma 2) bone-marrow suppression 3) CNS depression 4) severe liver or cardiac disease - prolonged QT interval 5) parkinsonism Caution: 1) patients receiving anticonvulsants 2) patients with seizures or abnormal EEG Dosage: 1) generally used in combination with anticholinergic agent, i.e. benztropine (Cogentin) [8] to prevent dystonia ]13] 2) 2-5 mg IM every 4-8 hours, PRN. 3) 0.5-5 mg PO BID/TID; doses up to 100 mg/day have been used 4) geriatrics: start 0.5 mg QD (PRN) 5) haloperidol decanoate: a) maximum injected volume should not exceed 3 mL b) 10-15 times the oral dose (if < 10 mg/day) c) monthly IM injection d) do NOT administer decanoate IV 6) infusion: 0.5-2 mg/hr up to max of 5 mg/min 7) may be appropriate to taper dose, rather than discontinue abruptly [7] Tabs: 0.5, 1, 2, 5, 10, 20 mg. Liquid: 2 mg/5 mL. Pharmacokinetics: 1) readily absorbed from GI tract 2) metabolized in liver by cyt P450 2D6 3) excreted in urine & feces Monitor: - electrocardiogram for QT prolongation Adverse effects: 1) common (> 10%) - extrapyramidal symptoms - parkinsonism - dystonia - akathisia - swelling of breasts - weight gain - blurry vision - constipation 2) less common (1-10%) - tardive dyskinesia - 10-20% of patients on long term therapy - generally irreversible - difficult urination, hallucinations, orthostatic hypotension, nausea/vomiting, drowsiness, photosensitivity 3) uncommon (< 1%) - agranulocytosis, heat stroke, obstructive jaundice, tardive dystonia, neuroleptic malignant syndrome, laryngospasm, respiratory depression, alopecia, altered central temperature regulation, hyperpigmentation, pruritus, rash, contact dermatitis, amenorrhea, galactorrhea, gynecomastia, adynamic ileus, GI upset, dry mouth, leukopenia (dose-related), retinal pigmentation, urinary retention, overflow incontinence, priapism, sexual dysfunction 4) other [3] - QT prolongation*, especially IV administration or high-dose [10] - low level of sedation - low anticholinergic effects - direct myocardial depression - increased risk of mortality in the elderly [9] - no increased risk of 30 day mortality [11] - see antipsychotic agent for number needed to harm - increased risk of out-of-hospital cardiac arrest (RR=2.43) [12] - no effect on length of ICU stay or hospital stay [11] 5) black box warning [11] - increased risk of hyperglycemia - increased risk of cerebrovascular events - increased risk of mortality in patients with dementia - 30 day mortality not increased [11] Drug interactions: 1) increased risk of drug interactions, especially QTc prolongation - haloperidol inhibits cyt P450 2D6, thus interactions with drugs metabolized by cyt P450 2D6 - haloperidol metabolized by cyt P450 2D6, thus inhibits its own metabolism - antiarrhythmic agents & cisapride in combination increases risk of QTc prolongation (torsades de pointes) 2) CNS depressants in combination may increase adverse effects 3) epinephrine in combination may cause hypotension 4) anticholinergic agents in combination may increase intraocular pressure 5) concurrent use of Li+ has caused acute encephalopathy-like syndrome Laboratory: 1) specimen: serum (heparin, EDTA), urine - haloperidol in serum/plasma - haloperidol in urine 2) methods: GLC, RIA, HPLC Mechanism of action: 1) high potency dopamine D2 receptor antagonist 2) non-sedating 3) does NOT suppress respiratory drive

Interactions

drug interactions drug adverse effects (more general classes)

Related

chlorpromazine (Thorazine, Ormazine, Propaphenin, Sonazine, Chloractil) cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6) torsades de pointes

General

antipsychotic agent butyrophenone dopaminergic receptor antagonist

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 12-24 HOURS therapeutic-range 6-245 NG/ML protein-binding 90% elimination by hemodialysis - peritoneal dialysis - pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1147
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  6. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  7. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  8. Rosenheck R et al Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial.. JAMA 290:2693, 2003 PMID: 14645311
  9. Schneeweiss S et al, Risk of death with use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007, 176:627 PMID: 17325327
  10. Prescriber's Letter 14(11): 2007 Intravenous Haloperidol (Haldol) Detail-Document#: 231110 (subscription needed) http://www.prescribersletter.com
  11. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  12. Weeke P et al. Antipsychotics and associated risk of out-of-hospital cardiac arrest. Clin Pharmacol Ther 2014 Jun 24 PMID: 24960522
  13. van Harten PN, Hoek HW, Kahn RS. Acute dystonia induced by drug treatment. BMJ. 1999 Sep 4;319(7210):623-6. PMID: 10473482 Free PMC article
  14. Duprey MS, Devlin JW, van der Hoeven JG et al Association Between Incident Delirium Treatment With Haloperidol and Mortality in Critically Ill Adults. Crit Care Med. 2021;49(8):1303-1311. PMID: 33861548 PMCID: PMC8282692 (available on 2022-08-01) https://www.medscape.com/viewarticle/955328
  15. George J Haloperidol for ICU Delirium Misses on Hard Endpoints. No difference from placebo on composite outcome in randomized trial. MedPage Today October 27, 2022 https://www.medpagetoday.com/neurology/generalneurology/101460 - Andersen-Ranberg NC, Poulsen LM, Perner A et al Haloperidol for the Treatment of Delirium in ICU Patients. N Eng J Med. 2022. Oct 26. PMID: 36286254 https://www.nejm.org/doi/full/10.1056/NEJMoa2211868
  16. Episode 785: Haloperidol for Agitation in Elderly Patients - How Low Can You Go? Pharmacy Joe. Jan 23, 2023 https://www.pharmacyjoe.com/haloperidol-for-agitation-in-elderly-patients-how-low-can-you-go/ - Yuksel JM et al Optimal Injectable Haloperidol Dose Assessment in the Older Hospitalized Inpatient. Annals of Pharmacotherapy. 2022. Sep 13;10600280221124615 PMID: 36113417 https://journals.sagepub.com/doi/10.1177/10600280221124615