Haloperidol

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Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradenames: Haldol, Halperon.

Indications

• symptomatic management of psychotic disorders
• management of sedation/ agitation/ delirium in the ICU
• management of nausea/vomiting in cancer patients
• management of intractable hiccups
• management of Gilles de la Tourette's syndrome
• PCP-induced psychosis
• cough not responsive to other therapies
• symptomatic relief of dyspnea

Contraindications

• narrow-angle glaucoma
• bone-marrow suppression
• CNS depression
• severe liver or cardiac disease
• parkinsonism

• Caution:

• patients receiving anticonvulsants
• patients with seizures or abnormal EEG
  

• pregnancy category = c
• safety in lactation = ?

Dosage

• (haloperidol and haloperidol decanoate)
• generally used in combination with anticholinergic agent, i.e. benztropine ( Cogentin) [8]
• 2-5 mg IM every 4-8 hours, PRN.
• 0.5-5 mg PO BID/ TID; doses up to 100 mg/day have been used
• geriatrics: start 0.5 mg QD ( PRN)
• decanoate:

• maximum injected volume should not exceed 3 mL
• 10-15 times the oral dose (if < 10 mg/day)
• monthly IM injection
• do NOT administer decanoate IV

• infusion: 0.5-2 mg/ hr up to max of 5 mg/min
• 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

• readily absorbed from GI tract
• metabolized in liver by cyt P450 2D6
• excreted in urine & feces
  

• elimination via liver
• elimination via kidney
• 1/2life = 12-24 hours
• protein binding = 90 %
• elimination by hemodialysis = -
• elimination by peritoneal dialysis = -

Adverse-effects

• common (> 10%)

• extrapyramidal symptoms

• parkinsonism
• dystonia

• akathisia
• swelling of breasts
• weight gain
• blurry vision
• constipation

• 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

• uncommon (< 1%)

• agranulocytosis, heat stroke, obstructive jaundice, tardive dystonia, neuroleptic malignant syndrome, laryngospasm, respiratory depression, alopecia, altered central temperature regulation, hyperpigmentation, pruritis, rash, contact dermatitis, amenorrhea, galactorrhea, gynecomastia, adynamic ileus, GI upset, dry mouth, leukopenia (dose-related), retinal pigmentation, urinary retention, overflow incontinence, priapism, sexual dysfunction

• other [3]

• low level of sedation
• low anticholinergic effects
• QT prolongation, especially IV administration or high-dose [10]
• direct myocardial depression
• increased risk of mortality in the elderly [9]
  
• drug adverse effects of antipsychotic agents

Drug-interactions

• antiarrhythmic agents & cisapride in combination increased risk of QT prolongation ( torsades de pointes)
• CNS depressants in combination may increase adverse effects
• epinephrine in combination may cause hypotension
• anticholinergic agents in combination may increase intraocular pressure
• concurrent use of Li+ has caused acute encephalopathy-like syndrome
• haloperidol inhibits cyt P450 2D6, thus inhibits its own metabolism
• see chlorpromazine
  
• drug interaction(s) of lithium carbonate with haloperidol
• drug interaction(s) of antipsycotics with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with haloperidol

Laboratory

• specimen: serum ( heparin, EDTA)
• methods: GLC, RIA, HPLC

Mechanism-of-action

• high potency dopamine D2 receptor antagonist
• non-sedating
• does NOT suppress respiratory drive

More General Terms

• butyrophenone
• antipsychotic agent
• dopaminergic receptor antagonist

Additional Terms

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

Internet Database

PubChem: 3559
PubChem: 88144
PubChem: 52919

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#: [1] (subscription needed) [2]
7. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
8. Rosenheck R et al, JAMA 290:2693, 2003 PMID: [3]
9. Schneeweiss S et al, Risk of death with use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007, 176:627 PMID: [4]
10. Prescriber's Letter 14(11): 2007 Intravenous Haloperidol (Haldol) Detail-Document#: [5] (subscription needed) [6]

haloperidol (Haldol, Halperon, Aloperidol, Halomonth)