haloperidol (Haldol, Haldol Decanoate, Haloperidol LA, Peridol)

Dosing and uses of Haldol, Haldol Decanoate (haloperidol)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

tablet

• 0.5mg
• 1mg
• 2mg
• 5mg
• 10mg
• 20mg

oral concentrate

• 2mg/mL

injectable solution, lactate

• 5mg/mL

injectable solution, decanoate

• 50mg/mL
• 100mg/mL

 

Schizophrenia, Psychosis

PO

• Moderate disease, 0.5-2 mg q8-12hr initially
• Severe disease, 3-5 mg q8-12hr initially; not to exceed 30 mg/day

IM lactate (prompt-acting)

• 2-5 mg q4-8hr PRN; may require q1hr in acute agitation; not to exceed 20 mg/day

IM decanoate (depot)

• Initial: IM dose 10-20 times daily PO dose administered monthly; not to exceed 100 mg; if conversion requires initial dose >100 mg, administer in 2 injections (eg, 100 mg initially, then remainder in 3-7 days)
• Maintenance: Monthly dose 10-15 times daily PO dose 

IV (Off-label)

• May be needed for ICU delirium; use only haloperidol lactate for IV administration; do not use haloperidol decanoate
• 2-10 mg initially, depending on degree of agitation; if response inadequate, may repeat bolus q15-30min, sequentially doubling initial bolus dose; when calm achieved, administer 25% of last bolus dose q6hr; taper dose after patient is controlled  
• Monitor ECG and QT interval (QT prolongation may occur with cumulative doses ≥35 mg; torsades de pointes reported with single doses ≥20 mg)

 

Tourette Disorder

0.5-2 mg PO q8-12hr initially; if severe symptoms necessitate increased dosage, titrate upward to 3-5 mg PO q8-12hr; if patient remains inadequately controlled, daily doses up to 100 mg have been used (safety not determined) 

 

Pediatric dosage forms and strengths

tablet

• 0.5mg
• 1mg
• 2mg
• 5mg
• 10mg
• 20mg

oral concentrate

• 2mg/mL

injectable solution, lactate

• 5mg/mL

injectable solution, decanoate

• 50mg/mL
• 100mg/mL

 

Schizophrenia, Psychosis/Sedation

<3 years: Safety and efficacy not established

3-12 years (15-40 kg): 0.25-0.5 mg/day PO divided q8-12hr initially; may be increased by 0.5 mg/day every 5-7 days PRN; maintenance: 0.05-0.15 mg/kg/day PO divided q8-12hr 

6-12 years: Lactate (prompt-acting): 1-3 mg IM q4-8hr PRN; not to exceed 0.15 mg/kg/day 

>12 years: Moderate disease, 0.5-2 mg PO q8-12hr initially; severe disease, 3-5 mg PO q8-12hr; not to exceed 30 mg/day 

 

Tourette Disorder

<3 years: Safety and efficacy not established

3-12 years: 0.5 mg/day PO initially; dose increased by 0.5 mg every 5-7 days until therapeutic effect achieved, then reduced to lowest effective maintenance level of 0.05-0.075 mg/kg/day PO divided q8-12hr

>12 years: 0.5-2 mg PO q8-12hr initially; if severe symptoms necessitate increased dosage, titrate upward to 3-5 mg PO q8-12hr; if patient remains inadequately controlled, daily doses up to 100 mg have been used (safety not determined)

 

Behavioral Disorders

<3 years: Safety and efficacy not established

3-12 years: 0.5 mg/day PO initially; dose increased PRN by 0.5 mg every 5-7 days until therapeutic effect achieved, then reduced to lowest effective maintenance level of 0.05-0.075 mg/kg/day PO divided q8-12hr

 

Acute Agitation

<12 years: Safety and efficacy not established

>12 years: 0.5-3 mg PO, repeated in 1 hour PRN; alternatively, 2-5 mg IM, repeated in 1 hr PRn

 

Geriatric dosage forms and strengths

 

Schizophrenia, Psychosis

PO: Lower initial doses and more gradual adjustments recommended; 0.25-0.5 mg PO q8-12hr initially

IM lactate (prompt-acting): Lower adult doses and longer dosing intervals recommended compared with typical adult doses

IM decanoate (depot): Lower initial doses and more gradual adjustments recommended; monthly dose 10-15 times daily PO dose

IV (off-label): 0.25-0.5 mg IV q4hr; use only lactate (not decanoate) for IV administration; monitor with ECG for prolonged QT intervaL

Not approved for dementia-related psychosis, because of increased risk of cardiovascular or infectious related deaths (see Black box warnings)

 

Tourette Disorder

Lower initial doses and more gradual adjustments recommended; 0.25-0.5 mg PO q8-12hr initially

 

Dosing Considerations

Elderly at higher risk for tardive dyskinesia associated with higher-potency antipsychotic agents such as haloperidol because of higher ratios of dopaminergic blockage to adrenergic/anticholinergic blockade

 

Haldol, Haldol Decanoate (haloperidol) adverse (side) effects

Frequency not defined

Extrapyramidal symptoms

• Akathisia
• Dystonia
• Muscle stiffness
• Neuroleptic malignant syndrome (NMS; infrequent but serious)
• Parkinsonism
• Tardive dyskinesia

Common

• Anticholinergic effects
• Sedation
• Weight gain
• Erectile dysfunction
• Oligomenorrhea or amenorrhea

Less common

• Orthostatic hypotension (after IM injection), tachycardia
• Agitation, anxiety, cerebral edema, depression, dizziness, euphoria, headache, insomnia, poikilothermia, restlessness, weakness, confusion
• Anorexia, constipation, dyspepsia, ileus, decreased gag reflex
• Lens opacities (prolonged use)

Uncommon

• ECG changes
• Photosensitivity
• Pruritus
• Diarrhea
• Blood dyscrasia
• Ejaculatory disorder
• Galactorrhea

Rare

• Seizure
• Cholestatic jaundice
• Priapism

 

Postmarketing Reports

Rhabdomyolysis

 

Warnings

Black box warnings

Patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk for death, as shown in short-term controlled trials; deaths in trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature

Not approved for treatment of patients with dementia-related psychosis

 

Contraindications

Documented hypersensitivity

Severe CNS depression (including coma), NMS, poorly controlled seizure disorder, Parkinson disease

 

Cautions

Risk of sudden death, torsades de pointes, and prolonged QT interval from off-label IV administration of higher than recommended dose: monitor ECG if administering IV

Conditions or drugs that prolong QT interval, congenital long QT syndrome

Safety of prolonged administration of 100 mg/day PO not established

Avoid use in narrow angle glaucoma, bone marrow suppression, and severe hypotension

FDA warning regarding off-label use for dementia in elderly

Leukopenia/neutropenia and agranulocytosis reported; possible risk factors include preexisting low white blood cell (WBC) count and history of drug-induced leukopenia/neutropenia

If patient has history of clinically significant presence of either risk factor, monitor complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of clinically significant WBC decline <1000/μL in absence of other causative factors, and continue monitoring WBC count until recovery

Severe neurotoxicity manifesting as rigidity or inability to walk or talk may occur in patients with thyrotoxicosis also receiving antipsychotics

If administering IV or IM, watch for hypotension; use with caution in diagnosed CNS depression, subcortical brain damage, or cardiac disease; if history of seizures, benefits must outweigh risks; significant increase in body temperature may indicate intolerance to antipsychotics (discontinue if this occurs)

U se caution in patients at risk of pneumonia (eg, Alzheimer's patients); antipsychotic use reported to be associated with esophageal dysmotility and aspiration

Extrapyramidal symptoms may occur including acute dystonic reactions, akathisia, tardive dyskinesia, and pseudoparkinsonism

Hyperprolactinemia may occur

Monitor for mental status changes, muscle rigidity, fever, and/or autonomic instability; neuroleptic malignant syndrome may occur

May cause orthostatic hypotension

Association with increased risk of pigmentary retinopathy reported

Impairment of core body temperature regulation reported; use caution with activities that may increase body temperature including strenuous exercise, heat exposure, dehydration, and concomitant medications with anticholinergic effects

Caution in patients receiving anticoagulants; isolated instance of interference occurred with effects of one anticoagulant (phenindione)

When used to control mania in cyclic disorders, there may be rapid mood swing to depression

May cause anticholinergic effects; use caution in patients with xerostomia, urinary retention, BPH, decreased gastrointestinal motility, paralytic ileus, or visual problems

May cause CNS depression; may impair ability to operate heavy machinery or driving

Decreased sensation of thirst due to central inhibition may lead to dehydration, hemoconcentration and reduced pulmonary ventilation; a number of cases of bronchopneumonia, some fatal, reported; if signs and symptoms appear, especially in the elderly, institute remedial therapy promptly

Use caution in patients with severe cardiovascular disorders, because of possibility of transient hypotension and/or precipitation of anginal pain; should hypotension occur and a vasopressor be required, epinephrine should not be used since haloperidol may block its vasopressor activity and paradoxical further lowering of the blood pressure may occur; use metaraminol, phenylephrine or norepinephrine instead

Use caution in patients receiving anticonvulsant medications, with a history of seizures, or with EEG abnormalities; haloperidol may lower convulsive threshold; if indicated, adequate anticonvulsant therapy should be concomitantly maintained

 

Pregnancy and lactation

Pregnancy category: C; neonates exposed to antipsychotic drugs during 3rd trimester of pregnancy are at risk for extrapyramidal or withdrawal symptoms after delivery; these complications vary in severity, in some cases being self-limited and in other cases necessitating ICU support and prolonged hospitalization

Lactation: Drug enters breast milk; not recommended

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Haldol, Haldol Decanoate (haloperidol)

Mechanism of action

Phenylbutylpiperadine; antagonizes dopamine D1 and D2 receptors in brain; depresses reticular activating system and inhibits release of hypothalamic and hypophyseal hormones

 

Absorption

Bioavailability: 60-70%

Onset: 30-60 min (IM/IV)

Duration: 2-4 weeks (decanoate)

Peak plasma time: 2-6 hr (PO); 10-20 minutes(IM); 6-7 days (decanoate)

 

Distribution

Protein bound: 90%

Vd: 8-18 L/kg

 

Metabolism

Metabolized by hepatic P450 enzyme CYP3A4

Metabolites: HydroxyhaloperidoL

Enzymes inhibited: CYP2D6

 

Elimination

Half-life: 18 hr; 3 weeks (decanoate)

Excretion: Urine (30%), feces (15%)

 

Administration

IV/IM Administration

Haloperidol lactate and haloperidol decanoate are both administered IM; haloperidol lactate has also been administered IV (off-label); haloperidol decanoate should not be administered IV