Haloperidol

Increased Mortality in Geriatric Patients with Dementia-related Psychosis
Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸¹ ¹⁸² ¹⁸³ ¹⁸⁴ ^g
Analyses of 17 placebo-controlled trials in geriatric patients mainly receiving atypical antipsychotic agents revealed an approximate 1.6- to 1.7-fold increase in mortality compared with that in patients receiving placebo.¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸⁴ ^g
Most fatalities appeared to result from cardiovascular-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸⁴ ^g
Observational studies suggest that conventional or first-generation antipsychotic agents also may increase mortality in such patients.¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸¹ ¹⁸² ¹⁸³ ^g

Antipsychotic agents, including haloperidol, are not approved for the treatment of dementia-related psychosis.

Introduction

Butyrophenone derivative;^a ^b ^c ^d ^e conventional (prototypical, first-generation) antipsychotic agent.¹⁸⁵

Uses for Haloperidol

Schizophrenia

Treatment of schizophrenia.^a ^b ^d ¹⁸⁵

Antipsychotic agents are used for all phases of schizophrenia, including acute psychotic episodes as well for long-term stabilization and to minimize risk of relapse.¹⁸⁵

Patients who do not respond to or tolerate one drug may be successfully treated with an agent from a different class or with a different adverse effect profile.¹³⁶ ¹³⁷ ¹³⁸ ¹⁸⁵

APA considers certain atypical (second-generation) antipsychotic agents first-line for the acute phase of schizophrenia, principally because of the decreased risk of adverse extrapyramidal effects and tardive dyskinesia, with the understanding that the relative advantages, disadvantages, and cost-effectiveness of atypical antipsychotic agents compared with first-generation antipsychotic agents remain controversial.¹⁸⁵

Conventional antipsychotic agents may be considered first-line in patients with acute psychotic episodes who have been treated successfully in the past with, or who prefer, conventional agents.¹⁸⁵

Long-acting haloperidol decanoate ester used principally for prolonged antipsychotic therapy (e.g., chronic schizophrenic disorder).¹⁰⁰ ¹⁰¹ ¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹¹⁰ ¹¹¹ ¹¹² ¹⁸⁵ Parenteral antipsychotic therapy with a long-acting preparation may be particularly useful in patients with a history of poor compliance.¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹¹⁰ ¹¹¹ ¹¹² ¹⁸⁵ However, should not be used in the acute management of severely agitated patients.¹⁰⁰ ¹⁰¹

Tourette’s Syndrome

Control of tics and vocal utterances of Tourette’s syndrome (Gilles de la Tourette’s syndrome).^b ^d ^e

May be used concomitantly with a stimulant for tic disorders (e.g., Tourette’s syndrome) and comorbid attention deficit hyperactivity disorder† (ADHD) in children in whom stimulants alone cannot control tics.¹⁴⁷ ¹⁴⁸

Disruptive Behavior Disorder and ADHD

Treatment of severe behavioral problems in children marked by combativeness and/or explosive hyperexcitable behavior (out of proportion to immediate provocations).^b ^d ^e

Short-term treatment in children with hyperactivity associated with excessive motor activity and accompanying conduct disorders that are manifested as impulsive behavior, difficulty sustaining attention, aggression, mood lability, and/or poor frustration tolerance.^b ^d ^e

Manufacturers recommend reserving for severe behavioral problems or ADHD, only after failure of psychotherapy or drug therapy other than antipsychotics.^d ^e Some experts recommend use only for comorbid tics in children with ADHD.¹⁴⁸

Delirium

Management of delirium†.¹²¹ ¹³⁰ ¹⁷²

Antipsychotic agents often considered drugs of choice for delirium†.¹²¹ ¹⁷² Haloperidol generally is considered the antipsychotic of choice for most patients with delirium† because of its relatively low risk of anticholinergic activity and of sedative and hypotensive effects.¹²¹ ¹³⁰ ¹³² ¹⁷⁰

Various antipsychotic agents may be given orally, IM, or IV, but IV† administration is considered most effective in emergency situations or where oral access is limited.¹²¹ IV administration also may be associated with less severe extrapyramidal effects.¹²¹ ¹²³ ¹³⁰

Consider risk of QT-interval prolongation, possibly leading to atypical ventricular tachycardia (torsades de pointes), ventricular fibrillation, and sudden death, if haloperidol is used IV† for delirium.¹²¹ ¹²⁴ ¹²⁵ ¹²⁶ ¹³⁰ ¹³¹ ¹³² ¹³³ ¹³⁴ ¹⁶⁹ Institute appropriate monitoring (e.g., ECG).¹²¹ ¹²⁴ ¹²⁵ ¹²⁶ ¹³⁰ ¹³¹ ¹³² ¹³³ ¹³⁴ ¹⁶² ¹⁶³ ¹⁶⁴(See Delirium under Dosage and Administration and see QT-interval Prolongation and Sudden Death under Cautions.)

Nausea and Vomiting

Has been used in the prevention and control of severe nausea and vomiting† (e.g., cancer chemotherapy-induced emesis).^a Appears to be as effective as phenothiazines in preventing cancer chemotherapy-induced emesis; additional studies required.^a

Haloperidol Dosage and Administration

Administration

Administer haloperidol orally as tablets.¹⁰² ¹⁰³

Administer haloperidol lactate orally as solution concentrate or IM;¹⁰² ¹⁰³ also has been administered by IV injection†¹²¹ ¹²³ ¹²⁴ ¹²⁵ ¹²⁷ ¹²⁸ ¹²⁹ ¹³⁰ ¹³¹ ¹³³ ¹³⁴ ¹³⁵ or infusion†.¹²¹ ¹²⁹

Administer haloperidol decanoate IM; do not administer IV.¹⁰⁰ ¹⁰¹

Avoid skin contact with haloperidol lactate oral solution and injection, since contact dermatitis has occurred rarely.^a

Oral Administration

Haloperidol or haloperidol lactate: Administer orally 2 or 3 times daily.¹⁰² ¹⁰³

IM Administration

Haloperidol decanoate: Administer by deep IM injection into the gluteal region using a 21-gauge needle, usually at monthly intervals;¹⁰⁰ ¹⁰¹ maximum volume should not exceed 3 mL per IM injection site.¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³

Haloperidol lactate: Administer IM at intervals based on patient response; may administer as often as every hour, although 4- to 8-hour intervals may be satisfactory.¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³

IM administration of haloperidol decanoate or lactate in pediatric patients is not recommended by the manufacturers.¹⁸⁷ ¹⁹¹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Haloperidol lactate: Has been administered by IV injection†¹²¹ ¹²³ ¹²⁴ ¹²⁵ ¹²⁷ ¹²⁸ ¹²⁹ ¹³⁰ ¹³¹ ¹³³ ¹³⁴ ¹³⁵ or infusion†.¹²¹ ¹²⁹

ECG monitoring is recommended whenever haloperidol is administered IV.¹²¹ ¹²⁵ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹⁶² ¹⁶³ ¹⁶⁴(See Delirium under Dosage and Administration and see QT-interval Prolongation and Sudden Death under Cautions.)

Dosage

Available as the base, decanoate (decanoic acid ester), and lactate salt; dosage is expressed in terms of haloperidol.¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³

There is considerable interindividual variation in optimum dosage requirements; carefully adjust dosage according to individual requirements and response, using the lowest possible effective dosage.^b ^c ^d ^e

Because of risk of adverse reactions associated with cumulative effects of butyrophenones, periodically evaluate patients with a history of long-term therapy with haloperidol and/or other antipsychotic agents to determine whether maintenance dosage can be decreased or drug therapy discontinued.^a

Pediatric Patients

Schizophrenia

Oral

Children 3–12 years of age (weighing 15–40 kg): Initially, 0.5 mg daily given in 2 or 3 divided doses.^d ^e Subsequent dosage may be increased by 0.5 mg daily at 5- to 7-day intervals, depending on the patient’s tolerance and therapeutic response; usual dosage range is 0.05–0.15 mg/kg daily given in 2 or 3 divided doses.^d ^e

Severely disturbed psychotic children may require higher dosages.^d ^e

During prolonged maintenance therapy, keep dosage at the lowest possible effective level; once an adequate response has been achieved, gradually reduce dosage and make subsequent adjustments according to patient response and tolerance.^d ^e

Tourette’s Syndrome

Oral

Once an adequate response is achieved, gradually reduce dosage and make subsequent adjustments according to patient response and tolerance.^d ^e

Disruptive Behavior Disorder and ADHD

Oral

Nonpsychotic or hyperactive behavioral problems in children may be acute, and short-term administration may be adequate.^d ^e

Maximum effective dosage for management of behavioral problems in children not established, but there is little evidence that improvement in behavior is further enhanced at dosages >6 mg daily.^d ^e

Adults

Schizophrenia

Moderate Symptomatology

Oral

Initially, 0.5–2 mg 2 or 3 times daily.^d ^e Carefully adjust subsequent dosage according to the patient’s tolerance and therapeutic response.^d ^e During prolonged maintenance therapy, keep dosage at lowest effective level.^d ^e

Severe Symptomatology

Oral

Initially, 3–5 mg 2 or 3 times daily.^d ^e

To achieve prompt control, higher dosages may be required in some patients.^d ^e Patients who remain severely disturbed or inadequately controlled may require dosage adjustment.^d ^e

Dosages up to 100 mg daily may be required in some severely psychotic patients.^d ^e

Occasionally, dosages >100 mg daily have been used for the management of severely resistant disorders in adults; however, safety of prolonged administration of such dosages has not been demonstrated.^d ^e

Chronic/Resistant Disorders

Oral

Initially, 3–5 mg 2 or 3 times daily.^d ^e

Patients who remain severely disturbed or inadequately controlled may require dosage adjustment.^d ^e

Dosages up to 100 mg daily may be required in some severely psychotic patients.^d ^e

IM (Haloperidol Decanoate)

May consider for patients requiring prolonged antipsychotic therapy (e.g., patients with chronic schizophrenic disorder).¹⁰⁰ ¹⁰¹ ¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹¹⁰ ¹¹¹ ¹¹² ¹⁸⁵

Initially, stabilize patient’s condition with an antipsychotic agent prior to attempting conversion to haloperidol decanoate.^c If patient is receiving an antipsychotic agent other than haloperidol, initial conversion to oral haloperidol is recommended to minimize risk of an unexpected adverse reaction that might not be readily reversible following use of the decanoate.¹⁰⁰ ¹⁰¹ ^c

Base initial IM decanoate dose on patient’s clinical history, physical condition, and response to previous antipsychotic therapy.¹⁰⁰ ¹⁰¹ ¹¹⁰

A precise formula for converting oral haloperidol dosage to IM haloperidol decanoate not established, but an initial IM dose 10–20 times the previous daily oral haloperidol dose, not >100 mg (regardless of previous antipsychotic dosage requirements) is suggested, although limited clinical experience suggests that a lower initial dosage of the decanoate may be adequate.^c (See Table: Haloperidol Decanoate Dosage Recommendations under Dosage and Administration.)

If conversion requires an initial haloperidol decanoate dosage >100 mg, administer in 2 injections (i.e., administer a maximum initial dose of 100 mg followed by the balance in 3–7 days); however, some clinicians have converted therapy to decanoate using a higher initial dose.^c

Haloperidol Decanoate Dosage Recommendationsc
Patient Population	Initial Therapy	Monthly Maintenance Therapy
Patients stabilized on low daily oral dosages (up to 10 mg daily), or geriatric or debilitated patients	10–15 times daily oral dosage	10–15 times previous daily oral dosage
Patients receiving high-dose oral therapy, at risk for relapse, or tolerant to oral haloperidol	20 times daily oral dosage	10–15 times previous daily oral dosage

Usually, administer at monthly intervals (i.e., every 4 weeks), but individual response may dictate need for adjusting dosing interval as well as the dose.¹⁰⁰ ¹⁰¹ ¹⁰⁸ ¹⁰⁹ ¹¹⁰ ¹¹¹

Observe closely during dosage titration to minimize risk of overdosage or emergence of psychotic manifestations prior to next dose; if supplemental antipsychotic therapy is necessary during periods of dosage titration or for control of acute exacerbations of psychotic manifestations, use a short-acting haloperidol preparation.¹⁰⁰ ¹⁰¹ ¹¹⁰

Experience with haloperidol decanoate dosages >450 mg monthly is limited.¹⁰⁰ ¹⁰¹

Acute Agitation

IM (Haloperidol Lactate)

Initially, 2–5 mg as a single dose for prompt control in patients with moderately severe to very severe symptoms.^b Depending on patient response, may repeat dose as often as every hour; however, administration every 4–8 hours may be adequate to control symptoms in some patients.¹⁰² ¹⁰³

Conversion from IM to Oral Therapy

Oral

Oral: Replace short-acting parenteral therapy with haloperidol lactate with oral therapy as soon as possible; depending on patient’s clinical status, give first oral dose within 12–24 hours after administration of last parenteral dose.^b

Use total parenteral dosage during preceding 24 hours for initial approximation of total daily oral dosage required; since this dosage is only an initial estimate, closely monitor patients being switched to oral therapy, particularly for efficacy, sedation, and adverse effects, for first several days following initiation of oral therapy.^b

Increase or decrease subsequent oral dosage according to patient tolerance and therapeutic response, using lowest possible effective dosage.^b

Tourette’s Syndrome

Moderate Symptomatology

Oral

Initially, 0.5–2 mg 2 or 3 times daily.^d ^e Carefully adjust subsequent dosage according to patient’s tolerance and therapeutic response.^d ^e

During prolonged maintenance therapy, keep dosage at lowest effective level.^d ^e

Severe Symptomatology and/or Chronic/Resistant Disorder

Oral

Initially, 3–5 mg 2 or 3 times daily.^d ^e

Patients who remain inadequately controlled may require dosage adjustment.^d ^e

Dosages up to 100 mg daily may be required in some patients to achieve optimal response.^d ^e

Occasionally, dosages >100 mg daily have been used for management of severely resistant disorders in adults; however, safety of prolonged administration of such dosages has not been demonstrated.^d ^e

Delirium†

IV (Haloperidol Lactate)

Optimum dosage not established.¹²¹ However, initiation of IV† haloperidol (as the lactate) with dosages of 1–2 mg every 2–4 hours has been suggested; ¹²¹ ¹²⁷ severely agitated adults may require titration to higher dosages.¹²¹ ¹²⁴ ¹²⁵ ¹²⁷

Although single IV doses up to 50 mg or total daily dosages of 500 mg have been reported,¹²¹ ¹²⁵ ¹²⁷ ¹²⁸ ¹³² must consider risk of adverse effects, particularly prolongation of the QT interval and torsades de pointes.¹²⁵ ¹³⁰ ¹³² ¹⁶²

Some evidence suggests that risk of torsades de pointes increases at total daily dosages of 35–50 mg or more.¹²⁵ ¹³² ¹⁶²

In patients requiring multiple IV injections of the drug to control delirium (e.g., more than eight 10-mg doses in 24 hours or >10 mg/hour for >5 consecutive hours), may consider continuous IV infusion†;¹²¹ ¹²⁹ in such patients, an initial 10-mg dose followed by an infusion of 5–10 mg/hour has been suggested.¹²¹ ¹²⁹ If agitation persists, can consider repeating 10-mg IV doses at 30-minute intervals, accompanied by a 5-mg/hour increase in the infusion rate.¹²⁹

Determine ECG at baseline and periodically or continuously thereafter, paying special attention to possible prolongation of the QT interval; reduce dosage or discontinue drug if clinically important QT prolongation (e.g., 15–25% or more over baseline) occurs or the QT_c interval exceeds 450 msec.¹²¹ ¹²⁵ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹⁶² ¹⁶³ ¹⁶⁴ (See QT-interval Prolongation and Sudden Death under Cautions.)

Prescribing Limits

Pediatric Patients

Oral

Maximum effective dosage not established, but there is little evidence that improvement in behavior is further enhanced at dosages >6 mg daily.^d ^e

IM

Safety and efficacy not established in children.^b ^c

Adults

Oral

Safety of prolonged administration of dosages >100 mg not demonstrated.^d ^e

IM

Experience with haloperidol decanoate dosages >450 mg monthly is limited.¹⁰⁰ ¹⁰¹

IV

Although single IV† doses ≤50 mg or total daily dosages of 500 mg of haloperidol (as the lactate) have reportedly been given for delirium†,¹²¹ ¹²⁵ ¹²⁷ ¹²⁸ ¹³² higher dosages (i.e., total daily dosages of ≥35–50 mg) and IV administration of the drug appear to be associated with a higher risk of QT-interval prolongation and torsades de pointes.¹²¹ ¹²⁴ ¹²⁵ ¹²⁸ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹⁶² ¹⁶³ ¹⁶⁴ ¹⁶⁷ ¹⁶⁸ ¹⁷⁰ ¹⁷¹

Consider continuous IV infusion† in patients requiring multiple IV injections to control delirium (e.g., more than eight 10-mg doses in 24 hours or >10 mg/hour for >5 consecutive hours).¹²¹ ¹²⁹(See Delirium under Dosage and Administration and see QT-interval Prolongation and Sudden Death under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations.^a ^g

Renal Impairment

No specific dosage recommendations.^a ^g

Geriatric/Debilitated Patients

In geriatric or debilitated patients, lower dosages may be required than those in younger adults; optimal response is usually obtained with more gradual dosage adjustments.^b (See Geriatric Use under Cautions.)

Initially, 0.5–2 mg orally 2 or 3 times daily; increase dosage more gradually in debilitated, emaciated, or geriatric patients than in younger adults.^d ^e

Lower IV† dosages (e.g., 0.25–0.5 mg every 4 hours as haloperidol lactate) have been suggested for geriatric patients with delirium.¹²¹

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Cautions for Haloperidol

Contraindications

Severe toxic CNS depression or comatose states from any cause.^b ^c ^d ^e
Parkinsonian syndrome.^a ^b ^c ^d ^e
Hypersensitivity to haloperidol.^b ^c ^d ^e

Warnings/Precautions

Warnings

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Increased risk of death with use of either conventional (first-generation) or atypical (second-generation) antipsychotics in geriatric patients with dementia-related psychosis.¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸¹ ¹⁸² ¹⁸³ ¹⁸⁴ ^g

Antipsychotic agents, including haloperidol, are not FDA labeled for the treatment of dementia-related psychosis.¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸¹ ^g (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

QT-interval Prolongation and Sudden Death

Sudden death, QT-interval prolongation, and torsades de pointes reported in patients receiving haloperidol.¹²⁴ ¹²⁵ ¹²⁶ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹⁶² ¹⁶³ ¹⁶⁴ ¹⁶⁷ ¹⁶⁸ ¹⁶⁹ ¹⁷⁰ ¹⁷¹

Use of higher than recommended doses of any haloperidol formulation and IV† administration of the drug appear to be associated with an increased risk of QT-interval prolongation and torsades de pointes.¹²⁴ ¹²⁵ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹⁶² ¹⁶³ ¹⁶⁴ ¹⁶⁷ ¹⁶⁸ ¹⁷⁰ ¹⁷¹

Although these effects have been reported in the absence of predisposing factors, use haloperidol with particular caution in patients with other conditions that prolong the QT interval, including electrolyte imbalance (particularly hypokalemia and hypomagnesemia), underlying cardiac abnormalities, hypothyroidism, and familial long QT syndrome, as well as in those concurrently receiving other drugs known to prolong the QT interval.¹³⁰ ¹³² ¹³³ ¹⁶² ¹⁶³ ¹⁶⁴ ¹⁷⁰ (See Drugs that Prolong QT Interval under Interactions.)

Monitor ECG whenever haloperidol is administered IV.¹²⁵ ¹³⁰ ¹⁶² ¹⁶³ ¹⁶⁴ (See Delirium under Dosage and Administration.) Prolongation of the QT_c interval to >450 msec or to >15–25% over that in previous ECGs may warrant telemetry, cardiology consultation, and dose reduction or discontinuance.¹²¹ ¹³⁰ ¹³² ¹³³

Monitor serum magnesium and potassium at baseline and periodically in critically ill patients,¹²¹ ¹³² ¹³³ especially those with baseline QT_c interval ≥440 msec, those receiving other drugs known to increase the QT interval, and those who have electrolyte disorders.¹²¹

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, reported with use of antipsychotic agents, including haloperidol.^b ^c ^d ^e ^g

Reserve long-term antipsychotic treatment for patients with chronic illness known to be responsive to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate.¹⁸⁷ ^g In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.¹⁸⁷

APA recommends assessing patients receiving first-generation antipsychotic agents for abnormal involuntary movements every 6 months; for patients at increased risk for tardive dyskinesia, assess every 3 months.¹⁸⁵ Consider discontinuance of haloperidol if signs and symptoms of tardive dyskinesia develop;^b ^c ^d ^e ^f ^g however, some patients may require treatment despite the presence of the syndrome.^f ^g

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, reported with antipsychotic agents, including haloperidol.¹⁰⁰ ¹⁰² ¹⁰³ ^b ^f ^g

Immediately discontinue therapy and initiate supportive and symptomatic therapy if NMS occurs.^gCareful monitoring recommended if therapy is reinstituted following recovery; the risk that NMS can recur must be considered.^f ^g

Hyperpyrexia and heat stroke not associated with NMS also reported.^b ^c ^d ^e

Fetal/Neonatal Morbidity and Mortality

Cases of limb malformations in offspring of women given haloperidol concurrently with other potentially teratogenic drugs during first trimester of pregnancy reported; causal relationship not established.^a ^b Teratogenic and fetotoxic in animals.^a ^b

Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms.¹⁸⁷ ¹⁸⁸ ¹⁸⁹ ¹⁹⁰ Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.¹⁸⁷ ¹⁸⁸ ¹⁸⁹ ¹⁹⁰

Use during pregnancy or in women likely to become pregnant only when potential benefits justify possible risks to fetus.^a ^b

Concomitant Therapy with Lithium

Acute encephalopathic syndrome reported occasionally in patients receiving lithium and an antipsychotic agent concurrently, especially when high serum lithium concentrations were present.^a ^b Observe patients receiving combined therapy for evidence of neurologic effects; promptly discontinue if manifestations appear.^a ^b

Respiratory Effects

Bronchopneumonia, sometimes fatal, reported with use of antipsychotic agents, including haloperidol.^a ^b Consider that lethargy and decreased thirst, resulting from central inhibition, may cause dehydration, hemoconcentration, and reduced pulmonary ventilation; if such manifestations occur, particularly in geriatric patients, promptly institute appropriate therapy.^a ^b

Ocular Effects

Ocular changes reported in patients receiving chemically related drugs, although not reported with haloperidol.^a

Sensitivity Reactions

Hypersensitivity

Skin reactions (i.e., maculopapular, acneiform) and isolated cases of photosensitivity reported;^b ^c ^d ^e contact dermatitis reported rarely with skin contact to haloperidol lactate oral solution and injection.^a

Use with caution in patients with known allergies or with a history of allergic reactions to drugs.^a

General Precautions

Hypotension and Angina

Possible transient hypotension and/or precipitation of angina; use with caution in patients with severe cardiovascular disorders¹⁶³ ¹⁶⁴ ¹⁶⁵ ¹⁶⁶

If hypotension occurs, may use metaraminol, norepinephrine, or phenylephrine; do not use epinephrine since haloperidol causes a reversal of epinephrine’s vasopressor effects and a further lowering of BP.¹⁶³ ¹⁶⁴ ¹⁶⁵ ¹⁶⁶

Seizures

Possible risk of seizures; may lower seizure threshold.¹⁰⁰ ¹⁰¹ ¹⁰³ ^b ^c ^d ^e Use with caution in patients with a history of seizures or EEG abnormalities or in those receiving anticonvulsant agents.¹⁰⁰ ¹⁰¹ ¹⁰³Maintain adequate anticonvulsant therapy.^a ^b

CNS Depression

Possible impairment of ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).^a ^b

Possible additive effects or potentiated action when used with alcohol or other CNS depressants.^a ^b ^c ^d ^e (See Specific Drugs under Interactions and also see Advice to Patients.)

Extrapyramidal Symptoms

Extrapyramidal symptoms occur frequently; if concomitant therapy with an antiparkinsonian drug is necessary to manage extrapyramidal symptoms, it may be necessary to continue the antiparkinsonian drug for a period of time after haloperidol discontinuance to prevent emergence of these symptoms.^a ^b

Thyrotoxicosis

Severe neurotoxicity (e.g., rigidity, inability to walk or talk) may occur in patients with thyrotoxicosis who are also receiving antipsychotic agents, including haloperidol.^a ^b

Bipolar Disorder

If used to control mania in patients with bipolar disorder, there may be a rapid mood swing to depression.^a ^b

Abrupt Withdrawal

Possible transient dyskinetic signs after abrupt withdrawal in some patients receiving maintenance therapy; in some cases, dyskinetic movements are indistinguishable from tardive dyskinesia except for duration.^b It is not known whether gradual withdrawal will reduce occurrence of withdrawal-emergent neurological signs; pending further evidence, withdraw gradually.^b

Endocrine Effects

Elevated prolactin concentrations possible; may persist during long-term therapy.^a ^b ^c ^d ^e ^g

Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, clinical importance of elevated prolactin concentrations for most patients has not been established.^a ^g

Use with caution in patients with previously diagnosed breast cancer, since in vitro tests indicate that about one-third of such tumors are prolactin dependent.^a ^g

Metabolic Effects

Decreased serum cholesterol concentrations reported in patients receiving chemically related agents.^b ^c ^d ^e

Hematologic Effects

Leukopenia and neutropenia temporally related to antipsychotic agents, including haloperidol, reported.¹⁸⁷ ^h Agranulocytosis (including fatal cases) also reported with other antipsychotic agents.¹⁸⁷

Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia.¹⁸⁷ ^h Monitor CBC frequently during the first few months of therapy in patients with such risk factors.¹⁸⁷ Discontinue haloperidol at the first sign of a decline in WBC count in the absence of other causative factors.¹⁸⁷

Carefully monitor patients with clinically significant neutropenia for fever or other signs and symptoms of infection and treat promptly if observed.¹⁸⁷ In patients with severe neutropenia (ANC <1000/mm³), discontinue haloperidol and monitor WBC until recovery occurs.¹⁸⁷

Specific Populations

Pregnancy

Category C.^c (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk.^a ^b Women receiving haloperidol should not breast-feed.^a ^b

Pediatric Use

Safety and efficacy of IM administration of haloperidol decanoate or lactate not established in pediatric patients.¹⁸⁷ ¹⁹¹

Safety and efficacy of orally administered haloperidol or haloperidol lactate not established in children <3 years of age.¹⁰² ¹⁰³

Hyperammonemia reported during postmarketing surveillance in a 5.5-year old child with citrullinemia, an inherited disorder of ammonia excretion, following haloperidol therapy.¹⁰⁰

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹⁰⁰ ¹⁰³ ^g Other reported clinical experience has not consistently identified differences in responses between geriatric and younger patients.¹⁰⁰ ¹⁰³ ^g

Prevalence of tardive dyskinesia appears to be highest among geriatric patients, particularly geriatric women.¹⁰⁰ ¹⁰³ ^g

Pharmacokinetics of haloperidol in geriatric patients generally warrant use of reduced dosages.¹⁰⁰ ¹⁰³ ^g (See Geriatric/Debilitated Patients under Dosage and Administration.)

Geriatric patients with dementia-related psychosis treated with either conventional or atypical antipsychotic agents are at an increased risk of death.¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸¹ ¹⁸² ¹⁸³ ¹⁸⁴ ^g (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Common Adverse Effects

Extrapyramidal reactions (e.g., Parkinson-like symptoms, akathisia, dystonia).^b ^c ^d ^e

Interactions for Haloperidol

Drugs that Prolong QT Interval

QT-interval prolongation and torsades de pointes reported;¹²⁴ ¹²⁵ ¹²⁶ ¹²⁹ ¹³⁰ ¹³² ¹³³ ¹⁶² ¹⁶³ ¹⁶⁴ ¹⁶⁷ ¹⁶⁸ ¹⁶⁹ ¹⁷⁰ ¹⁷¹patients receiving higher than recommended dosages of any haloperidol preparation and those receiving the drug IV appear to be at higher risk.¹⁶² ¹⁶³ ¹⁶⁴ Particular caution is advised when oral or parenteral haloperidol is used in patients concurrently receiving other drugs that prolong the QT interval.¹³² ¹⁶² ¹⁶³ (See Delirium under Uses, Delirium under Dosage and Administration, and QT-interval Prolongation and Sudden Death under Cautions.)

Specific Drugs

Drug	Interaction	Comments
Anticholinergic agents	Increases in intraocular pressure may occur in patients receiving anticholinergic drugs, including antiparkinsonian agents, concurrently with haloperidol^a ^b ^c ^d ^e
Anticoagulants	Antagonism of anticoagulant activity of phenindione (no longer commercially available in US) reported in 1 patient^b ^c ^d ^e	Further study needed to determine clinical importance^a
CNS depressants (e.g., alcohol, anesthetics, barbiturates or other sedatives, opiates or other analgesics)	Possible additive effects or potentiated action of other CNS depressants^a ^b ^c ^d ^e	Use concomitantly with caution to avoid excessive sedation^a
Lithium	An acute encephalopathic syndrome occasionally has occurred, especially when high serum lithium concentrations were present^a ^b ^c ^d ^e	Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appear^a ^b ^d ^e
Methyldopa	Possible dementia in patients receiving haloperidol and methyldopa concomitantly^a	Clinical importance of this possible interaction not determined; carefully observe patients for adverse psychiatric symptoms if used concurrently^a
Rifampin	Decreased (70%) mean plasma haloperidol concentrations and decreased antipsychotic efficacy with concomitant use¹⁰⁰ ¹⁰³ Following discontinuance of rifampin in other schizophrenic patients treated with oral haloperidol, mean haloperidol concentrations increased 3.3-fold¹⁰⁰ ¹⁰³	Careful monitoring of clinical status and appropriate dosage adjustment warranted whenever rifampin is initiated or discontinued in patients stabilized on haloperidol¹⁰⁰ ¹⁰³

Haloperidol Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract following oral administration, but appears to undergo first-pass metabolism in the liver.¹⁰² ¹⁰⁵ ¹⁰⁸ ¹¹¹ Oral bioavailability reported to average 60%.¹⁰² ¹¹⁸

Peak plasma concentrations occur within 2–6 hours after oral administration.¹⁰²

Following IM administration of haloperidol lactate, peak plasma haloperidol concentrations occur within 10–20 minutes.¹⁰²

Following IM administration of haloperidol decanoate, plasma haloperidol concentrations are usually evident within 1 day¹⁰⁷ ¹¹² and peak concentrations generally occur within about 6–7 days (range: 1–9 days).¹⁰⁰ ¹⁰¹ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹¹²

Onset

Following IM administration of haloperidol lactate, peak pharmacologic action occurs within 30–45 minutes;¹⁰² in acutely agitated patients, control of psychotic manifestations may become apparent within 30–60 minutes, with substantial improvement often occurring within 2–3 hours.¹⁰²

Duration

Haloperidol decanoate: Esterification of haloperidol results in slow and gradual release of haloperidol decanoate from fatty tissues, thus prolonging duration of action;¹⁰¹ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁹ ¹¹²administration of the ester in a sesame oil vehicle further delays rate of release.¹⁰⁶

Distribution

Extent

Distribution into human body tissues and fluids not fully characterized.^a In animals, the drug is distributed mainly into the liver, with lower concentrations being distributed into the brain, lungs, kidneys, spleen, and heart.^a

Following IM administration of haloperidol decanoate, the esterified compound is initially distributed into fatty tissue stores, from which the drug is then slowly and gradually released.¹⁰⁰ ¹⁰¹ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁹ ¹¹²

Distributed into milk.^a ^b

Plasma Protein Binding

About 92%.^a

Elimination

Metabolism

Exact metabolic fate not clearly established, but appears to be principally metabolized in the liver by oxidative N-dealkylation of the piperidine nitrogen to form fluorophenylcarbonic acids and piperidine metabolites (which appear to be inactive),¹⁰¹ ¹⁰² ¹¹⁷ and by reduction of the butyrophenone carbonyl to the carbinol, forming hydroxyhaloperidol.¹⁰¹ ¹⁰² ¹⁰⁶ ¹¹⁶

Limited data suggest that the reduced metabolite, hydroxyhaloperidol, has some pharmacologic activity, although its activity appears to be less than that of haloperidol.¹⁰⁶ ¹¹⁶

After distribution and slow and gradual release from fatty tissue stores following IM administration of haloperidol decanoate, the drug undergoes hydrolysis by plasma and/or tissue esterases to form haloperidol and decanoic acid.¹⁰⁰ ¹⁰¹ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁹ ¹¹² Subsequent distribution, metabolism, and excretion of haloperidol appear to be similar to those of orally administered drug.¹⁰¹

Elimination Route

Excreted slowly in urine and feces as unchanged drug and metabolites.^a Approximately 40% of a single oral dose is excreted in urine within 5 days.^a About 15% of an oral dose is excreted in feces via biliary elimination.^a Small amounts are excreted for about 28 days following oral administration.^a

Half-life

After IM administration of the decanoate, apparent half-life is approximately 3 weeks.¹⁰⁰ ¹⁰¹ ¹⁰⁵ ¹⁰⁶ ¹⁰⁹

Special Populations

Pharmacokinetics of haloperidol generally warrant the use of reduced dosages in geriatric patients.^b ^c ^d ^e ^g

Stability

Storage

Oral

Solution

Tight, light-resistant containers¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ at 15–30°C.^a Avoid freezing.¹⁰⁰ ¹⁰¹ ¹⁰³

Tablets

Tight, light-resistant containers¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ at 20–25°C.^a

Parenteral

Injection

Haloperidol decanoate: 15–30°C.^c Do not refrigerate or freeze.^c Protect from light.^c

Haloperidol lactate: 15–30°C.^b Do not freeze.^b Protect from light.^b

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Haloperidol Decanoate

Incompatible with sterile water for injection or sodium chloride injection and with other aqueous injections.¹⁰¹

Haloperidol Lactate

May be compatible with some drugs for a short period of time after mixing, but at least one manufacturer recommends that the lactate not be mixed with other drugs.¹⁰²

Solution Compatibility (haloperidol lactate)^HID

Compatible
Dextrose 5% in water
Variable
Dextrose 5% in sodium chloride 0.2%
Ringer’s injection, lactated
Sodium chloride 0.45 or 0.9%

Drug Compatibility

Admixture Compatibility (haloperidol lactate)HID
Compatible
Buprenorphine HCl with glycopyrrolate
Oxycodone HCl

Y-site Compatibility (haloperidol lactate)HID
Compatible
Alcohol 10% in dextrose 5%
Amifostine
Amsacrine
Aztreonam
Bivalirudin
Cimetidine HCl
Cladribine
Dexmedetomidine HCl
Dobutamine HCl
Docetaxel
Dopamine HCl
Doxorubicin HCl liposome injection
Etoposide phosphate
Famotidine
Fenoldopam mesylate
Fentanyl citrate
Filgrastim
Fludarabine phosphate
Gemcitabine HCl
Granisetron HCl
Hetastarch in lactated electrolyte injection (Hextend)
Hydromorphone HCl
Lidocaine HCl
Linezolid
Lorazepam
Melphalan HCl
Methadone HCl
Midazolam HCl
Morphine sulfate
Nitroglycerin
Norepinephrine bitartrate
Ondansetron HCl
Oxaliplatin
Paclitaxel
Pemetrexed disodium
Phenylephrine HCl
Propofol
Quinupristin-dalfopristin
Remifentanil HCl
Sufentanil citrate
Tacrolimus
Teniposide
Theophylline
Thiotepa
Vinorelbine tartrate
Incompatible
Allopurinol sodium
Amphotericin B cholesteryl sulfate complex
Cefepime HCl
Fluconazole
Foscarnet sodium
Gallium nitrate
Heparin sodium
Lansoprazole
Piperacillin sodium–tazobactam sodium
Sargramostim
Variable
Sodium nitroprusside

Syringe Compatibility (haloperidol lactate)HID

Compatible

Buprenorphine HCl with glycopyrrolate

Cyclizine lactate with diamorphine HCl

Hydromorphone HCl

Lorazepam

Morphine HCl

Sufentanil citrate

Incompatible

Diphenhydramine HCl

Heparin sodium

Hydroxyzine HCl

Ketorolac tromethamine

Morphine sulfate

Variable

Benztropine mesylate

Cyclizine lactate

Diamorphine HCl

Hydromorphone HCl

Actions

Principal pharmacologic effects are similar to those of piperazine-derivative phenothiazines.^a
Precise mechanism of antipsychotic action is unclear, but appears to depress the CNS at the subcortical level of the brain, midbrain, and brain stem reticular formation; appears to inhibit the ascending reticular activating system of the brain stem (possibly through the caudate nucleus), thereby interrupting the impulse between the diencephalon and the cortex.^a
May antagonize actions of glutamic acid within the extrapyramidal system.^a Inhibition of catecholamine receptors may also be important in the mode of action; may also inhibit the reuptake of various neurotransmitters in the midbrain.^a
Appears to have strong central antidopaminergic and weak central anticholinergic activity.^a
Precise mechanism of antiemetic action is unclear, but has been shown to directly affect the chemoreceptor trigger zone (CTZ), apparently by blocking dopamine receptors in the CTZ.^a
Like other dopamine receptor antagonists (e.g., phenothiazines), may cause extrapyramidal reactions, and there appears to be a very narrow range between effective therapeutic dosage for management of acute psychotic disorders and that causing extrapyramidal symptoms.^a
Produces less sedation, hypotension, and hypothermia than chlorpromazine.^a

Advice to Patients

Importance of advising patients and caregivers that geriatric patients with dementia-related psychoses treated with antipsychotic agents are at an increased risk of death.¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ^g Inform patients and caregivers that haloperidol is not approved for treating geriatric patients with dementia-related psychosis.¹⁷⁷ ¹⁷⁸ ¹⁷⁹ ¹⁸⁰ ¹⁸¹ ^g
Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery.^c
Importance of avoiding alcohol during therapy due to risk of additive effects and hypotension.^c
Importance of informing patients and caregivers about the risk of NMS, which can cause high fever, stiff muscles, sweating, fast or irregular heart beat, change in BP, and confusion.¹⁸⁷
Importance of informing patients in whom chronic haloperidol use is contemplated of risk of tardive dyskinesia.¹⁸⁷ ^f ^g Importance of advising patients to report any muscle movements that cannot be stopped to a healthcare professional.ⁱ
Risk of leukopenia/neutropenia.¹⁸⁷ Importance of advising patients with a preexisting low WBC count or history of drug-induced leukopenia/neutropenia that their CBC count should be monitored during haloperidol therapy.¹⁸⁷
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^b ^c ^d ^e
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁸⁷ ¹⁹⁰ Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Fetal/Neonatal Morbidity and Mortality under Cautions).¹⁸⁷ ¹⁹⁰ Importance of advising patients not to stop taking haloperidol if they become pregnant without consulting their clinician; abruptly discontinuing antipsychotic agents may cause complications.¹⁹⁰ Importance of advising patients not to breast-feed during haloperidol therapy.¹⁸⁷
Importance of informing patients of other important precautionary information.^b ^c ^d ^e (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Haloperidol
Routes	Dosage Forms	Strengths	Brand Names
Oral	Tablets	0.5 mg*	Haloperidol Tablets
		1 mg*	Haloperidol Tablets
		2 mg*	Haloperidol Tablets
		5 mg*	Haloperidol Tablets
		10 mg*	Haloperidol Tablets
		20 mg*	Haloperidol Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Haloperidol Decanoate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IM use only	50 mg (of haloperidol) per mL*	Haldol Decanoate	Ortho-McNeil-Janssen
			Haloperidol Decanoate Injection
		100 mg (of haloperidol) per mL*	Haldol Decanoate	Ortho-McNeil-Janssen
			Haloperidol Decanoate Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Haloperidol Lactate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	2 mg (of haloperidol) per mL*	Haloperidol Lactate Oral Solution Concentrate
Parenteral	Injection	5 mg (of haloperidol) per mL*	Haldol	Ortho-McNeil-Janssen
			Haloperidol Lactate Injection

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2012. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Haloperidol 0.5MG Tablets (SANDOZ): 90/$16.99 or 180/$22.97

Haloperidol 1MG Tablets (MYLAN): 90/$19.99 or 180/$27.98

Haloperidol 10MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 60/$72.99 or 180/$202.98

Haloperidol 2MG Tablets (MYLAN): 90/$20.99 or 270/$40.96

Haloperidol 20MG Tablets (SANDOZ): 60/$124.99 or 180/$342.97

Haloperidol 5MG Tablets (MYLAN): 90/$25.99 or 270/$55.98

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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