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Haloperidol

Brand name: Haldol
Drug class: Butyrophenones
VA class: CN709
CAS number: 52-86-8

Medically reviewed by Drugs.com on Dec 27, 2021. Written by ASHP.

Warning

    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.

  • 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.

  • Most fatalities appeared to result from cardiovascular-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).

  • Observational studies suggest that conventional or first-generation antipsychotic agents also may increase mortality in such patients.

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

Introduction

Butyrophenone derivative; conventional (prototypical, first-generation) antipsychotic agent.

Uses for Haloperidol

Schizophrenia

Treatment of schizophrenia.

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.

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.

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.

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.

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

Tourette’s Syndrome

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

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.

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).

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.

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

Delirium

Management of delirium.

Antipsychotic agents often considered drugs of choice for delirium. 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.

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. IV administration also may be associated with less severe extrapyramidal effects.

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. Institute appropriate monitoring (e.g., ECG). (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). Appears to be as effective as phenothiazines in preventing cancer chemotherapy-induced emesis; additional studies required.

Haloperidol Dosage and Administration

Administration

Administer haloperidol orally as tablets.

Administer haloperidol lactate orally as solution concentrate or IM; also has been administered by IV injection or infusion.

Administer haloperidol decanoate IM; do not administer IV.

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

Oral Administration

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

IM Administration

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

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.

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

IV Administration

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

Haloperidol lactate: Has been administered by IV injection or infusion.

ECG monitoring is recommended whenever haloperidol is administered IV. (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.

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

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.

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. 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.

Severely disturbed psychotic children may require higher initial dosages.

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.

Tourette’s Syndrome
Oral

Children 3–12 years of age (weighing 15–40 kg): Initially, 0.5 mg daily given in 2 or 3 divided doses. 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 0.05–0.075 mg/kg daily given in 2 or 3 divided doses.

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

Disruptive Behavior Disorder and ADHD
Oral

Children 3–12 years of age (weighing 15–40 kg): Initially, 0.5 mg daily given in 2 or 3 divided doses. 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 0.05–0.075 mg/kg daily given in 2 or 3 divided doses.

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

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.

Adults

Schizophrenia
Moderate Symptomatology
Oral

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

APA recommends 5–20 mg daily in all patients with schizophrenia. APA states that determining optimal antipsychotic dosage during the acute phase of schizophrenia is complicated because there usually is a delay between initiation of therapy and full therapeutic response. Initial response may take 2–4 weeks; up to 6 months or longer may be necessary for full or optimal response.

To achieve prompt control, higher initial dosages may be necessary in some patients. During prolonged maintenance therapy, keep dosage at lowest effective level.

Severe Symptomatology
Oral

Initially, 3–5 mg 2 or 3 times daily. Carefully adjust subsequent dosage according to the patient’s tolerance and therapeutic response.

APA recommends 5–20 mg daily in all patients with schizophrenia. APA states that determining optimal antipsychotic dosage during the acute phase of schizophrenia is complicated because there usually is a delay between initiation of therapy and full therapeutic response. Initial response may take 2–4 weeks; up to 6 months or longer may be necessary for full or optimal response.

To achieve prompt control, higher initial dosages may be required in some patients. During prolonged maintenance therapy, keep dosage at lowest effective level.

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

Some manufacturers state that dosages up to 100 mg daily may be required in some severely psychotic patients and dosages >100 mg daily have been used infrequently in adults with severely resistant disorders; however, safety of prolonged administration of such dosages has not been demonstrated.

Clinical experience suggests that higher-dosage regimens (i.e., ≥20–40 mg daily) are unlikely to be more effective in most patients with schizophrenia, including in those with refractory or chronic schizophrenia, and supports use of more moderate dosage regimens (i.e., ≤15–20 mg daily) in such patients. High-dosage regimens also are more likely to cause unacceptable short- and long-term adverse effects (see Cautions).

Chronic/Resistant Disorders
Oral

Initially, manufacturers recommend 3–5 mg 2 or 3 times daily.

APA recommends 5–20 mg daily in all patients with schizophrenia.

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

Some manufacturers state that dosages up to 100 mg daily may be required in some severely psychotic patients and dosages >100 mg daily have been infrequently used in adults with severely resistant disorders; however, safety of prolonged administration of such dosages has not been demonstrated.

Clinical experience suggests that higher-dosage regimens (i.e., ≥20–40 mg daily) are unlikely to be more effective in most patients with schizophrenia, including in those with refractory or chronic schizophrenia; more moderate dosage regimens (i.e., ≤15–20 mg daily) generally are recommended and better tolerated. High-dosage regimens also are more likely to cause unacceptable short- and long-term adverse effects (see Cautions).

IM (Haloperidol Decanoate)

May consider for patients requiring prolonged antipsychotic therapy (e.g., patients with chronic schizophrenic disorder).

Initially, stabilize patient’s condition with an antipsychotic agent prior to attempting conversion to haloperidol decanoate. 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.

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

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. (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.

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.

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.

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

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. 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.

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.

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.

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

Tourette’s Syndrome
Moderate Symptomatology
Oral

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

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

Severe Symptomatology and/or Chronic/Resistant Disorder
Oral

Initially, 3–5 mg 2 or 3 times daily.

Patients who remain inadequately controlled may require dosage adjustment.

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

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.

Delirium†
IV (Haloperidol Lactate)

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

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

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

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; in such patients, an initial 10-mg dose followed by an infusion of 5–10 mg/hour has been suggested. 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.

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 QTc interval exceeds 450 msec. (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.

IM

Safety and efficacy not established in children.

Adults

Oral

Some manufacturers state that dosages up to 100 mg daily may be required in some severely psychotic patients, and that dosages >100 mg daily have been used infrequently for the management of severely resistant disorders; however, safety of prolonged administration of such dosages not demonstrated.

Clinical experience suggests that higher-dosage regimens (i.e.,≥20–40 mg daily) are unlikely to be more effective in most patients with schizophrenia and are more likely to cause unacceptable short- and long-term adverse effects (see Cautions).

IM

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

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, 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.

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). (See Delirium under Dosage and Administration and see QT-interval Prolongation and Sudden Death under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

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. (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.

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

Cautions for Haloperidol

Contraindications

  • Severe toxic CNS depression or comatose states from any cause.

  • Parkinsonian syndrome.

  • Hypersensitivity to haloperidol.

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.

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

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.

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. (See Drugs that Prolong QT Interval under Interactions.)

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

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

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, reported with use of antipsychotic agents, including haloperidol.

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. In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.

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. Consider discontinuance of haloperidol if signs and symptoms of tardive dyskinesia develop; however, some patients may require treatment despite the presence of the syndrome.

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.

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

Hyperpyrexia and heat stroke not associated with NMS also reported.

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. Teratogenic and fetotoxic in animals.

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. Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.

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

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. Observe patients receiving combined therapy for evidence of neurologic effects; promptly discontinue if manifestations appear.

Respiratory Effects

Bronchopneumonia, sometimes fatal, reported with use of antipsychotic agents, including haloperidol. 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.

Ocular Effects

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

Sensitivity Reactions

Hypersensitivity

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

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

General Precautions

Hypotension and Angina

Possible transient hypotension and/or precipitation of angina; use with caution in patients with severe cardiovascular disorders

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.

Seizures

Possible risk of seizures; may lower seizure threshold. Use with caution in patients with a history of seizures or EEG abnormalities or in those receiving anticonvulsant agents. Maintain adequate anticonvulsant therapy.

CNS Depression

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

Possible additive effects or potentiated action when used with alcohol or other CNS depressants. (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.

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.

Bipolar Disorder

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

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. It is not known whether gradual withdrawal will reduce occurrence of withdrawal-emergent neurological signs; pending further evidence, withdraw gradually.

Endocrine Effects

Elevated prolactin concentrations possible; may persist during long-term therapy.

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.

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.

Metabolic Effects

Decreased serum cholesterol concentrations reported in patients receiving chemically related agents.

Hematologic Effects

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

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

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

Specific Populations

Pregnancy

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

Lactation

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

Pediatric Use

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

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

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

Geriatric Use

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

Prevalence of tardive dyskinesia appears to be highest among geriatric patients, particularly geriatric women.

Pharmacokinetics of haloperidol in geriatric patients generally warrant use of reduced dosages. (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. (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).

Interactions for Haloperidol

Drugs that Prolong QT Interval

QT-interval prolongation and torsades de pointes reported; patients receiving higher than recommended dosages of any haloperidol preparation and those receiving the drug IV appear to be at higher risk. Particular caution is advised when oral or parenteral haloperidol is used in patients concurrently receiving other drugs that prolong the QT interval. (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

Anticoagulants

Antagonism of anticoagulant activity of phenindione (no longer commercially available in US) reported in 1 patient

Further study needed to determine clinical importance

CNS depressants (e.g., alcohol, anesthetics, barbiturates or other sedatives, opiates or other analgesics)

Possible additive effects or potentiated action of other CNS depressants

Use concomitantly with caution to avoid excessive sedation

Lithium

An acute encephalopathic syndrome occasionally has occurred, especially when high serum lithium concentrations were present

Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appear

Methyldopa

Possible dementia in patients receiving haloperidol and methyldopa concomitantly

Clinical importance of this possible interaction not determined; carefully observe patients for adverse psychiatric symptoms if used concurrently

Rifampin

Decreased (70%) mean plasma haloperidol concentrations and decreased antipsychotic efficacy with concomitant use

Following discontinuance of rifampin in other schizophrenic patients treated with oral haloperidol, mean haloperidol concentrations increased 3.3-fold

Careful monitoring of clinical status and appropriate dosage adjustment warranted whenever rifampin is initiated or discontinued in patients stabilized on haloperidol

Haloperidol Pharmacokinetics

Absorption

Bioavailability

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

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

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

Following IM administration of haloperidol decanoate, plasma haloperidol concentrations are usually evident within 1 day and peak concentrations generally occur within about 6–7 days (range: 1–9 days).

Onset

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

Duration

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

Distribution

Extent

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

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.

Distributed into milk.

Plasma Protein Binding

About 92%.

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), and by reduction of the butyrophenone carbonyl to the carbinol, forming hydroxyhaloperidol.

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

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. Subsequent distribution, metabolism, and excretion of haloperidol appear to be similar to those of orally administered drug.

Elimination Route

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

Half-life

After IM administration of the decanoate, apparent half-life is approximately 3 weeks.

Special Populations

Pharmacokinetics of haloperidol generally warrant the use of reduced dosages in geriatric patients.

Stability

Storage

Oral

Solution

Tight, light-resistant containers at 15–30°C. Avoid freezing.

Tablets

Tight, light-resistant containers at 20–25°C.

Parenteral

Injection

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

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

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.

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.

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

Amifostine

Aztreonam

Bivalirudin

Ceftaroline fosamil

Cisatracurium besylate

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

Tacrolimus

Teniposide

Theophylline

Thiotepa

Tigecycline

Vinorelbine tartrate

Incompatible

Allopurinol sodium

Amphotericin B cholesteryl sulfate complex

Fluconazole

Foscarnet sodium

Gallium nitrate

Heparin sodium

Piperacillin sodium–tazobactam sodium

Sargramostim

Variable

Sodium nitroprusside

Syringe Compatibility (haloperidol lactate)HID

Compatible

Buprenorphine HCl with glycopyrrolate

Cyclizine lactate with diamorphine HCl

Lorazepam

Incompatible

Diphenhydramine HCl

Heparin sodium

Hydroxyzine HCl

Ketorolac tromethamine

Morphine sulfate

Variable

Benztropine mesylate

Cyclizine lactate

Diamorphine HCl

Hydromorphone HCl

Scopolamine butylbromide

Actions

  • Principal pharmacologic effects are similar to those of piperazine-derivative phenothiazines.

  • 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.

  • May antagonize actions of glutamic acid within the extrapyramidal system. Inhibition of catecholamine receptors may also be important in the mode of action; may also inhibit the reuptake of various neurotransmitters in the midbrain.

  • Appears to have strong central antidopaminergic and weak central anticholinergic activity.

  • 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.

  • 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.

  • Produces less sedation, hypotension, and hypothermia than chlorpromazine.

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. Inform patients and caregivers that haloperidol is not approved for treating geriatric patients with dementia-related psychosis.

  • Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery.

  • Importance of avoiding alcohol during therapy due to risk of additive effects and hypotension.

  • 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.

  • Importance of informing patients in whom chronic haloperidol use is contemplated of risk of tardive dyskinesia. Importance of advising patients to report any muscle movements that cannot be stopped to a healthcare professional.

  • Risk of leukopenia/neutropenia. 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.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Fetal/Neonatal Morbidity and Mortality under Cautions). Importance of advising patients not to stop taking haloperidol if they become pregnant without consulting their clinician; abruptly discontinuing antipsychotic agents may cause complications. Importance of advising patients not to breast-feed during haloperidol therapy.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

Haloperidol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

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

AHFS DI Essentials™. © Copyright 2022, Selected Revisions January 5, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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