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

Medically reviewed by Drugs.com on Dec 26, 2024. Written by ASHP.

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^{† [off-label]} (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^{† [off-label]}.^{121 130 172}

Antipsychotic agents often considered drugs of choice for delirium^{† [off-label]}.^{121 172} Haloperidol generally is considered the antipsychotic of choice for most patients with delirium^{† [off-label]} 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^{† [off-label]} 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.^{192 193 194} 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.^{192 193 194}

Severely disturbed psychotic children may require higher initial dosages.^{192 193 194}

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.^{192 193 194}

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.^{192 193 194} 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.^{192 193 194}

Once an adequate response is achieved, gradually reduce dosage and make subsequent adjustments according to patient response and tolerance.^{192 193 194}

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.^{192 193 194} 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.^{192 193 194}

Nonpsychotic or hyperactive behavioral problems in children may be acute, and short-term administration may be adequate.^{192 193 194}

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.^{192 193 194}

Adults

Schizophrenia

Moderate Symptomatology

Oral

Initially, 0.5–2 mg 2 or 3 times daily.^{192 193 194} Carefully adjust subsequent dosage according to the patient’s tolerance and therapeutic response.^{192 193 194}

APA recommends 5–20 mg daily in all patients with schizophrenia.¹⁸⁵ 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.¹⁸⁵ Initial response may take 2–4 weeks; up to 6 months or longer may be necessary for full or optimal response.¹⁸⁵

To achieve prompt control, higher initial dosages may be necessary in some patients.^{192 193 194} During prolonged maintenance therapy, keep dosage at lowest effective level.^{192 193 194}

Severe Symptomatology

Oral

Initially, 3–5 mg 2 or 3 times daily.^{192 193 194} Carefully adjust subsequent dosage according to the patient’s tolerance and therapeutic response.^{192 193 194}

APA recommends 5–20 mg daily in all patients with schizophrenia.¹⁸⁵ 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.¹⁸⁵ Initial response may take 2–4 weeks; up to 6 months or longer may be necessary for full or optimal response.¹⁸⁵

To achieve prompt control, higher initial dosages may be required in some patients.^{192 193 194} During prolonged maintenance therapy, keep dosage at lowest effective level.^{192 193 194}

Patients who remain severely disturbed or inadequately controlled may require dosage adjustment.^{192 193 194}

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.^{192 193 194}

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.^{185 195 196 197 198 199 200} High-dosage regimens also are more likely to cause unacceptable short- and long-term adverse effects (see Cautions).^{185 195 196 197 198 200}

Chronic/Resistant Disorders

Oral

Initially, manufacturers recommend 3–5 mg 2 or 3 times daily.^{192 193 194}

APA recommends 5–20 mg daily in all patients with schizophrenia.¹⁸⁵

Patients who remain severely disturbed or inadequately controlled may require dosage adjustment.^{192 193 194}

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.^{192 193 194}

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.^{185 195 196 197 198 199 200} High-dosage regimens also are more likely to cause unacceptable short- and long-term adverse effects (see Cautions).^{185 195 196 197 198 200}

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

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.^{192 193 194}

IM

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

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.^{192 193 194}

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).^{185 195 196 197 198 199 200}

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

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.^g Careful 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 b}

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 disorders^{163 164 165 166}

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.^{100 101 103} Maintain 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}

Drug Interactions

Drugs that Prolong QT Interval

QT-interval prolongation and torsades de pointes reported;^{124 125 126 129 130 132 133 162 163 164 167 168 169 170 171} patients 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

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 day^{107 112} 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;^{101 105 106 107 109 112} administration 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 containers^{100 101 102 103 104} at 15–30°C.^a Avoid freezing.^{100 101 103}

Tablets

Tight, light-resistant containers^{100 101 102 103 104} 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

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

Drug Compatibility

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.

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

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

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

Frequently asked questions

• What drugs cause tardive dyskinesia?

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