Uses & Dosage
DRUG INDUCED PSYCHOSIS
GILLES DE LA TOURETTE'S SYNDROME
PSYCHOSIS, ORGANIC, NOS
PSYCHOTIC DISORDER, PSYCHOSIS
|(Uses not currently included in the labeling approved by the US Food and Drug Administration.)
NAUSEA AND VOMITING FROM CHEMO
NAUSEA AND VOMITING FROM CHEMO AB'S
Haloperidol is used for the symptomatic management of psychotic disorders. Drug therapy is integral to the management of acute psychotic episodes and accompanying violent behavior in patients with schizophrenia and generally is required for long-term stabilization to improve symptoms between episodes and to minimize the risk of recurrent acute episodes.
Antipsychotic agents are the principal class of drugs used for the management of all phases of schizophrenia and generally are effective in allsubtypes of the disorder and subgroups of patients. Patient response and tolerance to antipsychotic agents are variable, and 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.
The long-acting decanoate ester of haloperidol is used principally in patients requiring prolonged antipsychotic therapy (e.g., patients with chronic schizophrenic disorder). Parenteral antipsychotic therapy with a long-acting preparation may be particularly useful in patients with a history of poor compliance. In addition, long-acting antipsychotic preparations may be useful in patients with suspected GI malabsorption or variable GI absorption of the drug.
The principal disadvantage of long-acting parenteral antipsychotics is the inability to terminate the drugs action when severe adverse reactions occur. Long-acting antipsychotic preparations should not be used in the acute management of severely agitated patients. Generally, patients should be stabilized on antipsychotic medication prior to conversion to haloperidol decanoate therapy and should have previously received and tolerated a shorter-acting haloperidol preparation so that the possibility of an unexpected adverse reaction that potentially could not be readily reversed following the decanoate can be minimized. For further information on the use of antipsychotic agents in the symptomatic treatment of schizophrenia, see Uses: Psychoneurologic Disorders in the Phenothiazines General Statement 28:16.08.
Antipsychotic agents, mainly haloperidol, are used in the management of delirium. Delirium is principally a disturbance of consciousness, attention, cognition, and perception but also may affect sleep, psychomotor activity, and emotions. It is a common psychiatric illness among medically compromised patients, particularly hospitalized patients, and may be a harbinger of substantial morbidity and mortality.
The prevalence of delirium in hospitalized medically ill patients ranges from 10-30%; in those who are elderly, delirium ranges up to 40%. Up to 25% of hospitalized cancer patients and 30-40% of hospitalized patients with acquired immunodeficiency syndrome (AIDS) develop delirium. Up to about 50% of postoperative patients develop delirium,and up to 80% of terminally ill patients develop it near death.
Prodromal manifestations may progress to full-blown delirium over 13 days; the duration of delirium generally ranges from less than a week to more than 2 months, but typically does not exceed 10-12 days. Symptoms persist for up to 30 days or longer in up to 15% of patients, and frequently persist for longer than 1 month in geriatric patients.
Although most patients recover fully, delirium may progress to stupor, coma, seizures, and death, particularly if untreated. Full recovery is less likely in geriatric patients and patients with AIDS, possibly because of underlying dementia in both populations.
Underlying general medical conditions associated with delirium include CNS disorders (e.g., head trauma, seizures, postictal state, vascular or degenerative disease), metabolic disorders (e.g., renal or hepatic failure, anemia, hypoxia, hypoglycemia, thiamine deficiency, endocrinopathy, fluid or electrolyte imbalance, acid-base imbalance), cardiopulmonary disorder (myocardial infarction, congestive heart failure, cardiac arrhythmia, shock, respiratory failure), and systemic illness (e.g., substance intoxication or withdrawal, infection, cancer, severe trauma, sensory deprivation, temperature dysregulation, postoperative state). EEG abnormalities, mainly generalized slowing, have fairly good sensitivity for aiding in the diagnosis of delirium, but the absence of such changes does not rule out the diagnosis.
Clinicians should undertake an essential array of psychiatric management tasks designed to provide immediate interventions for urgent general medical conditions, identify and treat the etiology of delirium, ensure safety of the patient and others incontact with the patient, and improve the patients functioning.
Environmental (e.g., varying light levels in intensive care units to heighten awareness about time of day and reduce the perception of timelessness) and supportive interventions (e.g., to deal with disorientation, to assure the patient that manifestations are temporary and reversible and do not reflect a persistent psychiatric disorder) also generally are offered to patients with delirium and are designed to reduce factors that may exacerbate delirium, to reorient patients, and to provide support.
Patients may have life-threatening medical conditions that require therapeutic intervention even before a specific or definitive cause of the delirium is determined. The goal of diagnosis is to identify potentially reversible causes of delirium and prevent complications through prompt treatment of these specific disorders. Psychiatric management is essential and should be undertaken for all patients with delirium. Somatic interventions principally consist of drug therapy. The choice of somatic intervention will depend on the specific features of the patients clinical condition, the underlying etiology of the delirium, and any associated comorbid conditions.
Antipsychotic agents often are the drugs of choice for the management of delirium. Although other drugs (e.g., phenothiazines, droperidol) have been used, 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. In addition, haloperidol has been studied most extensively, although few studies have used standardized definitions of delirium or reliable and valid delirium symptom rating measures to assess symptom severity before and after initiation of treatment. ]
For drugs other than haloperidol, there have been no large, prospective studies that included a control. Evidence of efficacy for such alternative therapies, including for relatively new antipsychotic agents (e.g., olanzapine, quetiapine, risperidone), is principally from small case series or case reports. In addition, interpretation of findings from many such case presentations is difficult because of use of nonstandardized delirium definitions and/or informal measures of delirium symptom severity.
In general, evidence of the efficacy of antipsychotics, including haloperidol, in the management of delirium comes from numerous case reportsand uncontrolled studies. However, evidence from a randomized, double-blind, comparator-drug controlled study (haloperidol, chlorpromazine, and lorazepam) in patients with AIDS that employed standardized clinical measures of delirium demonstrated clinical superiority of antipsychotic agents compared with benzodiazepines. Statistically significant improvement in the Delirium Rating Scale was evident after 2 days in patients receiving haloperidol or chlorpromazine but not in the lorazepam group (mean decreases in the score [i.e., improvement] were 8, 8.5, and 1, respectively). The symptomatic improvement in delirium occurred quickly among patients receiving antipsychotic therapy, usually before initiation of interventions directed at the medical etiologies of delirium.
Although various antipsychotic agents may be given orally, IM, or IV, IV administration is considered most effective in emergency situations or where oral access is limited. In addition, some evidence indicates that IV administration of antipsychotic agents may be associated with less severe extrapyramidal effects.
Because antipsychotic agents, particularly IV haloperidol, used in the management of delirium have been associated with lengthening of the QT interval, possibly leading to atypical ventricular tachycardia (torsades de pointes), ventricular fibrillation, and sudden death, baseline and periodic ECGs should be performed with special attention paid to the length of the QTc interval. Prolongation of the QTc interval to greater than 450 msec or to greater than 15-25% over that in previous ECGs may warrant telemetry, a cardiology consultation, and dose reduction or discontinuance. Serum concentrations of magnesium and potassium also should be monitored in critically ill patients, especially those with baseline QTc of 440 msec or longer, those receiving other drugs known to increase the QT interval, and those who have electrolyte disorders. Limited evidence suggests that the incidence of torsades de pointes in patients receiving haloperidol IV is about 0.43.6%, but may increase to greater than10% at relatively high IV doses (e.g., 35 mg or more over 24 hours).
Haloperidol is used for the control of tics and vocal utterances of Tourettes disorder (Gilles de la Tourettes syndrome) in children and adults.
Haloperidol is also used for the treatment of severe behavioral problems in children marked by combativeness and/or explosive hyperexcitable behavior (out of proportion to immediate provocations), and for the short-term treatment of hyperactive children who exhibit excessive motor activity with accompanying conduct disorders that are manifested as impulsive behavior, difficulty sustaining attention, aggression, mood lability, and/or poor frustration tolerance.
Haloperidol has been used in the adjunctive treatment of alcohol dependence. Further study is needed to determine the efficacy of haloperidol in the treatment of this disorder.
Haloperidol has also been used in the prevention and control of severe nausea and vomiting (e.g., cancer chemotherapy-induced emesis). Based on limited data, haloperidol appears to be as effective as phenothiazines in the prevention of cancer chemotherapy-induced emesis. Additional studies are required to determine the efficacy of haloperidol in the prevention and control of severe nausea and vomiting.
Dosage of haloperidol lactate and the decanoate is expressed in terms of haloperidol.
There is considerable interindividual variation in optimum dosage requirements of haloperidol, and dosage must be carefully adjusted according to individual requirements and response, using the lowest possible effective dosage.
Dosage should be increased more gradually in children and in debilitated, emaciated, or geriatric patients.
Because of the risk of adverse reactions associated with cumulative effects of butyrophenones, patients with a history of long-term therapy with haloperidol and/or other antipsychotic agents should be evaluated periodically to determine whether maintenance dosage could be decreased or drug therapy discontinued.
For the symptomatic management of psychotic disorders or Tourettes disorder in adults with moderate symptomatology and in geriatric or debilitated patients, the usual initial oral dosage of haloperidol is 0.52 mg 2 or 3 times daily. Subsequent dosage should be carefully adjusted according to the patients tolerance and therapeutic response. Dosage during prolonged maintenance therapy should be kept at the lowest effective level.
The usual initial oral dosage of haloperidol for adults with severe symptomatology and/or chronic or resistant disorders is 35 mg 2 or 3 times daily. To achieve prompt control, higher dosages may be required in some patients.
Patients who remain severely disturbed or inadequately controlled may require dosage adjustment. Oral dosages up to 100 mg daily may be required in some severely psychotic patients. Occasionally, dosages exceeding 100 mg daily have been used for the management of severely resistant disorders in adults; however, the safety of prolonged administration of such dosages has not been demonstrated.
The usual initial oral dosage of haloperidol in children 3-12 years of age and weighing 15-40 kg is 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 patients tolerance and therapeutic response.
For the symptomatic management of psychotic disorders in children 3-12 years of age, the usual oral dosage range is 0.050.15 mg/kg daily given in 2 or 3 divided doses; however, severely disturbed psychotic children may require higher dosages. Dosage during prolonged maintenance therapy should be kept at the lowest possible effective level; once an adequate response has been achieved, dosage should be gradually reduced and subsequently adjusted according to the patients therapeutic response and tolerance.
For the management of non-psychotic behavioral problems and for the control of Tourettes disorder in children 3-12 years of age, the usual oral dosage range is 0.050.075 mg/kg daily given in 2 or 3 divided doses.
Unlike psychotic disorders for which prolonged therapy is usually required, non-psychotic or hyperactive behavioral problems in children may be acute, and short-term administration of haloperidol may be adequate. A maximum effective dosage of haloperidol for the management of behavioralproblems in children has not been established; however, the manufacturers state that there is little evidence that improvement in behavior is further enhanced at dosages greater than 6 mg daily.
For the prompt control of acutely agitated patients with moderately severe to very severe symptoms, the usual initial adult IM dose of haloperidol lactate is 25 mg (of haloperidol) given as a single dose. Depending on the response of the patient, thisdose may be repeated as often as every hour; however, IM administration of haloperidol lactate every 48 hours may be adequate to control symptoms in some patients.
Oral therapy should replace short-acting parenteral therapy as soon as possible. Depending on the patients clinical status, the first oral dose should be given within 12-24 hours following administration of the last parenteral dose of haloperidol lactate.
Since bioavailability studies to establish bioequivalence between oral and parenteral dosage forms of haloperidol have not been conducted to date, the manufacturers suggest that the parenteral dosage administered during the preceding 24 hours be used for initial approximation of the total daily oral dosage required. Since this dosage is only an initial estimate, patients being switched from parenteral haloperidol lactate therapy to oral therapy should be closely monitored, particularly forclinical signs and symptoms of efficacy, sedation, and adverse effects, for the first several days following initiation of oral therapy. Subsequent dosage may be increased or decreased according to the patients tolerance and therapeutic response, using the lowest possible effective dosage.
For patients requiring prolonged antipsychotic therapy (e.g., patients with chronic schizophrenic disorder), the long-acting haloperidol decanoate injection may be considered. If the decanoate is used, the patients condition should initially be stabilized with an antipsychotic agent prior to attempting conversion to haloperidol decanoate.
In addition, if the patient is receiving an antipsychotic agent other than haloperidol, it is recommended that the patient initially be converted to oral haloperidol therapy in order to minimize the risk of an unexpected adverse reaction to the drug, which might not be readily reversible following use of the decanoate.
The initial IM dose of haloperidol decanoate should be based on the patients clinical history, physical condition, and response to previous antipsychotic therapy. To determine the minimum effective dosage, haloperidol decanoate therapy has been initiated at low initial doses and gradually titrated upward as necessary.
A precise formula for converting from oral haloperidol dosage to IM haloperidol decanoate has not been established, but an initial adult dose 10-20 times the previous daily dose of oral haloperidol, not exceeding 100 mg (regardless of previous antipsychotic dosage requirements), is suggested, although limited clinical experience suggests that lower initial dosage of the decanoate may be adequate. Some clinicians have converted therapy to the decanoate using a higher initial dose.
IM haloperidol decanoate has usually been administered at monthly intervals (i.e., every 4 weeks), but individual response may dictate the need for adjusting the dosing interval as well as the dose.
Lower initial doses (e.g., 10-15 times the previous daily dose of oral haloperidol) and more gradual upward titration are recommended for patients who are geriatric, debilitated, or stabilized on low oral dosages.
Close clinical observation is required during dosage titration in order to minimize the risk of overdosage and of emergence of psychotic manifestations prior to the next dose. If supplemental antipsychotic therapy is necessary during periods of dosage titration or for control of acute exacerbations of psychotic manifestations, a short-acting haloperidol preparation should be used. Experience with haloperidol decanoate dosages exceeding 450 mg (of haloperidol) monthly is limited.
The optimum dosage of haloperidol for the treatment of delirium has not been established. However, initiation of IV haloperidol with dosages of 12 mg every 24 hours in adults has been suggested. Lower IV dosages (e.g., 0.250.5 mg every 4 hours) have been suggested for geriatric patients with delirium; 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 in adults, the risk of adverse effects, particularly torsades de pointes, must be considered. (See Uses: Delirium.) Some evidence suggests that the risk of torsades de pointes increases at total daily dosages of 3550 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 more than 10 mg/hour for more than 5 consecutive hours), consideration can be given to continuous IV infusion of haloperidol; in such patients, an initial 10-mg dose followed by an infusionof 510 mg/hour has been suggested. If agitation persists, repeat 10-mg IV doses at 30-minute intervals, accompanied by a 5 mg/hour increase in the infusion rate, can be considered. ECG should be determined at baseline and periodically thereafter, with special attention paid to possible prolongation of the QT interval, and dosage should be reduced or the drug discontinued if clinically important QT prolongation (e.g., 15-25% or more over baseline) occurs or the QTc exceeds 450 msec. (See Uses: Delirium.)
Adverse Effects List & Discussion
|Incidence more frequent
||Incidence less frequent|
MENSTRUAL BLEEDING CHANGES
SEXUAL FUNCTION IMPAIRMENT
NEUROLEPTIC MALIGNANT SYNDROME
|Adverse Effects Discussion |
The most frequent adverse effects of haloperidol involve the CNS.
Extrapyramidal reactions occur frequently with haloperidol, especially during the first few days of therapy. In most patients, these reactions consist of parkinsonian symptoms (e.g., marked drowsiness and lethargy, drooling or hypersalivation, fixed stare), which are mild to moderate in severity and are usually reversible following discontinuance of the drug.
Other adverse neuromuscular reactions have been reported less frequently, but are often more severe, and include feelings of motor restlessness (i.e., akathisia), tardive dystonia, and dystonic reactions (e.g., hyperreflexia, opisthotonos, oculogyric crisis, torticollis, trismus).
Generally, the occurrence and severity of most extrapyramidal reactions are dose related, since they occur at relatively high dosages and disappear or become less severe following a reduction in dosage; however, severe extrapyramidal reactions have reportedly occurred at relatively low dosages.
Most patients respond rapidly to treatment with an anticholinergic antiparkinsonian drug (e.g., benztropine, trihexyphenidyl). If persistent extrapyramidal reactions occur, haloperidol therapy may have to be discontinued.
Neuroleptic malignant syndrome (NMS) may occur in patients receiving haloperidol or other antipsychotic therapy. NMS is potentially fatal and requires immediate discontinuance of the drug and initiation of intensive symptomatic and supportive care. For additional information on NMS, see Extrapyramidal Reactions in Cautions: Nervous System Effects in the Phenothiazines General Statement 28:16.08.
Like other antipsychotic agents (e.g., phenothiazines), haloperidol has been associated with persistent dyskinesias. Tardive dyskinesia may occur in some patients during long-term administration of haloperidol or it may occur following discontinuanceof the drug.
The risk of developing tardive dyskinesia appears to be greater in geriatric patients receiving high dosages of the drug, especially females. The symptoms are persistent, and in some patients appear to be irreversible.
Tardive dyskinesia is characterized by rhythmic involuntary movements of the tongue, face, mouth, or jaw (e.g., protrusion of the tongue, puffing of cheeks, chewing movements, puckering of the mouth), which sometimes may be accompanied by involuntary movements of theextremities and/or trunk.
Although not clearly established, the risk of developing the syndrome and the likelihood that it will become irreversible may increase with the duration of therapy and total cumulative dose of antipsychotic agent(s) administered; however, the syndrome may occur, although much less frequently, after relatively short periods of treatment with low dosages.
There is no proven or uniformly effective treatment for tardive dyskinesia; antiparkinsonian agents do not alleviate and tend to exacerbate the symptoms of this syndrome. If possible, antipsychotic agents should be discontinued if signs or symptoms of tardive dyskinesia occur.
The syndrome may partially or completely remit if antipsychotic agents are discontinued,although some patients may require many months for improvement. Tardive dyskinesia may be masked if therapy is reinstituted, dosage is increased, or therapy with another antipsychotic agent is initiated. The effect that masking of the symptoms may have on the long-term course of the syndrome is not known.
Fine vermicular movement of the tongue may be an early sign of the syndrome; prompt discontinuance of haloperidol after this sign occurs may prevent development of the syndrome.
In general, abrupt withdrawal of antipsychotic agents following short-term administration is not associated with adverse effects; however, transient dyskinetic signs have occurred following abrupt withdrawal in patients receiving prolonged maintenance therapy with haloperidol.
In some patients, the dyskinetic movements are indistinguishable, except on the basis of their duration, from tardive dyskinesia. It is not known whether gradual withdrawal of antipsychotic agents reduces the incidence of withdrawal-emergent neurologic signs; however, if haloperidol therapy must be discontinued, gradual withdrawal of the drug is recommended, if possible, pending further accumulation of data.
Other Nervous System Effects
Tardive dystonia, not associated with tardive dyskinesia, has occurred in patients receiving haloperidol. Tardive dystonia is characterized by delayed onset of choreic or dystonic movements, often is persistent, and potentially can become irreversible.
Other adverse nervous system effects of haloperidol include insomnia, restlessness, anxiety, euphoria, agitation, drowsiness, depression, lethargy, headache, confusion, vertigo, and tonic-clonic seizures.
Exacerbation of psychotic symptoms (including hallucinations and catatonic-like behavior), which may subside following discontinuance of therapy or treatment with anticholinergic agents, has also been reported.
Adverse anticholinergic effects of haloperidol include dry mouth (xerostomia), blurred vision, constipation, urinary retention, and diaphoresis. Priapism has also occurred.
Mild and usually transient leukopenia and leukocytosis have been reported in patients receiving haloperidol. Other adverse hematologic effects include anemia, minimal decreases in erythrocyte count, and a tendency toward lymphomonocytosis. Agranulocytosis has also been reported rarely in patients receiving haloperidol, but only when combined with other drugs.
Moderate engorgement of the breast with lactation has occurred in some females receiving haloperidol. Galactorrhea, mastalgia, gynecomastia, increased libido, impotence, hyperglycemia, hypoglycemia, and hyponatremia have also occurred in some patients.
Antipsychotic agents increase serum prolactin concentrations. (See Cautions: Carcinogenicity.) Although not reported to date with haloperidol, the manufacturers caution that decreases in serum cholesterol concentration have occurred in patients receiving chemically related drugs.
Tachycardia, hypotension, hypertension, and ECG changes, including those compatible with QT-interval prolongation and the polymorphous configuration of torsades de pointes, may occur in patients receiving haloperidol. Although many of the reported cases of QT-interval prolongation and torsades de pointes have been in patients receiving relatively high dosages of haloperidol IV (e.g., exceeding 35 mg daily), such effects also have been reported with low-dose IV or oral therapy. (See Uses: Delirium and see Acute Toxicity: Manifestations.)
Impaired liver function and/or jaundice, maculopapular and acneiform dermatologic reactions, photosensitivity, alopecia, anorexia, diarrhea, hypersalivation, dyspepsia, nausea, vomiting, cataracts, retinopathy, and visual disturbances have also been reported.
Hyperpyrexia and heat stroke, not associated with neuroleptic malignant syndrome (see Extrapyramidal Reactions in Cautions: Nervous System Effects), have been reported in some patients receiving haloperidol.
Sudden and unexpected deaths have occurred in patients receiving haloperidol; however, a direct causal relationship to the drug has not been established.
Laryngospasm, bronchospasm, and increased depth of respiration have occurred in patients receiving haloperidol. Bronchopneumonia, resulting in fatalities in some patients, has occurred following the use of antipsychotic agents, including haloperidol.
It has been suggested that lethargy and decreased thirst, resulting from central inhibition, may cause dehydration, hemoconcentration, and reduced pulmonary ventilation.
Hyperammonemia following haloperidol treatment has been reported in at least one child with citrullinemia, an inherited disorder of ammonia excretion.
Negative or inconsistent positive findings have been reported in vitro and in vivo in studies on the effects of conventional preparations of haloperidol on chromosome structure and number. However, the available cytogenetic evidence is considered too inconsistent to be conclusive at this time.
Although an increase in mammary neoplasms has been found in rodents following long-term administration of prolactin-stimulating antipsychotic agents, no clinical or epidemiologic studies conducted to date have shown an association between long-term administration of these drugs and mammary tumorigenesis in humans.
Current evidence is considered too limited to be conclusive, and further study is needed to determine the clinical importance in most patients of elevated serum prolactin concentrations associated with antipsychotic agents.
Since in vitro tests indicate that approximately one-third of human breast cancers are prolactin dependent, haloperidol should be used with caution in patients with previously detected breast cancer.
- May cause drowsiness. Alcohol may intensify this effect. Use care when operating a car or dangerous machines.
- Avoid prolonged or excessive exposure to direct and/or artificial sunlight while taking this medication.
- It is very important that you take or use this exactly as directed. Do not skip doses or discontinue unless directed by your doctor.
- Obtain medical advice before taking non-prescription drugs as some may affect the action of this medication.
- Dilute before administration.
- Warning: Do not use while you are breastfeeding. Consult your doctor or pharmacist.
|Drug Disease Contraindications |
|Most Significant |
|For these conditions, action to reduce the risk of adverse interaction is usually required
- LACTATING MOTHER
- NEUROLEPTIC MALIGNANT SYNDROME
|For these conditions, assess risk to patient and take action as needed
- CARDIOVASCULAR DISEASE
- URINARY RETENTION
|Possibly Significant |
|For these conditions, conservative measures are recommended until more is known.
- HEPATIC FUNCTION IMPAIRMENT
- PULMONARY INSUFFICIENCY
- RENAL FUNCTION IMPAIRMENT
Haloperidol shares the toxic potentials of other antipsychotic agents (e.g., phenothiazines), and the usual precautions associated with therapy with these agents should be observed. (See Cautions in the Phenothiazines General Statement 28:16.08.)
Patients should be warned that haloperidol may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle). Patients also should be warned that haloperidol may enhance their response to alcohol, barbiturates, or other CNS depressants.
Because of the possibility of transient hypotension and/or precipitation of angina, haloperidol should be used with caution in patients with severe cardiovascular disorders. If hypotension occurs, metaraminol, norepinephrine, or phenylephrine may beused; epinephrine should not be used since haloperidol causes a reversal of epinephrines vasopressor effects and a further lowering of blood pressure.
Since haloperidol may lower the seizure threshold, the drug should be used with caution in patients receiving anticonvulsant agents and in those with a history of seizures or EEG abnormalities. Adequate anticonvulsant therapy should be maintained during administration of haloperidol.
The manufacturers state that haloperidol should be used with caution in patients with known allergies or with a history of allergic reactions to drugs.
When concomitant therapy with an antiparkinsonian drug is necessary to manage haloperidol-induced extrapyramidal symptoms, it may be necessary to continue the antiparkinsonian drug for a period of time after discontinuance of haloperidol in order toprevent emergence of these symptoms.
The manufacturers caution that when haloperidol is used to control mania in patients with bipolar disorder, there may be a rapid mood swing to depression.
Haloperidol should be used with caution in patients with thyrotoxicosis since severe neurotoxicity (e.g., rigidity, inability to walk or talk) may occur in these patients during therapy with an antipsychotic agent.
Care should be taken to avoid skin contact with haloperidol lactate oral solution and injection, since contact dermatitis has occurred rarely.
Haloperidol is contraindicated in patients with severe toxic CNS depression or in those who are comatose from any cause. Haloperidol is also contraindicated in patients who are hypersensitive to the drug, and in those with parkinsonian syndrome.
Safety and efficacy of haloperidol decanoate injection in children have not been established, and safety and efficacy of other haloperidol preparations in children younger than 3 years of age have not been established. Hyperammonemia was reported during postmarketing surveillance in a 5.5-year old child with citrullinemia, an inherited disorder of ammonia excretion, following haloperidol therapy.
Clinical studies of haloperidol did not include sufficient numbers of geriatric patients 65 years of age and older to determine whether this age group responds differently from younger adults.
Other reported clinical experience has not consistently identified differences in responses between geriatric and younger patients. However, the prevalence of tardive dyskinesia appears to be highest among geriatric patients, particularly elderly women.
In addition, the pharmacokinetics of haloperidol generally warrant the use of reduced dosages in geriatric patients. (See Dosage and Administration: Dosage.)
Although there are no adequate and controlled studies to date in humans, 2 cases of limb malformations (e.g., phocomelia) have occurred in offspring of women who were given haloperidol concurrently with other potentially teratogenic drugs during the first trimester of pregnancy; these teratogenic effects have not been directly attributed to haloperidol.
Haloperidol has been shown to be teratogenic and fetotoxic in animals at dosages 2-20 times the usual maximum human dosage. Haloperidol should be used during pregnancy or in women likely to become pregnant only when the potential benefits justify the possible risks to the fetus.
The effect of haloperidol on fertility in humans is not known. Impotence, increased libido, priapism, and menstrual irregularities have occurred in some individuals during haloperidol therapy.
Haloperidol is distributed into milk. The manufacturers warn that nursing should not be undertaken by women receiving haloperidol.
These drug interactions are reviewed by an editorial panel at First DataBank and determined to be clinically significant. The list does not include every interaction ever reported.
- BEPRIDIL/QT PROLONGATING AGENTS
- CABERGOLINE; PERGOLIDE/ANTIPSYCHOTICS
- HALOFANTRINE/QT PROLONGATING AGNETS
- HALOPERIDOL; PIMOZIDE/QUINUPRISTIN-DALFOPRISTIN
- LEVOMETHADYL/QT PROLONGATING AGENTS
- MESORIDAZINE/QT PROLONGATING AGENTS
- PIMOZIDE/QT PROLONGATING AGENTS
- SPARFLOXACIN/QT PROLONGATING AGENTS
- THIORIDAZINE/QT PROLONGATING AGENTS
- ZIPRASIDONE/QT PROLONGATING AGENTS
|None listed |
|None listed |
|None listed |
|None listed |
|None listed |
|None listed |
Haloperidol may be additive with, or may potentiate the action of, other CNS depressants such as opiates or other analgesics, barbiturates or other sedatives, anesthetics, or alcohol. When haloperidol is used concomitantly with other CNS depressants, caution should be used to avoid excessive sedation.
Although most patients receiving lithium and an antipsychotic agent (e.g., haloperidol, phenothiazines) concurrently do not develop unusual adverse effects, an acute encephalopathic syndrome occasionally has occurred, especially when high serum lithium concentrations were present.
Patients receiving such combined therapy should be observed for evidence of adverse neurologic effects; treatment should be promptly discontinued if such signs or symptoms appear. (See Drug Interactions: Antipsychotic Agents, in the monograph on Lithium Salts 28:28.)
Haloperidol has been reported to antagonize the anticoagulant activity of phenindione in one patient. Further study is needed to determine the clinical importance of this interaction.
Concomitant oral therapy with rifampin and haloperidol in schizophrenic patients resulted in a mean 70% decrease in plasma haloperidol concentrations and decreased antipsychotic efficacy. 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 are warranted whenever rifampin is initiated or discontinued in patients stabilized on haloperidol.
The manufacturers caution that increases in intraocular pressure may occur in patients receiving anticholinergic drugs, including antiparkinsonian agents, concurrently with haloperidol.
Dementia has reportedly occurred in several patients who received haloperidol and methyldopa concomitantly. Although the clinical importance of this possible interaction has not been determined, patients should be carefully observed for adverse psychiatric symptoms if the drugs are used concurrently.
Overdose & Toxicity
In general, overdosage of haloperidol may be expected to produce effects that are extensions of common adverse reactions; severe extrapyramidal reactions, hypotension, and sedation have been the principal effects reported. Coma with respiratory depression and hypotension (sometimes shock-like) may occur.
Substantial prolongation of the QT interval and atypical ventricular tachycardia (torsades de pointes) have occurred following haloperidol overdosage. The possibility of ECG changes associated with torsades de pointes should be considered following haloperidol overdosage, and ECG and vital signs should be monitored for signs of QT prolongation or dysrhythmias, continuing such monitoring until the ECG is normal.
Following accidental overdosage in a 2-year old child, hypertension, rather than hypotension, reportedly occurred. Extrapyramidal reactions may consist of muscular weakness or rigidity and a generalized or localized tremor. Manifestations of overdosage with haloperidol decanoate injection may be prolonged.
Treatment of haloperidol overdosage generally involves symptomatic and supportive care. There is no specific antidote for haloperidol intoxication; however, anticholinergic or antiparkinsonian drugs may be useful in controlling extrapyramidal reactions associated with haloperidol overdosage.
Following acute ingestion of the drug, the stomach should be emptied by inducing emesis or by gastric lavage. If the patient is comatose, having seizures, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of gastric contents. Activated charcoal should be administered after gastric lavage and/or emesis.
ECG and vital signs should be monitored, particularly for signs of QT prolongation or dysrhythmias. Severe arrhythmias should be treated with appropriate antiarrhythmic measures. Appropriate therapy should be instituted if hypotension or excessive sedation occurs; epinephrine should not be used (see Cautions: Precautions and Contraindications).
Pharmacology & Chemistry
Haloperidol is a butyrophenone-derivative antipsychotic agent. The drug is structurally similar to droperidol. Haloperidol is commercially available as the base, decanoic acid ester (decanoate), and lactate salt.
Haloperidol occurs as a white to faintly yellowish, amorphous or microcrystalline powder and has solubilities of less than 0.1 mg/mL in water and of approximately 16.7 mg/mL in alcohol at 25°C. The drug has a pKa of 8.3.
Haloperidol decanoate occurs as a clear, light amber, oily liquid and is soluble in fixed oils (e.g., sesame oil) and in most organic solvents. The decanoate has a solubility of approximately 0.01 mg/mL in water. Haloperidol decanoate injection is commercially available as a sterile solution of the drug in sesame oil and contains benzyl alcohol as a preservative.
Haloperidol injection is prepared with the aid of lactic acid and contains the drug as the lactate salt; the injection is a sterile solution of the drug in water for injection. Commercially available injections are adjusted to pH 33.8 with lactic acid and also may contain parabens as preservatives. Haloperidol oral solution is also prepared with the aid of lactic acid and contains the drug as the lactate salt. The commercially available oral solution has a pH of 2.753.75.
Commercially available haloperidol preparations should be stored in tight, light-resistant containers at a temperature less than 40°C, preferably between 15-30°C; freezing of the oral solution and injections and refrigeration of the decanoate injectionshould be avoided.
Haloperidol lactate injection 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. Haloperidol decanoate injection is incompatible with sterile water for injection or sodium chloride injection and with other aqueous injections. Specialized references should be consulted for specific compatibility information.
The principal pharmacologic effects of haloperidol are similar to those of piperazine-derivative phenothiazines. The precise mechanism of antipsychotic action of haloperidol is unclear, but the drug appears to depress the CNS at the subcortical level of the brain, midbrain, and brain stem reticular formation.
Haloperidol 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.
The drug may antagonize the actions of glutamic acid within the extrapyramidal system. Inhibition of catecholamine receptors may also be important in the mode of action of haloperidol; the drug may also inhibit the reuptake of variousneurotransmitters in the midbrain.
Haloperidol appears to have strong central antidopaminergic and weak central anticholinergic activity. Like phenothiazines, haloperidol produces catalepsy and inhibits spontaneous motor activity and conditioned avoidance behaviors in animals.
Haloperidol inhibits the central and peripheral effects of apomorphine, produces ganglionic blockade, and reduces affective responses. The precise mechanism of antiemetic action of haloperidol is unclear, but like some phenothiazines (e.g., chlorpromazine, prochlorperazine), haloperidol 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), haloperidol may cause extrapyramidal reactions, and there appears to be a very narrow range between the effective therapeutic dosage for the management of acute psychotic disorders and that causing extrapyramidal symptoms.
Haloperidol produces less sedation, hypotension, and hypothermia than chlorpromazine.
Haloperidol is well absorbed from the GI tract following oral administration, but appears to undergo first-pass metabolism in the liver. Oral bioavailability of the drug has been reported to average 60%. The drug may undergo some enterohepatic circulation. Peak plasma concentrations of haloperidol occur within 26 hours following oral administration. Following IM administration of haloperidol lactate, peak plasma haloperidol concentrations occur within 10-20 minutes and 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 23 hours. Haloperidol concentrations are detectable in plasma for several weeks following administration of a single dose of the drug.
Esterification of haloperidol results in slow and gradual release of haloperidol decanoate from fatty tissues, thus prolonging the duration of action; administration of the ester in a sesame oil vehicle further delays the rate of release. FollowingIM administration of haloperidol decanoate, plasma haloperidol concentrations are usually evident within 1 day and peak concentrations generally occur within about 67 days (range: 19 days).
Steady-state plasma haloperidol concentrations are usually reached in approximately 3 months following once-monthly IM injection of the decanoate. In one group of patients receiving 20-400 mg monthly, data adjusted to 100-mg monthly doses suggested mean trough plasma haloperidol concentrations of 2 ng/mL after the first dose and of 4 ng/mL at steady state; accumulation during 24 months of therapy was not apparent. Within the usual dosage range, plasma haloperidol concentrations following IM administration of the decanoate are approximately proportional andlinearly related to dosage; however, there is considerable interindividual and intraindividual variation in plasma concentrations attained with a given dosage.
Distribution of haloperidol into human body tissues and fluids has not been fully characterized. Following administration of haloperidol in animals, the drug is distributed mainly into the liver, with lower concentrations being distributed into the brain, lungs, kidneys, spleen, and heart.
Haloperidol is about 92% bound to plasma proteins.
Haloperidol is distributed into milk.
Although the exact metabolic fate has not been clearly established, it appears that haloperidol is principally metabolized in the liver. The drug appears to be metabolized principally 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. Urinary metabolites in rats include p-fluorophenaceturic acid, beta-p-fluorobenzoylpropionic acid, and several unidentified acids.
Haloperidol and its metabolites are excreted slowly in urine and feces. Approximately 40% of a single oral dose of haloperidol is excreted in urine within 5 days. About 15% of an oral dose of the drug is excreted in feces via biliary elimination. Small amounts of the drug are excreted for about 28 days following oral administration.
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 and subsequently undergoes hydrolysis by plasma and/or tissue esterases to form haloperidol and decanoic acid. Subsequent distribution, metabolism, and excretion of haloperidol appears to be similar to those of orally administered drug. Following IM administration of the decanoate, the drug has an apparent half-life of approximately 3 weeks.
||Injection, for IM use only
||50 mg (of haloperidol) per mL*
||Haldol Decanoate ( with benzyl alcohol 1.2% in sesame oil),
||Ortho-McNeil (also promoted by Scios Nova) |
||100 mg (of haloperidol) per mL*
||Haldol Decanoate ( with benzyl alcohol 1.2% in sesame oil),
||Ortho-McNeil (also promoted by Scios Nova) |
||2 mg (of haloperidol) per mL*
||Haldol Concentrate ( with methylparaben),
||Haloperidol Intensol ( with parabens and propylene glycol),
||Injection, for IM use only
||5 mg (of haloperidol) per mL*
||Haldol ( with parabens),