Haloperidol Information
Haloperidol () Description
Haloperidol () is the first of the butyrophenone series of major tranquilizers. The chemical designation is 4-[4-(-chlorophenyl)-4-hydroxypiperidino]-4'-fluorobutyrophenone. It has the following structural formula.
Each Haloperidol () tablet, USP intended for oral administration contains Haloperidol () , USP 5 mg or 10 mg or 20 mg. In addition each tablet contains the following inactive ingredients: calcium stearate, dibasic calcium phosphate dihydrate, povidone (PVP K 30), sodium starch glycolate and starch. D & C Yellow #10 Aluminum Lake and FD & C Blue #1 Aluminum Lake; D & C Yellow #10 Aluminum Lake and FD & C Blue #1 Aluminum Lake; FD & C Yellow #6 Aluminum Lake and D & C Red #27 Aluminum Lake.
Haloperidol () Clinical Pharmacology
The precise mechanism of action has not been clearly established.
Haloperidol () Indications And Usage
Haloperidol () is indicated for use in the management of manifestations of psychotic disorders.
Haloperidol () is indicated for the control of tics and vocal utterances of Tourette’s Disorder in children and adults. Haloperidol () is effective for the treatment of severe behavior problems in children of combative, explosive hyperexcitability (which cannot be accounted for by immediate provocation). Haloperidol () is also effective in the short-term treatment of hyperactive children who show excessive motor activity with accompanying conduct disorders consisting of some or all of the following symptoms: impulsivity, difficulty sustaining attention, aggressivity, mood lability, and poor frustration tolerance. Haloperidol () should be reserved for these two groups of children only after failure to respond to psychotherapy or medications other than antipsychotics.
Haloperidol () Contraindications
Haloperidol () is contraindicated in severe toxic central nervous system depression or comatose states from any cause and in individuals who are hypersensitive to this drug or have Parkinson’s disease.
Haloperidol () Warnings
A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
Both the risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to antipsychotic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome. (For further information about the description of tardive dyskinesia and its clinical detection, please refer to
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.
Hyperpyrexia and heat stroke, not associated with the above symptom complex, have also been reported with Haloperidol () .
Rodents given 2 to 20 times the usual maximum human dose of Haloperidol () by oral or parenteral routes showed an increase in incidence of resorption, reduced fertility, delayed delivery and pup mortality. No teratogenic effect has been reported in rats, rabbits or dogs at dosages within this range, but cleft palate has been observed in mice given 15 times the usual maximum human dose. Cleft palate in mice appears to be a nonspecific response to stress or nutritional imbalance as well as to a variety of drugs, and there is no evidence to relate this phenomenon to predictable human risk for most of these agents.
There are no well controlled studies with Haloperidol () in pregnant women. There are reports, however, of cases of limb malformations observed following maternal use of Haloperidol () along with other drugs which have suspected teratogenic potential during the first trimester of pregnancy. Causal relationships were not established in these cases. Since such experience does not exclude the possibility of fetal damage due to Haloperidol () , this drug should be used during pregnancy or in women likely to become pregnant only if the benefit clearly justifies a potential risk to the fetus. Infants should not be nursed during drug treatment.
A number of cases of bronchopneumonia, some fatal, have followed the use of antipsychotic drugs, including Haloperidol () . It has been postulated that lethargy and decreased sensation of thirst due to central inhibition may lead to dehydration, hemoconcentration and reduced pulmonary ventilation. Therefore, if the above signs and symptoms appear, especially in the elderly, the physician should institute remedial therapy promptly.
Although not reported with Haloperidol () , decreased serum cholesterol and/or cutaneous and ocular changes have been reported in patients receiving chemically-related drugs.
Haloperidol () may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. The ambulatory patient should be warned accordingly.
The use of alcohol with this drug should be avoided due to possible additive effects and hypotension.
Haloperidol () Precautions
In clinical trial and postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including Haloperidol () tablets USP. Agranulocytosis (including fatal cases) has also been reported.
Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a preexisting low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue Haloperidol () tablets USP at the first sign of a decline in WBC in the absence of other causative factors.
Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count
Haloperidol () should be administered cautiously to patients:
If concomitant antiparkinson medication is required, it may have to be continued after Haloperidol () is discontinued because of the difference in excretion rates. If both are discontinued simultaneously, extrapyramidal symptoms may occur. The physician should keep in mind the possible increase in intraocular pressure when anticholinergic drugs, including antiparkinson agents, are administered concomitantly with Haloperidol () .
As with other antipsychotic agents, it should be noted that Haloperidol () may be capable of potentiating CNS depressants such as anesthetics, opiates, and alcohol.
In a study of 12 schizophrenic patients coadministered Haloperidol () and rifampin, plasma Haloperidol () levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. In 5 other schizophrenic patients treated with Haloperidol () and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in Haloperidol () concentrations. Thus, careful monitoring of clinical status is warranted when rifampin is administered or discontinued in Haloperidol () -treated patients.
When Haloperidol () is used to control mania in cyclic disorders, there may be a rapid mood swing to depression.
Severe neurotoxicity (rigidity, inability to walk or talk) may occur in patients with thyrotoxicosis who are also receiving antipsychotic medication, including Haloperidol () .
No mutagenic potential of Haloperidol () was found in the Ames Salmonella microsomal activation assay. Negative or inconsistent positive findings have been obtained in and studies of effects of Haloperidol () on chromosome structure and number. The available cytogenetic evidence is considered too inconsistent to be conclusive at this time.
Carcinogenicity studies using oral Haloperidol () were conducted in Wistar rats (dosed at up to 5 mg/kg daily for 24 months) and in Albino Swiss mice (dosed at up to 5 mg/kg daily for 18 months). In the rat study, survival was less than optimal in all dose groups, reducing the number of rats at risk for developing tumors. However, although a relatively greater number of rats survived to the end of the study in high-dose male and female groups, these animals did not have a greater incidence of tumors than control animals. Therefore, although not optimal, this study does suggest the absence of a Haloperidol () related increase in the incidence of neoplasia in rats at doses up to 20 times the usual daily human dose for chronic or resistant patients.
In female mice at 5 and 20 times the highest initial daily dose for chronic or resistant patients, there was a statistically significant increase in mammary gland neoplasia and total tumor incidence; at 20 times the same daily dose there was a statistically significant increase in pituitary gland neoplasia. In male mice, no statistically significant differences in incidences of total tumors or specific tumor types were noted.
Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent , a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.
There are no well controlled studies with Haloperidol () in pregnant women. There are reports, however, of cases of limb malformations observed following maternal use of Haloperidol () along with other drugs which have suspected teratogenic potential during the first trimester of pregnancy. Causal relationships were not established in these cases. Since such experience does not exclude the possibility of fetal damage due to Haloperidol () , this drug should be used during pregnancy or in women likely to become pregnant only if the benefit clearly justifies a potential risk to the fetus. Infants should not be nursed during drug treatment.
Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.
Haloperidol () should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Haloperidol () Adverse Reactions
Tachycardia, hypotension, and hypertension have been reported. QT prolongation and/or ventricular arrhythmias have also been reported, in addition to ECG pattern changes compatible with the polymorphous configuration of torsade de pointes, and may occur more frequently with high doses and in predisposed patients (see and
Cases of sudden and unexpected death have been reported in association with the administration of Haloperidol () . The nature of the evidence makes it impossible to determine definitively what role, if any, Haloperidol () played in the outcome of the reported cases. The possibility that Haloperidol () caused death cannot, of course, be excluded, but it is to be kept in mind that sudden and unexpected death may occur in psychotic patients when they go untreated or when they are treated with other antipsychotic drugs.
As with all antipsychotic agents, Haloperidol () has been associated with persistent dyskinesias. Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may appear in some patients on long-term therapy or may occur after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high-dose therapy, especially females. The symptoms are persistent and in some patients appear irreversible. The syndrome is characterized by rhythmical involuntary movements of tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities and the trunk.
There is no known effective treatment for tardive dyskinesia; antiparkinson agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, this syndrome may be masked.
It has been reported that fine vermicular movement of the tongue may be an early sign of tardive dyskinesia and if the medication is stopped at that time, the full syndrome may not develop.
Haloperidol () Dosage And Administration
There is considerable variation from patient to patient in the amount of medication required for treatment. As with all antipsychotic drugs, dosage should be individualized according to the needs and response of each patient. Dosage adjustments, either upward or downward, should be carried out as rapidly as practicable to achieve optimum therapeutic control.
To determine the initial dosage, consideration should be given to the patient’s age, severity of illness, previous response to other antipsychotic drugs, and any concomitant medication or disease state. Children, debilitated or geriatric patients, as well as those with a history of adverse reactions to antipsychotic drugs, may require less Haloperidol () . The optimal response in such patients is usually obtained with more gradual dosage adjustments and at lower dosage levels, as recommended below.
Clinical experience suggests the following recommendations:
Haloperidol () How Supplied
Haloperidol () Tablets USP, 5 mg are green, capsule-shaped, flat-faced, beveled-edge tablets debossed with the logo of ‘ZC’, ‘07’ and partial bisect, on one side and plain on the other side and are supplied as follows:
NDC 65841-626-01 in bottles of 100 tablets
NDC 65841-626-10 in bottles of 1000 tablets
Haloperidol () Tablets USP, 10 mg are light green, capsule-shaped, flat-faced, beveled-edge tablets debossed with the logo of ‘ZC’, ‘08’ and partial bisect, on one side and plain on the other side and are supplied as follows:
NDC 65841-627-01 in bottles of 100 tablets
NDC 65841-627-10 in bottles of 1000 tablets
Haloperidol () Tablets USP, 20 mg are coral, capsule-shaped, flat-faced, beveled-edge tablets debossed with the logo of ‘ZC’, ‘09’ and bisect on one side and plain on the other side and are supplied as follows:
NDC 65841-628-01 in bottles of 100 tablets
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container.
All trademarks are the property of Zydus group.
Haloperidol ()
Haloperidol () Package Label.principal Display Panel
NDC 65841-626-01 in bottle of 100 Tablets
Haloperidol () Tablets USP, 5 mg
Rx only
100 Tablets
ZYDUS
NDC 65841-627-01 in bottles of 100 tablets
Haloperidol () Tablets USP, 10 mg
R only
100 Tablets
ZYDUS
NDC 65841-628-01 in bottles of 100 tablets
Haloperidol () Tablets USP, 20 mg
R only
100 Tablets
ZYDUS
