Haloperidol 20 MG Oral Tablet
Generic Name: HALOPERIDOL
Brand Name: Haloperidol
- Substance Name(s):
Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Haloperidol is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING ).
Cardiovascular Effects Cases of sudden death, QT-prolongation, and Torsades de Pointes have been reported in patients receiving haloperidol.
Higher than recommended doses of any formulation of haloperidol appear to be associated with a higher risk of QT-prolongation and Torsades de Pointes.
Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QT-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QT, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome).
Tardive Dyskinesia 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cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.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 not 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 ADVERSE REACTIONS ).
Neuroleptic Malignant Syndrome (NMS) 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.
Falls Haloperidol may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.
For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.
Usage In Pregnancy Non-teratogenic Effects 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.
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.
Combined Use of Haloperidol and Lithium An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN, and FBS) followed by irreversible brain damage has occurred in a few patients treated with lithium plus haloperidol.
A causal relationship between these events and the concomitant administration of lithium and haloperidol has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear.
General 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.
Manifestations In general, the symptoms of overdosage would be an exaggeration of known pharmacologic effects and adverse reactions, the most prominent of which would be: 1) severe extrapyramidal reactions, 2) hypotension, or 3) sedation.
The patient would appear comatose with respiratory depression and hypotension which could be severe enough to produce a shock-like state.
The extrapyramidal reaction would be manifest by muscular weakness or rigidity and a generalized or localized tremor as demonstrated by the akinetic or agitans types respectively.
With accidental overdosage, hypertension rather than hypotension occurred in a two-year old child.
The risk of ECG changes associated with torsade de pointes should be considered.
(For further information regarding torsade de pointes, please refer to ADVERSE REACTIONS ).
Treatment Gastric lavage or induction of emesis should be carried out immediately followed by administration of activated charcoal.
Since there is no specific antidote, treatment is primarily supportive.
A patent airway must be established by use of an oropharyngeal airway or endotracheal tube or, in prolonged cases of coma, by tracheostomy.
Respiratory depression may be counteracted by artificial respiration and mechanical respirators.
Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma, or concentrated albumin, and vasopressor agents such as metaraminol, phenylephrine and norepinephrine.
Epinephrine should not be used.
In case of severe extrapyramidal reactions, antiparkinson medication should be administered.
ECG and vital signs should be monitored especially for signs of Q-T prolongation or dysrhythmias and monitoring should continue until the ECG is normal.
Severe arrhythmias should be treated with appropriate anti-arrhythmic measures.
Haloperidol is the first of the butyrophenone series of major tranquilizers.
The chemical designation is 4-[4-( p -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.
5 mg: D & C Yellow #10 Aluminum Lake and FD & C Blue #1 Aluminum Lake; 10 mg: D & C Yellow #10 Aluminum Lake and FD & C Blue #1 Aluminum Lake; 20 mg: FD & C Yellow #6 Aluminum Lake and D & C Red #27 Aluminum Lake.
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: Unit dose packages of 100 (10 x 10) NDC 60687-161-01 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: Unit dose packages of 100 (10 x 10) NDC 68084-249-01 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: Unit dose packages of 30 (3 x 10) NDC 68084-250-21 Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
FOR YOUR PROTECTION: Do not use if blister is torn or broken.
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Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088.
Geriatric Use Clinical studies of haloperidol did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience has not consistently identified differences in responses between the elderly and younger patients.
However, the prevalence of tardive dyskinesia appears to be highest among the elderly, especially elderly women (see WARNINGS: Tardive Dyskinesia ).
Also the pharmacokinetics of haloperidol in geriatric patients generally warrants the use of lower doses (see DOSAGE AND ADMINISTRATION ).
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.
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
WARNING Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.
Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.
Observational studies suggest that, similar to atypical antipsychotic drugs treatment with conventional antipsychotic drugs may increase mortality.
The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Haloperidol is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS ).
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: Oral Administration INITIAL DOSAGE RANGE Adults Moderate Symptomatology 0.5 mg to 2 mg b.i.d.
Severe Symptomatology 3 mg to 5 mg b.i.d.
To achieve prompt control, higher doses may be required in some cases.
Geriatric or Debilitated Patients 0.5 mg to 2 mg b.i.d.
Chronic or Resistant Patients 3 mg to 5 mg b.i.d.
Patients who remain severely disturbed or inadequately controlled may require dosage adjustment.
Daily dosages up to 100 mg may be necessary in some cases to achieve an optimal response.
Infrequently, haloperidol has been used in doses above 100 mg for severely resistant patients; however, the limited clinical usage has not demonstrated the safety of prolonged administration of such doses.
Children The following recommendations apply to children between the ages of 3 and 12 years (weight range 15 to 40 kg).
Haloperidol is not intended for children under 3 years old.
Therapy should begin at the lowest dose possible (0.5 mg per day).
If required, the dose should be increased by an increment of 0.5 mg at 5 to 7 day intervals until the desired therapeutic effect is obtained.
(see chart below).
The total dose may be divided, to be given b.i.d.
Psychotic Disorders 0.05 mg/kg/day to 0.15 mg/kg/day Non-Psychotic Behavior Disorders and Tourette’s Disorder 0.05 mg/kg/day to 0.075 mg/kg/day Severely disturbed psychotic children may require higher doses.
In severely disturbed, non-psychotic children or in hyperactive children with accompanying conduct disorders, who have failed to respond to psychotherapy or medications other than antipsychotics, it should be noted that since these behaviors may be short-lived, short-term administration of haloperidol may suffice.
There is no evidence establishing a maximum effective dosage.
There is little evidence that behavior improvement is further enhanced in dosages beyond 6 mg per day.
Maintenance Dosage Upon achieving a satisfactory therapeutic response, dosage should then be gradually reduced to the lowest effective maintenance level.
Switchover Procedure The oral form should supplant the injectable as soon as practicable.
In the absence of bioavailability studies establishing bioequivalence between these two dosage forms, the following guidelines for dosage are suggested.
For an initial approximation of the total daily dose required, the parenteral dose administered in the preceding 24 hours may be used.
Since this dose is only an initial estimate, it is recommended that careful monitoring of clinical signs and symptoms, including clinical efficacy, sedation, and adverse effects, be carried out periodically for the first several days following the initiation of switchover.
In this way, dosage adjustments, either upward or downward, can be quickly accomplished.
Depending on the patient’s clinical status, the first oral dose should be given within 12-24 hours following the last parenteral dose.