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:<br/>Oral AdministrationInitial Dosage Range:<br/>Adults: To achieve prompt control, higher doses may be required in some cases.<br/>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. or t.i.d.<br/>Maintenance Dosage: Upon achieving a satisfactory therapeutic response, dosage should then be gradually reduced to the lowest effective maintenance level.<br/>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 inthe 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 to 24 hours following the last parenteral dose.
Haloperidol is the first of the butyrophenone series of major tranquilizers. The chemical designation is 4-[4-(p-chloro-phenyl)-4-hydroxypiperidino]-4'���fluorobutyrophenone and it has the following structural formula: Haloperidol is supplied as tablets for oral administration containing 0.5 mg, 1 mg, 2 mg, and 5 mg of haloperidol, and contain the following inactive ingredients: colloidal silicon dioxide, FD&C Yellow No. 6, magnesium stearate, microcrystalline cellulose, pregelatinized starch and sodium lauryl sulfate.
The precise mechanism of action has not been clearly established.
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 Tablets, USP are available containing 0.5 mg, 1 mg, 2 mg and 5 mg of haloperidol. The 0.5 mg tablets are orange, round, scored tablets debossed with MYLAN 351. They are available as follows: NDC 0378-0351-01bottles of 100 tablets NDC 0378-0351-10bottles of 1000 tablets The 1 mg tablets are orange, round, scored tablets debossed with MYLAN 257. They are available as follows: NDC 0378-0257-01bottles of 100 tablets NDC 0378-0257-10bottles of 1000 tablets The 2 mg tablets are orange, round, scored tablets debossed with MYLAN 214. They are available as follows: NDC 0378-0214-01bottles of 100 tablets NDC 0378-0214-10bottles of 1000 tablets The 5 mg tablets are orange, round, scored tablets debossed with MYLAN 327. They are available as follows: NDC 0378-0327-01bottles of 100 tablets NDC 0378-0327-10bottles of 1000 tablets Store at 20��to 25��C (68��to 77��F). [See USP for Controlled Room Temperature.] Protect from light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
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. 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 in vitro and in vivo studies of effects of haloperidol on chromosome structure and number. The available cytogenetic evidence is considered too inconsistentto 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 animalsdid 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 in vitro, 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.<br/>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 . Also, the pharmacokinetics of haloperidol in geriatric patients generally warrants the use of lower doses .
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 2 year old child. The risk of ECG changes associated with torsade de pointes should be considered.<br/>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 or 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.
CNS Effects:<br/>Extrapyramidal Symptoms (EPS): EPS during the administration of haloperidol have been reported frequently, often during the first few days of treatment. EPS can be categorized generally as Parkinson-like symptoms, akathisia, or dystonia (including opisthotonos and oculogyric crisis). While all can occur at relatively low doses, they occur more frequently and with greater severity at higher doses. The symptoms may be controlled with dose reductions or administration of antiparkinson drugs such as benztropine mesylate, USP or trihexyphenidyl hydrochloride, USP. It should be noted that persistent EPS have been reported; the drug may have to be discontinued in such cases.<br/>Dystonia:<br/>Withdrawal Emergent Neurological Signs: Generally, patients receiving short-term therapy experience no problems with abrupt discontinuation of antipsychotic drugs. However, some patients on maintenance treatment experience transient dyskinetic signs after abrupt withdrawal. In certain of these cases the dyskinetic movements are indistinguishable from the syndrome described below under "Tardive Dyskinesia" except for duration. It is not known whether gradual withdrawal of antipsychotic drugs will reduce the rate of occurrence of withdrawal emergent neurological signs but until further evidence becomes available, it seems reasonable to gradually withdraw use of haloperidol.<br/>Tardive Dyskinesia: 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 ofmouth, 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 syndromemay 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.<br/>Tardive Dystonia: Tardive dystonia, not associated with the above syndrome, has also been reported. Tardive dystonia is characterized by delayed onset of choreic or dystonic movements, is often persistent, and has the potential of becoming irreversible.<br/>Other CNS Effects: Insomnia, restlessness, anxiety, euphoria, agitation, drowsiness, depression, lethargy, headache, confusion, vertigo, grand mal seizures, exacerbation of psychotic symptoms including hallucinations and catatonic-like behavioral states which may be responsive to drug withdrawal and/or treatment with anticholinergic drugs. Body as a Whole: Neuroleptic malignant syndrome (NMS), hyperpyrexia and heat stroke have been reported with haloperidol. Cardiovascular Effects: Tachycardia, hypotension, hypertension and ECG changes including prolongation of the Q-T interval and ECG pattern changes compatible with the polymorphous configuration of Torsades de pointes. Hematologic Effects: Reports have appeared citing the occurrence of mild and usually transient leukopenia and leukocytosis, minimal decreases in red blood cell counts, anemia, or a tendency toward lymphomonocytosis. Agranulocytosis has rarely been reported to have occurred with the use of haloperidol, and then only in association with other medication. Liver Effects: Impaired liver function and/or jaundice have been reported. Dermatologic Reactions: Maculopapular and acneiform skin reactions and isolated cases of photosensitivity and loss of hair. Endocrine Disorders: Lactation, breast engorgement, mastalgia, menstrual irregularities, gynecomastia, impotence, increased libido, hyperglycemia, hypoglycemia and hyponatremia. Gastrointestinal Effects: Anorexia, constipation, diarrhea, hypersalivation, dyspepsia, nausea and vomiting. Autonomic Reactions: Dry mouth, blurred vision, urinary retention, diaphoresis and priapism. Respiratory Effects: Laryngospasm, bronchospasm and increased depth of respiration. Special Senses: Cataracts, retinopathy and visual disturbances. Other: 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.<br/>Post-marketing Events: Hyperammonemia has been reported in a 5��year old child with citrullinemia, an inherited disorder of ammonia excretion, following treatment with haloperidol.
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.