Haldol Drops

/ J-C Health Care Ltd

The dosages as suggested below are only averages, one should always try to tailor the dose to the patient’s response. This often implies an upward titration in the acute phase, and a gradual reduction in the maintenance phase, in order to determine the minimal effective dose. Higher doses should only be given to patients responding poorly to lower dosages.
Adults: 2 mg haloperidol per ml. 1 ml=20 drops. Moderate symptomatology: 0.5-2 mg, 2 or 3 times daily. Severe symptomatology: 3-5 mg, 2 or 3 times daily. Geriatric or debilitated patients: 0.5-2 mg, 2 or 3 times daily. Chronic or resistant patients: 3-5 mg, 2 or 3 times daily. 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.
Children 3-12 Years of Age (15-40 kg body weight): The initial dosage is 0.5 mg/day. If required, dosage should be increased by an increment of 0.5 mg at 5- to 7-day intervals, until the desired therapeutic effect is achieved. The total dosage may be administered in divided doses, 2-3 times daily.
Maintenance Dosage: After a satisfactory response has been achieved, dosage should then be gradually reduced to the lowest effective maintenance level.
Treatment withdrawal: Gradual withdrawal of haloperidol is advisable (see Warnings and Precautions – Additional considerations)

Antipsychotic, psychomotor sedative. Additionally, in pediatrics, for short-term treatment of tics and vomiting (Gilles de la tourettes syndrome).

Comatose states, Central nervous system (CNS) depression due to alcohol or other depressant drug, Parkinson’s disease, Known hypersensitivity to haloperidol, Lesion of the basal ganglia. In common with other neuroleptics, haloperidol has the potential to cause rare prolongation of the QT interval. Use of haloperidol is therefore contra-indicated in patients with clinically significant cardiac disorders e.g. recent acute myocardial infarction, uncompensated heart failure, arrhythmias treated with class IA and III antiarrhythmic medicinal products, QTc interval prolongation, history of ventricular arrhythmia or torsades de pointes clinically significant bradycardia, second or third degree heart block and uncorrected hypokalaemia. Haloperidol should not be used concomitantly with other QT prolonging drugs.

Rare cases of sudden death have been reported in psychiatric patients receiving antipsychotic drugs, including Haldol. 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. Very rare reports of QT prolongation and/or ventricular arrhythmias, in addition to rare reports of sudden death, have been reported with haloperidol. They may occur more frequently with high doses and in predisposed patients. As QT-prolongation has been observed during Haldol treatment caution is advised in patients with QT-prolonging conditions (long QT-syndrome, hypokalaemia, electrolyte imbalance, drugs known to prolong QT, cardiovascular diseases, family history of QT prolongation), especially if Haldol is given parenterally. The risk of QT prolongation and/or ventricular arrhythmias may be increased with higher doses or with parenteral use, particularly intravenous administration. ECG monitoring should be performed for QT interval prolongation and for serious cardiac dysrhythmias if Haldol is administered intravenously. Tachycardia and hypotension have also been reported in occasional patients.
Neuroleptic malignant syndrome: In common with other antipsychotic drugs, Haldol has been associated with neuroleptic malignant syndrome: a rare idiosyncratic response characterized by hyperthermia, generalised muscle rigidity, autonomic instability, altered consciousness. Hyperthermia is often an early sign of this syndrome. Antipsychotic treatment should be withdrawn immediately and appropriate supportive therapy and careful monitoring instituted.
Tardive dyskinesia As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or after drug discontinuation. The syndrome is mainly characterized by rhythmic involuntary movements of the tongue, face, mouth or jaw. The manifestations may be permanent in some patients. The syndrome may be masked when treatment is reinstituted, when the dosage is increased or when a switch is made to a different antipsychotic drug. Treatment should be discontinued as soon as possible.
Extrapyramidal symptoms: In common with all neuroleptics, extrapyramidal symptoms may occur, e.g. tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia. Antiparkinson drugs of the anticholinergic type may be prescribed as required, but should not be prescribed routinely as a preventive measure. If concomitant antiparkinson medication is required, it may have to be continued after stopping Haldol if its excretion is faster than that of Haldol in order to avoid the development or aggravation of extrapyramidal symptoms. The physician should keep in mind the possible increase in intraocular pressure when anticholinergic drugs, including antiparkinson agents, are administered concomitantly with Haldol.
Seizures/Convulsions: It has been reported that seizures can be triggered by Haldol. Caution is advised in patients suffering from epilepsy and in conditions predisposing to convulsions (e.g., alcohol withdrawal and brain damage).
Hepatobiliary concerns: As Haldol is metabolized by the liver, caution is advised in patients with liver disease. Isolated cases of liver function abnormalities or hepatitis, most often cholestatic, have been reported.
Endocrine system concerns: Thyroxin may facilitate Haldol toxicity. Antipsychotic therapy in patients with hyperthyroidism should be used only with great caution and must always be accompanied by therapy to achieve a euthyroid state. Hormonal effects of antipsychotic neuroleptic drugs include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligo- or amenorrhoea. Very rare cases of hypoglycaemia and of Syndrome of Inappropriate ADH Secretion have been reported.
Additional considerations: In schizophrenia, the response to antipsychotic drug treatment may be delayed. Also, if drugs are withdrawn, recurrence of symptoms may not become apparent for several weeks or months. Acute withdrawal symptoms including nausea, vomiting and insomnia have very rarely been described after abrupt cessation of high doses of antipsychotic drugs. Relapse may also occur and gradual withdrawal is advisable. As with all antipsychotic agents, Haldol should not be used alone where depression is predominant. It may be combined with antidepressants to treat those conditions in which depression and psychosis coexist. An approximately 3-fold increase risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Haloperidol should be used with caution in patients with risk factors for stroke. Caution is advised in patients with renal failure and phaeochromocytoma.

Neuromuscular (extrapyramidal) reactions, tachycardia, low blood pressure, mild and usually transient leukopenia and leukocytosis, hepatic changes, maculopapular and acneiform skin reactions, photosensitivity, loss of hair, anorexia, constipation, diarrhea, hypersalivation, pepsia, nausea and vomiting, dry mouth, blurred vision, urinary retention, diaphoresis and priapism, laryngospasm, bronchospasm, increased depth of respiration, visual disturbances.
Clinical Trial Data: Placebo-Controlled Double-Blind Data – Adverse Drug Reactions Reported at 1% Incidence. The safety of this product (2-20 mg/day) was evaluated in 566 subjects (of which 284 were treated with this product, 282 were given placebo) who participated in 3 placebo-controlled, double-blind clinical trials, two in the treatment of schizophrenia and the third in the treatment of bipolar disorder.
For full details see prescribing information.

As with other antipsychotics, caution is advised when prescribing Haloperidol with medications known to prolong the QT interval. Haloperidol is metabolized by several routes, including glucuronidation and the cytochrome P450 enzyme system (particularly CYP 3A4 or CYP 2D6). Inhibition of these routes of metabolism by another drug or a decrease in CYP 2D6 enzyme activity may result in increased haloperidol concentrations and an increased risk of adverse events, including QT-prolongation. In pharmacokinetic studies, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs characterized as substrates or inhibitors of CYP 3A4 or CYP 2D6 isozymes, such as, itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, and promethazine. A decrease in CYP2D6 enzyme activity may result in increased haloperidol concentrations. Increases in QTc have been observed when haloperidol was given with a combination of the metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day). It may be necessary to reduce the haloperidol dosage. Caution is advised when used in combination with drugs known to cause electrolyte imbalance.
Effect of Other Drugs on Haloperidol: When prolonged treatment with enzyme-inducing drugs such as carbamazepine, phenobarbital, rifampicine is added to Haldol therapy, this results in a significant reduction of haloperidol plasma levels. Therefore, during combination treatment, the Haldol dose should be adjusted, when necessary. After stopping such drugs, it may be necessary to reduce the dosage of Haldol. Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.
Effect of Haloperidol on Other Drugs: In common with all neuroleptics, Haldol can increase the central nervous system depression produced by other CNS-depressant drugs, including alcohol, hypnotics, sedatives or strong analgesics. An enhanced CNS effect, when combined with methyldopa, has also been reported. Haldol may antagonise the action of adrenaline and other sympathomimetic agents and reverse the bloodpressure- lowering effects of adrenergic-blocking agents such as guanethidine. Haldol may impair the antiparkinson effects of levodopa. Haloperidol is an inhibitor of CYP 2D6. Haldol inhibits the metabolization of tricyclic antidepressants, thereby increasing plasma levels of these drugs.
Other Forms of Interaction: In rare cases the following symptoms were reported during the concomitant use of lithium and haloperidol: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, brain stem disorder, acute brain syndrome and coma. Most of these symptoms were reversible. It remains unclear whether this represents a distinct clinical entity. Nonetheless, it is advised that in patients, who are treated concomitantly with lithium and Haldol, therapy should be stopped immediately if such symptoms occur. Antagonism of the effect of the anticoagulant phenindione has been reported.

Pregnancy: Neonates exposed to antipsychotic drugs (including haloperidol) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms that may vary in severity following delivery. These symptoms in the neonates may include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Haloperidol has shown no significant increase in fetal anomalies in large population studies. There have been isolated case reports of birth defects following fetal exposure to Haloperidol, mostly in combination with other drugs. Haloperidol should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.
Lactation: Haloperidol is excreted in breast milk. If the use of Haloperidol is considered essential, the benefits of breast-feeding should be balanced against its potential risks. Extrapyramidal symptoms have been observed in breast-fed infants of Haloperidol treated women.

The manifestations of haloperidol overdose are an exaggeration of the known pharmacological effects and adverse reactions. The most prominent symptoms are: severe extrapyramidal reactions, hypotension, sedation. An extrapyramidal reaction is manifest by muscular rigidity and a generalised or localised tremor. Hypertension rather than hypotension is also possible. In extreme cases, the patient would appear comatose with respiratory depression and hypotension that could be severe enough to produce a shock-like state. The risk of ventricular arrhythmias, possibly associated with QT-prolongation, should be considered.
Treatment: There is no specific antidote. Treatment is largely supportive. Activated charcoal may be administered. For comatose patients, a patent airway should be established by use of an oropharyngeal airway or endotracheal tube. Respiratory depression may necessitate artificial respiration. ECG and vital signs should be monitored and monitoring should continue until the ECG is normal. Severe arrhythmias should be treated with appropriate anti-arrhythmic measures. Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma, or concentrated albumin and vasopressor agents such as dopamine or noradrenaline. Adrenaline should not be used, since it might cause profound hypotension in the presence of Haloperidol. In cases of severe extrapyramidal reactions, antiparkinson medication (e.g. benztropine mesylate 1 to 2 mg IM or IV) should be administered parenterally.