HALOPERIDOL

Posology Adults A low initial dose is recommended, which subsequently may be adjusted according to the patient’s response. 2). The dose recommendations for Haloperidol Tablets are presented in Table 1.

Table 1:

Haloperidol dose recommendations for adults aged 18 years and above Treatment of schizophrenia and schizoaffective disorder • 2 to 10 mg/day orally, as a single dose or in 2 divided doses. Patients with first- episode schizophrenia generally respond to 2 to 4 mg/day, whereas patients with multiple-episode schizophrenia may need doses up to 10 mg /day.

• Adjustments to the dose may be made every 1 to 7 days. • Doses above 10 mg/day have not demonstrated superior efficacy to lower doses in the majority of patients and may cause an increased incidence of extrapyramidal symptoms. The individual benefit-risk should be assessed when considering doses above 10 mg/day.

• The maximum dose is 20 mg/day because safety concerns outweigh the clinical benefits of treatment at higher doses. Acute treatment of delirium when non-pharmacological treatments have failed • 1 to 10 mg/day orally, as a single dose or in 2 to 3 divided doses.

• Treatment should be started at the lowest possible dose, and the dose should be adjusted in increments at 2- to 4-hour intervals if agitation continues, up to a maximum of 10 mg/day. Treatment of moderate to severe manic episodes associated with bipolar I disorder • 2 to 10 mg/day orally, as a single dose or in 2 divided doses.

• Adjustments to the dose may be made every 1 to 3 days. • Doses above 10 mg/day have not demonstrated superior efficacy to lower doses in the majority of patients and may cause an increased incidence of extrapyramidal symptoms. The individual benefit-risk should be assessed when considering doses above 10 mg/day.

• The maximum dose is 15 mg/day because safety concerns outweigh the clinical benefits of treatment at higher doses. 4). Treatment of acute psychomotor agitation associated with psychotic disorder or manic episodes of bipolar I disorder • 5 to 10 mg orally, repeated after 12 hours if necessary to a maximum of 20 mg/day.

4). • When switching from haloperidol intramuscular injection, haloperidol orally should be initiated at a 1:1 dose conversion rate followed by dose adjustment according to clinical response. 5 to 5 mg/day orally, as a single dose or in 2 divided doses.

The safety of haloperidol was evaluated in 284 haloperidol-treated patients who participated in 3 placebo-controlled clinical studies and in 1295 haloperidol-treated patients who participated in 16 double-blind active comparator-controlled clinical studies.

Based on pooled safety data from these clinical studies, the most commonly reported adverse reactions were: extrapyramidal disorder (34%), insomnia (19%), agitation (15%), hyperkinesia (13%), headache (12%), psychotic disorder (9%), depression (8%), weight increased (8%), tremor (8%), hypertonia (7%), orthostatic hypotension (7%), dystonia (6%) and somnolence (5%).

In addition, the safety of haloperidol decanoate was evaluated in 410 patients who participated in 3 comparator studies (1 comparing haloperidol decanoate versus fluphenazine and 2 comparing the decanoate formulation to oral haloperidol), 9 open label studies and 1 dose response study.

Table 3 lists adverse reactions as follows: • Reported in clinical studies with haloperidol. • Reported in clinical studies with haloperidol decanoate and relate to the active moiety. • From postmarketing experience with haloperidol and haloperidol decanoate.

Adverse reaction frequencies are based on (or estimated from) clinical trials or epidemiology studies with haloperidol, and classified using the following convention: Very common: ≥1/10 Common: ≥1/100 to <1/10 Uncommon: ≥1/1,000 to <1/100 Rare: ≥1/10,000 to <1/1,000 Very rare: <1/10,000 Not known: cannot be estimated from the available data.

The adverse reactions are presented by System Organ Class and in order of decreasing seriousness within each frequency category. 6) Reproductive system and breast disorders Erectile dysfunction Amenorrhoea Galactorrhoea Dysmenorrhoea Breast pain Breast discomfort Menorrhagia Menstrual disorder Sexual dysfunction Priapism Gynaecomastia General disorders and administration site conditions Hyperthermia Oedema Gait disturbance Sudden death Face oedema Hypothermia Investigations Weight increased Weight decreased Electrocardiogram QT prolonged Electrocardiogram QT prolonged, ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia), torsade de pointes and sudden death have been reported with haloperidol.

Increased mortality in elderly people with dementia. 8). Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. 7 times the risk of death in placebo-treated patients. 6% in the placebo group.

g. g. pneumonia) in nature. Observational studies suggest that treatment of elderly patients with haloperidol is also associated with increased mortality. This association may be stronger for haloperidol than for atypical antipsychotic medicinal products, is most pronounced in the first 30 days after the start of treatment, and persists for at least 6 months.

8). The risk of these events appears to increase with high doses, high plasma concentrations, in predisposed patients or with parenteral use, particularly intravenous administration. Caution is advised in patients with bradycardia, cardiac disease, family history of QTc prolongation or history of heavy alcohol exposure.

4, Poor metabolisers of CYP2D6). A baseline ECG is recommended before treatment. During therapy, the need for ECG monitoring for QTc interval prolongation and for ventricular arrhythmias must be assessed for all patients. Whilst on therapy, it is recommended to reduce the dose if QTc is prolonged, but haloperidol must be discontinued if the QTc exceeds 500 ms.

Electrolyte disturbances such as hypokalaemia and hypomagnesaemia increase the risk for ventricular arrhythmias and must be corrected before treatment with haloperidol is started. Therefore, baseline and periodic electrolyte monitoring is recommended.

8). Caution is recommended when haloperidol is administered to patients manifesting hypotension or orthostatic hypotension. Cerebrovascular events In randomised, placebo controlled clinical studies in the dementia population there was an approximately 3-fold increased risk of cerebrovascular adverse events with some atypical antipsychotics.

1. • Comatose state. • Central nervous system (CNS) depression. • Parkinson’s disease. • Dementia with Lewy bodies. • Progressive supranuclear palsy. • Known QTc interval prolongation or congenital long QT syndrome. • Recent acute myocardial infarction.

• Uncompensated heart failure. • History of ventricular arrhythmia or torsades de pointes. • Uncorrected hypokalaemia. • Concomitant treatment with medicinal products that prolong the QT interval. 5).