Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

Increased mortality in elderly people with dementia

Rare cases of sudden death have been reported in psychiatric patients receiving antipsychotics, including haloperidol (see section 4.8).

Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death. Analyses of seventeen placebo-controlled studies (modal duration of 10 weeks), largely in patients taking atypical antipsychotics, revealed a risk of death in 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 study, the rate of death in patients treated with antipsychotics 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 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. The extent to which this association is attributable to the medicinal product, as opposed to being confounded by patient characteristics, has not yet been elucidated.

Cardiovascular effects

QTc prolongation and/or ventricular arrhythmias, in addition to sudden death, have been reported with haloperidol (see sections 4.3 and 4.8). 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. Caution is also required in patients with potentially high plasma concentrations (see section 4.4, 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 in 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.

Tachycardia and hypotension (including orthostatic hypotension) have also been reported (see section 4.8). 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. Observational studies comparing the stroke rate in elderly patients exposed to any antipsychotic to the stroke rate in those not exposed to such medicinal products found an increased stroke rate among exposed patients. This increase may be higher with all butyrophenones, including haloperidol. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other patient populations. HALDOL must be used with caution in patients with risk factors for stroke.

Neuroleptic malignant syndrome

Haloperidol has been associated with neuroleptic malignant syndrome: a rare idiosyncratic response characterized by hyperthermia, generalised muscle rigidity, autonomic instability, altered consciousness and increased serum creatine phosphokinase levels. Hyperthermia is often an early sign of this syndrome. Antipsychotic treatment must be withdrawn immediately and appropriate supportive therapy and careful monitoring instituted.

Tardive dyskinesia

Tardive dyskinesia may appear in some patients on long-term therapy or after discontinuation of the medicinal product. 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 dose is increased or when a switch is made to a different antipsychotic. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all antipsychotics, including HALDOL, must be considered.

Extrapyramidal symptoms

Extrapyramidal symptoms may occur (e.g. tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia). The use of haloperidol has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move, often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.

Acute dystonia may occur during the first few days of treatment with HALDOL, but later onset as well as onset after dose increases has been reported. Dystonic symptoms can include, but are not limited to, torticollis, facial grimacing, trismus, tongue protrusion, and abnormal eye movements, including oculogyric crisis. Males and younger age groups are at higher risk of experiencing such reactions.
Acute dystonia may necessitate stopping the medicinal product.

Antiparkinson medicinal products of the anticholinergic type may be prescribed as required to manage extrapyramidal symptoms, but it is recommended that they are not prescribed routinely as a preventive measure. If concomitant treatment with an antiparkinson medicinal product is required, it may have to be continued after stopping HALDOL if its excretion is faster than that of haloperidol in order to avoid the development or aggravation of extrapyramidal symptoms. The possible increase in intraocular pressure must be considered when anticholinergic medicinal products, including antiparkinson medicinal products, are administered concomitantly with HALDOL.

Seizures/convulsions

It has been reported that seizures can be triggered by haloperidol. Caution is advised in patients suffering from epilepsy and in conditions predisposing to seizures (e.g. alcohol withdrawal and brain damage).

Hepatobiliary concerns

As haloperidol is metabolised by the liver, dose adjustment and caution is advised in patients with hepatic impairment (see sections 4.2 and 5.2). Isolated cases of liver function abnormalities or hepatitis, most often cholestatic, have been reported (see section 4.8).

Endocrine system concerns

Thyroxin may facilitate haloperidol toxicity. Antipsychotic therapy in patients with hyperthyroidism must be used only with caution and must always be accompanied by therapy to achieve a euthyroid state.

Hormonal effects of antipsychotics include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligomenorrhea or amenorrhoea (see section 4.8). Tissue culture studies suggest that cell growth in human breast tumours may be stimulated by prolactin. Although no clear association with the administration of antipsychotics and human breast tumours has been demonstrated in clinical and epidemiological studies, caution is recommended in patients with relevant medical history. HALDOL must be used with caution in patients with pre-existing hyperprolactinaemia and in patients with possible prolactin-dependent tumours (see section 5.3).

Hypoglycaemia and syndrome of inappropriate antidiuretic hormone secretion have been reported with haloperidol (see section 4.8).

Venous thromboembolism

Cases of venous thromboembolism (VTE) have been reported with antipsychotics. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with HALDOL and preventive measures undertaken.

Treatment response and withdrawal

In schizophrenia, the response to antipsychotic treatment may be delayed.
If antipsychotics are withdrawn, recurrence of symptoms related to the underlying condition may not become apparent for several weeks or months.

There have been very rare reports of acute withdrawal symptoms (including nausea, vomiting and insomnia) after abrupt withdrawal of high doses of antipsychotics. Gradual withdrawal is advisable as a precautionary measure.

Patients with depression

It is recommended that HALDOL is not used alone in patients in whom depression is predominant. It may be combined with antidepressants to treat those conditions in which depression and psychosis coexist (see section 4.5).

Switch from mania to depression

There is a risk in the treatment of manic episodes of bipolar disorder for patients to switch from mania to depression. Monitoring of patients for the switch to a depressive episode with the accompanying risks such as suicidal behaviour is important in order to intervene when such switches occur.

Poor metabolisers of CYP2D6

HALDOL should be used with caution in patients who are known poor metabolisers of cytochrome P450 (CYP) 2D6 and who are coadministered a CYP3A4 inhibitor.

Paediatric population

Available safety data in the paediatric population indicate a risk of developing extrapyramidal symptoms, including tardive dyskinesia, and sedation. Limited long-term safety data are available.


Excipients of HALDOL
5 mg tablets:
HALDOL 5 mg tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

HALDOL 5 mg tablets contain less than 1 mmol (23 mg) sodium per 4 tablets (equivalent to the maximum daily dose of HALDOL), that is to say essentially ‘sodium-free’.

Oral solution:
HALDOL oral solution contains methyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).

Effects on Driving

4.7    Effects on ability to drive and use machines

HALDOL has a moderate influence on the ability to drive and use machines. Some degree of sedation or impairment of alertness may occur, particularly with higher doses and at the start of treatment and may be potentiated by alcohol. It is recommended that patients be advised not to drive or operate machines during treatment, until their susceptibility is known.