1. NAME OF THE MEDICINAL PRODUCT

Haloperidol Injection USP 5mg/ml Taj Pharma
Haloperidol Injection USP 50mg/10ml Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

    a) Each ml of solution contains:
    Haloperidol USP……………………5mg/ml

    b) Each ml of solution contains:
    Haloperidol USP……………………5mg/ml

Excipient with known effect

Contains sodium less than 1mmol per dose

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Solution for Injection.

Clear, colourless sterile solution

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmasolution for injection is indicated in adult patients for:

  • Rapid control of severe acute psychomotor agitation associated with psychotic disorder or manic episodes of bipolar I disorder when oral therapy is not appropriate.
  • Acute treatment of delirium when non-pharmacological treatments have failed.
  • Treatment of mild to moderate chorea in Huntington’s disease, when other medicinal products are ineffective or not tolerated, and oral therapy is not appropriate.
  • Single or combination prophylaxis in patients at moderate to high risk of postoperative nausea and vomiting, when other medicinal products are ineffective or not tolerated.
  • Combination treatment of postoperative nausea and vomiting when other medicinal products are ineffective or not tolerated.

4.2 Posology and method of administration

Posology

Adults

A low initial dose is recommended and this must be adjusted according to the patient’s response in order to determine the minimal effective dose (see section 5.2).

The dose recommendations for Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmasolution for injection are presented in Table 1.

Table 1: Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Parma  dose recommendations for adults aged 18 years and above

Rapid control of severe acute psychomotor agitation associated with psychotic disorder or manic episodes of bipolar I disorder when oral therapy is not appropriate

• 5 mg intramuscularly.

• May be repeated hourly until sufficient symptom control is achieved.

• In the majority of patients, doses of up to 15 mg/day are sufficient. The maximum dose is 20 mg/day.

• The continued use of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmashould be evaluated early in treatment (see section 4.4). Treatment with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma solution for injection must be discontinued as soon as clinically indicated and, if further treatment is needed, oral Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma should be initiated at a 1:1 dose conversion rate followed by dose adjustment according to clinical response.

Acute treatment of delirium when non-pharmacological treatments have failed

• 1 to 10 mg intramuscularly.

• 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 mild to moderate chorea in Huntington’s disease, when other medicinal products are ineffective or not tolerated, and oral therapy is not appropriate

• 2 to 5 mg intramuscularly.

• May be repeated hourly until sufficient symptom control is achieved or up to a maximum of 10 mg/day.

Single or combination prophylaxis in patients at moderate to high risk of postoperative nausea and vomiting, when other medicinal products are ineffective or not tolerated

• 1 to 2 mg intramuscularly, at induction or 30 minutes before the end of anaesthesia.

Combination treatment of postoperative nausea and vomiting when other medicinal products are ineffective or not tolerated

• 1 to 2 mg intramuscularly.

Treatment withdrawal

Gradual withdrawal of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmais advisable (see section 4.4).

Special populations

Elderly

The recommended initial Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Parma dose in elderly patients is half the lowest adult dose.

Further doses may be administered and adjusted according to the patient’s response. Careful and gradual dose up-titration in elderly patients is recommended.

The maximum dose is 5 mg/day.

Doses above 5 mg/day should only be considered in patients who have tolerated higher doses and after reassessment of the patient’s individual benefit-risk profile.

Renal impairment

The influence of renal impairment on the pharmacokinetics of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Parma has not been evaluated. No dose adjustment is recommended, but caution is advised when treating patients with renal impairment. However, patients with severe renal impairment may require a lower initial dose, with further doses administered and adjusted according to the patient’s response (see section 5.2).

Hepatic impairment

The influence of hepatic impairment on the pharmacokinetics of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmahas not been evaluated. Since Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmais extensively metabolised in the liver, it is recommended to halve the initial dose. Further doses may be administered and adjusted according to the patient’s response (see sections 4.4 and 5.2).

Paediatric population

The safety and efficacy of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmasolution for injection in children and adolescents below 18 years of age have not been established. No data are available.

Method of administration

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmasolution for injection is recommended for intramuscular administration only (see section 4.4). For instructions on handling Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmasolution for injection, see section 6.6.

4.3 Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
  • 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 (see section 4.5).

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 Injection USP 5mg/ml / 50mg/10ml Taj Pharma (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 Injection USP 5mg/ml / 50mg/10ml Taj Pharmais also associated with increased mortality. This association may be stronger for Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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.

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmasolution for injection is not indicated for the treatment of dementia-related behavioural disturbances.

Cardiovascular effects

QTc prolongation and/or ventricular arrhythmias, in addition to sudden death, have been reported with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma (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.

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma solution for injection is recommended for intramuscular administration only. However, if administered intravenously, continuous ECG monitoring must be performed for QTc interval prolongation and for ventricular arrhythmias.

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 intramuscular dosing. During therapy, the need for ECG monitoring for QTc interval prolongation and for ventricular arrhythmias must be assessed in all patients, but continuous ECG monitoring is recommended for repeated intramuscular doses. ECG monitoring is recommended up to 6 hours after administration of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmasolution for injection to patients for prophylaxis or treatment of postoperative nausea and vomiting.

Whilst on therapy, it is recommended to reduce the dose if QTc is prolonged, but Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmamust 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 Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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 Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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 Injection USP 5mg/ml / 50mg/10ml Taj Parma. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other patient populations. Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharmamust be used with caution in patients with risk factors for stroke.

Neuroleptic malignant syndrome

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma, must be considered.

Extrapyramidal symptoms

Extrapyramidal symptoms may occur (e.g. tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia). The use of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma, 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 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma if its excretion is faster than that of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma.

Seizures/Convulsions

It has been reported that seizures can be triggered by Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma. 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 Injection USP 5mg/ml / 50mg/10ml Taj Pharma is metabolised by the liver, half the initial dose 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 Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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 antipsychotic neuroleptic drugs include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligo 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. Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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 Injection USP 5mg/ml / 50mg/10ml Taj Pharma (see section 4.8).

Venous thromboembolism

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. 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 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma should be used with caution in patients who are known poor metabolisers of cytochrome P450 (CYP) 2D6 and who are coadministered a CYP3A4 inhibitor.

4.5 Interaction with other medicinal products and other forms of interaction

Interaction studies have only been performed in adults.

Cardiovascular effects

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is contraindicated in combination with medicinal products known to prolong the QTc interval (see section 4.3). Examples include:

  • Class IA antiarrhythmics (e.g. disopyramide, quinidine).
  • Class III antiarrhythmics (e.g. amiodarone, dofetilide, dronedarone, ibutilide, sotalol).
  • Certain antidepressants (e.g. citalopram, escitalopram).
  • Certain antibiotics (e.g. azithromycin, clarithromycin, erythromycin, levofloxacin, moxifloxacin, telithromycin).
  • Other antipsychotics (e.g. phenothiazine derivatives, sertindole, pimozide, ziprasidone)
  • Certain antifungals (e.g. pentamidine).
  • Certain antimalarials (e.g. halofantrine).
  • Certain gastrointestinal medicinal products (e.g. dolasetron).
  • Certain medicinal products used in cancer (e.g. toremifene, vandetanib).
  • Certain other medicinal products (e.g. bepridil, methadone).

This list is not exhaustive.

Caution is advised when Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is used in combination with medicinal products known to cause electrolyte imbalance (see section 4.4).

Medicinal products that may increase Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma concentrations

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is metabolised by several routes (see section 5.2). The major pathways are glucuronidation and ketone reduction. The cytochrome P450 enzyme system is also involved, particularly CYP3A4 and, to a lesser extent, CYP2D6. Inhibition of these routes of metabolism by another medicinal product or a decrease in CYP2D6 enzyme activity may result in increased Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma concentrations. The effect of CYP3A4 inhibition and of decreased CYP2D6 enzyme activity may be additive (see section 5.2). Based on limited and sometimes conflicting information, the potential increase in Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma concentrations when a CYP3A4 and/or CYP2D6 inhibitor is coadministered may range between 20 to 40%, although in some cases, increases of up to 100% have been reported. Examples of medicinal products that may increase Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma concentrations (based on clinical experience or drug interaction mechanism) include:

  • CYP3A4 inhibitors – alprazolam, fluvoxamine, indinavir, itraconazole, ketoconazole, nefazodone, posaconazole, saquinavir, verapamil, voriconazole.
  • CYP2D6 inhibitors – bupropion, chlorpromazine, duloxetine, paroxetine, promethazine, sertraline, venlafaxine.
  • Combined CYP3A4 and CYP2D6 inhibitors: fluoxetine, ritonavir.
  • Uncertain mechanism – buspirone.

This list is not exhaustive.

Increased Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma concentrations may result in an increased risk of adverse events, including QTc-prolongation (see section 4.4). Increases in QTc have been observed when Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma was given with a combination of the metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day).

It is recommended that patients who take Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma concomitantly with such medicinal products be monitored for signs or symptoms of increased or prolonged pharmacologic effects of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma, and the Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma dose be decreased as deemed necessary.

Medicinal products that may decrease Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma concentrations

Coadministration of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma with potent enzyme inducers of CYP3A4 may gradually decrease the plasma concentrations of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma to such an extent that efficacy may be reduced. Examples include:

  • Carbamazepine, phenobarbital, phenytoin, rifampicin, St John’s Wort (Hypericum, perforatum).

This list is not exhaustive.

Enzyme induction may be observed after a few days of treatment. Maximal enzyme induction is generally seen in about 2 weeks and may then be sustained for the same period of time after the cessation of therapy with the medicinal product. During combination treatment with inducers of CYP3A4, it is recommended that patients be monitored and the Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma dose increased as deemed necessary. After withdrawal of the CYP3A4 inducer, the concentration of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma may gradually increase and therefore it may be necessary to reduce the Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma dose.

Sodium valproate is known to inhibit glucuronidation, but does not affect Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma concentrations.

Effect of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma on other medicinal products

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma can increase the CNS depression produced by alcohol or CNS-depressant medicinal products, including hypnotics, sedatives or strong analgesics. An enhanced CNS effect, when combined with methyldopa, has also been reported.

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma may antagonise the action of adrenaline and other sympathomimetic medicinal products (e.g. stimulants like amphetamines) and reverse the blood pressure-lowering effects of adrenergic-blocking medicinal products such as guanethidine.

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma may antagonise the effect of levodopa and other dopamine agonists.

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is an inhibitor of CYP2D6. Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma inhibits the metabolism of tricyclic antidepressants (e.g. imipramine, desipramine), thereby increasing plasma concentrations of these medicinal products.

Other Forms of Interaction

In rare cases the following symptoms were reported during the concomitant use of lithium and Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, 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 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma, therapy must be stopped immediately if such symptoms occur.

Antagonism of the effect of the anticoagulant phenindione has been reported.

4.6 Fertility, pregnancy and lactation

Pregnancy

A moderate amount of data on pregnant women (more than 400 pregnancy outcomes) indicate no malformative or foeto/ neonatal toxicity of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma. However, there have been isolated case reports of birth defects following foetal exposure to Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma, mostly in combination with other medicinal products. Animal studies have shown reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma during pregnancy.

Newborn infants exposed to antipsychotics (including Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, it is recommended that newborn infants be monitored carefully.

Breast-feeding

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is excreted in human milk. Small amounts of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma have been detected in plasma and urine of breast-fed newborns of mothers treated with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma. There is insufficient information on the effects of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma in breast-fed infants. A decision must be made whether to discontinue breastfeeding or to discontinue Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma elevates prolactin level. Hyperprolactinaemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients (see section 4.4).

4.7 Effects on ability to drive and use machines

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma 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.

4.8 Undesirable effects

The safety of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma was evaluated in 284 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma-treated patients who participated in 3 placebo-controlled clinical studies and in 1295 Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma-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 Injection USP 5mg/ml / 50mg/10ml Taj Pharma decanoate was evaluated in 410 patients who participated in 3 comparator studies (1 comparing Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma decanoate versus fluphenazine and 2 comparing the decanoate formulation to oral Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma), 9 open label studies and 1 dose response study.

Table 2 lists adverse reactions as follows:

  • Reported in clinical studies with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma.
  • Reported in clinical studies with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma decanoate and relate to the active moiety.
  • From postmarketing experience with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma and Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma decanoate.

Adverse reaction frequencies are based on (or estimated from) clinical trials or epidemiology studies with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma, and classified using the following convention:

Very common:

Common:

Uncommon:

Rare:

Very rare:

Not known:

≥ 1/10

≥1/100 to < 1/10

≥ 1/1,000 to < 1/100

≥ 1/10,000 to <1/1,000

<1/10,000

cannot be estimated form the available data

The adverse reactions are presented by System Organ Class and in order of decreasing seriousness within each frequency category.

Table 2: Adverse reactions

System Organ ClassAdverse Reactions
Frequency
Very CommonCommonUncommonRareNot Known
Blood and lymphatic system disordersLeukopeniaAgranulocytosis; Neutropenia; Pancytopenia; Thrombocytopenia
Immune system disordersHypersensitivityAnaphylactic reaction
Endocrine disordersHyperprolactinaemiaInappropriate antidiuretic hormone secretion
Metabolic and nutritional disordersHypoglycaemia
Psychiatric disordersAgitation; InsomniaDepression; Psychotic disorderConfusional state; Libido Decreased; Loss of libido; Restlessness
Nervous system disordersExtrapyramidal disorder; Hyperkinesia; HeadacheTardive dyskinesia; Dystonia; Dyskinesia; Akathisia; Bradykinesia; Hypokinesia; Hypertonia; Somnolence; Tremor; DizzinessConvulsion; Parkinsonism; Sedation; Muscle Contractions InvoluntaryMotor dysfunction; Neuroleptic malignant syndrome; Nystagmus;Akinesia; Cogwheel rigidity; Masked Facies
Eye disordersOculogyric Crisis; Visual disturbanceVision blurred
Cardiac disordersTachycardiaVentricular Fibrillation; Torsade de pointes; Ventricular Tachycardia; Extrasystoles
Vascular disordersOrthostatic Hypotension; Hypotension
Respiratory, thoracic and mediastinal disordersDyspnoeaBronchospasmLaryngeal Oedema; Laryngospasm
Gastrointestinal disordersConstipation; Dry mouth; Salivary hypersecretion; Nausea; Vomiting
Hepatobiliary disordersLiver function test abnormalHepatitis; JaundiceAcute Hepatic Failure; Cholestasis
Skin and subcutaneous tissue disordersRashPhotosensitivity Reaction; Urticaria; Pruritus; HyperhidrosisAngioedema; Leukocytoclastic Vasculitis; Dermatitis Exfoliative
Musculoskeletal and connective tissue disordersTorticollis; Muscle rigidity; Muscle Spasms; Musculoskeletal stiffnessTrismus; Muscle TwitchingRhabdomyolysis
Renal and urinary disordersUrinary retention
Pregnancy, puerperium and perinatal conditionsDrug withdrawal syndrome neonatal (see 4.6)
Reproductive system and breast disordersErectile dysfunctionAmenorrhoea; Dysmenorrhoea; Galactorrhoea; Breast Discomfort; Breast Pain;Menorrhagia; Menstrual Disorder; Sexual DysfunctionPriapism Gynaecomastia,
General disorders and administration site conditionsGait disturbance; Hyperthermia; OedemaSudden Death; Face Oedema; Hypothermia
InvestigationsWeight increased; Weight decreasedElectrocardiogram QT prolonged

Electrocardiogram QT prolonged, ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia), torsade de pointes and sudden death have been reported with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma.

Class effects of antipsychotics

Cardiac arrest has been reported with antipsychotics.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis, have been reported with antipsychotics. The frequency is unknown.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important

4.9 Overdose

Symptoms and signs:

The manifestations of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma overdose are an exaggeration of the known pharmacological effects and adverse reactions. The most prominent symptoms are severe extrapyramidal reactions, hypotension and 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 QTc prolongation, must be considered.

Management:

There is no specific antidote. Treatment is supportive. Dialysis is not recommended in the treatment of overdose because it removes only very small amounts of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma (see section 5.2).

For comatose patients, a patent airway must be established by use of an oropharyngeal airway or endotracheal tube. Respiratory depression may necessitate artificial respiration.

It is recommended that ECG and vital signs be monitored, and that monitoring continues until the ECG is normal. Treatment of severe arrhythmias with appropriate anti-arrhythmic measures is recommended.

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 must not be used because it might cause profound hypotension in the presence of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma.

In cases of severe extrapyramidal reactions, parenteral administration of an antiparkinson medicinal product is recommended.

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: psycholeptics; antipsychotics; butyrophenone derivatives

Mechanism of action

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is an antipsychotic belonging to the butyrophenones group. It is a potent central dopamine type 2 receptor antagonist, and at recommended doses, has low alpha-1 antiadrenergic activity and no antihistaminergic or anticholinergic activity.

Pharmacodynamic effects

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma suppresses delusions and hallucinations as a direct consequence of blocking dopaminergic signalling in the mesolimbic pathway. The central dopamine blocking effect has activity on the basal ganglia (nigrostriatal bundles). Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma causes efficient psychomotor sedation, which explains the favourable effect on mania and other agitation syndromes.

The activity on the basal ganglia probably underlies the undesirable extrapyramidal motor effects (dystonia, akathisia and parkinsonism).

The antidopaminergic effects of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma on lactotropes in the anterior pituitary explain hyperprolactinaemia due to inhibition of dopamine-mediated tonic inhibition of prolactin secretion. Additionally, the antidopaminergic effect on the chemoreceptor-trigger zone of the area postrema explains the activity against nausea and vomiting.

5.2 Pharmacokinetic properties

Absorption

Following intramuscular administration, Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is completely absorbed. Peak plasma concentrations of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma are attained within 20 to 40 minutes.

Distribution

Mean Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma protein binding in adults is approximately 88 to 92%. There is a high inter-subject variability for plasma protein binding. Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is rapidly distributed to various tissues and organs, as indicated by the large volume of distribution (mean values 8 to 21 l/kg after intravenous dosing). Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma crosses the blood-brain barrier easily. It also crosses the placenta and is excreted in breast milk.

Biotransformation

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is extensively metabolised in the liver. The main metabolic pathways of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma in humans include glucuronidation, ketone reduction, oxidative N-dealkylation and formation of pyridinium metabolites. The metabolites of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma are not considered to make a significant contribution to its activity; however, the reduction pathway accounts approximately for 23% of the biotransformation, and back-conversion of the reduced metabolite of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma to Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma cannot be fully ruled out. The cytochrome P450 enzymes CYP3A4 and CYP2D6 are involved in Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma metabolism. Inhibition or induction of CYP3A4, or inhibition of CYP2D6, may affect Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma metabolism. A decrease in CYP2D6 enzyme activity may result in increased Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma concentrations.

Elimination

The terminal elimination half-life of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is on average 21 hours (range 13 to 36 hours) after intramuscular administration. Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma apparent clearance after extravascular administration ranges from 0.9 to 1.5 l/h/kg and is reduced in poor metabolisers of CYP2D6. Reduced CYP2D6 enzyme activity may result in increased concentrations of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma. The inter-subject variability (coefficient of variation, %) in Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma clearance was estimated to be 44% in a population pharmacokinetic analysis in patients with schizophrenia. After intravenous Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma administration, 21% of the dose was eliminated in the faeces and 33% in the urine. Less than 3% of the dose is excreted unchanged in the urine.

Linearity/non-linearity

A linear relationship exists between Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma dose and plasma concentrations in adults.

Special populations

Elderly

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma concentrations in elderly patients were higher than in younger adults administered the same dose. Results from small clinical studies suggest a lower clearance and a longer elimination half-life of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma in elderly patients. The results are within the observed variability in Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma pharmacokinetics. Dose adjustment is recommended in elderly patients (see section 4.2).

Renal impairment

The influence of renal impairment on the pharmacokinetics of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma has not been evaluated. About one-third of a Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma dose is excreted in urine, mostly as metabolites. Less than 3% of administered Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma is eliminated unchanged in the urine. Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma metabolites are not considered to make a significant contribution to its activity, although for the reduced metabolite of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma, back-conversion to Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma cannot be fully ruled out. Even though impairment of renal function is not expected to affect Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma elimination to a clinically relevant extent, caution is advised in patients with renal impairment, and especially those with severe impairment, due to the long half-life of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma and its reduced metabolite, and the possibility of accumulation (see section 4.2).

Because of the high Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma distribution volume and its high protein binding, only very small amounts are removed by dialysis.

Hepatic impairment

The influence of hepatic impairment on the pharmacokinetics of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma has not been evaluated. However, hepatic impairment may have significant effects on the pharmacokinetics of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma because it is extensively metabolised in the liver. Therefore, half the initial dose and caution is advised in patients with hepatic impairment (see sections 4.2 and 4.4).

Pharmacokinetic/pharmacodynamics relationships

Therapeutic concentrations

Based on published data from multiple clinical studies, therapeutic response is obtained in most patients with acute or chronic schizophrenia at plasma concentrations of 1 to 10 ng/ml. A subset of patients may require higher concentrations as a consequence of a high inter-subject variability in Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma pharmacokinetics.

In patients with first-episode schizophrenia, therapeutic response may be obtained at concentrations as low as 0.6 to 3.2 ng/ml, as estimated based on measurements of D2 receptor occupancy and assuming that a D2 receptor occupancy level of 60 to 80% is most appropriate for obtaining therapeutic response and limiting extrapyramidal symptoms. On average, concentrations in this range would be obtained with doses of 1 to 4 mg daily.

Due to the high inter-subject variability in Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma pharmacokinetics and the concentration-effect relationship, it is recommended to adjust the individual Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma dose based on the patient’s response, taking into account data suggesting a lag time of 5 days to reach half of the maximal therapeutic response. Measurement of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma blood concentrations may be considered in individual cases.

Cardiovascular effects

The risk of QTc prolongation increases with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma dose and with Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma plasma concentrations.

Extrapyramidal symptoms

Extrapyramidal symptoms can occur within the therapeutic range, although the frequency is usually higher with doses producing higher than therapeutic concentrations.

5.3 Preclinical safety data

Non-clinical data reveal no special hazards for humans based on conventional studies of repeat dose toxicity and genotoxicity. In rodents, Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma administration showed a decrease in fertility, limited teratogenicity as well as embryo-toxic effects.

In a carcinogenicity study of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma, dose-dependent increases in pituitary gland adenomas and mammary gland carcinomas were seen in female mice. These tumours may be caused by prolonged dopamine Dantagonism and hyperprolactinaemia. The relevance of these tumour findings in rodents in terms of human risk is unknown.

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma has been shown to block the cardiac hERG channel in several published studies in vitro. In a number of in vivo studies, intravenous administration of Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma in some animal models has caused significant QTc prolongation at doses around 0.3 mg/kg, producing Cmax plasma levels at least 7 to 14 times higher than the therapeutic plasma concentrations of 1 to 10 ng/ml that were effective in the majority of patients in clinical studies. These intravenous doses, which prolonged QTc, did not cause arrhythmias. In some animal studies, higher intravenous Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma doses of 1 mg/kg or greater caused QTc prolongation and/or ventricular arrhythmias at Cmax plasma levels at least 38 to 137 times higher than the therapeutic plasma concentrations that were effective in the majority of patients in clinical studies.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactic Acid

Sodium Hydroxide (as 10% w/v solution), Water for injections

6.2 Incompatibilities

Haloperidol Injection USP 5mg/ml / 50mg/10ml Taj Pharma Injection should not be mixed with other products unless their compatibility is known.

6.3 Shelf life

Unopened: 3 years

The product should be used immediately after opening.

6.4 Special precautions for storage

Do not store above 25°C.

Store in the original carton in order to protect from light

6.5 Nature and contents of container

1ml & 2 ml clear One Point Cut (OPC) glass ampoules, glass type 1 Ph. Eur. borosilicate glass packed in cardboard cartons to contain 10x1ml ampoules and 10x2ml ampoules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

For single use only.

If only part of the contents of an ampoule is used, the remaining solution should be discarded.

Do not use if the solution is cloudy, discoloured or if there are any particles present.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

HALOPERIDOL INJECTION USP
5MG/ML / 50MG/10ML
TAJ PHARMA

Haloperidol

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or nurse.
  • If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

The product is known by the name above but will be referred to as Haloperidol Injection throughout the rest of this leaflet.

WHAT IS IN THIS LEAFLET

  1. What Haloperidol Injection is and what it is used for
  2. What you need to know before you are given Haloperidol Injection
  3. How you will be given Haloperidol Injection
  4. Possible side effects
  5. How to store Haloperidol Injection
  6. Contents of the pack and other information

    1. WHAT HALOPERIDOL INJECTION IS AND WHAT IT IS USED FOR

Haloperidol Injection contains the active substance haloperidol. This belongs to a group of medicines called ‘antipsychotics’.

Haloperidol Injection is used in adults for illnesses affecting the way you think, feel or behave. These include mental health problems (such as schizophrenia and bipolar disorder) and behavioural problems.

These illnesses may make you:

  • Feel confused (delirium)
  • See, hear, feel or smell things that are not there (hallucinations)
  • Believe things that are not true (delusions)
  • Feel unusually suspicious (paranoia)
  • Feel very excited, agitated, enthusiastic, impulsive or hyperactive
  • Feel very aggressive, hostile or violent.

Haloperidol Injection is also used in adults:

  • To help control movements in Huntington’s disease
  • To prevent or treat nausea and vomiting (feeling and being sick) after surgery.

Haloperidol Injection may be used on its own or with other medicine, and is sometimes used when other medicines or treatments have not worked, caused unacceptable side effects, or cannot be taken by mouth.

  1. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN HALOPERIDOL INJECTION

Do not use Haloperidol Injection if:

  • You are allergic to haloperidol or any of the other ingredients of this medicine (listed in section 6)
  • You are less aware of things around you or your reactions become unusually slow
  • You have Parkinson’s disease
  • You have a type of dementia called ‘Lewy body dementia’
  • You have progressive supranuclear palsy (PSP)
  • You have a heart condition called ‘prolonged QT interval’, or any other problem with your heart rhythm that shows as an abnormal tracing on an ECG (electrocardiogram)
  • You have heart failure or recently had a heart attack
  • You have a low level of potassium in your blood, which has not been treated
  • You take any of the medicines listed under ‘Other medicines and Haloperidol – Do not use Haloperidol injection if you are taking certain medicines for’.

This medicine must not be used if any of the above applies to you. If you are not sure, talk to your doctor, pharmacist or nurse before being given haloperidol injection.

Warnings and precautions

Serious side effects

Haloperidol injection can cause problems with the heart, problems controlling body or limb movements and a serious side effect called ‘neuroleptic malignant syndrome’. It can also cause severe allergic reactions and blood clots. You must be aware of serious side effects while you are using Haloperidol injection because you may need urgent medical treatment. See ‘Look out for serious side effects’ in section 4.

Elderly people and people with dementia

A small increase in deaths and strokes has been reported for elderly people with dementia who are taking antipsychotic medicines. Talk to your doctor before being given Haloperidol injection if you are elderly, particularly if you have dementia.

Talk to your doctor if you have:

  • A slow heart beat, heart disease or anyone in your close family has died suddenly of heart problems
  • Low blood pressure, or feel dizzy upon sitting up or standing up
  • A low level of potassium or magnesium (or other ‘electrolyte’) in your blood. Your doctor will decide how to treat this
  • Ever had bleeding in the brain, or your doctor has told you that you are more likely than other people to have a stroke
  • Epilepsy or have ever had fits (convulsions)
  • Problems with your kidneys, liver or thyroid gland
  • A high level of the hormone ‘prolactin’ in your blood, or cancer that may be caused by high prolactin levels (such as breast cancer)
  • A history of blood clots, or someone else in your family has a history of blood clots
  • Depression, or you have bipolar disorder and start to feel depressed.

You may need to be more closely monitored, and the amount of Haloperidol injection you are given may have to be altered.

If you are not sure if any of the above applies to you, talk to your doctor or nurse before you are given Haloperidol injection.

Medical check ups

Your doctor may want to take an electrocardiogram (ECG) before or during your treatment with Haloperidol Injection. The ECG measures the electrical activity of your heart.

Blood tests

Your doctor may want to check the levels of potassium or magnesium (or other electrolytes) in your blood before or during your treatment with Haloperidol injection.

Children and adolescents

Haloperidol Injection should not be used in children and adolescents below 18 years. This is because it has not been studied in these age groups.

Other medicines and Haloperidol Injection

Tell your doctor or nurse if you are taking or have recently taken or might take any other medicines.

Do not use Haloperidol injection if you are taking certain medicines for:

  • Problems with your heart beat (such as amiodarone, dofetilide, disopyramide, dronedarone, ibutilide, quinidine and sotalol)
  • Depression (such as citalopram and escitalopram)
  • Psychoses (such as fluphenazine, levomepromazine, perphenazine, pimozide, prochlorperazine, promazine, sertindole, thiorizadine, trifluoperazine, triflupromazine and ziprasidone)
  • Bacterial infections (such as azithromycin, clarithromycin, erythromycin, levofloxacin, moxifloxacin and telithromycin)
  • Fungal infections (such as pentamidine)
  • Malaria (such as halofantrine)
  • Nausea and vomiting (such as dolasetron)
  • Cancer (such as toremifene and vandetanib).

Also tell your doctor if you are taking bepridil (for chest pain or to lower blood pressure) or methadone (a pain killer or to treat drug addiction).

These medicines may make heart problems more likely, so talk to your doctor if you are taking any of these and do not use Haloperidol Injection (see ‘Do not use Haloperidol Injection if’).

Special monitoring may be needed if you are using lithium and Haloperidol injection at the same time.

Tell your doctor straight away and stop taking both medicines if you get:

  • Fever you can’t explain or movements you can’t control
  • Confused, disoriented, a headache, balance problems and feel sleepy

These are signs of a serious condition.

Certain medicines may affect the way that Haloperidol injection works or may make heart problems more likely

Tell your doctor if you are taking:

  • Alprazolam or buspirone (for anxiety)
  • Duloxetine, fluoxetine, fluvoxamine, nefazodone, paroxetine, sertraline, St John’s Wort (Hypericum, perforatum) or venlafaxine (for depression)
  • Bupropion (for depression or to help you stop smoking)
  • Carbamazepine, phenobarbital or phenytoin (for epilepsy)
  • Rifampicin (for bacterial infections)
  • Itraconazole, posaconazole or voriconazole (for fungal infections)
  • Ketoconazole tablets (to treat Cushing’s syndrome)
  • Indinavir, ritonavir or saquinavir (for human immunodeficiency virus or HIV)
  • Chlorpromazine or promethazine (for nausea and vomiting)
  • Verapamil (for blood pressure or heart problems).

Also tell your doctor if you are taking any other medicines to lower blood pressure, such as water tablets (diuretics).

Your doctor may have to change your dose of Haloperidol Injection if you are taking any of these medicines.

Haloperidol injection can affect the way the following types of medicine work

Tell your doctor if you are taking medicines for:

  • Calming you down or helping you to sleep (tranquillisers)
  • Pain (strong pain killers)
  • Depression (‘tricyclic antidepressants’)
  • Lowering blood pressure (such as guanethidine and methyldopa)
  • Severe allergic reactions (adrenaline)
  • Attention deficit hyperactivity disorder (ADHD) or narcolepsy (known as ‘stimulants’)
  • Parkinson’s disease (such as levodopa)
  • Thinning the blood (phenindione).

Talk to your doctor or nurse before being given Haloperidol Injection if you are taking any of these medicines.

Haloperidol Injection with alcohol

Drinking alcohol while you are using Haloperidol Injection might make you feel sleepy and less alert. This means you should be careful how much alcohol you drink. Talk to your doctor about drinking alcohol while using Haloperidol Injection, and let your doctor know how much you drink.

Pregnancy, breast-feeding and fertility

Pregnancy – if you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice. Your doctor may advise you not to use Haloperidol Injection while you are pregnant.

The following problems may occur in newborn babies of mothers that use Haloperidol Injection in the last 3 months of their pregnancy (the last trimester):

  • Muscle tremors, stiff or weak muscles
  • Being sleepy or agitated
  • Problems breathing or feeding.

The exact frequency of these problems is unknown. If you used Haloperidol Injection while pregnant and your baby develops any of these side effects, contact your doctor.

Breast-feeding – talk to your doctor if you are breast-feeding or planning to breast-feed. This is because small amounts of the medicine may pass into the mother’s milk and on to the baby. Your doctor will discuss the risks and benefits of breast-feeding while you are using Haloperidol Injection.

Fertility – Haloperidol Injection may increase your levels of a hormone called ‘prolactin’, which may affect fertility in men and women. Talk to your doctor if you have any questions about this.

Driving and using machines

Haloperidol Injection can affect your ability to drive and use tools or machines. Side effects, such as feeling sleepy, may affect your alertness, particularly when you first start using it or after a high dose. Do not drive or use any tools or machines without discussing this with your doctor first.

Haloperidol Injection contains sodium

This medicine contains less than 1 mmol sodium (23mg) per dose, i.e. is essentially sodium free.

  1. HOW TO USE HALOPERIDOL INJECTION

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

How much medicine will be given to you

Your doctor will decide how much Haloperidol Injection you need and for how long. It may be some time before you feel the full effect of the medicine. Your doctor will normally give you a low dose to start, and then adjust the dose to suit you. Your dose of haloperidol will depend on:

  • Your age
  • What condition you are being treated for
  • Whether you have problems with your kidneys or liver
  • Other medicines you are taking.

Adults:

  • Your starting dose will normally be between 1 and 5 mg.
  • You may be given extra doses, normally 1 to 4 hours apart.
  • You will not be given more than a total of 20 mg each day.

Elderly people

  • Elderly people will normally start on half the lowest adult dose.
  • The dose will then be adjusted until the doctor finds the dose that suits you best.
  • You will not be given more than a total of 5 mg each day unless your doctor decides a higher dose is needed.

How Haloperidol Injection is given

Haloperidol Injection will be given by a doctor or nurse. It is for intramuscular use, and is given as an injection into a muscle.

If you stop using Haloperidol Injection

Unless your doctor decides otherwise, Haloperidol Injection will be stopped gradually. Stopping treatment suddenly may cause effects such as:

  • Nausea and vomiting
  • Difficulty sleeping.

Always follow your doctor’s instructions carefully.

If you miss a dose or have too much Haloperidol Injection

A doctor or nurse will give this medicine to you, so it is unlikely that you will miss a dose or be given too much. If you are worried, tell the doctor or nurse.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Look out for serious side effects

Tell your doctor or nurse straight away if you notice or suspect any of the following. You may need urgent medical treatment.

Problems with the heart:

  • Abnormal heart rhythm – this stops the heart working normally and may cause loss of consciousness
  • Abnormally fast heart beat
  • Extra heart beats.

Heart problems are uncommon in people using Haloperidol Injection (may affect up to 1 in 100 people). Sudden deaths have occurred in patients using this medicine, but the exact frequency of these deaths is unknown. Cardiac arrest (the heart stops beating) has also occurred in people taking antipsychotic medicines.

A serious problem called ‘neuroleptic malignant syndrome’.

This causes a high fever, severe muscle stiffness, confusion and loss of consciousness. It is rare in people using Haloperidol Injection (may affect up to 1 in 1,000 people).

Problems controlling movements of the body or limbs (extrapyramidal disorder), such as:

  • Movements of the mouth, tongue, jaw and sometimes limbs (tardive dyskinesia)
  • Feeling restless or difficulty sitting still, increased body movements
  • Slow or reduced body movements, jerking or twisting movements
  • Muscle tremors or stiffness, a shuffling walk
  • Being unable to move
  • Lack of normal facial expression that sometimes looks like a mask.

These are very common in people using Haloperidol Injection (may affect more than 1 in 10 people). If you get any of these effects, you may be given an additional medicine.

Severe allergic reaction that may include:

  • A swollen face, lips, mouth, tongue or throat
  • Difficulty swallowing or breathing
  • Itchy rash (hives)

An allergic reaction is uncommon in people using Haloperidol (may affect up to 1 in 100 people).

Blood clots in the veins, usually in the legs (deep vein thrombosis or DVT). These have been reported in people taking antipsychotic medicines. The signs of a DVT in the leg include swelling, pain and redness in the leg, but the clot may move to the lungs causing chest pain and difficulty in breathing. Blood clots can be very serious, so tell your doctor straight away if you notice any of these problems.

Tell your doctor straight away if you notice any of the serious side effects above:

Other side effects

Tell your doctor if you notice or suspect any of the following side effects.

Very common (may affect more than 1 in 10 people):

  • Feeling agitated
  • Difficulty sleeping

Common (may affect up to 1 in 10 people):

  • Serious mental health problem, such as believing things that are not true (delusions) or seeing, feeling, hearing or smelling things that are not there (hallucinations)
  • Depression
  • Abnormal muscle tension
  • Feeling dizzy, including upon sitting up or standing up
  • Feeling sleepy
  • Upward movement of the eyes or fast eye movements that you cannot control
  • Problems with vision, such as blurred vision
  • Low blood pressure
  • Nausea, vomiting
  • Constipation
  • Dry mouth or increased saliva
  • Skin rash
  • Being unable to pass urine or empty the bladder completely
  • Difficulty getting and keeping an erection (impotence)
  • Weight gain or loss
  • Changes that show up in blood tests of the liver.

Uncommon (may affect up to 1 in 100 people)

  • Effects on blood cells – low number of all types of blood cells, including severe decrease in white blood cells and low number of ‘platelets’ (cells that help blood to clot)
  • Feeling confused
  • Loss of sex drive or decreased sex drive
  • Fits (seizures)
  • Stiff muscles and joints
  • Muscle spasms, twitching or contractions that you cannot control, including a spasm in the neck causing the head to twist to one side
  • Problems walking
  • Being short of breath
  • Inflamed liver, or liver problem that causes yellowing of the skin or eyes (jaundice)
  • Increased sensitivity of the skin to sunlight
  • Itching
  • Excessive sweating
  • Changes in menstrual cycle (periods), such as no periods, or long, heavy, painful periods
  • Unexpected production of breast milk
  • Breast pain or discomfort
  • High body temperature
  • Swelling caused by fluid build up in the body.

Rare (may affect up to 1 in 1,000 people):

  • High level of the hormone ‘prolactin’ in the blood
  • Narrowed airways in the lungs, causing difficulty breathing
  • Difficulty or being unable to open the mouth
  • Problems having sex.

The following side effects have also been reported, but their exact frequency is unknown:

  • High level of ‘antidiuretic hormone’ in the blood (syndrome of inappropriate antidiuretic hormone secretion)
  • Low level of sugar in the blood
  • Swelling around the voice box or brief spasm of the vocal cords, which may cause difficulty speaking or breathing
  • Sudden liver failure
  • Decreased bile flow in the bile duct
  • Flaking or peeling skin
  • Inflamed small blood vessels, leading to a skin rash with small red or purple bumps
  • Breakdown of muscle tissue (rhabdomyolysis)
  • Persistent and painful erection of the penis
  • Enlarged breasts in men
  • Low body temperature.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

  1. HOW TO STORE HALOPERIDOL INJECTION

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the ampoule and carton. The expiry date refers to the last day of that month.

Do not store above 25°C. Store in the original package in order to protect from light.

Do not use this medicine if the solution is cloudy, discoloured or if there are any particles present, it should be returned unused to the pharmacist.

If only part used, discard the remaining solution.

This product should be used immediately after opening.

For single use only.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What Haloperidol Injection contains

a) Each ml of solution contains:
Haloperidol USP……………………5mg/ml

b) Each ml of solution contains:
Haloperidol USP……………………5mg/ml

The other ingredients are lactic acid and sodium hydroxide in water for injections.

What Haloperidol Injection looks like and contents of the pack

Haloperidol Injection is a clear, colourless sterile solution in 1ml and 2ml clear glass ampoules. Each carton contains 10 ampoules. Not all pack sizes may be marketed.

  1. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com