FDA

Haloperidol

Approved 9 Mar 2001InjectionInjectable

The FDA lists this product in 31 strengths and forms.

Boxed warningThe FDA label of this medicine carries a boxed warning, the strongest warning the FDA gives. Read it under warnings and precautions.

Indications

Haloperidol injection is indicated for use in the treatment of schizophrenia. Haloperidol is indicated for the control of tics and vocal utterances of Tourette's Disorder.

Contraindications

Haloperidol injection is contraindicated in severe toxic central nervous system depression or comatose states from any cause and in individuals who are hypersensitive to this drug or have Parkinson’s disease.

Warnings and precautions

Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Haloperidol injection is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING ). Cardiovascular Effects Cases of sudden death, QT-prolongation, and Torsades de Pointes have been reported in patients receiving haloperidol injection.

Higher than recommended doses of any formulation and intravenous administration of haloperidol injection appear to be associated with a higher risk of QT-prolongation and Torsades de Pointes. Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QT-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QT, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome).

HALOPERIDOL INJECTION IS NOT APPROVED FOR INTRAVENOUS ADMINISTRATION. If haloperidol injection is administered intravenously, the ECG should be monitored for QT-prolongation and arrhythmias. Tardive Dyskinesia A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs (see ADVERSE REACTIONS) . Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome.

Warnings and precautions

Interactions

Drug Interactions Drug-drug interactions can be pharmacodynamic (combined pharmacologic effects) or pharmacokinetic (alteration of plasma levels). The risks of using haloperidol in combination with other drugs have been evaluated as described below. Pharmacodynamic Interactions Since QTc interval-prolongation has been observed during haloperidol treatment, caution is advised when prescribing to a patient with QT-prolongation conditions or to patients receiving medications known to prolong the QTc-interval (see WARNINGS, Cardiovascular Effects ).

Examples include (but are not limited to): Class 1A antiarrhythmics (e.g., procainamide, quinidine, disopyramide); Class 3 antiarrhythmics (e.g., amiodarone, sotalol); and other drugs such as citalopram, erythromycin, levofloxacin, methadone, and ziprasidone. Caution is advised when haloperidol is used in combination with drugs known to cause electrolyte imbalance (e.g., diuretics or corticosteroids) because hypokalemia, hypomagnesemia, and hypocalcemia are risk factors for QT prolongation.

Haloperidol may impair the antiparkinson effects of levodopa and other dopamine agonists. If concomitant antiparkinson medication is required, it may have to be continued after haloperidol is discontinued because of the difference in excretion rates. If both are discontinued simultaneously, extrapyramidal symptoms may occur. The physician should keep in mind the possible increase in intraocular pressure when anticholinergic drugs, including antiparkinson agents, are administered concomitantly with haloperidol.

As with other antipsychotic agents, it should be noted that haloperidol may be capable of potentiating CNS depressants such as anesthetics, opioids, and alcohol. Pharmacokinetic Interactions Drugs that May Increase Haloperidol Plasma Concentrations Haloperidol is metabolized by several routes. 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 drug or a decrease in CYP2D6 enzyme may result in increased haloperidol concentrations. The effect of CYP3A4 inhibition and of decreased CYP2D6 enzyme activity may be additive. The haloperidol plasma concentrations increased when a CYP3A4 and/or CYP2D6 inhibitor was coadministered with haloperidol. Examples include: CYP3A4 inhibitors – alprazolam; itraconazole, ketoconazole, nefazodone, ritonavir.

CYP2D6 inhibitors – chlorpromazine; promethazine; quinidine; paroxetine, sertraline, venlafaxine. Combined CYP3A4 and CYP2D6 inhibitors – fluoxetine, fluvoxamine; ritonavir. Buspirone. Increased haloperidol plasma concentrations may result in an increased risk of adverse events, including QTc interval prolongation (see WARNINGS – Cardiovascular Effects ). 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 is recommended that patients who take haloperidol concomitantly with such medicinal products be monitored for signs or symptoms of increased or prolonged pharmacologic effects of haloperidol, and the haloperidol injection dose be decreased as deemed necessary. Valproate: Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations. Drugs that May Decrease Haloperidol Plasma Concentrations Coadministration of haloperidol with potent enzyme inducers of CYP3A4 may gradually decrease the plasma concentrations of haloperidol to such an extent that efficacy may be reduced.

Examples include (but are not limited to): carbamazepine, phenobarbital, phenytoin, rifampin, St John's Wort ( Hypericum, perforatum ). Rifampin: In a study of 12 patients with schizophrenia coadministered oral haloperidol and rifampin, plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. In 5 other patients with schizophrenia treated with oral haloperidol and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations.

Carbamazepine: In a study in 11 patients with schizophrenia coadministered haloperidol and increasing doses of carbamazepine, haloperidol plasma concentrations decreased linearly with increasing carbamazepine concentrations. During combination treatment with inducers of CYP3A4, it is recommended that patients be monitored and the haloperidol injection dose increased as deemed necessary. After withdrawal of the CYP3A4 inducer, the concentration of haloperidol may gradually increase and therefore it may be necessary to reduce the dose of haloperidol injection.

Effect of Haloperidol on Other Drugs Haloperidol is an inhibitor of CYP2D6. Plasma concentrations of CYP2D6 substrates (e.g., tricyclic antidepressants such as desipramine or imipramine) may increase when they are co-administered with haloperidol.

Adverse reactions

The following adverse reactions are discussed in more detail in other sections of the labeling: WARNINGS, Increased mortality in Elderly Patients with Dementia-Related Psychosis WARNINGS, Cardiovascular Effects WARNINGS, Tardive Dyskinesia WARNINGS, Neuroleptic Malignant Syndrome WARNINGS, Treatment Withdrawal WARNINGS, Falls WARNINGS, Usage in Pregnancy WARNINGS, Combined Use of Haloperidol injection and Lithium WARNINGS, General PRECAUTIONS, Leukopenia, Neutropenia, and Agranulocytosis PRECAUTIONS, Other Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.

The data described below reflect exposure to haloperidol in the following: 284 patients who participated in 3 double-blind, placebo-controlled clinical trials with haloperidol (oral formulation, 2 to 20 mg/day); two trials were in the treatment of schizophrenia and one in the treatment of bipolar disorder. 1295 patients who participated in 16 double-blind, active comparator-controlled clinical trials with haloperidol (injection or oral formulation, 1 to 45 mg/day) in the treatment of schizophrenia.

Based on the pooled safety data, the most common adverse reactions in haloperidol-treated patients from these double-blind placebo-controlled clinical trials (≥5%) were: extrapyramidal disorder, hyperkinesia, tremor, hypertonia, dystonia, and somnolence. Adverse Reactions Reported at ≥1% Incidence in Double-Blind Placebo-Controlled Clinical Trials with Oral Haloperidol Adverse reactions occurring in ≥1% of haloperidol-treated patients and at higher rate than placebo in 3 double-blind, parallel, placebo-controlled, clinical trials with the oral formulation are shown in Table 1.

Additional Adverse Reactions Reported in Double-Blind, Placebo- or Active Comparator-Controlled Clinical Trials with Injectable or Oral Haloperidol Additional adverse reactions that are listed below were reported by haloperidol-treated patients in double-blind, active comparator-controlled clinical trials with the injectable or oral formulation, or at <1% incidence in double-blind, parallel, placebo-controlled, clinical trials with the oral formulation.

Cardiac Disorders: Tachycardia Endocrine Disorders: Hyperprolactinemia Eye Disorders: Vision blurred Investigations: Weight Increased Musculoskeletal and Connective Tissue Disorders: Torticollis, Trismus, Muscle rigidity, Muscle twitching Nervous System Disorders: Akathisia, Dizziness, Dyskinesia, Hypokinesia, Neuroleptic malignant syndrome, Nystagmus, Oculogyric crisis, Parkinsonism, Sedation, Tardive dyskinesia Psychiatric Disorders: Loss of libido, Restlessness Reproductive System and Breast Disorders: Amenorrhea, Galactorrhea, Dysmenorrhea, Erectile dysfunction, Menorrhagia, Breast discomfort Skin and Subcutaneous Tissue Disorders: Acneiform skin reactions Vascular Disorders: Hypotension, Orthostatic hypotension Postmarketing Experience The following adverse reactions relating to the active moiety haloperidol have been identified during postapproval use of haloperidol or haloperidol decanoate.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: Pancytopenia, Agranulocytosis, Thrombocytopenia, Leukopenia, Neutropenia Cardiac Disorders: Ventricular fibrillation, Torsade de pointes, Ventricular tachycardia, Extrasystoles Endocrine Disorders: Inappropriate antidiuretic hormone secretion Gastrointestinal Disorders: Vomiting, Nausea General Disorders and Administration Site Conditions: Sudden death, Face edema, Edema, Hyperthermia, Hypothermia Hepatobiliary Disorders: Acute hepatic failure, Hepatitis, Cholestasis, Jaundice, Liver function test abnormal Immune System Disorders: Anaphylactic reaction, Hypersensitivity Investigations: Electrocardiogram QT prolonged, Weight decreased Metabolic and Nutritional Disorders: Hypoglycemia Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis Nervous System Disorders: Convulsion, Headache, Opisthotonus, Tardive dystonia Pregnancy, Puerperium and Perinatal Conditions: Drug withdrawal syndrome neonatal Psychiatric Disorders: Agitation, Confusional state, Depression, Insomnia Renal and Urinary Disorders: Urinary retention Reproductive System and Breast Disorders: Priapism, Gynecomastia Respiratory, Thoracic and Mediastinal Disorders: Laryngeal edema, Bronchospasm, Laryngospasm, Dyspnea Skin and Subcutaneous Tissue Disorders: Dermatitis exfoliative, Hypersensitivity vasculitis, Photosensitivity reaction, Urticaria, Pruritis, Rash, Hyperhidrosis ADVERSE REACTIONS

Haloperidol

Indications

Contraindications

Warnings and precautions

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Haloperidol

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information

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