Haloperidol 5 mg/mL Injection, 25 vials — NDC 0143-9501-25 (Billing 00143-9501-25)

WARNINGS 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, QTc interval-prolongation, and Torsades de Pointes have been reported in patients receiving haloperidol (see ADVERSE REACTIONS ).

Higher than recommended doses of any formulation and intravenous administration of haloperidol appear to be associated with a higher risk of QTc interval-prolongation and Torsades de Pointes. Also, a QTc interval that exceeds 500 msec is associated with an increased risk of Torsades de Pointes. Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QTc-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QTc, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome).

HALOPERIDOL INJECTION IS NOT APPROVED FOR INTRAVENOUS ADMINISTRATION. If haloperidol is administered intravenously, the ECG should be monitored for QTc prolongation and arrhythmias. Tachycardia and hypotension (including orthostatic hypotension) have also been reported in occasional patients (see ADVERSE REACTIONS ).

Cerebrovascular Adverse Reactions In controlled trials, elderly patients with dementia-related psychosis treated with some antipsychotics had an increased risk (compared to placebo) of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities. The mechanism for this increased risk is not known. An increased risk cannot be excluded for haloperidol, other antipsychotics, or other patient populations.

Haloperidol should be used with caution in patients with risk factors for cerebrovascular adverse reactions. 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.

Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. Both the risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is discontinued. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long‑term course of the syndrome is unknown.

Given these considerations, antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to antipsychotic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought.

The need for continued treatment should be reassessed periodically. If signs and symptoms of… [Excerpted — this section continues on DailyMed.]

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, Hypersensitivity Reactions WARNINGS, Falls WARNINGS, Usage in Pregnancy WARNINGS, Combined Use of Haloperidol and Lithium WARNINGS, General PRECAUTIONS, Leukopenia, Neutropenia, and Agranulocytosis PRECAUTIONS, Withdrawal Emergent Dyskinesia 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. Table 1. Adverse Reactions Occurring in ≥1% of Haloperidol-Treated Patients in Double-Blind, Parallel Placebo-Controlled Clinical Trials (Oral Haloperidol) System/Organ Class Adverse Reaction Haloperidol (n=284) % Placebo (n=282) % Gastrointestinal Disorders Constipation 4.2

1.8Dry mouth 1.8

0.4Salivary hypersecretion 1.2

0.7Nervous System Disorders Extrapyramidal disorder a 50.7 16 Hyperkinesia 10.2

2.5Tremor 8.1

3.6Hypertonia 7.4

0.7Dystonia 6.7

0.4Bradykinesia 4.2

0.4Somnolence 5.3 1.1 a Represents the total reporting rate for extrapyramidal disorder (reported term) and individual symptoms of extrapyramidal disorder, including events that did not meet the threshold of ≥1% for inclusion in this table. 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 Adverse Reactions Identified in Clinical Trials with Haloperidol Decanoate The adverse reactions listed below were identified in clinic… [Excerpted — this section continues on DailyMed.]

PRECAUTIONS Leukopenia, Neutropenia, and Agranulocytosis Class Effect: In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including haloperidol. Agranulocytosis has also been reported. Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia.

Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of Haloperidol Injection should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur.

Patients with severe neutropenia (absolute neutrophil count <1000/mm 3 ) should discontinue Haloperidol Injection and have their WBC followed until recovery. Withdrawal Emergent Dyskinesia Generally, patients receiving short-term therapy experience no problems with abrupt discontinuation of antipsychotic drugs. However, some patients on maintenance treatment experience transient dyskinetic signs after abrupt withdrawal.

In certain of these cases the dyskinetic movements are indistinguishable from tardive dyskinesia (see WARNINGS, Tardive Dyskinesia ) except for duration. It is not known whether gradual withdrawal of antipsychotic drugs will reduce the rate of occurrence of withdrawal emergent neurological signs but until further evidence becomes available, it seems reasonable to gradually withdraw use of haloperidol (see WARNINGS, Usage in Pregnancy ). Other Haloperidol should be administered cautiously to patients: •with severe cardiovascular disorders, because of the possibility of transient hypotension and/or precipitation of anginal pain.

Should hypotension occur and a vasopressor be required, epinephrine must not be used since haloperidol may block its vasopressor activity and paradoxical further lowering of the blood pressure may occur. Instead, metaraminol, phenylephrine or norepinephrine should be used. •receiving anticonvulsant medications, with a history of seizures, or with EEG abnormalities, because haloperidol may lower the convulsive threshold. If indicated, adequate anticonvulsant therapy should be concomitantly maintained. •with known allergies, or with a history of allergic reactions to drugs. •receiving anticoagulants, since an isolated instance of interference occurred with the effects of one anticoagulant (phenindione).

When haloperidol is used to control mania in cyclic disorders, there may be a rapid mood swing to depression. Severe neurotoxicity (rigidity, inability to walk or talk) may occur in patients with thyrotoxicosis who are also receiving antipsychotic medication, including haloperidol. 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 corticosteroi… [Excerpted — this section continues on DailyMed.]