Haloperidol

INDICATIONS AND USAGE Haloperidol is indicated for the treatment of patients with schizophrenia.

DOSAGE AND ADMINISTRATION There is considerable variation from patient to patient in the amount of medication required for treatment. As with all drugs used to treat schizophrenia, dosage should be individualized according to the needs and response of each patient. Dosage adjustments, either upward or downward, should be carried out as rapidly as practicable to achieve optimum therapeutic control. To determine the initial dosage, consideration should be given to the patient's age, severity of illness, previous response to other antipsychotic drugs, and any concomitant medication or disease state. Debilitated or geriatric patients, as well as those with a history of adverse reactions to antipsychotic drugs, may require less haloperidol. The optimal response in such patients is usually obtained with more gradual dosage adjustments and at lower dosage levels. Parenteral medication, administered intramuscularly in doses of 2 to 5 mg, is utilized for prompt control of the acutely agitated schizophrenic patient with moderately severe to very severe symptoms. Depending on the response of the patient, subsequent doses may be given, administered as often as every hour, although 4 to 8 hour intervals may be satisfactory. The maximum dose is 20 mg/day. Controlled trials to establish the safety and effectiveness of intramuscular administration in children have not been conducted. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Switchover Procedure An oral form should supplant the injectable as soon as practicable. In the absence of bioavailability studies establishing bioequivalence between these two dosage forms the following guidelines for dosage are suggested. For an initial approximation of the total daily dose required, the parenteral dose administered in the preceding 24 hours may be used. Since this dose is only an initial estimate, it is recommended that careful monitoring of clinical signs and symptoms, including clinical efficacy, sedation, and adverse effects, be carried out periodically for the first several days following the initiation of switchover. In this way, dosage adjustments, either upward or downward, can be quickly accomplished. Depending on the patient's clinical status, the first oral dose should be given within 12 to 24 hours following the last parenteral dose.

CONTRAINDICATIONS Haloperidol Injection is contraindicated in patients with: Severe toxic central nervous system depression or comatose states from any cause. Hypersensitivity to this drug – hypersensitivity reactions have included anaphylactic reaction and angioedema (see WARNINGS, Hypersensitivity Reactions and ADVERSE REACTIONS ). Parkinson’s disease (see WARNINGS, Neurological Adverse Reactions in Patients with Parkinson’s Disease or Dementia with Lewy Bodies ). Dementia with Lewy bodies (see WARNINGS, Neurological Adverse Reactions in Patients with Parkinson’s Disease or Dementia with Lewy Bodies ).

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 1.8 Dry mouth 1.8 0.4 Salivary hypersecretion 1.2 0.7 Nervous System Disorders Extrapyramidal disorder a 50.7 16 Hyperkinesia 10.2 2.5 Tremor 8.1 3.6 Hypertonia 7.4 0.7 Dystonia 6.7 0.4 Bradykinesia 4.2 0.4 Somnolence 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 …

DESCRIPTION Haloperidol is the first of the butyrophenone series of major antipsychotics. The chemical designation is 4-[4-( p -Chlorophenyl)-4-hydroxypiperidino]-4'-fluorobutyrophenone and it has the following structural formula: M.F. =C 21 H 23 ClFNO 2 M.W.=375.86 Haloperidol Injection, USP is available as a sterile parenteral form for intramuscular injection. Each mL of Haloperidol Injection, USP contains 5 mg haloperidol (as the lactate) with 1.8 mg methylparaben 0.2 mg propylparaben and lactic acid for pH adjustment between 3.0 to 3.8. Haloperidol Lactate Structural Formula

OVERDOSAGE Manifestations In general, the symptoms of overdosage would be an exaggeration of known pharmacologic effects and adverse reactions, the most prominent of which would be: 1) severe extrapyramidal reactions, 2) hypotension, or 3) sedation. The patient would appear comatose with respiratory depression and hypotension which could be severe enough to produce a shock-like state. The extrapyramidal reactions would be manifested by muscular weakness or rigidity and a generalized or localized tremor as demonstrated by the akinetic or agitans types respectively. With accidental overdosage, hypertension rather than hypotension occurred in a two-year old child. The risk of ECG changes associated with torsade de pointes should be considered. (For further information regarding torsade de pointes, please refer to ADVERSE REACTIONS .) Treatment Since there is no specific antidote, treatment is primarily supportive. Dialysis is not recommended in the treatment of overdose because it removes only very small amounts of haloperidol. A patent airway must be established by use of an oropharyngeal airway or endotracheal tube or, in prolonged cases of coma, by tracheostomy. Respiratory depression may be counteracted by artificial respiration and mechanical respirators. Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma, or concentrated albumin, and vasopressor agents such as metaraminol, phenylephrine and norepinephrine. Epinephrine must not be used. In case of severe extrapyramidal reactions, antiparkinson medication should be administered. ECG and vital signs should be monitored especially for signs of QTc‐interval prolongation or dysrhythmias and monitoring should continue until the ECG is normal. Severe arrhythmias should be treated with appropriate anti‐arrhythmic measures. In case of an overdose, consult a Certified Poison Control Center (1-800-222-1222).

HOW SUPPLIED Haloperidol Injection, USP, equivalent to 5 mg/mL haloperidol (as the lactate), is supplied as follows: NDC 0143-9319-25 - 1 mL Single-dose vial in carton of 25. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light . Do not freeze . To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. `For Product Inquiry call 1-877-845-0689. PREMIER ProRx® Manufactured by: HIKMA FARMACÊUTICA (PORTUGAL), S.A. Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL Distributed by Hikma Pharmaceuticals USA Inc. Eatontown, NJ 07724 PREMIERProRx® is a registered trademark of Premier Healthcare Alliance, L.P., used under license. Revised September 2021 PIN493-PRE/3