ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling:oSudden Death, Torsades de Pointes, and QTc Interval Prolongation [see Warnings and Precautions (5.2)]oTachycardia and Hypotension [see Warnings and Precautions (5.3)]oTardive Dyskinesia [see Warnings and Precautions (5.5)]oNeuroleptic Malignant Syndrome [see Warnings and Precautions (5.6)]oSeizures [see Warnings and Precautions (5.8)]oHypersensitivity Reactions [see Warnings and Precautions (5.9)]oLeukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.13)]oHyperprolactinemia [see Warnings and Precautions (5.14)]oRisk of Severe Neurotoxicity in Patients with Thyrotoxicosis [see Warnings and Precautions (5.15)]. oSudden Death, Torsades de Pointes, and QTc Interval Prolongation [see Warnings and Precautions (5.2)]. oTachycardia and Hypotension [see Warnings and Precautions (5.3)]. oTardive Dyskinesia [see Warnings and Precautions (5.5)]. oNeuroleptic Malignant Syndrome [see Warnings and Precautions (5.6)]. oSeizures [see Warnings and Precautions (5.8)]. oHypersensitivity Reactions [see Warnings and Precautions (5.9)]. oLeukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.13)]. oHyperprolactinemia [see Warnings and Precautions (5.14)]. oRisk of Severe Neurotoxicity in Patients with Thyrotoxicosis [see Warnings and Precautions (5.15)]. The most common adverse reactions (incidence >= 5%) were oculogyric crisis and parkinsonism (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.. Adverse Reactions Identified in Clinical Trials with Haloperidol Decanoate Injection. The data described below reflect exposure to 15 mg to 500 mg (1.7 times the maximum recommended dosage) of haloperidol decanoate injection monthly in 13 clinical trials of410 adult patients with schizophrenia or an unapproved condition. These clinical trials comprised of:o1 double-blind, active comparator-controlled trial with fluphenazine decanoate (Trial 1).o2 trials comparing haloperidol decanoate injection to oral haloperidol (Trials and 3).o9 open-label trials.o1 dose-response trial.The most common adverse reactions that occurred in >= 5% of haloperidol decanoate injection-treated patients in Trial were Parkinsonism and oculogyric crisis.Adverse reactions that occurred in >= 1% of haloperidol decanoate injection-treated patients in Trial are shown in Table 2. Trial was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the haloperidol decanoate injection and fluphenazine decanoate treatment groups.Table 2: Adverse Reactions that Occurred in >= 1% of Haloperidol Decanoate Injection-treated Patients and Fluphenazine Decanoate-treated Patients in Trial 1The study was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the haloperidol decanoate injection and the fluphenazine decanoate treatment groups. Haloperidol Decanoate Injection (n 36)Fluphenazine Decanoate(n 36)Extrapyramidal disorder: Parkinsonism31%44% Oculogyric crisis6%0% Akinesia3%22% Akathisia3%14% Tremor3%0%Abdominal pain3%0%Headache3%0%Less common adverse reactions (< 1%) that occurred in Trial and other adverse reactions that occurred in Trials and 3, and open-label and dose-response clinical trials of haloperidol decanoate injection are listed below.oCardiac Disorders: TachycardiaoEndocrine Disorders: HyperprolactinemiaoEye Disorders: Vision blurredoGastrointestinal Disorders: Constipation, Dry mouth, Salivary hypersecretionoGeneral Disorders and Administration Site Conditions: Weight increased, Injection site reactionoMusculoskeletal and Connective Tissue Disorders: Muscle rigidityoNervous System Disorders: Dyskinesia, Dystonia, Cogwheel rigidity, Hypertonia, Masked facies, Sedation, SomnolenceoReproductive System Disorders: Erectile dysfunction. o1 double-blind, active comparator-controlled trial with fluphenazine decanoate (Trial 1).. o2 trials comparing haloperidol decanoate injection to oral haloperidol (Trials and 3).. o9 open-label trials.. o1 dose-response trial.. oCardiac Disorders: Tachycardia. oEndocrine Disorders: Hyperprolactinemia. oEye Disorders: Vision blurred. oGastrointestinal Disorders: Constipation, Dry mouth, Salivary hypersecretion. oGeneral Disorders and Administration Site Conditions: Weight increased, Injection site reaction. oMusculoskeletal and Connective Tissue Disorders: Muscle rigidity. oNervous System Disorders: Dyskinesia, Dystonia, Cogwheel rigidity, Hypertonia, Masked facies, Sedation, Somnolence. oReproductive System Disorders: Erectile dysfunction. Adverse Reactions Identified in Clinical Trials with Immediate-Release Haloperidol Products. Based on clinical trials with immediate-release haloperidol products that included 1,579 patients, the following adverse reactions were reported:oMusculoskeletal and Connective Tissue Disorders: Torticollis, Trismus, Muscle twitchingoNervous System Disorders: Neuroleptic malignant syndrome, Tardive dyskinesia, Bradykinesia, Hyperkinesia, Hypokinesia, Dizziness, NystagmusoPsychiatric Disorders: Loss of libido, RestlessnessoReproductive System and Breast Disorders: Amenorrhea, Galactorrhea, Dysmenorrhea, Menorrhagia, Breast discomfortoSkin and Subcutaneous Tissue Disorders: Acneiform skin reactionsoVascular Disorders: Hypotension, Orthostatic hypotension. oMusculoskeletal and Connective Tissue Disorders: Torticollis, Trismus, Muscle twitching. oNervous System Disorders: Neuroleptic malignant syndrome, Tardive dyskinesia, Bradykinesia, Hyperkinesia, Hypokinesia, Dizziness, Nystagmus. oPsychiatric Disorders: Loss of libido, Restlessness. oReproductive System and Breast Disorders: Amenorrhea, Galactorrhea, Dysmenorrhea, Menorrhagia, Breast discomfort. oSkin and Subcutaneous Tissue Disorders: Acneiform skin reactions. oVascular Disorders: Hypotension, Orthostatic hypotension. 6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of haloperidol, including haloperidol decanoate injection. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.oBlood and Lymphatic System Disorders: Pancytopenia, Agranulocytosis, Thrombocytopenia, Leukopenia, NeutropeniaoCardiac Disorders: Ventricular fibrillation, Torsade de pointes, Ventricular tachycardia, Extrasystoles, QTc interval prolongationoEndocrine Disorders: Inappropriate antidiuretic hormone secretionoGastrointestinal Disorders: Vomiting, NauseaoGeneral Disorders and Administration Site Conditions: Sudden death, Face edema, Edema, Hyperthermia, Hypothermia, Injection site abscess, Weight decreasedoHepatobiliary Disorders: Acute hepatic failure, Hepatitis, Cholestasis, Jaundice, Liver function test abnormaloImmune System Disorders: Anaphylactic reaction, HypersensitivityoMetabolic and Nutritional Disorders: HypoglycemiaoMusculoskeletal and Connective Tissue Disorders: RhabdomyolysisoNervous System Disorders: Convulsion, Opisthotonus, Tardive dystoniaoPregnancy, Puerperium and Perinatal Conditions: Neonatal drug withdrawal syndromeoPsychiatric Disorders: Agitation, Confusional state, Depression, InsomniaoRenal and Urinary Disorders: Urinary retentionoReproductive System and Breast Disorders: Priapism, GynecomastiaoRespiratory, Thoracic and Mediastinal Disorders: Laryngeal edema, Bronchospasm, Laryngospasm, DyspneaoSkin and Subcutaneous Tissue Disorders: Angioedema, Dermatitis exfoliative, Hypersensitivity vasculitis, Photosensitivity reaction, Urticaria, Pruritus, Rash, Hyperhidrosis. oBlood and Lymphatic System Disorders: Pancytopenia, Agranulocytosis, Thrombocytopenia, Leukopenia, Neutropenia. oCardiac Disorders: Ventricular fibrillation, Torsade de pointes, Ventricular tachycardia, Extrasystoles, QTc interval prolongation. oEndocrine Disorders: Inappropriate antidiuretic hormone secretion. oGastrointestinal Disorders: Vomiting, Nausea. oGeneral Disorders and Administration Site Conditions: Sudden death, Face edema, Edema, Hyperthermia, Hypothermia, Injection site abscess, Weight decreased. oHepatobiliary Disorders: Acute hepatic failure, Hepatitis, Cholestasis, Jaundice, Liver function test abnormal. oImmune System Disorders: Anaphylactic reaction, Hypersensitivity. oMetabolic and Nutritional Disorders: Hypoglycemia. oMusculoskeletal and Connective Tissue Disorders: Rhabdomyolysis. oNervous System Disorders: Convulsion, Opisthotonus, Tardive dystonia. oPregnancy, Puerperium and Perinatal Conditions: Neonatal drug withdrawal syndrome. oPsychiatric Disorders: Agitation, Confusional state, Depression, Insomnia. oRenal and Urinary Disorders: Urinary retention. oReproductive System and Breast Disorders: Priapism, Gynecomastia. oRespiratory, Thoracic and Mediastinal Disorders: Laryngeal edema, Bronchospasm, Laryngospasm, Dyspnea. oSkin and Subcutaneous Tissue Disorders: Angioedema, Dermatitis exfoliative, Hypersensitivity vasculitis, Photosensitivity reaction, Urticaria, Pruritus, Rash, Hyperhidrosis.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis. Carcinogenicity studies using oral haloperidol were conducted in Wistar rats (dosed at up to mg/kg daily for 24 months) and in Albino Swiss mice (dosed at up to mg/kg daily for 18 months).oIn the rat study, survival was reduced in all haloperidol dose groups, decreasing the number of rats at risk for developing tumors. However, relatively greater number of rats survived to the end of the study in the high dose haloperidol male and female groups. These haloperidol-treated rats at doses up to approximately 2.5 times the maximum recommended human oral dose (MRHD) of haloperidol of 20 mg/day based on mg/m2 body surface area did not have greater incidence of tumors than control-treated rats.oIn female mice, there was statistically significant increase in mammary gland neoplasia and total tumor incidence at haloperidol doses approximately 0.3 and 1.2 times the oral MRHD based on mg/m2 body surface area and there was statistically significant increase in pituitary gland neoplasia at approximately 1.2 times the oral MRHD. In male mice, no statistically significant differences in incidences of total tumors or specific tumor types were noted.Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, factor of potential importance if the prescription of these drugs is contemplated in patient with previously detected breast cancer. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs [see Warnings and Precautions (5.14)].. oIn the rat study, survival was reduced in all haloperidol dose groups, decreasing the number of rats at risk for developing tumors. However, relatively greater number of rats survived to the end of the study in the high dose haloperidol male and female groups. These haloperidol-treated rats at doses up to approximately 2.5 times the maximum recommended human oral dose (MRHD) of haloperidol of 20 mg/day based on mg/m2 body surface area did not have greater incidence of tumors than control-treated rats.. oIn female mice, there was statistically significant increase in mammary gland neoplasia and total tumor incidence at haloperidol doses approximately 0.3 and 1.2 times the oral MRHD based on mg/m2 body surface area and there was statistically significant increase in pituitary gland neoplasia at approximately 1.2 times the oral MRHD. In male mice, no statistically significant differences in incidences of total tumors or specific tumor types were noted.. Mutagenesis. No mutagenic potential of haloperidol decanoate was found in the Ames Salmonella assay. Negative or inconsistent positive findings have been obtained in in vitro and in vivo studies of effects of haloperidol on chromosome structure and number. The available cytogenetic evidence is considered too inconsistent to be conclusive.. Impairment of Fertility. Haloperidol was orally administered to male rats at doses of 0.5, 2.5, and 15 mg/kg/day (approximately 0.2 to times the oral MRHD based on mg/m2 body surface area) for 63 days prior to mating with untreated females. Decreases in mating performance and fertility, as well as markedly decreased motor activity, was observed at seven times the oral MRHD based on mg/m2 body surface area. The NOAEL of 2.5 mg/kg/day is approximately equal to the oral MRHD based on mg/m2 body surface area.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of haloperidol decanoate injection for the treatment of schizophrenia in adults is unclear. However, its effect in schizophrenia could be mediated through its activity as an antagonist at central dopamine type receptors. Haloperidol also binds to alpha-1 adrenergic receptors, but with lower affinity, and displays minimal binding to muscarinic cholinergic and histaminergic (H1) receptors.. 12.2 Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of haloperidol have not been fully characterized.. 12.3 Pharmacokinetics Absorption. The plasma concentrations of haloperidol gradually rise, reaching peak at about days after the haloperidol decanoate injection, and fall thereafter, with an apparent half-life of about weeks. Steady state plasma concentrations of haloperidol are achieved within to months in patients receiving monthly haloperidol decanoate injections.The relationship between the haloperidol decanoate injection dosage and plasma haloperidol concentration is roughly linear for dosages below 450 mg (1.5 times the maximum recommended dosage [see Dosage and Administration (2.1)]; however, the pharmacokinetics of haloperidol following intramuscular injections can be quite variable between patients.. Elimination. Metabolism 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 lesser extent, CYP2D6.. Excretion Less than 3% of administered haloperidol is eliminated unchanged in the urine. The apparent half-life of haloperidol following intramuscular injection of haloperidol decanoate injection is about weeks.. Specific Populations. Patients with Hepatic Impairment Studies in patients with hepatic impairment have not been conducted. Haloperidol is extensively metabolized in the liver, therefore, haloperidol concentrations may be higher in patients with hepatic impairment compared to patients with normal hepatic function [see Use in Specific Populations (8.6)].. Geriatric Patients Haloperidol plasma concentrations in geriatric patients were higher than in younger adult patients when administered the same dosage. Results from small clinical studies suggest lower clearance and longer elimination half-life of haloperidol in geriatric patients. The results are within the observed variability in haloperidol pharmacokinetics [see Use in Specific Populations (8.5)].. Patients with Renal Impairment Studies in patients with renal impairment have not been conducted.. Drug Interaction Studies. Ketoconazole and Paroxetine The haloperidol plasma concentrations increased when ketoconazole (400 mg/day, strong CYP3A4 inhibitor) and paroxetine (20 mg/day, strong CYP2D6 inhibitor) were concomitantly administered with haloperidol [see Drug Interactions (7.2)].. Valproate Sodium valproate, drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.. Rifampin In study with 12 patients with schizophrenia, concomitant administration of oral haloperidol and rifampin, strong CYP3A4 inducer, resulted in decreased plasma haloperidol concentrations by mean of 70% and increased mean scores on the Brief Psychiatric Rating Scale from baseline. In five other patients with schizophrenia treated with oral haloperidol and rifampin, discontinuation of rifampin resulted in mean 3.3-fold increase in haloperidol concentrations [see Drug Interactions (7.2)].. Carbamazepine In study with 11 patients with schizophrenia, concomitant administration of haloperidol and increasing doses of carbamazepine, CYP3A4 strong inducer, resulted in decreased haloperidol plasma concentrations in linear manner with increasing carbamazepine concentrations [see Drug Interactions (7.2)].. Effect of Haloperidol on Other Drugs Haloperidol is an inhibitor of CYP2D6. Plasma concentrations of CYP2D6 substrates may increase when they are concomitantly administered with haloperidol [see Drug Interactions (7.2)].

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION oAdminister haloperidol decanoate injection by deep intramuscular injection every weeks by healthcare provider. Do not administer intravenously (2.1).oFor the recommended dosage, including the first recommended dose and the maintenance dosage, see the Dosage and Administration section (2.1).oIf schizophrenia symptoms worsen during dosage modification of haloperidol decanoate injection, consider administering an immediate-release oral haloperidol product in addition to haloperidol decanoate injection therapy (2.2).. oAdminister haloperidol decanoate injection by deep intramuscular injection every weeks by healthcare provider. Do not administer intravenously (2.1).. oFor the recommended dosage, including the first recommended dose and the maintenance dosage, see the Dosage and Administration section (2.1).. oIf schizophrenia symptoms worsen during dosage modification of haloperidol decanoate injection, consider administering an immediate-release oral haloperidol product in addition to haloperidol decanoate injection therapy (2.2).. 2.1Recommended Dosage and Administration Administer haloperidol decanoate injection by deep intramuscular injection every weeks by health care professional. Do not administer haloperidol decanoate injection intravenously. When injecting haloperidol decanoate injection, use 21-gauge needle. The maximum volume per injection site is mL. Table below describes the recommended dosage for haloperidol decanoate injection. The maximum recommended initial dose is 100 mg. If the calculated first recommended dose of haloperidol decanoate injection is greater than 100 mg, then administer two deep intramuscular injections as follows:o100 mg on the first dayoRemainder of the amount to days later.Table 1: Haloperidol Decanoate Injection Recommended DosagePopulationFirst Recommended DoseMaintenance DosageClinical experience with haloperidol decanoate injection at dosage greater than 450 mg every weeks has been limited.Adult patients less than 65 years old stabilized on <= 10 mg of daily immediate-release oral haloperidol with normal hepatic function.10-15 times previous daily dose of immediate-release oral haloperidol.10-15 times previous daily dose of immediate-release oral haloperidol administered every weeks.Adult patients less than 65 years old stabilized on <= 10 mg of daily immediate-release oral haloperidol with hepatic impairment OR Adult patients 65 years and older10-15 times previous daily dose of immediate-release oral haloperidol. Consider starting at the low end of the dosing range [see Use in Specific Populations (8.5, 8.6) and Clinical Pharmacology (12.3)].The dosage may be increased by increments of 50 mg or less every weeks until an optimal therapeutic effect is obtained. The typical effective dosage range is between 50 and 200 mg every weeks.Adult patients less than 65 years old stabilized on 10 mg of daily immediate-release oral haloperidol10-20 times previous daily dose of immediate-release oral haloperidol10-15 times previous daily dose of immediate-release oral haloperidol administered every weeks. The dosage may be increased by increments of 50 mg or less every weeks until an optimal therapeutic effect is obtained.. o100 mg on the first day. oRemainder of the amount to days later.. 2.2Recommended Supplemental Immediate-Release Oral Haloperidol Therapy If schizophrenia symptoms worsen during dosage modification of haloperidol decanoate injection, consider administering an immediate-release oral haloperidol product in addition to haloperidol decanoate injection therapy.. 2.3Preparation Instructions Visually inspect haloperidol decanoate injection for particulate matter and discoloration prior to administration. Do not use if the solution has debris or is not clear or not colorless to pink or amber in color.Discard unused portion.

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS oDrugs that Prolong QTc Interval: Avoid concomitant use with haloperidol decanoate injection (7.1).oSee full prescribing information for additional clinically significant drug interactions with haloperidol decanoate injection (7.2).. oDrugs that Prolong QTc Interval: Avoid concomitant use with haloperidol decanoate injection (7.1).. oSee full prescribing information for additional clinically significant drug interactions with haloperidol decanoate injection (7.2).. 7.1Drugs that Prolong the QTc Interval Avoid concomitant use of haloperidol decanoate injection with other drugs with known potential to prolong the QTc interval. If concomitant use cannot be avoided [see Warnings and Precautions (5.2)]:oObtain ECGs when initiating and during concomitant use as clinically indicated.oObtain serum electrolytes (including potassium, calcium, phosphorus, and magnesium) when initiating and during concomitant use as clinically indicated.QTc interval prolongation has been observed with haloperidol decanoate injection treatment. Concomitant use of haloperidol decanoate injection with other products that prolong the QTc interval may result in greater increase in the QTc interval, and adverse reactions associated with QTc interval prolongation, including torsade de pointes, other serious arrythmias, and sudden death [see Warnings and Precautions (5.2)].. oObtain ECGs when initiating and during concomitant use as clinically indicated.. oObtain serum electrolytes (including potassium, calcium, phosphorus, and magnesium) when initiating and during concomitant use as clinically indicated.. 7.2Other Clinically Significant Drug Interactions Table describes other clinically significant drug interactions of haloperidol decanoate injection.Table 3: Other Clinically Significant Drugs InteractionsSee www.fda.gov/CYPandTransporterInteractingDrugs for examples of CYP3A4 and/or CYP2D6 inhibitors, CYP3A4 inducers, and CYP2D6 substrates. CNS DepressantsClinicalImpact Haloperidol may potentiate CNS depressants.Prevention or ManagementAvoid concomitant use of haloperidol decanoate injection with CNS depressants such as anesthetics, opioids, and alcohol.CYP3A4 and/or CYP2D6 InhibitorsClinicalImpactCYP3A4 and/or CYP2D6 inhibitors increase haloperidol exposure (haloperidol is CYP3A4 and CYP2D6 substrate) [see Clinical Pharmacology (12.3)]. Concomitant use of haloperidol decanoate injection and CYP3A4 and/or CYP2D6 inhibitors may increase the risk of haloperidol-associated adverse reactions.Prevention or ManagementMonitor for signs or symptoms of increased or prolonged pharmacologic effects of haloperidol. Decrease the dosage of haloperidol decanoate injection as clinically necessary.CYP3A4 InducersClinicalImpactCYP3A4 inducers decrease haloperidol exposure (haloperidol is CYP3A4 substrate) [see Clinical Pharmacology (12.3)]. Concomitant use of haloperidol decanoate injection with CYP3A4 inducers may reduce the effectiveness of haloperidol decanoate injection.Prevention or ManagementMonitor patients and if necessary, increase the dosage of haloperidol decanoate injection.CYP2D6 SubstratesClinicalImpactHaloperidol is CYP2D6 inhibitor. Plasma concentrations of CYP2D6 substrates may increase when they are concomitantly administered with haloperidol decanoate injection.Prevention or ManagementMonitor plasma concentrations of the CYP2D6 substrate, if possible. Consider reducing the dosage of the CYP2D6 substrate, if necessary. Refer to the Prescribing Information of the CYP2D6 substrate.Dopaminergic DrugsClinicalImpactHaloperidol may antagonize the effects of levodopa, dopamine agonists, and other drugs intended to increase dopamine levels.Prevention or ManagementHaloperidol decanoate injection is contraindicated in patients with Parkinsons disease and dementia with Lewy bodies. For conditions other than Parkinsons disease and dementia with Lewy bodies, when possible, avoid concomitant use of haloperidol decanoate injection with dopaminergic drugs [see Warnings and Precautions (5.7)].Anticholinergic DrugsClinicalImpactThe healthcare provider should keep in mind the possible increase in intraocular pressure when anticholinergic drugs are administered concomitantly with haloperidol decanoate injection.Prevention or ManagementMonitor and manage patients as clinically appropriate.LithiumClinicalImpactConcomitant use of haloperidol decanoate injection with lithium may cause an encephalopathic syndrome followed by irreversible brain damage [see Warnings and Precautions (5.12)].Prevention or ManagementMonitor patients who concomitantly use haloperidol decanoate injection with lithium closely for early signs of neurological toxicity, and discontinue haloperidol decanoate injection or both haloperidol decanoate injection and lithium promptly if such signs appear.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION Sudden Death, Torsades de Pointes, and QTc Interval Prolongation Inform patients that there have been reports of sudden death, Torsades de Pointes, and QTc interval prolongation in haloperidol-treated patients. Advise patients or caregivers to seek immediate medical attention if they suspect or develop signs or symptoms associated with the clinical consequences of QTc interval prolongation [see Warnings and Precautions (5.2)].Tardive Dyskinesia Inform patients that tardive dyskinesia (TD) may develop with haloperidol decanoate injection. Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their healthcare provider if these abnormal movements occur [see Warnings and Precautions (5.5)].Neuroleptic Malignant Syndrome Counsel patients about potentially fatal adverse reaction, Neuroleptic Malignant Syndrome (NMS), that has been reported with administration of antipsychotic drugs. Advise patients, family members, or caregivers to contact the health care provider or to report to the emergency room if they experience signs and symptoms of NMS [see Warnings and Precautions (5.6)].Hypersensitivity Reactions Inform patients of the potential risk of hypersensitivity reactions. Advise patients to stop taking haloperidol decanoate injection and seek immediate attention if signs or symptoms of hypersensitivity reaction occur [see Warnings and Precautions (5.9)].Falls Inform patients that haloperidol decanoate injection can cause somnolence, orthostatic hypotension, motor instability and sensory abnormality that may lead to falls. Advise patients to notify their healthcare provider if any of these symptoms occur [see Warnings and Precautions (5.10)].Potential for Cognitive and Motor Impairment Inform patients of the risk and advise them to not drive motor vehicle or operate hazardous machinery until they are reasonably certain that treatment with haloperidol decanoate injection does not impair their cognitive and motor functions [see Warnings and Precautions (5.11)].Leukopenia/Neutropenia Advise patients with pre-existing low WBC or history of drug induced leukopenia or neutropenia that they should have their CBC monitored while taking haloperidol decanoate injection [see Warnings and Precautions (5.13)].Hyperprolactinemia Counsel patients on signs and symptoms of hyperprolactinemia that may be associated with chronic use of haloperidol decanoate injection. Advise the patients to seek medical attention if they experience any of the following: amenorrhea, galactorrhea, erectile dysfunction or gynecomastia [see Warnings and Precautions (5.14)].Pregnancy Advise pregnant patients to notify their health care provider if they become pregnant or intend to become pregnant during treatment with haloperidol decanoate injection. Advise patients that haloperidol decanoate injection exposure during the third trimester of pregnancy may cause adverse effects in the neonate, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and decreased feeding [see Use in Specific Populations (8.1)].Lactation Advise breastfeeding patients using haloperidol decanoate injection to monitor infants for excess sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements) and to seek medical care if they notice these signs [see Use in Specific Populations (8.2)].Infertility Advise females and males of reproductive potential that haloperidol decanoate injection may impair fertility due to an increase in serum prolactin levels [see Use in Specific Populations (8.3)].Drug Interactions Advise patients to inform their health care provider before starting or discontinuing prescription drug, nonprescription drug, or supplement [see Warnings and Precautions (5.2) and Drug Interactions (7)].Distributed by: Mylan Institutional LLC, Viatris Company Morgantown, WV 26505 U.S.A. Manufactured by: Mylan Laboratories Limited Bangalore, IndiaRevised: 1/2026MI:HALDECIJ:R1.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis. Carcinogenicity studies using oral haloperidol were conducted in Wistar rats (dosed at up to mg/kg daily for 24 months) and in Albino Swiss mice (dosed at up to mg/kg daily for 18 months).oIn the rat study, survival was reduced in all haloperidol dose groups, decreasing the number of rats at risk for developing tumors. However, relatively greater number of rats survived to the end of the study in the high dose haloperidol male and female groups. These haloperidol-treated rats at doses up to approximately 2.5 times the maximum recommended human oral dose (MRHD) of haloperidol of 20 mg/day based on mg/m2 body surface area did not have greater incidence of tumors than control-treated rats.oIn female mice, there was statistically significant increase in mammary gland neoplasia and total tumor incidence at haloperidol doses approximately 0.3 and 1.2 times the oral MRHD based on mg/m2 body surface area and there was statistically significant increase in pituitary gland neoplasia at approximately 1.2 times the oral MRHD. In male mice, no statistically significant differences in incidences of total tumors or specific tumor types were noted.Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, factor of potential importance if the prescription of these drugs is contemplated in patient with previously detected breast cancer. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs [see Warnings and Precautions (5.14)].. oIn the rat study, survival was reduced in all haloperidol dose groups, decreasing the number of rats at risk for developing tumors. However, relatively greater number of rats survived to the end of the study in the high dose haloperidol male and female groups. These haloperidol-treated rats at doses up to approximately 2.5 times the maximum recommended human oral dose (MRHD) of haloperidol of 20 mg/day based on mg/m2 body surface area did not have greater incidence of tumors than control-treated rats.. oIn female mice, there was statistically significant increase in mammary gland neoplasia and total tumor incidence at haloperidol doses approximately 0.3 and 1.2 times the oral MRHD based on mg/m2 body surface area and there was statistically significant increase in pituitary gland neoplasia at approximately 1.2 times the oral MRHD. In male mice, no statistically significant differences in incidences of total tumors or specific tumor types were noted.. Mutagenesis. No mutagenic potential of haloperidol decanoate was found in the Ames Salmonella assay. Negative or inconsistent positive findings have been obtained in in vitro and in vivo studies of effects of haloperidol on chromosome structure and number. The available cytogenetic evidence is considered too inconsistent to be conclusive.. Impairment of Fertility. Haloperidol was orally administered to male rats at doses of 0.5, 2.5, and 15 mg/kg/day (approximately 0.2 to times the oral MRHD based on mg/m2 body surface area) for 63 days prior to mating with untreated females. Decreases in mating performance and fertility, as well as markedly decreased motor activity, was observed at seven times the oral MRHD based on mg/m2 body surface area. The NOAEL of 2.5 mg/kg/day is approximately equal to the oral MRHD based on mg/m2 body surface area.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics Absorption. The plasma concentrations of haloperidol gradually rise, reaching peak at about days after the haloperidol decanoate injection, and fall thereafter, with an apparent half-life of about weeks. Steady state plasma concentrations of haloperidol are achieved within to months in patients receiving monthly haloperidol decanoate injections.The relationship between the haloperidol decanoate injection dosage and plasma haloperidol concentration is roughly linear for dosages below 450 mg (1.5 times the maximum recommended dosage [see Dosage and Administration (2.1)]; however, the pharmacokinetics of haloperidol following intramuscular injections can be quite variable between patients.. Elimination. Metabolism 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 lesser extent, CYP2D6.. Excretion Less than 3% of administered haloperidol is eliminated unchanged in the urine. The apparent half-life of haloperidol following intramuscular injection of haloperidol decanoate injection is about weeks.. Specific Populations. Patients with Hepatic Impairment Studies in patients with hepatic impairment have not been conducted. Haloperidol is extensively metabolized in the liver, therefore, haloperidol concentrations may be higher in patients with hepatic impairment compared to patients with normal hepatic function [see Use in Specific Populations (8.6)].. Geriatric Patients Haloperidol plasma concentrations in geriatric patients were higher than in younger adult patients when administered the same dosage. Results from small clinical studies suggest lower clearance and longer elimination half-life of haloperidol in geriatric patients. The results are within the observed variability in haloperidol pharmacokinetics [see Use in Specific Populations (8.5)].. Patients with Renal Impairment Studies in patients with renal impairment have not been conducted.. Drug Interaction Studies. Ketoconazole and Paroxetine The haloperidol plasma concentrations increased when ketoconazole (400 mg/day, strong CYP3A4 inhibitor) and paroxetine (20 mg/day, strong CYP2D6 inhibitor) were concomitantly administered with haloperidol [see Drug Interactions (7.2)].. Valproate Sodium valproate, drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.. Rifampin In study with 12 patients with schizophrenia, concomitant administration of oral haloperidol and rifampin, strong CYP3A4 inducer, resulted in decreased plasma haloperidol concentrations by mean of 70% and increased mean scores on the Brief Psychiatric Rating Scale from baseline. In five other patients with schizophrenia treated with oral haloperidol and rifampin, discontinuation of rifampin resulted in mean 3.3-fold increase in haloperidol concentrations [see Drug Interactions (7.2)].. Carbamazepine In study with 11 patients with schizophrenia, concomitant administration of haloperidol and increasing doses of carbamazepine, CYP3A4 strong inducer, resulted in decreased haloperidol plasma concentrations in linear manner with increasing carbamazepine concentrations [see Drug Interactions (7.2)].. Effect of Haloperidol on Other Drugs Haloperidol is an inhibitor of CYP2D6. Plasma concentrations of CYP2D6 substrates may increase when they are concomitantly administered with haloperidol [see Drug Interactions (7.2)].

PREGNANCY SECTION.

8.1 Pregnancy Risk Summary. Available data from published epidemiologic studies of pregnant patients exposed to haloperidol have not established drug-associated risk of major birth defects or miscarriage. Case reports of limb malformations in neonates have been reported in haloperidol-treated mothers; however, causal relationships were not established in these cases. There are risks to the pregnant patient from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide (see Clinical Considerations). Haloperidol decanoate injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and decreased feeding) following delivery (see Clinical Considerations).The estimated background risk of major birth defects and miscarriage in patients with schizophrenia is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.. Clinical Considerations. Disease-associated Maternal and/or Embryo/Fetal Risk There is risk to the pregnant patient from untreated schizophrenia, including increased risk of schizophrenia relapse, hospitalization, and suicide. Schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is direct result of the illness or other comorbid factors.. Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and decreased feeding have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. Transient neonatal dyskinesia has also been reported. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal, withdrawal, and dyskinesia symptoms and manage symptoms appropriately.. Data. Animal Data Rats or rabbits administered oral haloperidol at doses of 0.5 to 7.5 mg/kg (approximately 0.2 to times the maximum recommended human oral dose (MRHD) of 20 mg/day based on mg/m2 body surface area) showed an increase in incidence of resorption, reduced fertility, delayed delivery, and pup mortality. No fetal abnormalities were observed at these doses in rats or rabbits. Cleft palate has been observed in mice administered oral haloperidol at dose of 0.5 mg/kg, which is approximately 0.1 times the oral MRHD based on mg/m2 body surface area.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS oPregnancy: Neonates exposed to haloperidol decanoate injection during the third trimester of pregnancy may develop extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and decreased feeding) (8.1).oLactation: Monitor breastfed infants for excessive sedation, irritability, poor feeding, abnormal muscle movements, and tremors (8.2).. oPregnancy: Neonates exposed to haloperidol decanoate injection during the third trimester of pregnancy may develop extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and decreased feeding) (8.1).. oLactation: Monitor breastfed infants for excessive sedation, irritability, poor feeding, abnormal muscle movements, and tremors (8.2).. 8.1 Pregnancy Risk Summary. Available data from published epidemiologic studies of pregnant patients exposed to haloperidol have not established drug-associated risk of major birth defects or miscarriage. Case reports of limb malformations in neonates have been reported in haloperidol-treated mothers; however, causal relationships were not established in these cases. There are risks to the pregnant patient from untreated schizophrenia, including increased risk of relapse, hospitalization, and suicide (see Clinical Considerations). Haloperidol decanoate injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and decreased feeding) following delivery (see Clinical Considerations).The estimated background risk of major birth defects and miscarriage in patients with schizophrenia is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.. Clinical Considerations. Disease-associated Maternal and/or Embryo/Fetal Risk There is risk to the pregnant patient from untreated schizophrenia, including increased risk of schizophrenia relapse, hospitalization, and suicide. Schizophrenia is associated with increased adverse perinatal outcomes, including preterm birth. It is not known if this is direct result of the illness or other comorbid factors.. Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and decreased feeding have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. Transient neonatal dyskinesia has also been reported. Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal, withdrawal, and dyskinesia symptoms and manage symptoms appropriately.. Data. Animal Data Rats or rabbits administered oral haloperidol at doses of 0.5 to 7.5 mg/kg (approximately 0.2 to times the maximum recommended human oral dose (MRHD) of 20 mg/day based on mg/m2 body surface area) showed an increase in incidence of resorption, reduced fertility, delayed delivery, and pup mortality. No fetal abnormalities were observed at these doses in rats or rabbits. Cleft palate has been observed in mice administered oral haloperidol at dose of 0.5 mg/kg, which is approximately 0.1 times the oral MRHD based on mg/m2 body surface area.. 8.2 Lactation Risk Summary. Literature reports suggest that haloperidol is detected in human milk of haloperidol-treated mothers with relative infant dose ranging from 2% to 12%. Haloperidol has also been detected in the plasma and urine of breastfed infants. There has been report of lethargy, poor feeding, and slowing of motor movements in an infant exposed to haloperidol through human milk. Haloperidol may increase prolactin levels in some patients which can lead to galactorrhea.Monitor infants exposed to haloperidol decanoate via human milk for excessive sedation, irritability, poor feeding, and extrapyramidal symptoms (tremors and abnormal muscle movements).The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for haloperidol decanoate injection and any potential adverse effects on the breastfed child from haloperidol decanoate injection or from the mothers underlying condition.. 8.3 Females and Males of Reproductive Potential Infertility. Females Based on the pharmacologic action of haloperidol (D2 receptor antagonism), treatment with haloperidol decanoate injection may result in an increase in serum prolactin levels, which may lead to reduction in fertility in females of reproductive potential.. Males Based on animal studies, male fertility may be impaired by treatment with haloperidol [see Nonclinical Toxicology (13.1)].. 8.4 Pediatric Use Safety and effectiveness of haloperidol decanoate injection have not been established in pediatric patients.. 8.5 Geriatric Use Clinical studies of haloperidol decanoate injection did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.The exposure of haloperidol may be higher in geriatric patients compared to young adult patients. Results from small clinical studies suggest lower clearance and longer elimination half-life of haloperidol in geriatric patients [see Clinical Pharmacology (12.3)]. Consider starting at the low end of the recommended dosing range for the first haloperidol decanoate injection dose in geriatric patients [see Dosage and Administration (2.1)].Antipsychotic drugs increase the risk of death in elderly patients with dementia-related psychosis. Haloperidol decanoate injection is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.1)].Elderly patients with dementia-related psychosis treated with antipsychotics had an increased risk of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) including fatalities, compared to those treated with placebo [see Warnings and Precautions (5.4)].Antipsychotic drugs increase the risk of tardive dyskinesia and this risk appears to be highest among the elderly, particularly elderly women [see Warnings and Precautions (5.5)].. 8.6Hepatic Impairment Haloperidol is extensively metabolized in the liver, therefore, haloperidol concentrations may be higher in patients with hepatic impairment compared to patients with normal hepatic function. In patients with hepatic impairment, consider starting at the low end of the recommended dosing range for the first haloperidol decanoate injection dose [see Dosage and Administration (2.1)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS oSudden Death, Torsades de Pointes (TdP), and QTc Interval Prolongation: Avoid use of haloperidol decanoate injection in patients who are at risk of developing TdP. Avoid concomitant use of haloperidol decanoate injection with drugs that may increase risk of QTc interval prolongation or increase haloperidol exposure. Obtain ECG and serum electrolytes at baseline and during treatment as clinically indicated (5.2).oTachycardia and Hypotension: Monitor orthostatic vital signs (5.3).oCerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis: Use with caution in patients with schizophrenia who have risk factors for cerebrovascular adverse reactions (5.4).oTardive Dyskinesia: Discontinue treatment if clinically appropriate (5.5).oNeuroleptic Malignant Syndrome (NMS): Immediately discontinue and monitor closely (5.6).oSeizures: Haloperidol decanoate injection is generally not recommended in patients receiving antiseizure drugs or who have history of seizures or EEG abnormalities. If clinically, indicated, maintain patients taking haloperidol decanoate injection on adequate antiseizure therapy (5.8).oPotential for Cognitive and Motor Impairment: Advise patients to not drive motor vehicle or operate hazardous machinery until they are reasonably certain haloperidol decanoate injection does not impair their cognitive and motor functions (5.11).oRisk of Encephalopathic Syndrome with Concomitant Use of Lithium: Monitor closely for early signs of neurological toxicity and discontinue haloperidol decanoate injection if such signs appear (5.12).oLeukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing haloperidol decanoate injection if clinically significant decline in WBC occurs in absence of other causative factors. Discontinue haloperidol decanoate injection in patients with clinically significant neutropenia or an absolute neutrophile count of 1,000/mm3 (5.13).oHyperprolactinemia: Elevated prolactin levels may occur during acute and chronic use (5.14).. oSudden Death, Torsades de Pointes (TdP), and QTc Interval Prolongation: Avoid use of haloperidol decanoate injection in patients who are at risk of developing TdP. Avoid concomitant use of haloperidol decanoate injection with drugs that may increase risk of QTc interval prolongation or increase haloperidol exposure. Obtain ECG and serum electrolytes at baseline and during treatment as clinically indicated (5.2).. oTachycardia and Hypotension: Monitor orthostatic vital signs (5.3).. oCerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis: Use with caution in patients with schizophrenia who have risk factors for cerebrovascular adverse reactions (5.4).. oTardive Dyskinesia: Discontinue treatment if clinically appropriate (5.5).. oNeuroleptic Malignant Syndrome (NMS): Immediately discontinue and monitor closely (5.6).. oSeizures: Haloperidol decanoate injection is generally not recommended in patients receiving antiseizure drugs or who have history of seizures or EEG abnormalities. If clinically, indicated, maintain patients taking haloperidol decanoate injection on adequate antiseizure therapy (5.8).. oPotential for Cognitive and Motor Impairment: Advise patients to not drive motor vehicle or operate hazardous machinery until they are reasonably certain haloperidol decanoate injection does not impair their cognitive and motor functions (5.11).. oRisk of Encephalopathic Syndrome with Concomitant Use of Lithium: Monitor closely for early signs of neurological toxicity and discontinue haloperidol decanoate injection if such signs appear (5.12).. oLeukopenia, Neutropenia, and Agranulocytosis: Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. Consider discontinuing haloperidol decanoate injection if clinically significant decline in WBC occurs in absence of other causative factors. Discontinue haloperidol decanoate injection in patients with clinically significant neutropenia or an absolute neutrophile count of 1,000/mm3 (5.13).. oHyperprolactinemia: Elevated prolactin levels may occur during acute and chronic use (5.14).. 5.1Increased 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. In an analysis of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, the risk of death in antipsychotic drug-treated patients was 1.6 to 1.7 times the risk of death in placebo- treated patients. Over the course of typical 10-week controlled trial, the incidence of death in antipsychotic drug-treated patients was about 4.5%, compared to an incidence of about 2.6% in placebo-treated patients. 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.Haloperidol decanoate injection is not approved for the treatment of patients with dementia- related psychosis [see Indications and Usage (1)].. 5.2Sudden Death, Torsades de Pointes, and QTc Interval Prolongation Cases of sudden death, torsades de pointes (TdP) and QTc interval prolongation have been reported in haloperidol-treated patients [see Adverse Reactions (6.1, 6.2)]. Cases have been reported even in the absence of predisposing factors. Higher than recommended haloperidol dosages were associated with higher risk of TdP and QTc interval prolongation.Avoid use of haloperidol decanoate injection in patients who are at significant risk of developing TdP including those with congenital long QT syndrome, uncontrolled or significant cardiac disease, recent myocardial infarction, ischemic cardiomyopathy, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism. Avoid the concomitant use of haloperidol decanoate injection with drugs that may increase the risk of the QTc interval prolongation or increase haloperidol exposure. Assess the QTc interval via an ECG at baseline, and during treatment as clinically indicated. Obtain serum electrolytes (including potassium, calcium, phosphorus, and magnesium) at baseline and during treatment as clinically indicated, and correct electrolyte abnormalities.. 5.3Tachycardia and Hypotension Tachycardia and hypotension (including orthostatic hypotension) have been reported in patients treated with haloperidol [see Adverse Reactions (6.1)]. Orthostatic vital signs should be monitored in patients who are at risk for hypotension (e.g., geriatric patients, patients with dehydration, hypovolemia, and concomitantly treated with antihypertensive medications), patients with known cardiovascular disease (history of myocardial infarction, ischemic heart disease, heart failure, or conduction abnormalities), and patients with cerebrovascular disease.Should hypotension occur and vasopressor be required, epinephrine must not be used since haloperidol decanoate injection may block its vasopressor activity, and paradoxically lower blood pressure. Instead, metaraminol, phenylephrine or norepinephrine should be used.. 5.4Cerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials, elderly patients with dementia-related psychosis treated with antipsychotics had an increased risk of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack) including fatalities, compared to those treated with placebo.The mechanism for this increased risk is not known.Haloperidol decanoate injection is not approved for the treatment of patients with dementia- related psychosis. Haloperidol decanoate injection should be used with caution in patients with schizophrenia who have risk factors for cerebrovascular adverse reactions.. 5.5Tardive Dyskinesia Tardive dyskinesia (TD) may develop in patients treated with antipsychotic drugs, including haloperidol decanoate injection [see Adverse Reactions (6.1)]. TD can develop after relatively brief treatment period at low dosages and may also occur after discontinuation of treatment. If antipsychotic treatment is discontinued, TD may partially or completely remit. Antipsychotic treatment, however, may suppress or partially suppress the signs and symptoms of TD and may mask the underlying process. The effect that symptomatic suppression has upon the long-term course of TD is unknown.The TD risk in patients treated with antipsychotic drugs appears to be highest among the elderly, especially elderly women, but it is not possible to predict, which patients are likely to develop TD. The TD risk and the likelihood that TD will become irreversible increase with the duration of antipsychotic drug treatment and the cumulative dosage.In patients who require chronic antipsychotic treatment, use the lowest dosage and the shortest duration of treatment that produces satisfactory clinical response. Periodically reassess the need for continued treatment. If signs and symptoms of TD appear in haloperidol decanoate injection-treated patients, consider drug discontinuation. However, some patients may require haloperidol decanoate injection treatment despite the presence of TD.. 5.6Neuroleptic Malignant Syndrome Neuroleptic Malignant Syndrome (NMS), potentially fatal symptom complex, has been reported in association with the use of antipsychotic drugs [see Adverse Reactions (6.1)]. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, delirium, and autonomic instability, and additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.If NMS is suspected, immediately discontinue haloperidol decanoate injection and provide intensive symptomatic treatment and monitoring.. 5.7Neurological Adverse Reactions in Patients with Parkinsons Disease or Dementia with Lewy Bodies Patients with Parkinsons disease or Dementia with Lewy bodies may experience increased sensitivity to haloperidol. Manifestations of this increased sensitivity include severe extrapyramidal symptoms (e.g., tremor, rigidity, bradykinesia), confusion, sedation, and falls. Haloperidol decanoate injection is contraindicated in patients with Dementia with Lewy bodies and in patients with Parkinsons disease.. 5.8Seizures Haloperidol decanoate injection may lower the seizure threshold. Haloperidol decanoate injection is generally not recommended in patients receiving antiseizure drugs or have history of seizures or EEG abnormalities. If clinically indicated, maintain patients taking haloperidol decanoate injection on adequate antiseizure therapy.. 5.9Hypersensitivity Reactions There have been postmarketing reports of hypersensitivity reactions with haloperidol including anaphylactic reaction, angioedema, dermatitis exfoliative, hypersensitivity vasculitis, rash, urticaria, face edema, laryngeal edema, bronchospasm, and laryngospasm [see Adverse Reactions (6.2)].Haloperidol decanoate injection is contraindicated in patients with known hypersensitivity to haloperidol or any components of haloperidol decanoate injection.. 5.10Falls Antipsychotics, including haloperidol decanoate injection, may cause somnolence, orthostatic hypotension, motor instability and sensory abnormality, which may lead to falls and, consequently, fractures and other injuries.If patients have condition (or take concomitant drugs) that could exacerbate these effects, complete fall risk assessments when initiating haloperidol decanoate injection treatment and periodically during long-term treatment.. 5.11Potential for Cognitive and Motor Impairment Haloperidol decanoate injection may impair judgement, thinking, or motor skills. Inform patients of the risk and advise them to not drive motor vehicle or operate hazardous machinery until they are reasonably certain that treatment with haloperidol decanoate injection does not impair their cognitive and motor functions.. 5.12Risk of Encephalopathic Syndrome with Concomitant Use of Lithium An encephalopathic syndrome, characterized by weakness, lethargy, fever, tremulousness, confusion, extrapyramidal symptoms, leukocytosis, and elevated serum enzymes (AST, ALT, GGT, alkaline phosphatase, CK, and LDH), BUN, and fasting blood sugar, followed by irreversible brain damage has occurred in few patients treated with concomitant haloperidol and lithium.Monitor patients who concomitantly use haloperidol decanoate injection and lithium closely for early signs of neurological toxicity, and discontinue haloperidol decanoate injection or both haloperidol decanoate injection and lithium promptly if such signs appear.. 5.13Leukopenia, Neutropenia, and Agranulocytosis Leukopenia, neutropenia and agranulocytosis (including fatal cases) have been reported during treatment with antipsychotic drugs, including haloperidol decanoate injection [see Adverse Reactions (6.2)].Possible risk factors for antipsychotic drug-associated leukopenia and neutropenia include pre-existing low WBC and history of drug-induced leukopenia and neutropenia.Perform frequent complete blood count (CBC) monitoring during the first few months of haloperidol decanoate injection therapy in patients with history of clinically significant low WBC, drug-induced leukopenia or neutropenia. Consider discontinuing haloperidol decanoate injection in patients who have clinically significant decline in their WBC in the absence of other causative factors. Discontinue haloperidol decanoate injection in patients with clinically significant neutropenia or an absolute neutrophil count of 1,000/mm3 and monitor closely until the neutropenia resolves.. 5.14Hyperprolactinemia Antipsychotic drugs elevate prolactin levels during acute and chronic use and may result in galactorrhea, amenorrhea, gynecomastia, and impotence which have been reported with antipsychotic drugs [see Adverse Reactions (6.1, 6.2) and Use in Specific Populations (8.3)].Published epidemiologic studies have shown inconsistent results regarding the potential association between hyperprolactinemia and breast cancer [see Nonclinical Toxicology (13.1)].. 5.15Risk of Severe Neurotoxicity in Patients with Thyrotoxicosis Severe neurotoxicity (rigidity, inability to walk or talk) may occur in patients with thyrotoxicosis who are also receiving antipsychotic drugs, including haloperidol decanoate injection.