Haldol Decanoate

1 INDICATIONS AND USAGE HALDOL DECANOATE is indicated for the treatment of schizophrenia in adults who were previously taking a stable dosage of an immediate-release oral haloperidol product. HALDOL DECANOATE is a typical antipsychotic indicated for the treatment of schizophrenia in adults who were previously taking a stable dosage of an immediate-release oral haloperidol product ( 1 ).

2 DOSAGE AND ADMINISTRATION Administer HALDOL DECANOATE by deep intramuscular injection every 4 weeks by a healthcare provider. Do not administer intravenously ( 2.1 ). For the recommended dosage, including the first recommended dose and the maintenance dosage, see the Dosage and Administration section ( 2.1 ). If schizophrenia symptoms worsen during dosage modification of HALDOL DECANOATE, consider administering an immediate-release oral haloperidol product in addition to HALDOL DECANOATE therapy ( 2.2 ). 2.1 Recommended Dosage and Administration Administer HALDOL DECANOATE by deep intramuscular injection every 4 weeks by a health care professional. Do not administer HALDOL DECANOATE intravenously. When injecting HALDOL DECANOATE, use a 21-gauge needle. The maximum volume per injection site is 3 mL. Table 1 below describes the recommended dosage for HALDOL DECANOATE. The maximum recommended initial dose is 100 mg. If the calculated first recommended dose of HALDOL DECANOATE is greater than 100 mg, then administer two deep intramuscular injections as follows: 100 mg on the first day Remainder of the amount 3 to 7 days later. Table 1: HALDOL DECANOATE Recommended Dosage Population First Recommended Dose Maintenance Dosage Clinical experience with HALDOL DECANOATE at a dosage greater than 450 mg every 4 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 4 weeks. The dosage may be increased by increments of 50 mg or less every 4 weeks until an optimal therapeutic effect is obtained. The typical effective dosage range is between 50 and 200 mg every 4 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 older 10–15 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) ]. Adult patients less than 65 years old stabilized on >10 mg of daily immediate-release oral haloperidol 10–20 times previous daily dose of immediate-release oral haloperidol 10–15 times previous daily dose of immediate-release oral haloperidol administered every 4 weeks. The dosage may be increased by increments of 50 mg or less every 4 weeks until an optimal therapeutic effect is obtained. 2.2 Recommended Supplemental Immediate-release Oral Haloperidol Therapy If schizophrenia symptoms worsen during dosage modification of HALDOL DECANOATE, consider administering an immediate-release oral haloperidol product in addition to HALDOL DECANOATE therapy. 2.3 Preparation Instructions Visually inspect HALDOL DECANOATE for particulate matter and discoloration prior to administration. Do not use if the solution has debris or is not clear or not yellow to light amber in color. Instructions for breaking the ampule are as follows: Step 1 Figure A 1. Because some fluid may be in the top of the ampule, lightly tap the top of the ampule with your finger until all fluid moves to the bottom portion of the ampule before breaking the ampule. The colored ring and colored point of the ampule aid the placement of fingers while breaking the ampule (see Figure A ). Step 2 Figure B 2. Hold the ampule between the thumb and index finger with the colored point facing you (see Figure B ). Step 3 Figure C 3. Position the index finger of the other hand to support the neck of the ampule. Position the thumb of the same hand so that it covers the colored point and is parallel to the colored ring (see Figure C ). Step 4 Figure D 4. With the thumb on the colored point and index fingers close together, apply firm pressure on the colored point and push away from your body, in the direction of the arrow, to snap the ampule open at the breaking level (see Figure D ). Figure A Figure B Figure C Figure D

4 CONTRAINDICATIONS HALDOL DECANOATE is contraindicated in patients with: Severe toxic central nervous system depression or comatose states from any cause. Known hypersensitivity to haloperidol or any components of HALDOL DECANOATE. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with haloperidol [see Warnings and Precautions (5.9) and Adverse Reactions (6.2) ] . Parkinson's disease [see Warnings and Precautions (5.7) ]. Dementia with Lewy bodies [see Warnings and Precautions (5.7) ] . Severe toxic central nervous system depression or comatose states from any cause ( 4 ). Known hypersensitivity to haloperidol or any components of HALDOL DECANOATE ( 4 ). Parkinson's disease ( 4 , 5.7 , 6.1 ). Dementia with Lewy bodies ( 4 , 5.7 ).

5 WARNINGS AND PRECAUTIONS Sudden Death, Torsades de Pointes (TdP), and QTc Interval Prolongation: Avoid use of HALDOL DECANOATE in patients who are at risk of developing TdP. Avoid concomitant use of HALDOL DECANOATE 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 ). Tachycardia and Hypotension: Monitor orthostatic vital signs ( 5.3 ). Cerebrovascular 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 ). Tardive Dyskinesia: Discontinue treatment if clinically appropriate ( 5.5 ). Neuroleptic Malignant Syndrome (NMS): Immediately discontinue and monitor closely ( 5.6 ). Seizures: HALDOL DECANOATE is generally not recommended in patients receiving antiseizure drugs or who have a history of seizures or EEG abnormalities. If clinically, indicated, maintain patients taking HALDOL DECANOATE on adequate antiseizure therapy ( 5.8 ). Potential for Cognitive and Motor Impairment: Advise patients to not drive a motor vehicle or operate hazardous machinery until they are reasonably certain HALDOL DECANOATE does not impair their cognitive and motor functions ( 5.11 ). Risk of Encephalopathic Syndrome with Concomitant Use of Lithium: Monitor closely for early signs of neurological toxicity and discontinue HALDOL DECANOATE if such signs appear ( 5.12 ). Leukopenia, 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 HALDOL DECANOATE if clinically significant decline in WBC occurs in absence of other causative factors. Discontinue HALDOL DECANOATE in patients with clinically significant neutropenia or an absolute neutrophile count of <1,000/mm 3 ( 5.13 ). Hyperprolactinemia: Elevated prolactin levels may occur during acute and chronic use ( 5.14 ). 5.1 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. 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 a 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. HALDOL DECANOATE is not approved for the treatment of patients with dementia-related psychosis [see Indications and Usage (1) ] . 5.2 Sudden 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 a higher risk of TdP and QTc interval prolongation. Avoid use of HALDOL DECANOATE 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 HALDOL DECANOATE 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. 5.3 Tachycardia 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 a vasopressor be required, epinephrine must not be used since HALDOL DECANOATE may block its vasopressor activity, and paradoxically lower blood pressure. Instead, metaraminol, phenylephrine or norepinephrine should be used. 5.4 Cerebrovascular 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. HALDOL DECANOATE is not approved for the treatment of patients with dementia-related psychosis. HALDOL DECANOATE should be used with caution in patients with schizophrenia who have risk factors for cerebrovascular adverse reactions. 5.5 Tardive Dyskinesia Tardive dyskinesia (TD) may develop in patients treated with antipsychotic drugs, including HALDOL DECANOATE [see Adverse Reactions (6.1) ] . TD can develop after a 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 a satisfactory clinical response. Periodically reassess the need for continued treatment. If signs and symptoms of TD appear in HALDOL DECANOATE-treated patients, consider drug discontinuation. However, some patients may require HALDOL DECANOATE treatment despite the presence of TD. 5.6 Neuroleptic Malignant Syndrome Neuroleptic Malignant Syndrome (NMS), a 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 HALDOL DECANOATE and provide intensive symptomatic treatment and monitoring. 5.7 Neurological Adverse Reactions in Patients with Parkinson's Disease or Dementia with Lewy Bodies Patients with Parkinson's 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. HALDOL DECANOATE is contraindicated in patients with Dementia with Lewy bodies and in patients with Parkinson's disease. 5.8 Seizures HALDOL DECANOATE may lower the seizure threshold. HALDOL DECANOATE is generally not recommended in patients receiving antiseizure drugs or have a history of seizures or EEG abnormalities. If clinically indicated, maintain patients taking HALDOL DECANOATE on adequate antiseizure therapy. 5.9 Hypersensitivity 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) ] . HALDOL DECANOATE is contraindicated in patients with known hypersensitivity to haloperidol or any components of HALDOL DECANOATE. 5.10 Falls Antipsychotics, including HALDOL DECANOATE, may cause somnolence, orthostatic hypotension, motor instability and sensory abnormality, which may lead to falls and, consequently, fractures and other injuries. If patients have a condition (or take concomitant drugs) that could exacerbate these effects, complete fall risk assessments when initiating HALDOL DECANOATE treatment and periodically during long-term treatment. 5.11 Potential for Cognitive and Motor Impairment HALDOL DECANOATE may impair judgement, thinking, or motor skills. Inform patients of the risk and advise them to not drive a motor vehicle or operate hazardous machinery until they are reasonably certain that treatment with HALDOL DECANOATE does not impair their cognitive and motor functions. 5.12 Risk 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 a few patients treated with concomitant haloperidol and lithium. Monitor patients who concomitantly use HALDOL DECANOATE and lithium closely for early signs of neurological toxicity, and discontinue HALDOL DECANOATE or both HALDOL DECANOATE and lithium promptly if such signs appear. 5.13 Leukopenia, Neutropenia, and Agranulocytosis Leukopenia, neutropenia and agranulocytosis (including fatal cases) have been reported during treatment with antipsychotic drugs, including HALDOL DECANOATE [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 HALDOL DECANOATE therapy in patients with a history of a clinically significant low WBC, drug-induced leukopenia or neutropenia. Consider discontinuing HALDOL DECANOATE in patients who have a clinically significant decline in their WBC in the absence of other causative factors. Discontinue HALDOL DECANOATE in patients with clinically significant neutropenia or an absolute neutrophil count of <1,000/mm 3 and monitor closely until the neutropenia resolves. 5.14 Hyperprolactinemia 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) ] . 5.15 Risk 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 HALDOL DECANOATE.

7 DRUG INTERACTIONS Drugs that Prolong QTc Interval: Avoid concomitant use with HALDOL DECANOATE ( 7.1 ). See full prescribing information for additional clinically significant drug interactions with HALDOL DECANOATE ( 7.2 ). 7.1 Drugs that Prolong the QTc Interval Avoid concomitant use of HALDOL DECANOATE with other drugs with a known potential to prolong the QTc interval. If concomitant use cannot be avoided [see Warnings and Precautions (5.2) ] : Obtain ECGs when initiating and during concomitant use as clinically indicated. Obtain serum electrolytes (including potassium, calcium, phosphorus, and magnesium) when initiating and during concomitant use as clinically indicated. QTc interval prolongation has been observed with HALDOL DECANOATE treatment. Concomitant use of HALDOL DECANOATE with other products that prolong the QTc interval may result in a 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) ]. 7.2 Other Clinically Significant Drug Interactions Table 3 describes other clinically significant drug interactions of HALDOL DECANOATE. Table 3: Other Clinically Significant Drugs Interactions See www.fda.gov/CYPandTransporterInteractingDrugs for examples of CYP3A4 and/or CYP2D6 inhibitors, CYP3A4 inducers, and CYP2D6 substrates. CNS Depressants Clinical Impact Haloperidol may potentiate CNS depressants. Prevention or Management Avoid concomitant use of HALDOL DECANOATE with CNS depressants such as anesthetics, opioids, and alcohol. CYP3A4 and/or CYP2D6 Inhibitors Clinical Impact CYP3A4 and/or CYP2D6 inhibitors increase haloperidol exposure (haloperidol is a CYP3A4 and CYP2D6 substrate) [see Clinical Pharmacology (12.3) ]. Concomitant use of HALDOL DECANOATE and CYP3A4 and/or CYP2D6 inhibitors may increase the risk of haloperidol-associated adverse reactions. Prevention or Management Monitor for signs or symptoms of increased or prolonged pharmacologic effects of haloperidol. Decrease the dosage of HALDOL DECANOATE as clinically necessary. CYP3A4 Inducers Clinical Impact CYP3A4 inducers decrease haloperidol exposure (haloperidol is a CYP3A4 substrate) [see Clinical Pharmacology (12.3) ]. Concomitant use of HALDOL DECANOATE with CYP3A4 inducers may reduce the effectiveness of HALDOL DECANOATE. Prevention or Management Monitor patients and if necessary, increase the dosage of HALDOL DECANOATE. CYP2D6 Substrates Clinical Impact Haloperidol is a CYP2D6 inhibitor. Plasma concentrations of CYP2D6 substrates may increase when they are concomitantly administered with HALDOL DECANOATE. Prevention or Management Monitor 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 Drugs Clinical Impact Haloperidol may antagonize the effects of levodopa, dopamine agonists, and other drugs intended to increase dopamine levels. Prevention or Management HALDOL DECANOATE is contraindicated in patients with Parkinson's disease and dementia with Lewy bodies. For conditions other than Parkinson's disease and dementia with Lewy bodies, when possible, avoid concomitant use of HALDOL DECANOATE with dopaminergic drugs [see Warnings and Precautions (5.7) ] . Anticholinergic Drugs Clinical Impact The healthcare provider should keep in mind the possible increase in intraocular pressure when anticholinergic drugs are administered concomitantly with HALDOL DECANOATE. Prevention or Management Monitor and manage patients as clinically appropriate. Lithium Clinical Impact Concomitant use of HALDOL DECANOATE with lithium may cause an encephalopathic syndrome followed by irreversible brain damage [see Warnings and Precautions (5.12) ] . Prevention or Management Monitor patients who concomitantly use HALDOL DECANOATE with lithium closely for early signs of neurological toxicity, and discontinue HALDOL DECANOATE or both HALDOL DECANOATE and lithium promptly if such signs appear.

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Sudden Death, Torsades de Pointes, and QTc Interval Prolongation [see Warnings and Precautions (5.2) ] Tachycardia and Hypotension [see Warnings and Precautions (5.3) ] Tardive Dyskinesia [see Warnings and Precautions (5.5) ] Neuroleptic Malignant Syndrome [see Warnings and Precautions (5.6) ] Seizures [see Warnings and Precautions (5.8) ] Hypersensitivity Reactions [see Warnings and Precautions (5.9) ] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions (5.13) ] Hyperprolactinemia [see Warnings and Precautions (5.14) ] Risk 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 Janssen Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. Adverse Reactions Identified in Clinical Trials with HALDOL DECANOATE The data described below reflect exposure to 15 mg to 500 mg (1.7 times the maximum recommended dosage) of HALDOL DECANOATE monthly in 13 clinical trials of 410 adult patients with schizophrenia or an unapproved condition. These clinical trials comprised of: 1 double-blind, active comparator-controlled trial with fluphenazine decanoate (Trial 1). 2 trials comparing HALDOL DECANOATE to oral haloperidol (Trials 2 and 3). 9 open-label trials. 1 dose-response trial. The most common adverse reactions that occurred in ≥5% of HALDOL DECANOATE-treated patients in Trial 1 were Parkinsonism and oculogyric crisis. Adverse reactions that occurred in ≥1% of HALDOL DECANOATE-treated patients in Trial 1 are shown in Table 2. Trial 1 was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the HALDOL DECANOATE and fluphenazine decanoate treatment groups. Table 2: Adverse Reactions that Occurred in ≥1% of HALDOL DECANOATE-treated Patients and Fluphenazine Decanoate-treated Patients in Trial 1 The study was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the HALDOL DECANOATE and the fluphenazine decanoate treatment groups. HALDOL DECANOATE (n=36) Fluphenazine decanoate (n=36) Extrapyramidal disorder: Parkinsonism 31% 44% Oculogyric crisis 6% 0% Akinesia 3% 22% Akathisia 3% 14% Tremor 3% 0% Abdominal pain 3% 0% Headache 3% 0% Less common adverse reactions (<1%) that occurred in Trial 1 and other adverse reactions that occurred in Trials 2 and 3, and open-label and dose-response clinical trials of HALDOL DECANOATE are listed below. Cardiac Disorders: Tachycardia Endocrine Disorders: Hyperprolactinemia Eye Disorders: Vision blurred Gastrointestinal Disorders: Constipation, Dry mouth, Salivary hypersecretion General Disorders and Administration Site Conditions: Weight increased, Injection site reaction Musculoskeletal and Connective Tissue Disorders: Muscle rigidity Nervous System Disorders: Dyskinesia, Dystonia, Cogwheel rigidity, Hypertonia, Masked facies, Sedation, Somnolence Reproductive 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: Musculoskeletal and Connective Tissue Disorders: Torticollis, Trismus, Muscle twitching Nervous System Disorders: Neuroleptic malignant syndrome, Tardive dyskinesia, Bradykinesia, Hyperkinesia, Hypokinesia, Dizziness, Nystagmus Psychiatric Disorders: Loss of libido, Restlessness Reproductive System and Breast Disorders: Amenorrhea, Galactorrhea, Dysmenorrhea, Menorrhagia, Breast discomfort Skin and Subcutaneous Tissue Disorders: Acneiform skin reactions Vascular Disorders: Hypotension, Orthostatic hypotension 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of haloperidol, including HALDOL 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, QTc interval prolongation Endocrine Disorders: Inappropriate antidiuretic hormone secretion Gastrointestinal Disorders: Vomiting, Nausea General Disorders and Administration Site Conditions: Sudden death, Face edema, Edema, Hyperthermia, Hypothermia, Injection site abscess, Weight decreased Hepatobiliary Disorders: Acute hepatic failure, Hepatitis, Cholestasis, Jaundice, Liver function test abnormal Immune System Disorders: Anaphylactic reaction, Hypersensitivity Metabolic and Nutritional Disorders: Hypoglycemia Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis Nervous System Disorders: Convulsion, Opisthotonus, Tardive dystonia Pregnancy, Puerperium and Perinatal Conditions: Neonatal drug withdrawal syndrome 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: Angioedema, Dermatitis exfoliative, Hypersensitivity vasculitis, Photosensitivity reaction, Urticaria, Pruritus, Rash, Hyperhidrosis

8.1 Pregnancy Risk Summary Available data from published epidemiologic studies of pregnant patients exposed to haloperidol have not established a 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 ) . HALDOL DECANOATE 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 a 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 a 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 7 times the maximum recommended human oral dose (MRHD) of 20 mg/day based on mg/m 2 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 a dose of 0.5 mg/kg, which is approximately 0.1 times the oral MRHD based on mg/m 2 body surface area.