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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
HALDOL (NDA-018701)
(HALOPERIDOL DECANOATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
10/30/2025 (SUPPL-77)
5 Warnings and Precautions
The following subsections created to comply with Physician’s Labeling Rule (PLR) format; please refer to label for complete information.
5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis
5.2 Sudden Death, Torsades de Pointes, and QTc Interval Prolongation
5.3 Tachycardia and Hypotension
5.4 Cerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis
5.5 Tardive Dyskinesia
5.6 Neuroleptic Malignant Syndrome
5.7 Neurological Adverse Reactions in Patients with Parkinson’s Disease or Dementia with Lewy Bodies
5.8 Seizures
5.9 Hypersensitivity Reactions
5.10 Falls
5.11 Potential for Cognitive and Motor Impairment
5.12 Risk of Encephalopathic Syndrome with Concomitant Use of Lithium
5.13 Leukopenia, Neutropenia, and Agranulocytosis
5.14 Hyperprolactinemia
5.15 Risk of Severe Neurotoxicity in Patients with Thyrotoxicosis
7 Drug Interactions
The following subsections created to comply with Physician’s Labeling Rule (PLR) format; please refer to label for complete information.
7.1 Drugs that Prolong the QTc Interval
7.2 Other Clinically Significant Drug Interactions
8 Use in Specific Populations
8.1 Pregnancy
PLLR conversion:
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/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 a 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
PLLR conversion:
Risk Summary
Literature reports suggest that haloperidol is detected in human milk of haloperidol- treated mothers with a relative infant dose ranging from 2% to 12%. Haloperidol has also been detected in the plasma and urine of breastfed infants. There has been a 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 HALDOL 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 mother’s clinical need for HALDOL DECANOATE and any potential adverse effects on the breastfed child from HALDOL DECANOATE or from the mother’s underlying condition.
8.3 Females and Males of Reproductive Potential
PLLR conversion:
Infertility
Females: Based on the pharmacologic action of haloperidol (D2 receptor antagonism), treatment with HALDOL DECANOATE may result in an increase in serum prolactin levels, which may lead to a 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)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONSection created to comply with Physician’s Labeling Rule (PLR) format; please refer to label for complete information.
Other
Physician’s Labeling Rule (PLR) conversion.
01/22/2025 (SUPPL-78)
5 Warnings and Precautions
PRECAUTIONS
Additions and/or revisions underlined:
…
Carcinogenesis, Mutagenesis, and Impairment of Fertility
An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs. Published epidemiologic studies have shown inconsistent results when exploring the potential association between hyperprolactinemia and breast cancer.
11/17/2020 (SUPPL-71)
5 Warnings and Precautions
WARNINGSNewly added information:
Cerebrovascular Adverse Reactions
In controlled trials, elderly patients with dementia-related psychosis treated with some antipsychotics had an increased risk (compared to placebo) of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack), including fatalities. The mechanism for this increased risk is not known. An increased risk cannot be excluded for HALDOL, other antipsychotics, or other patient populations. HALDOL should be used with caution in patients with risk factors for cerebrovascular adverse reactions.
Usage in Pregnancy
Pregnancy Category removed
Additions and/or revisions underlined:
Rats or rabbits administered oral haloperidol at doses of 0.5 to 7.5 mg/kg. which are approximately 0.2 to7 times the maximum recommended human 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 a dose of 0.5 mg/kg, which is approximately 0.1 times the MRHD based on mg/m2 body surface area.
11/17/2020 (SUPPL-76)
5 Warnings and Precautions
PRECAUTIONSOther
Additions and/or revisions underlined:
… Should hypotension occur, and a vasopressor be required, epinephrine must not be used since HALDOL may block its vasopressor activity and paradoxical further lowering of the blood pressure may occur …
Drug Interactions
Pharmacodynamic Interactions
Since QTc interval-prolongation has been observed during HALDOL treatment, caution is advised when prescribing to a patient with QT-prolongation conditions or to patients receiving medications known to prolong the QTc-interval (see WARNINGS, Cardiovascular Effects). Examples include (but are not limited to): Class 1A antiarrhythmics (e.g., procainamide, quinidine, disopyramide); Class 3 antiarrhythmics (e.g., amiodarone, sotalol); and other drugs such as citalopram, erythromycin, levofloxacin, methadone, and ziprasidone.
Caution is advised when HALDOL is used in combination with drugs known to cause electrolyte imbalance (e.g., diuretics or corticosteroids because hypokalemia, hypomagnesemia, and hypocalcemia are risk factors for QT prolongation …
… As with other antipsychotic agents, it should be noted that haloperidol may be capable of potentiating CNS depressants such as anesthetics, opioids, and alcohol.
Pharmacokinetic Interactions
Drugs that May Increase Haloperidol Plasma Concentrations
Haloperidol is metabolized by several routes. The major pathways are glucuronidation and ketone reduction. The cytochrome P450 enzyme system is also involved, particularly CYP3A4 and, to a lesser extent, CYP2D6. Inhibition of these routes of metabolism by another drug or a decrease in CYP2D6 enzyme may result in increased haloperidol concentrations. The effect of CYP3A4 inhibition and of decreased CYP2D6 enzyme activity may be additive.
The haloperidol plasma concentrations increased when a CYP3A4 and/or CYP2D6 inhibitor was coadministered with haloperidol. Examples include :
CYP3A4 inhibitors – alprazolam; itraconazole, ketoconazole, nefazodone, ritonavir.
CYP2D6 inhibitors – chlorpromazine; promethazine; quinidine; paroxetine, sertraline, venlafaxine.
Combined CYP3A4 and CYP2D6 inhibitors – fluoxetine, fluvoxamine; ritonavir.
Buspirone.
Increased haloperidol plasma concentrations may result in an increased risk of adverse events, including QTc interval prolongation (see WARNINGS – Cardiovascular Effects). Increases in QTc have been observed when haloperidol was given with a combination of the metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day).
It is recommended that patients who take haloperidol concomitantly with such medicinal products be monitored for signs or symptoms of increased or prolonged pharmacologic effects of haloperidol, and the HALDOL dose be decreased as deemed necessary.
Valproate: Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.
Drugs that May Decrease Haloperidol Plasma Concentrations
Coadministration of haloperidol with potent enzyme inducers of CYP3A4 may gradually decrease the plasma concentrations of haloperidol to such an extent that efficacy may be reduced. Examples include (but are not limited to): carbamazepine, phenobarbital, phenytoin, rifampin, St John’s Wort (Hypericum, perforatum) …
… During combination treatment with inducers of CYP3A4, it is recommended that patients be monitored, and the HALDOL dose increased as deemed necessary. After withdrawal of the CYP3A4 inducer, the concentration of haloperidol may gradually increase and therefore it may be necessary to reduce the dose of HALDOL.
Effect of Haloperidol on Other Drugs
Haloperidol is an inhibitor of CYP2D6 …
Cardiovascular Effects
Additions and/or revisions underlined:
Cases of sudden death, QTc interval-prolongation, and Torsades de Pointes have been reported in patients receiving HALDOL (see ADVERSE REACTIONS). Higher than recommended doses of any formulation and intravenous administration of HALDOL appear to be associated with a higher risk of QTc interval-prolongation and Torsades de Pointes. Also, a QTc interval that exceeds 500 msec is associated with an increased risk of Torsades de Pointes. Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QTc- prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QTc, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome). HALDOL INJECTION IS NOT APPROVED FOR INTRAVENOUS ADMINISTRATION. If HALDOL is administered intravenously, the ECG should be monitored for QTc prolongation and arrhythmias.
Tachycardia and hypotension (including orthostatic hypotension) have also been reported in occasional patients (see ADVERSE REACTIONS).
6 Adverse Reactions
Clinical Trials ExperienceNewly added information:
Adverse Reactions Identified in Clinical Trials with Haloperidol Decanoate
The adverse reactions listed below were identified in clinical trials with haloperidol decanoate (long-acting depot formulation) and reflect exposure to the active moiety haloperidol in 410 patients who participated in 13 clinical trials with haloperidol decanoate (15 to 500 mg/month) in the treatment of schizophrenia or schizoaffective disorder. These clinical trials comprised:
1 double-blind, active comparator-controlled trial with fluphenazine decanoate.
2 trials comparing the decanoate formulation to oral haloperidol.
9 open-label trials.
1 dose-response trial.
Nervous System Disorders: Akinesia, Cogwheel rigidity, Masked facies.
03/08/2019 (SUPPL-73)
4 Contraindications
(additions underlined)
HALDOL (haloperidol) is contraindicated in patients with:
Severe toxic central nervous system depression or comatose states from any cause
Hypersensitivity to this drug – hypersensitivity reactions have included anaphylactic reaction and angioedema (see WARNINGS, Hypersensitivity Reactions and ADVERSE REACTIONS).
Parkinson’s disease (see WARNINGS, Neurological Adverse Reactions in Patients with Parkinson’s Disease or Dementia with Lewy Bodies).
Dementia with Lewy bodies (see WARNINGS, Neurological Adverse Reactions in Patients with Parkinson’s Disease or Dementia with Lewy Bodies).
5 Warnings and Precautions
PRECAUTIONS(additions underlined)
Other
…
Haloperidol may impair the antiparkinson effects of levodopa and other dopamine agonists.
…
(additions underlined)
…
Neurological Adverse Reactions in Patients with Parkinson’s Disease or Dementia with Lewy Bodies
Patients with Parkinson’s Disease or Dementia with Lewy Bodies are reported to have an increased sensitivity to antipsychotic medication. Manifestations of this increased sensitivity with haloperidol treatment include severe extrapyramidal symptoms, confusion, sedation, and falls. In addition, haloperidol may impair the antiparkinson effects of levodopa and other dopamine agonists. HALDOL Decanoate is contraindicated in patients with Parkinson’s Disease or Dementia with Lewy Bodies (see CONTRAINDICATIONS).
Hypersensitivity Reactions
There have been postmarketing reports of hypersensitivity reactions with haloperidol. These include anaphylactic reaction, angioedema, dermatitis exfoliative, hypersensitivity vasculitis, rash, urticaria, face edema, laryngeal edema, bronchospasm, and laryngospasm (see ADVERSE REACTIONS). HALDOL Decanoate is contraindicated in patients with hypersensitivity to this drug (see CONTRAINDICATIONS).
…
7 Drug Interactions
(additions underlined)
…
Haloperidol is an inhibitor of CYP2D6. Plasma concentrations of CYP2D6 substrates (e,g. tricyclic antidepressants such as desipramine or imipramine) may increase when they are co-administered with haloperidol.
…
8 Use in Specific Populations
Use in Hepatic Impairment(new subsection added)
Studies in patients with hepatic impairment have not been conducted. Haloperidol concentrations may increase in hepatically impaired patients, because it is primarily metabolized by the liver and protein binding may decrease.
12/05/2017 (SUPPL-70)
5 Warnings and Precautions
PRECAUTIONSUsage in Pregnancy
Additions and/or revisions underlined:
Rodents given up to 3 times the usual maximum human dose of haloperidol decanoate showed an increase in incidence of resorption, fetal mortality, and pup mortality. No fetal abnormalities were observed.
Cleft palate has been observed in mice … Since such experience does not exclude the possibility of fetal damage due to HALDOL, haloperidol decanoate should be used during pregnancy …
6 Adverse Reactions
The following line listing added:
The following adverse reactions are discussed in more detail in other sections of the labeling:
WARNINGS, Increased mortality in Elderly Patients with Dementia-Related Psychosis
WARNINGS, Cardiovascular Effects
WARNINGS, Tardive Dyskinesia
WARNINGS, Neuroleptic Malignant Syndrome
WARNINGS, Falls
WARNINGS, Combined Use of HALDOL and Lithium
WARNINGS, General
PRECAUTIONS, Leukopenia, Neutropenia, and Agranulocytosis
PRECAUTIONS, Other
PRECAUTIONS, Usage in Pregnancy
Newly added information:
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.
The data described below reflect exposure to haloperidol in 410 patients who participated in 13 clinical trials with haloperidol decanoate (15 to 500 mg/month) in the treatment of schizophrenia or schizoaffective disorder. These clinical trials comprised:
1 double-blind, active comparator-controlled trial with fluphenazine decanoate.
2 trials comparing the decanoate formulation to oral haloperidol.
9 open-label trials.
1 dose-response trial.
The most common adverse reactions in haloperidol decanoate-treated patients in the double-blind, active comparator-controlled clinical trial with fluphenazine decanoate (greater than or equal to5%) were: Parkinsonism, and oculogyric crisis.
Adverse Reactions Reported at greater than or equal to 1% Incidence in a Double-Blind Active Comparator-Controlled Clinical Trial
Adverse reactions occurring in greater than or equal to 1% of haloperidol decanoate-treated patients in a double-blind, clinical trial with the active comparator fluphenazine decanoate are shown in Table 1.
Table 1. Adverse Reactions Reported by greater than or equal to 1% of Haloperidol Decanoate-treated Patients in a Double-Blind Active Comparator-Controlled Clinical Trial with Fluphenazine Decanoate Newly added; please refer to label for complete information.
Additional Adverse Reactions Reported in Double-Blind, Comparator, Open-Label and Dose-Response Clinical Trials
Additional adverse reactions that are listed below were reported by haloperidol decanoate-treated patients in comparator, open-label, and dose-response clinical trials, or at less than 1% incidence in a double-blind, active comparator-controlled clinical trial with fluphenazine decanoate.
Cardiac Disorders: Tachycardia Endocrine Disorders: Hyperprolactinemia
Eye Disorders: Vision blurred
Gastrointestinal Disorders: Constipation, Dry mouth, Salivary hypersecretion
General Disorders and Administration Site Conditions: Injection site reaction
Investigations: Weight increased
Musculoskeletal and Connective Tissue Disorders: Muscle rigidity
Nervous System Disorders: Dyskinesia, Dystonia, Cogwheel rigidity, Hypertonia, Masked Facies, Sedation, Somnolence
Reproductive System and Breast Disorders: Erectile dysfunction
Adverse Reactions Identified in Clinical Trials with Haloperidol (Non-Decanoate Formulations)
The adverse reactions listed below were identified with non-decanoate formulations, and reflect exposure to the active moiety haloperidol in the following:
284 patients who participated in 3 double-blind, placebo-controlled clinical trials with haloperidol (injection or oral formulation, 2 to 20 mg/day); two trials were in the treatment of schizophrenia and one in the treatment of bipolar disorder.
1295 patients who participated in 16 double-blind, active comparator-controlled clinical trials with haloperidol (injection or oral formulation, 1 to 45 mg/day) in the treatment of schizophrenia.
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
Postmarketing Experience
The following adverse reactions relating to the active moiety haloperidol have been identified during postapproval use of haloperidol or haloperidol decanoate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: Pancytopenia, Agranulocytosis, Thrombocytopenia, Leukopenia, Neutropenia
Cardiac Disorders: Ventricular fibrillation, Torsade de pointes, Ventricular tachycardia, Extrasystoles
Endocrine Disorders: Inappropriate antidiuretic hormone secretion
Gastrointestinal Disorders: Vomiting, Nausea
General Disorders and Administration Site Conditions: Sudden death, Face edema, Edema, Hyperthermia, Hypothermia, Injection site abscess
Hepatobiliary Disorders: Acute hepatic failure, Hepatitis, Cholestasis, Jaundice, Liver function test abnormal
Immune System Disorders: Anaphylactic reaction, Hypersensitivity
Investigations: Electrocardiogram QT prolonged, Weight decreased
Metabolic and Nutritional Disorders: Hypoglycemia
Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis
Nervous System Disorders: Convulsion, Opisthotonus, Tardive dystonia
Pregnancy, Puerperium and Perinatal Conditions: Drug withdrawal syndrome neonatal
Psychiatric Disorders: Agitation, Confusional state, Depression, Insomnia
Renal and Urinary Disorders: Urinary retention
Reproductive System and Breast Disorders: Priapism, Gynecomastia
Respiratory, Thoracic and Mediastinal Disorders: Laryngeal edema, Bronchospasm, Laryngospasm, Dyspnea
Skin and Subcutaneous Tissue Disorders: Dermatitis exfoliative, Hypersensitivity vasculitis, Photosensitivity reaction, Urticaria, Pruritis, Rash, Hyperhidrosis
02/23/2017 (SUPPL-74)
5 Warnings and Precautions
Falls(Newly added subsection)
Motor instability, somnolence, and orthostatic hypotension have been reported with the use of antipsychotics, including HALDOL Decanoate, which may lead to falls and, consequently, fractures or other fall-related injuries. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently during treatment.
05/18/2016 (SUPPL-72)
6 Adverse Reactions
Postmarketing Events- Rhabdomyolysis has been reported.