FDA

Haloperidol Decanoate

Approved 12 May 2017InjectionInjectable

The FDA lists this product in 24 strengths and forms.

Indications

Haloperidol decanoate injection is indicated for the treatment of schizophrenia in adults who were previously taking a stable dosage of an immediate-release oral haloperidol product. Haloperidol decanoate injection 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

Contraindications

Haloperidol decanoate injection 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 haloperidol decanoate injection. 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 haloperidol decanoate injection ( 4 ).
Parkinson’s disease ( 4 , 5.7 , 6.1 ).
Dementia with Lewy bodies ( 4 , 5.7 ).

Warnings and precautions

Sudden Death, Torsades de Pointes (TdP), and QTc Interval Prolongation : Avoid use of haloperidol decanoate in patients who are at risk of developing TdP. Avoid concomitant use of haloperidol 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 : Haloperidol 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 haloperidol decanoate on adequate antiseizure therapy ( 5.8 ).

At a glance

Brand name: Haloperidol Decanoate
Route: Injection
Dosage form: Injectable
Applicant: Gland
Status: Prescription
FDA approval: 12 May 2017
Application: ANDA205241-002

Indications

Contraindications

Haloperidol decanoate injection 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 haloperidol decanoate injection. 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 haloperidol decanoate injection ( 4 ).
Parkinson’s disease ( 4 , 5.7 , 6.1 ).
Dementia with Lewy bodies ( 4 , 5.7 ).

Warnings and precautions

Sudden Death, Torsades de Pointes (TdP), and QTc Interval Prolongation : Avoid use of haloperidol decanoate in patients who are at risk of developing TdP. Avoid concomitant use of haloperidol 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 : Haloperidol 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 haloperidol decanoate on adequate antiseizure therapy ( 5.8 ).

Interactions

Drugs that Prolong QTc Interval: Avoid concomitant use with haloperidol decanoate ( 7.1 ).
See full prescribing information for additional clinically significant drug interactions with haloperidol decanoate ( 7.2 ).

7.1 Drugs that Prolong the QTc Interval Avoid concomitant use of haloperidol 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 haloperidol decanoate treatment. Concomitant use of haloperidol 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 )].

7.2Other Clinically Significant Drug Interactions Table

3 describes other clinically significant drug interactions of haloperidol decanoate. Table 3: Other Clinically Significant Drugs Interactions 1 CNS Depressants Clinical Impact Haloperidol may potentiate CNS depressants. Prevention or Management Avoid concomitant use of haloperidol 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 haloperidol 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 haloperidol 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 haloperidol decanoate with CYP3A4 inducers may reduce the effectiveness of haloperidol decanoate. Prevention or Management Monitor patients and if necessary, increase the dosage of haloperidol decanoate. CYP2D6 Substrates Clinical Impact Haloperidol is a CYP2D6 inhibitor. Plasma concentrations of CYP2D6 substrates may increase when they are concomitantly administered with haloperidol 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 Haloperidol 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 haloperidol 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 haloperidol decanoate. Prevention or Management Monitor and manage patients as clinically appropriate.

Lithium Clinical Impact Concomitant use of haloperidol 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 haloperidol decanoate with lithium closely for early signs of neurological toxicity, and discontinue haloperidol decanoate or both haloperidol decanoate and lithium promptly if such signs appear. 1 See www.fda.gov/CYPandTransporterInteractingDrugs for examples of CYP3A4 and/or CYP2D6 inhibitors, CYP3A4 inducers, and CYP2D6 substrates.

Pregnancy and breastfeeding

8.1Pregnancy 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 ).

Haloperidol 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 to 4% and 15 to 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.

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 Gland Pharma at 866-770-7144 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 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 Haloperidol Decanoate The data described below reflect exposure to 15 mg to 500 mg (1.7 times the maximum recommended dosage) of haloperidol 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 haloperidol decanoate injection 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 haloperidol decanoate-treated patients in Trial 1 were Parkinsonism and oculogyric crisis. Adverse reactions that occurred in ≥1% of haloperidol 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 haloperidol decanoate and fluphenazine decanoate treatment groups. Table 2: Adverse Reactions that Occurred in ≥1% of Haloperidol Decanoate-treated Patients and Fluphenazine Decanoate-treated Patients in Trial 1 a Haloperidol 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% a The study was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the haloperidol decanoate and the fluphenazine decanoate treatment groups. 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 haloperidol 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

6.2Postmarketing 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 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

Haloperidol Decanoate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Haloperidol Decanoate

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis

5.2Sudden Death,

5.3Tachycardia and Hypotension Tachycardia

5.4Cerebrovascular Adverse Reactions Including Stroke in Elderly Patients with Dementia-Related Psychosis

5.5Tardive Dyskinesia

5.6Neuroleptic Malignant Syndrome Neuroleptic Malignant Syndrome (NMS),

Interactions

7.2Other Clinically Significant Drug Interactions Table

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information