Haloperidol Decanoate Prescribing Information
Haloperidol decanoate injection, 50 mg/mL and haloperidol decanoate injection, 100 mg/mL are indicated for the treatment of patients with schizophrenia who require prolonged parenteral antipsychotic therapy.
Haloperidol decanoate injection 50 mg/mL and haloperidol decanoate injection 100 mg/mL should be administered by deep intramuscular injection. A 21 gauge needle is recommended. The maximum volume per injection site should not exceed 3 mL. DO NOT ADMINISTER INTRAVENOUSLY.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Haloperidol decanoate injection 50 mg/mL and haloperidol decanoate injection 100 mg/mL are intended for use in schizophrenic patients who require prolonged parenteral antipsychotic therapy. These patients must be previously stabilized on antipsychotic medication before considering a conversion to haloperidol decanoate. Furthermore, it is recommended that patients being considered for haloperidol decanoate therapy have been treated with, and tolerate well, short-acting haloperidol in order to reduce the possibility of an unexpected adverse sensitivity to haloperidol. Close clinical supervision is required during the initial period of dose adjustment in order to minimize the risk of overdosage or reappearance of psychotic symptoms before the next injection. During dose adjustment or episodes of exacerbation of symptoms of schizophrenia, haloperidol decanoate therapy can be supplemented with short-acting forms of haloperidol.
The dose of haloperidol decanoate injection 50 mg/mL or haloperidol decanoate injection 100 mg/mL should be expressed in terms of its haloperidol content. The starting dose of haloperidol decanoate should be based on the patient's age, clinical history, physical condition, and response to previous antipsychotic therapy. The preferred approach to determining the minimum effective dose is to begin with lower initial doses and to adjust the dose upward as needed. For patients previously maintained on low doses of antipsychotics (e.g., up to the equivalent of 10 mg/day oral haloperidol), it is recommended that the initial dose of haloperidol decanoate be 10 - 15 times the previous daily dose in oral haloperidol equivalents; limited clinical experience suggests that lower initial doses may be adequate.
Since the pharmacologic and clinical actions of haloperidol decanoate injection, 50 mg/mL and haloperidol decanoate injection, 100 mg/mL are attributed to haloperidol as the active medication, Contraindications, Warnings, and additional information are those of haloperidol, modified only to reflect the prolonged action.
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).
The following adverse reactions are discussed in more detail in other sections of the labeling:
- WARNINGS, Increased mortality in Elderly Patients with Dementia-Related Psychosis
- WARNINGS, Cardiovascular Effects
- WARNINGS, Tardive Dyskinesia
- WARNINGS, Neuroleptic Malignant Syndrome
- WARNINGS, Hypersensitivity Reactions
- WARNINGS, Falls
- WARNINGS, Combined Use of Haloperidol and Lithium
- WARNINGS, General
- PRECAUTIONS, Leukopenia, Neutropenia, and Agranulocytosis
- PRECAUTIONS, Other
- PRECAUTIONS, Usage in Pregnancy
Drug-drug interactions can be pharmacodynamic (combined pharmacologic effects) or pharmacokinetic (alteration of plasma levels). The risks of using haloperidol in combination with other drugs have been evaluated as described below.
Pharmacodynamic Interactions
Since QTc interval-prolongation has been observed during haloperidol 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 haloperidol decanoate 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
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 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 haloperidol decanoate dose be decreased as deemed necessary.
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 (
During combination treatment with inducers of CYP3A4, it is recommended that patients be monitored and the haloperidol decanoate dose increased or the dosage interval adjusted, 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 haloperidol decanoate, or adjust the dosage interval.
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.