DailyMed Label: Haldol Decanoate

DailyMed Label: Haldol Decanoate

2024

DailyMed Prescription

Haldol Decanoate

Haloperidol Decanoate

Janssen Pharmaceuticals, Inc.

NDC: 50458-253

NDC: 50458-254

NDC: 50458-253

NDC: 50458-254

NDC: 50458-253

NDC: 50458-254

NDC: 50458-253

NDC: 50458-254

NDC: 50458-253

NDC: 50458-254

NDC: 50458-253

NDC: 50458-253

NDC: 50458-254

NDC: 50458-254

Haloperidol decanoate is the decanoate ester of the butyrophenone, HALDOL (haloperidol). It has a markedly extended duration of effect. It is available in sesame oil in sterile form for intramuscular (IM) injection. The structural formula of haloperidol decanoate, 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-4 piperidinyl decanoate, is: Haloperidol decanoate is almost insoluble in water (0.01 mg/mL), but is soluble in most organic solvents. Each mL of HALDOL decanoate 50 for IM injection contains 50 mg haloperidol (present as haloperidol decanoate 70.52 mg) in a sesame oil vehicle, with 1.2% (w/v) benzyl alcohol as a preservative. Each mL of HALDOL decanoate 100 for IM injection contains 100 mg haloperidol (present as haloperidol decanoate 141.04 mg) in a sesame oil vehicle, with 1.2% (w/v) benzyl alcohol as a preservative. Chemical Structure

HALDOL decanoate 50 and HALDOL decanoate 100 are indicated for the treatment of patients with schizophrenia who require prolonged parenteral antipsychotic therapy.

HALDOL decanoate 50 and HALDOL decanoate 100 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. HALDOL decanoate 50 and HALDOL decanoate 100 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 HALDOL (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 HALDOL decanoate 50 or HALDOL decanoate 100 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. Conversion from oral haloperidol to haloperidol decanoate can be achieved by using an initial dose of haloperidol decanoate that is 10 to 20 times the previous daily dose in oral haloperidol equivalents. In patients who are elderly, debilitated, or stable on low doses of oral haloperidol (e.g. up to the equivalent of 10 mg/day oral haloperidol), a range of 10 to 15 times the previous daily dose in oral haloperidol equivalents is appropriate for initial conversion. In patients previously maintained on higher doses of antipsychotics for whom a low dose approach risks recurrence of psychiatric decompensation and in patients whose long-term use of haloperidol has resulted in a tolerance to the drug, 20 times the previous daily dose in oral haloperidol equivalents should be considered for initial conversion, with downward titration on succeeding injections. The initial dose of haloperidol decanoate should not exceed 100 mg regardless of previous antipsychotic dose requirements. If, therefore, conversion requires more than 100 mg of haloperidol decanoate as an initial dose, that dose should be administered in two injections, i.e. a maximum of 100 mg initially followed by the balance in 3 to 7 days. The maintenance dosage of haloperidol decanoate must be individualized with titration upward or downward based on therapeutic response. The usual maintenance range is 10 to 15 times the previous daily dose in oral haloperidol equivalents dependent on the clinical response of the patient. HALDOL DECANOATE DOSING RECOMMENDATIONS Monthly Patients 1 st Month Maintenance Stabilized on low daily oral doses (up to 10 mg/day) 10–15 × Daily Oral Dose 10–15 × Previous Daily Oral Dose Elderly or Debilitated High dose Risk of relapse 20 × Daily Oral Dose 10–15 × Previous Daily Oral Dose Tolerant to oral haloperidol Close clinical supervision is required during initiation and stabilization of haloperidol decanoate therapy. Haloperidol decanoate is usually administered monthly or every 4 weeks. However, variation in patient response may dictate a need for adjustment of the dosing interval as well as the dose (see CLINICAL PHARMACOLOGY ). Clinical experience with haloperidol decanoate at doses greater than 450 mg per month has been limited.

Since the pharmacologic and clinical actions of HALDOL decanoate 50 and HALDOL decanoate 100 are attributed to HALDOL (haloperidol) as the active medication, Contraindications, Warnings, and additional information are those of HALDOL, modified only to reflect the prolonged action. HALDOL 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 ).

Class Effect: In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including HALDOL decanoate. Agranulocytosis has also been reported. Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of HALDOL decanoate should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm 3 ) should discontinue HALDOL decanoate and have their WBC followed until recovery. HALDOL decanoate 50 and HALDOL decanoate 100 should be administered cautiously to patients: with severe cardiovascular disorders, because of the possibility of transient hypotension and/or precipitation of anginal pain. Should hypotension occur and a vasopressor be required, epinephrine must not be used since HALDOL (haloperidol) may block its vasopressor activity, and paradoxical further lowering of the blood pressure may occur. Instead, metaraminol, phenylephrine or norepinephrine should be used. receiving anticonvulsant medications, with a history of seizures, or with EEG abnormalities, because HALDOL may lower the convulsive threshold. If indicated, adequate anticonvulsant therapy should be concomitantly maintained. with known allergies, or with a history of allergic reactions to drugs. receiving anticoagulants, since an isolated instance of interference occurred with the effects of one anticoagulant (phenindione). Haloperidol may impair the antiparkinson effects of levodopa and other dopamine agonists. If concomitant antiparkinson medication is required, it may have to be continued after HALDOL decanoate 50 or HALDOL decanoate 100 is discontinued because of the prolonged action of haloperidol decanoate. If both drugs are discontinued simultaneously, extrapyramidal symptoms may occur. The physician should keep in mind the possible increase in intraocular pressure when anticholinergic drugs, including antiparkinson agents, are administered concomitantly with HALDOL Decanoate. When HALDOL decanoate is used to control mania in cyclic disorders, there may be a rapid mood swing to depression. Severe neurotoxicity (rigidity, inability to walk or talk) may occur in patients with thyrotoxicosis who are also receiving antipsychotic medication, including HALDOL. Haloperidol decanoate may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. The ambulatory patient should be warned accordingly. The use of alcohol with this drug should be avoided due to possible additive effects and hypotension. 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. 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 decanoate is used in combination with drugs known to cause electrolyte imbalance (e.g., diuretics or corticosteroids) because hypokalemia, hypomagnesmia, 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, opiods, and alcohol. 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 HALDOL decanoate dose be decreased as deemed necessary.Valproate: Sodium valproate, a drug known to inhibit glucuronidation, does not affect 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 ). In a study of 12 patients with schizophrenia coadministered oral haloperidol and rifampin, plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. In 5 other patients with schizophrenia treated with oral haloperidol and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations. In a study in 11 patients with schizophrenia coadministered haloperidol and increasing doses of carbamazepine, haloperidol plasma concentrations decreased linearly with increasing carbamazepine concentrations. During combination treatment with inducers of CYP3A4, it is recommended that patients be monitored and the HALDOL 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 HALDOL 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. 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 short-acting haloperidol on chromosome structure and number. The available cytogenetic evidence is considered too inconsistent to be conclusive at this time. Carcinogenicity studies using oral haloperidol were conducted in Wistar rats (dosed at up to 5 mg/kg daily for 24 months) and in Albino Swiss mice (dosed at up to 5 mg/kg daily for 18 months). In the rat study survival was reduced in all dose groups, decreasing the number of rats at risk for developing tumors. However, a relatively greater number of rats survived to the end of the study in high-dose male and female groups, these animals did not have a greater incidence of tumors than control animals. Therefore, although not optimal, this study does suggest the absence of a haloperidol related increase in the incidence of neoplasia in rats at doses up to approximately 2.5 times the maximum recommended human dose (MRHD) of 20 mg/day based on mg/m 2 body surface area. In female micethere was a statistically significant increase in mammary gland neoplasia and total tumor incidence at doses approximately 0.3 and 1.2 times the MRHD based on mg/m 2 body surface area and there was a statistically significant increase in pituitary gland neoplasia at approximately 1.2 times the MRHD In male mice, no statistically significant differences in incidences of total tumors or specific tumor types were noted. Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro , a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time. Rats or rabbits administered oral haloperidol at doses of 0.5 to 7.5 mg/kg, which are approximately 0.2 to 7 times the maximum recommended human 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 MRHD based on mg/m 2 body surface area. There are no adequate and well-controlled studies in pregnant women. There are reports, however, of cases of limb malformations observed following maternal use of HALDOL along with other drugs which have suspected teratogenic potential during the first trimester of pregnancy. Causal relationships were not established with these cases. Since such experience does not exclude the possibility of fetal damage due to HALDOL, haloperidol decanoate should be used during pregnancy or in women likely to become pregnant only if the benefit clearly justifies a potential risk to the fetus. Neonates exposed to antipsychotic drugs (including haloperidol) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. HALDOL decanoate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Since haloperidol is excreted in human breast milk, infants should not be nursed during drug treatment with haloperidol decanoate. Safety and effectiveness of haloperidol decanoate in children have not been established. Clinical studies of haloperidol did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not consistently identified differences in responses between the elderly and younger patients. However, the prevalence of tardive dyskinesia appears to be highest among the elderly, especially elderly women (see WARNINGS, Tardive Dyskinesia ). Also, the pharmacokinetics of haloperidol in geriatric patients generally warrants the use of lower doses (see DOSAGE AND ADMINISTRATION ). 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.

The following adverse reactions are discussed in more detail in other sections of the labeling:

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. 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 decanoate is used in combination with drugs known to cause electrolyte imbalance (e.g., diuretics or corticosteroids) because hypokalemia, hypomagnesmia, 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, opiods, and alcohol. 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 HALDOL decanoate dose be decreased as deemed necessary.Valproate: Sodium valproate, a drug known to inhibit glucuronidation, does not affect 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 ). In a study of 12 patients with schizophrenia coadministered oral haloperidol and rifampin, plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. In 5 other patients with schizophrenia treated with oral haloperidol and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations. In a study in 11 patients with schizophrenia coadministered haloperidol and increasing doses of carbamazepine, haloperidol plasma concentrations decreased linearly with increasing carbamazepine concentrations. During combination treatment with inducers of CYP3A4, it is recommended that patients be monitored and the HALDOL 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 HALDOL 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.

HALDOL (haloperidol) decanoate 50 for IM injection, 50 mg haloperidol as 70.52 mg per mL haloperidol decanoate: NDC 50458-253-03 3 × 1 mL ampules. HALDOL (haloperidol) decanoate 100 for IM injection, 100 mg haloperidol as 141.04 mg per mL haloperidol decanoate: NDC 50458-254-14, 5 × 1 mL ampules. Store at controlled room temperature (15°–30° C, 59°–86° F). Do not refrigerate or freeze. Protect from light. Keep out of reach of children.

HALDOL decanoate 50 and HALDOL decanoate 100 are the long-acting forms of HALDOL (haloperidol), an antipsychotic. The mechanism of action of haloperidol for the treatment of schizophrenia is unclear. However, its efficacy could be mediated through its activity as an antagonist at central dopamine type 2 receptros. Haloperidol also binds to alpha-1 adrenergic receptors, but with lower affinity, and displays minimal binding to muscarinic cholinergic and histaminergic (H 1 ) receptors. Administration of haloperidol decanoate in sesame oil results in slow and sustained release of haloperidol. The plasma concentrations of haloperidol gradually rise, reaching a peak at about 6 days after the injection, and falling thereafter, with an apparent half-life of about 3 weeks. Steady state plasma concentrations are achieved within 2 to 4 months in patient receiving monthly injections. The relationship between dose of haloperidol decanoate and plasma haloperidol concentration is roughly linear for doses below 450 mg. It should be noted, however, that the pharmacokinetics of haloperidol decanoate following intramuscular injections can be quite variable between subjects.

NDC 50458-253-03 IM Use Only Haldol ® (HALOPERIDOL) Decanoate 50 50 INJECTION 50 mg/mL* 3 x 1-mL AMPULS Sterile *Each mL contains 50 mg haloperidol   as 70.5 mg haloperidol decanoate in   a sesame oil vehicle, with 1.2% (w/v)   benzyl alcohol as a preservative.   Store at controlled room temperature   (15°-30°C, 59°-86°F).   Do not refrigerate or freeze.    Rx only.   For Intramuscular Use Only. PROTECT FROM LIGHT. For dosage and other prescribing information, see accompanying product literature. The dose of HALDOL Decanoate 50 should be expressed in terms of its haloperidol content. Dispense in a light-resistant container as defined in the official compendium. Keep out of reach of children. Janssen Principal Display Panel - 50 mg/mL box