HALOPERIDOL DECANOATE- haloperidol decanoate injection
Teva Parenteral Medicines, Inc.
Rx only For Intramuscular Injection Only
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. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 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 rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. 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. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Haloperidol decanoate injection is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS).
Haloperidol decanoate, USP is the decanoate ester of the butyrophenone, 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:
C31 H41 ClFNO3 M.W. 530.11
Haloperidol decanoate, USP is almost insoluble in water (0.01 mg/mL), but is soluble in most organic solvents.
Haloperidol Decanoate Injection is a clear colorless to light pink or light yellow viscous liquid.
Each mL of Haloperidol Decanoate Injection, 50 mg/mL, contains 50 mg haloperidol (present as haloperidol decanoate, USP 70.52 mg) in a sesame oil vehicle, with 1.2% (w/v) benzyl alcohol as a preservative.
Each mL of Haloperidol Decanoate Injection, 100 mg/mL, contains 100 mg haloperidol (present as haloperidol decanoate, USP 141.04 mg) in a sesame oil vehicle, with 1.2% (w/v) benzyl alcohol as a preservative.
Haloperidol decanoate injection 50 mg/mL and haloperidol decanoate injection 100 mg/mL are the long-acting forms of haloperidol. The basic effects of haloperidol decanoate are no different from those of haloperidol with the exception of duration of action. Haloperidol blocks the effects of dopamine and increases its turnover rate; however, the precise mechanism of action is unknown.
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 after the third or fourth dose. 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.
Haloperidol decanoate injection 50 mg/mL and haloperidol decanoate injection 100 mg/mL are indicated for the treatment of schizophrenic patients who require prolonged parenteral antipsychotic therapy.
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).
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Haloperidol decanoate injection is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING).
Cases of sudden death, QT-prolongation, and Torsades de Pointes have been reported in patients receiving haloperidol. Higher than recommended doses of any formulation and intravenous administration of haloperidol appear to be associated with a higher risk of QT-prolongation and Torsades de Pointes. Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QT-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QT, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome). HALOPERIDOL DECANOATE MUST NOT BE ADMINISTERED INTRAVENOUSLY.
A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs (see ADVERSE REACTIONS). Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.
Both the risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.
There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that 1) is known to respond to antipsychotic drugs, and 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
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