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Haloperidol Decanoate Is the Long-Acting Form CLINICAL PHARMACOLOGY: Alcohol Asapreservative

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Haloperidol Decanoate Is the Long-Acting Form CLINICAL PHARMACOLOGY: Alcohol Asapreservative 5AV WARNING viduals who are hypersensitive to this drug or a diagnosis, it is important to identify cases malities, because haloperidol may lower the Carbamazepine Increased Mortality in Elderly Patients have Parkinson’s disease. where the clinical presentation includes both convulsive threshold. If indicated, adequate In a study in 11 schizophrenic patients co- with Dementia-Related Psychosis – WARNINGS: serious medical illness (e.g., pneumonia, sys- anticonvulsant therapy should be concomi- administered haloperidol and increasing Elderly patients with dementia-related psy- Increased Mortality in Elderly Patients with temic infection, etc.) and untreated or inad- tantly maintained. doses of carbamazepine, haloperidol plasma chosis treated with antipsychotic drugs are Dementia-Related Psychosis equately treated extrapyramidal signs and • with known allergies, or with a history of concentrations decreased linearly with increas- at an increased risk of death. Analyses of Elderly patients with dementia-related psy- symptoms (EPS). Other important consid- allergic reactions to drugs. ing carbamazepine concentrations. seventeen placebo-controlled trials (modal chosis treated with antipsychotic drugs are erations in the differential diagnosis include • receiving anticoagulants, since an isolated Thus, careful monitoring of clinical status is duration of 10 weeks), largely in patients at an increased risk of death. Haloperidol central anticholinergic toxicity, heat stroke, instance of interference occurred with the warranted when enzyme inducing drugs such taking atypical antipsychotic drugs, Decanoate Injection is not approved for the drug fever and primary central nervous system effects of one anticoagulant (phenindione). as rifampin or carbamazepine are administered revealed a risk of death in drug-treated treatment of patients with dementia-related (CNS) pathology. If concomitant antiparkinson medication is or discontinued in haloperidol-treated patients. patients of between 1.6 to 1.7 times the psychosis (see BOXED WARNING). The management of NMS should include required, it may have to be continued after hal- During combination treatment, the haloperidol 1) immediate discontinuation of antipsychotic risk of death in placebo-treated patients. Cardiovascular Effects operidol decanoate is discontinued because dose should be adjusted, when necessary. Over the course of a typical 10-week con- Cases of sudden death, QT-prolongation, and drugs and other drugs not essential to con- of the prolonged action of haloperidol decano- After discontinuation of such drugs, it may be trolled trial, the rate of death in drug-treated Torsades de Pointes have been reported in current therapy, 2) intensive symptomatic ate. If both drugs are discontinued simultane- necessary to reduce the dosage of haloperidol. patients was about 4.5%, compared to a patients receiving haloperidol. Higher than treatment and medical monitoring, and 3) ously, extrapyramidal symptoms may occur. Valproate rate of about 2.6% in the placebo group. recommended doses of any formulation and treatment of any concomitant serious medi- The physician should keep in mind the pos- Sodium valproate, a drug known to inhibit Although the causes of death were varied, intravenous administration of haloperidol cal problems for which specific treatments sible increase in intraocular pressure when glucuronidation, does not affect haloperidol most of the deaths appeared to be either appear to be associated with a higher risk of are available. There is no general agreement anticholinergic drugs, including antiparkinson plasma concentrations. about specific pharmacological treatment regi- cardiovascular (e.g., heart failure, sud- QT-prolongation and Torsades de Pointes. agents, are administered concomitantly with Carcinogenesis, Mutagenesis, den death) or infectious (e.g., pneumonia) Although cases have been reported even in mens for uncomplicated NMS. haloperidol decanoate. If a patient requires antipsychotic drug treat- Impairment of Fertility in nature. Observational studies suggest the absence of predisposing factors, particular When haloperidol decanoate is used to con- No mutagenic potential of haloperidol deca- that, similar to atypical antipsychotic caution is advised in treating patients with ment after recovery from NMS, the potential trol mania in cyclic disorders, there may be a reintroduction of drug therapy should be care- noate was found in the Ames Salmonella drugs, treatment with conventional anti- other QT-prolonging conditions (including rapid mood swing to depression. microsomal activation assay. Negative or psychotic drugs may increase mortality. electrolyte imbalance [particularly hypoka- fully considered. The patient should be care- Severe neurotoxicity (rigidity, inability to fully monitored, since recurrences of NMS inconsistent positive findings have been The extent to which the findings of in- lemia and hypomagnesemia], drugs known walk or talk) may occur in patients with thyro- obtained in in vitro and in vivo studies of creased mortality in observational studies to prolong QT, underlying cardiac abnor- have been reported. toxicosis who are also receiving antipsychotic Hyperpyrexia and heat stroke, not associ- effects of short-acting haloperidol on chro- may be attributed to the antipsychotic drug malities, hypothyroidism, and fami lial long medication, including haloperidol. mosome structure and number. The available as opposed to some characteristic(s) of QT-syndrome). HALOPERIDOL DECANOATE ated with the above symptom complex, have also been reported with haloperidol. Information for Patients cytogenetic evidence is considered too incon- the patients is not clear. Haloperidol Dec- INJECTION MUST NOT BE ADMINISTERED Haloperidol decanoate may impair the mental sistent to be conclusive at this time. anoate Injection is not approved for the INTRAVENOUSLY. Combined Use of Haloperidol and Lithium and/or physical abilities required for the per- Carcinogenicity studies using oral haloperi- treatment of patients with dementia-related Tardive Dyskinesia An encephalopathic syndrome (characterized formance of hazardous tasks such as oper- dol were conducted in Wistar rats (dosed at up psychosis (see WARNINGS). A syndrome consisting of potentially irre- by weakness, lethargy, fever, tremulousness ating machinery or driving a motor vehicle. to 5 mg/kg daily for 24 months) and in Albino versible, involuntary, dyskinetic movements and confusion, extrapyramidal symptoms, The ambulatory patient should be warned Swiss mice (dosed at up to 5 mg/kg daily for DESCRIPTION: leukocytosis, elevated serum enzymes, BUN, Haloperidol decanoate is the decanoate ester may develop in patients treated with anti- accordingly. 18 months). In the rat study survival was less psychotic drugs. Although the prevalence of and fasting blood sugar) followed by irre- The use of alcohol with this drug should be than optimal in all dose groups, reducing the of the butyrophenone, haloperidol. It has a versible brain damage has occurred in a few markedly extended duration of effect. It is the syndrome appears to be highest among avoided due to possible additive effects and number of rats at risk for developing tumors. the elderly, especially elderly women, it is patients treated with lithium plus haloperidol. hypotension. However, although a relatively greater number available as a colorless/pink to yellow amber A causal relationship between these events solution in sesame oil in sterile form for intra- impossible to rely upon prevalence estimates Drug Interactions of rats survived to the end of the study in high- to predict, at the inception of antipsychotic and the concomitant administration of lithium dose male and female groups, these animals muscular (IM) injection. The structural formula and haloperidol has not been established; Drug-drug interactions can be pharmacody- of haloperidol decanoate, 4-(4-chlorophenyl)- treatment, which patients are likely to develop namic (combined pharmacologic effects) or did not have a greater incidence of tumors the syndrome. Whether antipsychotic drug however, patients receiving such combined than control animals. Therefore, although not 1-[4-(4-fluorophenyl)-4-oxobutyl]-4 piperidinyl therapy should be monitored closely for early pharmacokinetic (alteration of plasma levels). decanoate, is: products differ in their potential to cause tar- The risks of using haloperidol in combina- optimal, this study does suggest the absence dive dyskinesia is unknown. evidence of neurological toxicity and treatment of a haloperidol-related increase in the inci- m discontinued promptly if such signs appear. tion with other drugs have been evaluated as Both the risk of developing tardive dyski- described below. dence of neoplasia in rats at doses up to 20 General nesia and the likelihood that it will become Pharmacodynamic Interactions times the usual daily human dose for chronic irreversible are believed to increase as the A number of cases of broncho pneumonia, or resistant patients. some fatal, have followed the use of antipsy- Since QT-prolongation has been observed dur- duration of treatment and the total cumulative ing haloperidol treatment, caution is advised In female mice at 5 and 20 times the high- dose of antipsychotic drugs administered to chotic drugs, including haloperidol. It has est initial daily dose for chronic or resistant been postulated that lethargy and decreased when prescribing to patient with QT-prolon- the patient increase. However, the syndrome gation conditions
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