Haloperidol LactateHaloperidolmarketed under the trade name Haldol among others, is a typical antipsychotic medication. Hakoperidol may result in a movement disorder known steroid injections for back pain efficacy tardive dyskinesia which may be permanent. Haloperidol was haloperidol lactate mechanism of action in by Paul Janssen. Haloperidol was considered indispensable for treating psychiatric emergency situations,   although the newer atypical drugs have gained greater role in a number of situations as outlined haloperidol lactate mechanism of action a series of consensus reviews published between and In a comparison of 15 antipsychotics in schizophrenia, haloperidol demonstrated standard effectiveness. Data from animal experiments indicate haloperidol is not teratogenicbut is embryotoxic in high doses. In humans, no controlled studies exist.
Haloperidol - DrugBank
Updated February 26, If you are a consumer or patient please visit this version. 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. Over the course of a typical week controlled trial, the rate of death in drug-treated patients was about 4.
Although the causes of death were varied, most of the deaths appeared to be either cardiovascular e. 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 is the first of the butyrophenone series of major antipsychotics. The chemical designation is 4-[4- p-chlorophenyl hydroxypiperidino]-4'-fluorobutyrophenone and it has the following structural formula:.
Haloperidol Injection, USP is available as a sterile parenteral form for intramuscular injection. Each mL contains 5 mg haloperidol as the lactate with 1. 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.
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.
Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status including catatonic signs and evidence of autonomic instability irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias. Additional signs may include elevated creatine phosphokinase, myoglobinuria rhabdomyolysis and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness e. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system CNS pathology.
The management of NMS should include 1 immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2 intensive symptomatic treatment and medical monitoring, and 3 treatment of any concomitant serious medical problems for which specific treatments are available.
There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported. Hyperpyrexia and heat stroke, not associated with the above symptom complex, have also been reported with haloperidol.
Generally, patients receiving short-term therapy experience no problems with abrupt discontinuation of antipsychotic drugs. However, some patients on maintenance treatment experience transient dyskinetic signs after abrupt withdrawal. It is not known whether gradual withdrawal of antipsychotic drugs will reduce the rate of occurrence of withdrawal emergent neurological signs but until further evidence becomes available, it seems reasonable to gradually withdraw use of haloperidol see WARNINGS, Usage in Pregnancy.
Motor instability, somnolence, and orthostatic hypotension have been reported with the use of antipsychotics, including Haloperidol Injection, which may lead to falls and, consequently, fractures or other fall-related injuries. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients receiving repeated doses.
Rodents given 2 to 20 times the usual maximum human dose of haloperidol by oral or parenteral routes showed an increase in incidence of resorption, reduced fertility, delayed delivery and pup mortality. No teratogenic effect has been reported in rats, rabbits or dogs at dosages within this range, but cleft palate has been observed in mice given 15 times the usual maximum human dose. Cleft palate in mice appears to be a nonspecific response to stress or nutritional imbalance as well as to a variety of drugs, and there is no evidence to relate this phenomenon to predictable human risk for most of these agents.
There are no well controlled studies with haloperidol in pregnant women. There are reports, however, of cases of limb malformations observed following maternal use of haloperidol along with other drugs which have suspected teratogenic potential during the first trimester of pregnancy.
Causal relationships were not established in these cases. Since such experience does not exclude the possibility of fetal damage due to haloperidol, this drug should be used during pregnancy or in women likely to become pregnant only if the benefit clearly justifies a potential risk to the fetus.
Infants should not be nursed during drug treatment. 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.
Haloperidol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. An encephalopathic syndrome characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN, and fasting blood sugar followed by irreversible brain damage has occurred in a few patients treated with lithium plus haloperidol.
A causal relationship between these events and the concomitant administration of lithium and haloperidol has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear.
A number of cases of bronchopneumonia, some fatal, have followed the use of antipsychotic drugs, including haloperidol. It has been postulated that lethargy and decreased sensation of thirst due to central inhibition may lead to dehydration, hemoconcentration and reduced pulmonary ventilation. Therefore, if the above signs and symptoms appear, especially in the elderly, the physician should institute remedial therapy promptly.
Agranulocytosis has also been reported. 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.
When haloperidol 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 haloperidol.
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 QT-prolongation has been observed during haloperidol treatment, caution is advised when prescribing to a patient with QT-prolongation conditions long QT-syndrome, hypokalemia, electrolyte imbalance or to patients receiving medications known to prolong the QT-interval or known to cause electrolyte imbalance.
If concomitant antiparkinson medication is required, it may have to be continued after haloperidol is discontinued because of the difference in excretion rates.
If both 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 haloperidol. As with other antipsychotic agents, it should be noted that haloperidol may be capable of potentiating CNS depressants such as anesthetics, opiates and alcohol.
Ketoconazole is a potent inhibitor of CYP3A4. It may be necessary to reduce the haloperidol dosage. Haloperidol is metabolized by several routes, including the glucuronidation and the cytochrome P enzyme system. Inhibition of these routes of metabolism by another drug may result in increased haloperidol concentrations and potentially increase the risk of certain adverse events, including QT-prolongation.
In pharmacokinetic studies, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs characterized as substrates or inhibitors of CYP3A4 or CYP2D6 isoenzymes, such as itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, and promethazine. When prolonged treatment 1 to 2 weeks with enzyme-inducing drugs such as rifampin or carbamazepine is added to haloperidol therapy, this results in a significant reduction of haloperidol plasma levels.
In 5 other schizophrenic patients treated with haloperidol and rifampin, discontinuation of rifampin produced a mean 3. In a study in 11 schizophrenic patients co-administered haloperidol and increasing doses of carbamazepine, haloperidol plasma concentrations decreased linearly with increasing carbamazepine concentrations. Thus, careful monitoring of clinical status is warranted when enzyme inducing drugs such as rifampin or carbamazepine are administered or discontinued in haloperidol-treated patients.
During combination treatment, the haloperidol dose should be adjusted, when necessary. After discontinuation of such drugs, it may be necessary to reduce the dosage of haloperidol. Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations. The ambulatory patient should be warned accordingly. The use of alcohol with this drug should be avoided due to possible additive effects and hypotension. No mutagenic potential of haloperidol was found in the Ames Salmonella microsomal activation assay.
Negative or inconsistent positive findings have been obtained in in vitro and in vivo studies of effects of haloperidol on chromosome structure and number. The available cytogenetic evidence is considered too inconsistent to be conclusive at this time. In the rat study survival was less than optimal in all dose groups, reducing the number of rats at risk for developing tumors.
However, although 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 20 times the usual daily human dose for chronic or resistant patients. In female mice at 5 and 20 times the highest initial daily dose for chronic or resistant patients, there was a statistically significant increase in mammary gland neoplasia and total tumor incidence; at 20 times the same daily dose there was a statistically significant increase in pituitary gland neoplasia.
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.
Since haloperidol is excreted in human breast milk, infants should not be nursed during drug treatment with haloperidol. Clinical studies of haloperidol did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.