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Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. 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 the syndrome 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cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.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 disease process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.
Given these considerations, antipsychotics 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. (See ADVERSE REACTIONS and Information for Patients sections).
Neuroleptic Malignant Syndrome (NMS)
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias).
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.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). 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.
Loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) , like other antipsychotics, may impair mental and/or physical abilities, especially during the first few days of therapy. Therefore, ambulatory patients should be warned about activities requiring alertness (e.g., operating vehicles or machinery) and about concomitant use of alcohol and other CNS depressants.
Loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) has not been evaluated for the management of behavioral complications in patients with mental retardation, and therefore, it cannot be recommended.
Loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) should be used with extreme caution in patients with a history of convulsive disorders since it lowers the convulsive threshold. Seizures have been reported in patients receiving loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) at antipsychotic dose levels, and may occur in epileptic patients even with maintenance of routine anticonvulsant drug therapy.
Loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) has an antiemetic effect in animals. Since this effect may also occur in man, loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) may mask signs of overdosage of toxic drugs and may obscure conditions such as intestinal obstruction and brain tumor.
Loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) should be used with caution in patients with cardiovascular disease. Increased pulse rates have been reported in the majority of patients receiving antipsychotic doses; transient hypotension has been reported. In the presence of severe hypotension requiring vasopressor therapy, the preferred drugs may be norepinephrine or angiotensin. Usual doses of epinephrine may be ineffective because of inhibition of its vasopressor effect by loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) .
The possibility of ocular toxicity from loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) cannot be excluded at this time. Therefore, careful observation should be made for pigmentary retinopathy and lenticular pigmentation since these have been observed in some patients receiving certain other antipsychotic drugs for prolonged periods.
Because of possible anticholinergic action, the drug should be used cautiously in patients with glaucoma or a tendency to urinary retention, particularly with concomitant administration of anticholinergic-type antiparkinson medication.
Experience to date indicates the possibility of a slightly higher incidence of extrapyramidal effects following intramuscular administration than normally anticipated with oral formulations. The increase may be attributable to higher plasma levels following intramuscular injection.
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.
Usage in Pregnancy
Safe use of loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) during pregnancy or lactation has not been established; therefore, its use in pregnancy, in nursing mothers, or in women of childbearing potential requires that the benefits of treatment be weighed against the possible risks to mother and child. No embryotoxicity or teratogenicity was observed in studies in rats, rabbits, or dogs although, with the exception of one rabbit study, the highest dosage was only two times the maximum recommended human dose and in some studies it was below this dose. Perinatal studies have shown renal papillary abnormalities in offspring of rats treated from mid-pregnancy with doses of 0.6 and 1.8 mg/kg, doses which approximate the usual human dose but which are considerably below the maximum recommended human dose.
The extent of the excretion of loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) or its metabolites in human milk is not known. However, loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) and its metabolites have been shown to be transported into the milk of lactating dogs. Loxapine (loxapine (loxapine (loxapine succinate) succinate) succinate) administration to nursing women should be avoided if clinically possible.
Safety and effectiveness of loxapine (loxapine succinate) in pediatric patients have not been established.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 2/14/2017
Additional Loxapine Information
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