ment 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cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.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, 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 has not been evaluated for the management of behavioral complications in patients with mental retardation, and therefore, it cannot be recommended. falls loxapine may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. for patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

the possibility of ocular toxicity from loxapine 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.

th symptom control; many patients have been maintained satisfactorily at dosages in the range of 20 mg to 60 mg daily.

cessive salivation, and masked facies. akathisia (motor restlessness) also has been reported relatively frequently. these symptoms are usually not severe and can be controlled by reduction of loxapine dosage or by administration of antiparkinson drugs in usual dosage. dystonia - class effect: symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. while these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. an elevated risk of acute dystonia is observed in males and younger age groups. persistent tardive dyskinesia - as with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. the risk appears to be greater in elderly patients on high-dose therapy, especially females. the symptoms are persistent and in some patients appear to be irreversible. the syndrome is characterized by rhythmical involuntary movement of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). sometimes these may be accompanied by involuntary movements of extremities. there is no known effective treatment for tardive dyskinesia; antiparkinson agents usually do not alleviate the symptoms of this syndrome. it is suggested that all antipsychotic agents be discontinued if these symptoms appear. should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. it has been suggested that fine vermicular movements of the tongue may be an early sign of the syndrome, and if the medication is stopped at that time the syndrome may not develop. cardiovascular effects: tachycardia, hypotension, hypertension, orthostatic hypotension, lightheadedness, and syncope have been reported. a few cases of ecg changes similar to those seen with phenothiazines have been reported. it is not known whether these were related to loxapine administration. hematologic: rarely, agranulocytosis, thrombocytopenia, leukopenia. skin: dermatitis, edema (puffiness of face), pruritus, rash, alopecia, and seborrhea have been reported with loxapine. anticholinergic effects: dry mouth, nasal congestion, constipation, blurred vision, urinary retention, and paralytic ileus have occurred. gastrointestinal: nausea and vomiting have been reported in some patients. hepatocellular injury (i.e., sgot/sgpt elevation) has been reported in association with loxapine administration and rarely, jaundice and/or hepatitis questionably related to loxapine treatment. other adverse reactions: weight gain, weight loss, dyspnea, ptosis, hyperpyrexia, flushed facies, headache, paresthesia, and polydipsia have been reported in some patients. rarely, galactorrhea, amenorrhea, gynecomastia, and menstrual irregularity of uncertain etiology have been reported. to report suspected adverse events, contact actavis at 1-800-272-5525 or fda at 1-800-fda-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

r 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.

ely and is excreted mainly in the first 24 hours. metabolites are excreted in the urine in the form of conjugates and in the feces unconjugated.

° to 25°c (68° to 77°f) [see usp controlled room temperature]. dispense in a tight, child-resistant container. manufactured by: watson pharma private limited verna, salcette goa 403 722 india distributed by: actavis pharma, inc. parsippany, nj 07054 usa revised: december 2016