LOXITANE loxapine, a dibenzoxazepine compound, represents a subclass of tricyclic antipsychotic agents, chemically distinct from the thioxanthenes, butyrophenones, and phenothiazines. Chemically, it is 2-Chloro-11-(4-methyl-1-piperazinyl)-dibenz[ b,f ] [1,4]oxazepine. It is present in capsules as the succinate salt, and in the concentrate and parenteral primarily as the hydrochloride salt.


CAPSULES -- Each capsule contains loxapine succinate equivalent to 5, 10, 25, or 50 mg of loxapine base and the following inactive ingredients: Blue 1, Gelatin, Lactose, Magnesium Stearate, Titanium Dioxide, and Yellow 10. Additionally, the 5 mg capsule contains Red 33, the 10 mg capsule contains Red 28 and Red 33, and the 25 mg capsule contains FD&C Yellow No. 6.

ORAL CONCENTRATE -- Each mL contains loxapine hydrochloride equivalent to 25 mg of loxapine base and propylene glycol as an inactive ingredient.

Hydrochloric acid and, if necessary, sodium hydroxide are used to adjust pH to approximately 5.8 during manufacture.

INTRAMUSCULAR -- (Sterile) - Not for Intravenous Use - Each mL contains loxapine hydrochloride equivalent to 50 mg of loxapine base. Inactive Ingredients: Polysorbate 80 NF 5% w/v, Propylene Glycol 70% v/v, and Water for Injection qs ad 100% v.

Hydrochloric acid and, if necessary, sodium hydroxide are used to adjust pH to approximately 5.5 during manufacture.


Pharmacologically, loxapine is a tranquilizer for which the exact mode of action has not been established. However, changes in the level of excitability of subcortical inhibitory areas have been observed in several animal species in association with such manifestations of tranquilization as calming effects and suppression of aggressive behavior.

In normal human volunteers, signs of sedation were seen within 20 to 30 minutes after administration, were most pronounced within 1 1/2 to three hours, and lasted through 12 hours. Similar timing of primary pharmacologic effects was seen in animals.

Absorption, Distribution, Metabolism, and Excretion

After administration of LOXITANE as an oral solution, systemic bioavailability of the parent drug was only about one third that after an equivalent intramuscular dose (25 mg base) in male volunteers. C max for the parent drug was similar for the IM and oral administrations, whereas T max was significantly longer for the IM administration than the oral administration (approximately 5 vs 1 hour). The lower systemic availability of the parent drug after oral administration as compared to the IM administration may be due to first pass metabolism of the oral form.

This is supported by the finding that two metabolites found in serum (8-hydroxyloxapine and 8-hydroxydesmethylloxapine) were formed to a lesser extent after IM administration of loxapine as compared to oral administration.

The apparent half-life of loxapine after oral and IM administration is approximately four hours (range, 1 to 14 hours) and 12 hours (range, 8 to 23 hours), respectively. The extended half-life for the IM administration as compared to the oral administration may be explained by prolonged absorption of loxapine from the muscle during the concurrent elimination process.

Loxapine is extensively metabolized, and urinary recovery over 48 hours resulted in recoveries of approximately 30% and 40% of an IM and orally administered loxapine dose as five metabolites.

LOXITANE is indicated for the management of the manifestations of psychotic disorders. The antipsychotic efficacy of LOXITANE was established in clinical studies which enrolled newly hospitalized and chronically hospitalized acutely ill schizophrenic patients as subjects.


LOXITANE is contraindicated in comatose or severe drug-induced depressed states (alcohol, barbiturates, narcotics, etc.).

LOXITANE is contraindicated in individuals with known hypersensitivity to dibenzoxazepines.

Tardive Dyskinesia

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with neuroleptic (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 neuroleptic treatment, which patients are likely to develop the syndrome. Whether neuroleptic 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 neuroleptic 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 neuroleptic treatment is withdrawn. Neuroleptic 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, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, (1) is known to respond to neuroleptic 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 neuroleptics, 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.

LOXITANE, like other tranquilizers, 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.

LOXITANE has not been evaluated for the management of behavioral complications in patients with mental retardation, and therefore, it cannot be recommended.



LOXITANE 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 LOXITANE at antipsychotic dose levels, and may occur in epileptic patients even with maintenance of routine anticonvulsant drug therapy.

LOXITANE has an antiemetic effect in animals. Since this effect may also occur in man, LOXITANE may mask signs of overdosage of toxic drugs and may obscure conditions such as intestinal obstruction and brain tumor.

LOXITANE 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 LOXITANE.

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.

Neuroleptic 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 neuroleptic 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.

Information for Patients

Given the likelihood that some patients exposed chronically to neuroleptics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.

Drug Interactions

There have been rare reports of significant respiratory depression, stupor and/or hypotension with the concomitant use of loxapine and lorazepam.

The risk of using loxapine in combination with CNS-active drugs has not been systematically evaluated. Therefore, caution is advised if the concomitant administration of loxapine and CNS-active drugs is required.

Usage in Pregnancy

Safe use of LOXITANE 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 midpregnancy 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.

Nursing Mothers

The extent of the excretion of LOXITANE or its metabolites in human milk is not known. However, LOXITANE and its metabolites have been shown to be transported into the milk of lactating dogs. LOXITANE administration to nursing women should be avoided if clinically possible.

Pediatric Use

Safety and effectiveness of LOXITANE in pediatric patients have not been established.


CNS Effects: Manifestations of adverse effects on the central nervous system, other than extrapyramidal effects, have been seen infrequently. Drowsiness, usually mild, may occur at the beginning of therapy or when dosage is increased. It usually subsides with continued LOXITANE® therapy. The incidence of sedation has been less than that of certain aliphatic phenothiazines and slightly more than the piperazine phenothiazines. Dizziness, faintness, staggering gait, shuffling gait, muscle twitching, weakness, insomnia, agitation, tension, seizures, akinesia, slurred speech, numbness, and confusional states have been reported. Neuroleptic malignant syndrome (NMS) has been reported (see ).

Extrapyramidal Reactions - Neuromuscular (extrapyramidal) reactions during the administration of LOXITANE have been reported frequently, often during the first few days of treatment. In most patients, these reactions involved parkinsonian-like symptoms such as tremor, rigidity, excessive 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 LOXITANE dosage or by administration of antiparkinson drugs in usual dosage. Dystonic and dyskinetic reactions have occurred less frequently, but may be more severe. Dystonias include spasms of muscles of the neck and face, tongue protrusion, and oculogyric movement. Dyskinetic reactions have been described in the form of choreoathetoid movements. These reactions sometimes require reduction or temporary withdrawal of loxapine dosage in addition to appropriate counteractive drugs.

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, light-headedness, 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 LOXITANE 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 LOXITANE 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.


Signs and symptoms of overdosage will depend on the amount ingested and individual patient tolerance. As would be expected from the pharmacologic actions of the drug, the clinical findings may range from mild depression of the CNS and cardiovascular systems to profound hypotension, respi-ratory depression, and unconsciousness. The possibility of occurrence of extrapyramidal symptoms and/or convulsive seizures should be kept in mind. Renal failure following loxapine overdosage has also been reported.

The treatment of overdosage is essentially symptomatic and supportive. Early gastric lavage and extended dialysis might be expected to be beneficial. Centrally-acting emetics may have little effect because of the antiemetic action of loxapine. In addition, emesis should be avoided because of the possibility of aspiration of vomitus. Avoid analeptics, such as pentylenetetrazol, which may cause convulsions. Severe hypotension might be expected to respond to the administration of levarterenol or phenylephrine. EPINEPHRINE SHOULD NOT BE USED SINCE ITS USE IN A PATIENT WITH PARTIAL ADRENERGIC BLOCKADE MAY FURTHER LOWER THE BLOOD PRESSURE. Severe extrapyramidal reactions should be treated with anticholinergic antiparkinson agents or diphenhydramine hydrochloride, and anticonvulsant therapy should be initiated as indicated. Additional measures include oxygen and intravenous fluids.


LOXITANE is administered, usually in divided doses, two to four times a day. Daily dosage (in terms of base equivalents) should be adjusted to the individual patient' needs as assessed by the severity of symptoms and previous history of response to antipsychotic drugs.

Oral Administration

Initial dosage of 10 mg twice daily is recommended, although in severely disturbed patients initial dosage up to a total of 50 mg daily may be desirable. Dosage should then be increased fairly rapidly over the first seven to ten days until there is effective control of psychotic symptoms. The usual therapeutic and maintenance range is 60 to 100 mg daily. However, as with other antipsychotic drugs, some patients respond to lower dosage and others require higher dosage for optimal benefit. Daily dosage higher than 250 mg is not recommended.

LOXITANE C Oral Concentrate should be mixed with orange or grapefruit juice shortly before administration. Use only the enclosed calibrated (10 mg, 15 mg, 25 mg, 50 mg) dropper for dosage.

Maintenance Therapy

For maintenance therapy, dosage should be reduced to the lowest level compatible with symptom control; many patients have been maintained satisfactorily at dosages in the range of 20 to 60 mg daily.

Intramuscular Administration

LOXITANE IM is utilized for prompt symptomatic control in the acutely agitated patient and in patients whose symptoms render oral medication temporarily impractical. During clinical trial there were only rare reports of significant local tissue reaction.

LOXITANE IM is administered by intramuscular (not intravenous) injection in doses of 12.5 mg (1/4 mL) to 50 mg (1 mL) at intervals of four to six hours or longer, both dose and interval depending on patient response. Many patients have responded satisfactorily to twice-daily dosage. As described above for oral administration, attention is directed to the necessity for dosage adjustment on an individual basis over the early days of loxapine administration.

Once the desired symptomatic control is achieved and the patient is able to take medication orally, loxapine should be administered in capsule or oral concentrate form. Usually this should occur within five days.


LOXITANE®, loxapine succinate, Capsules are available in the following base equivalent strengths:

5 mg -
Hard shell, opaque, dark-green capsules printed with " images/78/67040001.jpg" over "WATSON" on one half and "LOXITANE" over "5 mg" on the other, are supplied as follows: NDC 52544-811-01 - Bottle of 100s
10 mg -

Hard shell, opaque, with yellow body and a dark-green cap, printed with " images/78/67040001.jpg" over "WATSON" on one half and "LOXITANE" over "10 mg" on the other, are supplied as follows:

NDC 52544-812-01 - Bottle of 100s

NDC 52544-812-10 - Bottle of 1000s

25 mg -

Hard shell, opaque, with a light-green body and a dark-green cap, printed with " images/78/67040001.jpg" over "WATSON" on one half and "LOXITANE" over "25 mg" on the other, are supplied as follows:

NDC 52544-813-01 - Bottle of 100s

NDC 52544-813-10 - Bottle of 1000s

50 mg -

Hard shell, opaque, with a blue body and a dark-green cap, printed with " images/78/67040001.jpg" over "WATSON" on one half and "LOXITANE" over "50 mg" on the other, are supplied as follows:

NDC 52544-814-01 - Bottle of 100s

NDC 52544-814-10 - Bottle of 1000s

Store at controlled room temperature 15°-30°C (59°-86°F).

LOXITANE® C, loxapine hydrochloride, Oral Concentrate is supplied as follows:

NDC 52544-815-34 - 4 fl oz (120 mL) with calibrated dropper.

Each mL contains loxapine HCl equivalent to 25 mg of loxapine base.

Store at controlled room temperature 20°-25°C (68°-77°F).



a subsidiary of Watson Laboratories, Inc.

Corona, CA 92880


of American Cyanamid Company

Pearl River, NY 10965

LOXITANE® IM, loxapine hydrochloride, for intramuscular use only is supplied as follows:

NDC 52544-816-79 - 10 mL multi-dose vial

Each mL contains loxapine HCl equivalent to 50 mg of loxapine base.

Keep package closed to protect from light. Intensification of the straw color to a light amber will not alter potency or therapeutic efficacy; if noticeably discolored, ampul or vial should not be used.

Store at controlled room temperature 15°-30°C (59°-86°F).


Rx only


a subsidiary of Watson Laboratories, Inc.

Corona, CA 92880


Carolina, Puerto Rico 00987

CI 5062-1                                       Issued July 16, 1998


NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer and reproduced in full color by PDR as a quick-reference identification aid. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug' identity should be verified by chemical analysis.