Loxapine

327.812

327.81

217-835-3

LER583670J

DTXSID7023229

Pale yellowish crystals from petroleum ether

N05AH01|N - Nervous system

28.1

3.6

Solid

1.2299 (rough estimate)

109-110 °C

1.5800 (estimate)

1.03e-01 g/L

1.36E-08mmHg at 25°C

175.7 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

P264, P270, P301+P310, P321, P330, P405, P501

H301

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 160 companies from 3 notifications to the ECHA C&L Inventory.

LD50=65 mg/kg (Orally in mice)

Liver test abnormalities have been reported to occur in a small proportion of patients on long term therapy with loxapine, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Instances of clinically apparent acute liver injury have been reported due to loxapine and to the structurally related tricylic amoxapine (not available in the United States), but cases are rare. In reported cases, the onset of jaundice was within 4 to 8 weeks, and the pattern of serum enzyme elevations was typically hepatocellular. Immunoallergic features and autoantibody formation were not prominent. All cases were self-limited without fatalities or residual chronic liver injury.

LOXAPINE MAY BE ADDITIVE WITH OR MAY POTENTIATE ACTION OF OTHER CNS DEPRESSANTS (INCLUDING BARBITURATES & ALCOHOL) OR ANTICHOLINERGIC AGENTS...INHIBITS VASOPRESSOR EFFECT OF EPINEPHRINE|Concurrent use /with alcohol or other central nervous system (CNS) depression-producing medications, especially anesthetics, barbiturates, and opiod (narcotic) analgesics/ may potentiate and prolong the CNS depressant effects of either these medications or loxapine; dosage adjustments to approximately 1/2 to 1/4 of the ususal dose may be necessary.|Concurrent use /with amphetamines/ may decrease the effects of amphetamines since loxapine produces alpha-adrenergic blockade.|Concurrent use /with antacids or adsorbent antidiarrheals/ may inhibit the absorption of orally administered loxapine.|For more Interactions (Complete) data for LOXAPINE (18 total), please visit the HSDB record page.

LD50 Rat oral 151 mg/kg|LD50 Rat ip 35 mg/kg|LD50 Rat sc 350 mg/kg|LD50 Rat iv 18 mg/kg|For more Non-Human Toxicity Values (Complete) data for LOXAPINE (8 total), please visit the HSDB record page.

For the management of the manifestations of psychotic disorders such as schizophrenia|Adasuve is indicated for the rapid control of mild-to-moderate agitation in adult patients with schizophrenia or bipolar disorder. Patients should receive regular treatment immediately after control of acute agitation symptoms.|Treatment of bipolar disorder, Treatment of schizophrenia

Loxapine is a conventional antipsychotic used in the therapy of schizophrenia. Loxapine therapy is commonly associated with minor serum aminotransferase elevations and in very rare instances has been linked to clinically apparent acute liver injury.

Antipsychotic Agents

Antipsychotic Agents; Dopamine Antagonists|THIS DIBENZOXAZEPINE DERIVATIVE IS EFFECTIVE IN TREATMENT OF SCHIZOPHRENIA BUT IT IS NOT CLEAR WHETHER IT HAS ANY ADVANTAGE OVER OTHER ANTIPSYCHOTIC AGENTS. /SUCCINATE/|Loxapine is indicated for the management of symptoms and characteristics of psychotic conditions. /Included in US product labeling/|Loxapine has been used to treat anxiety neurosis with depression. /NOT included in US product labeling/

...LOXAPINE SHOULD BE RESERVED FOR USE IN PT WHO ARE REFRACTORY TO ESTABLISHED ANTIPSYCHOTIC AGENTS. /SUCCINATE/|Safe use of loxapine during pregnancy has not been established; therefore, the drug should not be used in pregnant women or women who might become pregnant unless the potential benefits outweigh the possible risk to the woman or fetus.|Pending accumulation of clinical data on the use of the drug in children, loxapine is not recommended for use in children younger than 16 years of age.|Loxapine should be used with caution, particularly in conjunction with anticholinergic antiparkinsonian agents and in patients with glaucoma or a tendency toward urinary retention because of possible anticholinergic activity. Since loxapine may have an aniemetic effect, it is possible that the drug could mask the sign of overdosage of toxic agents or interfere with the diagnosis of such conditions as intestinal obstruction or brain tumor. Loxapine is contraindicated in comatose patients, patients who have severe CNS depression from any cause, or known hypersensitivity to the drug.|For more Drug Warnings (Complete) data for LOXAPINE (13 total), please visit the HSDB record page.

A 2500 mg ingestion ... proved fatal ...

Loxapine, a dibenzoxazepine compound, represents a subclass of tricyclic antipsychotic agents, chemically distinct from the thioxanthenes, butyrophenones, and phenothiazines. Pharmacologically, Loxapine is a tranquilizer for which the exact mode of action has not been established, however, it is believed that by antagonising dopamine and serotonin receptors, there is a marked cortical inhibition which can manifest as tranquilization and suppression of aggression.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. (See all compounds classified as Antipsychotic Agents.)|Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME. (See all compounds classified as Dopamine Antagonists.)

Systemic bioavailability of the parent drug was only about one third that after an equivalent intramuscular dose (25 mg base) in male volunteers|Metabolites are excreted in the urine in the form of conjugates and in the feces unconjugated.|Animal studies with radioactive drug indicate that loxapine and/or its metabolites are widely distributed in body tissues with highest concentrations in brain, lungs, heart, liver, and pancreas. The drug appears in the CSF.|Loxapine is rapidly and almost completely absorbed from the GI tract. The drug is also almost completely absorbed following IM administration.|RAPIDLY & ALMOST COMPLETELY ABSORBED FROM GI TRACT. PEAK LOXAPINE SERUM LEVELS /WITHIN 2 HR, RANGE FROM 0.006 TO 0.013 MCG/ML AFTER/ 25 MG ORAL DOSE...MAJOR /ACTIVE/ METABOLITE IN SERUM IS 8-HYDROXYLOXAPINE /MAX CONCN 0.012-0.038 MCG/ML WITHIN 2-4 HR AFTER ORAL LOXAPINE. HUMAN/|LOXAPINE AND/OR METABOLITES...WIDELY DISTRIBUTED IN BODY TISSUES...HIGHEST CONCN IN BRAIN, LUNGS, HEART, LIVER, & PANCREAS...APPEARS IN CSF...CROSSES PLACENTA...IN MILK OF NURSING MOTHERS /ANIMALS, RADIOACTIVE DRUG/|METABOLITES /7- & 8-HYDROXY-, 7- & 8-HYDROXYDESMETHYLLOXAPINE; N-OXIDES OF LOXAPINE, 7- & 8-HYDROXYLOXAPINE/ EXCRETED IN URINE & FECES. LITTLE OR NO UNMETABOLIZED DRUG...FOUND...METABOLITES /PRIMARILY GLUCURONIDE OR SULFATE CONJUGATES IN URINE, PRIMARILY UNCONJUGATED IN FECES. HUMAN, ORAL/

Hepatic|RAPIDLY & EXTENSIVELY METABOLIZED IN LIVER BY AROMATIC HYDROXYLATION, N-DEMETHYLATION & N-OXIDATION. MAJOR METABOLITES...8-HYDROXYLOXAPINE, & 7-HYDROXYLOXAPINE WHICH ARE ACTIVE...8-HYDROXYDESMETHYLLOXAPINE, 7-HYDROXYDESMETHYLLOXAPINE & LOXAPINE-N-OXIDE WHICH ARE INACTIVE /HUMAN, ORAL/|SIGNIFICANT AMT OF N-OXIDES OF /7-HYDROXY- & 8-HYDROXYLOXAPINES, METABOLITES FORMED BY HYDROXYLATION & N-OXIDATION/, PRESENT...LOXAPINE METABOLITES ARE EXCRETED IN URINE PRIMARILY AS GLUCURONIDE OR SULFATE CONJUGATES /HUMAN, ORAL/|2 METABOLITES: 8-HYDROXYLOXAPINE & 8-HYDROXYAMOXAPINE, INCR ON ORAL MEDICATION.|Loxapine is rapidly and extensively metabolized in the liver by aromatic hydroxylation, N-oxidation. The major metabolites of loxapine are 8-hydroxyloxapine and 7-hydroxyloxapine which are active and 8-hydroxydesmethylloxapine, 7-hydroxydesmethylloxapine, and loxapine N-oxide which are inactive. Significant amounts of the N-oxides of the hydroxyloxapines are also present.|Loxepine has known human metabolites that include Loxepine N-glucuronide.

Oral-4 hours|SERUM LEVELS OF LOXAPINE & METABOLITES DECLINE IN BIPHASIC MANNER. HALF-LIFE DURING 1ST PHASE...5 HR...DURING 2ND PHASE...19 HR. /AFTER SINGLE 25 MG ORAL DOSE, SEDATIVE EFFECT BEGINS IN 20-30 MIN; PEAK EFFECT WITHIN 1.5-3 HR; DURATION APPROX 12 HR. HUMAN/

Loxapine is a dopamine antagonist, and also a serotonin 5-HT2 blocker. The exact mode of action of Loxapine 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.|STUDIES HAVE SHOWN THAT LOXAPINE PRODUCES SEDATION & PRONOUNCED EXTRAPYRAMIDAL REACTIONS, DECR CONVULSIVE THRESHOLD, & HAS ANTIADRENERGIC & ANTICHOLINERGIC EFFECTS. /SUCCINATE/

Overdosage of loxapine presumably may be manifested by seizures, severe extrapyramidal symptoms, and other effects ranging from mild CNS depression to profound hypotension and coma.

2-Chloro-11-(4-methyl-1-piperazinyl)-dibenz(b,f)(1,4)oxazepine

LOXITANE (LEDERLE). ORAL: CAPSULES 10, 25, & 50 MG (EXPRESSED IN TERMS OF BASE). /SUCCINATE/

GLC ANALYSIS OF LOXAPINE, AMOXAPINE & THEIR METABOLITES IN SERUM & URINE.

Human drugs -> Adasuve -> EMA Drug Category|Nervous sytem -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals