Loxapin

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

178.56 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

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.

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 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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

loxapine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

◉ Summary of Use during Lactation

◈ What is loxapine?

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.

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.

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.

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/