ASENDIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ASENDIN (ASENDIN).
Amoxapine, a dibenzoxazepine tricyclic antidepressant, primarily inhibits the reuptake of norepinephrine and serotonin. Its metabolite, 7-hydroxyamoxapine, exhibits dopamine D2 receptor antagonism, contributing to its antipsychotic effects.
| Metabolism | Primarily hepatic via CYP450 enzymes, notably CYP2D6 and CYP3A4. Major metabolites: 7-hydroxyamoxapine (active) and 8-hydroxyamoxapine. |
| Excretion | Renal (approximately 50% as unchanged drug and metabolites), biliary/fecal (30-40%), with the remainder as other metabolites; <10% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 24-30 hours. Clinical context: Steady-state is reached within 5-7 days; the half-life supports once-daily dosing in most patients. |
| Protein binding | 90-95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 8-10 L/kg, indicating extensive tissue distribution and accumulation in peripheral compartments. |
| Bioavailability | Oral bioavailability is approximately 70-80% due to first-pass metabolism. No parenteral formulation is available; only oral route. |
| Onset of Action | Oral: Therapeutic effects (antidepressant) begin within 2-4 weeks; immediate anxiolytic effects may be seen within hours but are not considered clinically significant. |
| Duration of Action | Duration of action is approximately 24 hours for the antidepressant effect, consistent with once-daily dosing. Clinical note: Due to the long half-life, effects persist for several days after discontinuation. |
50 mg orally three times daily, increased gradually to 100-200 mg/day in divided doses. Max 300 mg/day.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-60 mL/min: reduce dose by 25-50%. CrCl <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh class C: contraindicated. Child-Pugh class B: reduce dose by 50%. |
| Pediatric use | Not recommended for use in children due to lack of safety data. |
| Geriatric use | Initial dose 25 mg twice daily, increase slowly with close monitoring due to increased sensitivity and anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ASENDIN (ASENDIN).
| Breastfeeding | Amoxapine is excreted in human breast milk. M/P ratio is unknown. Due to limited safety data, breastfeeding is not recommended during therapy. If essential, monitor infant for sedation, poor feeding, and weight loss. |
| Teratogenic Risk | ASENDIN (amoxapine) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies show fetal toxicity at high doses. Risk of congenital malformations cannot be excluded. Second and third trimesters: Neonates may exhibit transient withdrawal symptoms (jitteriness, respiratory depression) or serotonin syndrome if used near term. Avoid use unless benefit outweighs risk. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
["Hypersensitivity to amoxapine or any component","Concomitant use with MAOIs or within 14 days of MAOI discontinuation","Acute recovery phase after myocardial infarction","Known alcohol or barbiturate intoxication"]
| Precautions | ["Suicidality risk","Neuroleptic malignant syndrome","Tardive dyskinesia","Seizure threshold lowering","Cardiotoxicity (QT prolongation, arrhythmias)","Anticholinergic effects","Hypotension","Hepatic impairment"] |
| Food/Dietary | Avoid ethanol; may cause additive CNS depression. No specific food interactions; however, taking with food may reduce GI upset. |
Loading safety data…
| Fetal Monitoring | Maternal: Baseline and periodic liver function tests, CBC, and ECG (risk of QTc prolongation). Monitor for extrapyramidal symptoms and neuroleptic malignant syndrome. Fetal/neonatal: Assess for withdrawal symptoms after delivery; monitor for respiratory depression and feeding difficulties. |
| Fertility Effects | Amoxapine may cause hyperprolactinemia leading to galactorrhea, menstrual irregularities, and reversible infertility in females. In males, may cause sexual dysfunction (decreased libido, erectile dysfunction). Effect on fertility is generally reversible upon discontinuation. |
| Clinical Pearls | Asendin (amoxapine) is a dibenzoxazepine antidepressant with a 7-hydroxy metabolite that confers dopamine blockade, giving it a unique antipsychotic profile. Monitor for extrapyramidal symptoms and tardive dyskinesia, especially in elderly patients. Due to significant anticholinergic effects, use cautiously in patients with benign prostatic hyperplasia, narrow-angle glaucoma, or cognitive impairment. Avoid coadministration with MAOIs; allow at least 14 days between therapies. May cause a false-positive urine amphetamine screen due to structural similarity. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly or adjust dose without consulting your doctor. · Avoid alcohol and other CNS depressants as they can increase drowsiness and dizziness. · May cause dry mouth; use sugar-free gum or candy to alleviate. · Report any unusual movements, especially of the face or tongue, or severe muscle stiffness. · May increase sensitivity to sunlight; use sunscreen and protective clothing. · Inform all healthcare providers you are taking this medication. |