AMOXAPINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AMOXAPINE (AMOXAPINE).
Selective inhibitor of serotonin reuptake and, to a lesser extent, norepinephrine reuptake. Also exhibits weak dopamine D2 receptor antagonism and alpha1-adrenergic blockade.
| Metabolism | Primarily hepatic via CYP2D6 and CYP3A4; major metabolite is 8-hydroxyamoxapine, which is pharmacologically active. |
| Excretion | Primarily renal (approximately 60-70% as metabolites, <5% unchanged); minimal fecal elimination (<10%) |
| Half-life | Parent drug: 8-12 hours; active metabolite (8-hydroxyamoxapine): approximately 30 hours; steady-state achieved in 3-5 days |
| Protein binding | Approximately 80-90%, primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive tissue distribution |
| Bioavailability | Oral: approximately 60-70% due to first-pass metabolism |
| Onset of Action | Oral: 1-2 weeks for antidepressant effect; acute sedation within hours |
| Duration of Action | Antidepressant effect: sustained with daily dosing; half-life supports once-daily dosing |
| Molecular Weight | 313.78 |
200-300 mg/day orally in divided doses, initially 50 mg three times daily; maximum 400 mg/day
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: reduce dose by 50%; GFR <10 mL/min: avoid use or reduce dose by 75% |
| Liver impairment | Child-Pugh Class A: start at 25 mg twice daily; Class B: 25 mg once daily; Class C: avoid use |
| Pediatric use | Not recommended for use in children under 16 years |
| Geriatric use | Initial dose 25 mg twice daily, increase slowly; maximum 300 mg/day |
| 1st trimester | Avoid. Risk of teratogenicity, especially cardiac defects, based on limited human data. |
| 2nd trimester | Avoid. Use only if benefit outweighs risk; limited safety data. |
| 3rd trimester | Avoid. Risk of neonatal withdrawal (irritability, feeding problems) and possible serotonin syndrome. |
Clinical note
Comprehensive clinical and safety monograph for AMOXAPINE (AMOXAPINE).
| Placental transfer | Crosses placenta; detected in cord blood. |
| Breastfeeding | Excreted into breast milk in small amounts; potential for adverse effects in infant (e.g., sedation, irritability). Not recommended unless essential. |
| Lactation Rating |
■ 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 other dibenzoxazepine derivativesConcomitant use with MAOIsRecent myocardial infarctionAcute recovery phase of myocardial infarction
| Precautions | Suicidality risk in young adults, Serotonin syndrome when combined with other serotonergic drugs, Extrapyramidal symptoms due to weak D2 blockade, Seizure risk, Cardiotoxicity (prolonged QT interval) at high doses, Agranulocytosis (rare) |
| Food/Dietary | Avoid alcohol and beverages with high tyramine content (e.g., aged cheese, cured meats, fermented foods) only if patient is also on MAOIs; not a specific requirement for amoxapine alone. Grapefruit juice may inhibit metabolism; advise caution or avoid large amounts. For patients with hypertension or seizure disorders, avoid excessive caffeine. |
Loading safety data…
| L4 - Possibly Hazardous |
| Teratogenic Risk | First trimester: Limited data; risk of neural tube defects? Second trimester: No specific associations. Third trimester: Risk of neonatal withdrawal (irritability, feeding difficulties). Overall: FDA Category C; avoid in first trimester if possible. |
| Fetal Monitoring | Monitor maternal mood and suicidality; fetal growth ultrasound in third trimester; neonatal withdrawal symptoms (irritability, respiratory distress) after delivery. |
| Fertility Effects | May cause hyperprolactinemia via dopamine blockade; can lead to menstrual irregularities, galactorrhea, and decreased fertility; effects reversible upon discontinuation. |
| Clinical Pearls | Amoxapine is a dibenzoxazepine antidepressant with both tricyclic-like reuptake inhibition and dopamine receptor blocking properties. Monitor for extrapyramidal symptoms (EPS) and tardive dyskinesia, especially in elderly. Due to dopamine blockade, it may cause hyperprolactinemia. For patients with seizures, use cautiously; dose-dependent seizure risk is higher than with other TCAs. Onset of antidepressant effect may be 2-4 weeks. Use lower initial doses in elderly and hepatic impairment. Avoid in recent myocardial infarction. |
| Patient Advice | Take exactly as prescribed; do not increase or stop abruptly without consulting your doctor. · May cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how the medication affects you. · Avoid alcohol and other CNS depressants. · Report any muscle stiffness, tremor, restlessness, or unusual movements of the face or tongue. · Notify your doctor if you experience rapid or irregular heartbeat, difficulty urinating, or blurred vision. · May cause dry mouth; use sugarless candy or gum and maintain good oral hygiene. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Do not take any other medications, including over-the-counter products, without approval from your healthcare provider. |