REMERON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REMERON (REMERON).
Mirtazapine is an antagonist at central presynaptic α2-adrenergic receptors, which increases central noradrenergic and serotonergic activity. It is also a potent antagonist of 5-HT2 and 5-HT3 receptors and H1 histamine receptors.
| Metabolism | Primarily metabolized by CYP1A2, CYP2D6, and CYP3A4. Major metabolites include demethylmirtazapine, which is less active. |
| Excretion | Renal: 75% (as metabolites, <1% unchanged); Fecal: 25% (as metabolites) |
| Half-life | Terminal elimination half-life: 20-40 hours (mean 30 hours); longer in elderly (up to 60 hours) and patients with hepatic impairment |
| Protein binding | 85% bound to plasma proteins (primarily alpha1-acid glycoprotein and albumin) |
| Volume of Distribution | Vd: 1.1-1.5 L/kg, indicating extensive tissue distribution |
| Bioavailability | Oral bioavailability: 50% (due to first-pass metabolism) |
| Onset of Action | Oral: 2-4 weeks for antidepressant effect; sedation occurs within hours of first dose |
| Duration of Action | Antidepressant effect persists for weeks; sedation may persist for 24-48 hours after single dose |
Initial: 15 mg orally once daily at bedtime, may increase every 1-2 weeks; usual effective dose: 15-45 mg/day; maximum: 45 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 50%; GFR <30 mL/min: reduce dose by 75% or use alternative. |
| Liver impairment | Child-Pugh Class A or B: reduce dose by 50%; Child-Pugh Class C: contraindicated. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Initial dose: 7.5 mg orally once daily; increase cautiously; maximum dose: 45 mg/day; monitor for sedation and orthostatic hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REMERON (REMERON).
| Breastfeeding | Excreted in breast milk; M/P ratio approximately 1.1. Limited data; monitor infant for drowsiness, poor feeding, and weight gain. Use caution, especially with high doses or prolonged use. |
| Teratogenic Risk | Pregnancy Category C. First trimester: limited human data; animal studies show increased fetal loss and growth retardation. Second/third trimester: risk of neonatal withdrawal syndrome (irritability, abnormal crying, tremor) and possible persistent pulmonary hypertension of the newborn (PPHN). |
| Fetal Monitoring |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Mirtazapine is not approved for use in pediatric patients.
| Serious Effects |
["Hypersensitivity to mirtazapine or any component of the formulation","Concomitant use with MAOIs or within 14 days of MAOI use","Concomitant use with linezolid or intravenous methylene blue"]
| Precautions | ["Suicidality in children, adolescents, and young adults","Agranulocytosis (rare but serious)","Serotonin syndrome","Increased cholesterol and triglycerides","QT prolongation","Hyponatremia","Drowsiness and sedation"] |
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| Monitor maternal serum levels if toxicity suspected; fetal ultrasound for growth parameters; neonatal monitoring for withdrawal symptoms and respiratory adaptation at delivery. |
| Fertility Effects | May alter reproductive function via hyperprolactinemia in females (galactorrhea, amenorrhea) and decreased libido in both sexes; reversible upon discontinuation. |