Mirtazapine (Remeron) Dosing in Renal Impairment
Reduce the mirtazapine dose in patients with moderate to severe renal impairment, as clearance is decreased by approximately 30% when GFR is 11-39 mL/min/1.73 m² and by 50% when GFR is <10 mL/min/1.73 m². 1
Dosing Algorithm by Renal Function
Moderate Renal Impairment (GFR 11-39 mL/min/1.73 m²):
- Start with 7.5-15 mg once daily at bedtime 1, 2
- Titrate cautiously with close monitoring for adverse effects 1
- Maximum dose should be reduced compared to patients with normal renal function 1
Severe Renal Impairment (GFR <10 mL/min/1.73 m²):
- Start with 7.5 mg once daily at bedtime 1, 2
- Titrate very slowly due to 50% reduction in clearance 1
- Consider maximum dose of 30 mg/day rather than the standard 45 mg/day 1
Hemodialysis Patients:
- Use the same dosing as severe renal impairment (GFR <10 mL/min/1.73 m²) 1
- Timing relative to dialysis is not critical, as approximately 75% of mirtazapine is excreted via urine but the drug is extensively protein-bound (85%) 1, 2
Key Pharmacokinetic Considerations
Why dose reduction is necessary:
- Mirtazapine and its metabolites are eliminated predominantly (75%) via urine 1
- Total body clearance is reduced by 30% in moderate renal impairment and 50% in severe renal impairment 1, 2
- The elimination half-life of 20-40 hours may be prolonged in renal dysfunction 1, 2
Critical Monitoring Parameters
Enhanced monitoring is essential in renal impairment:
- Sedation and somnolence: The most common adverse effect, which may be exacerbated by drug accumulation 1, 3
- Orthostatic hypotension: Due to peripheral α1-adrenergic receptor blockade, particularly problematic in elderly patients with renal dysfunction 1, 4
- Weight gain and increased appetite: Monitor closely as these effects occur in 10-11% of patients and may worsen with higher drug levels 3, 5
Special Population Considerations
Elderly patients with renal impairment require extra caution:
- Clearance is already reduced by 40% in elderly males and 10% in elderly females compared to younger patients 1
- Combined renal and age-related clearance reductions necessitate starting at the lowest possible dose (7.5 mg) 1
- Elderly patients are at greater risk for confusion, over-sedation, and hyponatremia 1
Females with renal impairment:
- Elimination half-life is significantly longer in females (mean 37 hours) versus males (mean 26 hours) 1
- This gender difference combined with renal impairment may require even more conservative dosing 1
Common Pitfalls to Avoid
- Do not use standard dosing (15-45 mg/day) without adjustment in patients with GFR <40 mL/min/1.73 m², as this will lead to drug accumulation and increased adverse effects 1
- Avoid rapid titration in renally impaired patients; allow at least 1-2 weeks between dose increases to assess steady-state effects 2
- Do not assume hemodialysis removes significant amounts of drug; mirtazapine is 85% protein-bound and dialysis contributes minimally to clearance 1, 2
- Monitor for drug interactions with CYP3A4 inhibitors (e.g., ketoconazole), which can increase mirtazapine levels by 50% on top of renal impairment 1
Practical Dosing Summary
| Renal Function | Starting Dose | Titration | Maximum Dose |
|---|---|---|---|
| Normal (GFR ≥60) | 15 mg qHS | Increase by 15 mg every 1-2 weeks | 45 mg/day [1] |
| Moderate (GFR 11-39) | 7.5-15 mg qHS | Increase by 7.5-15 mg every 2 weeks | 30 mg/day [1] |
| Severe (GFR <10) | 7.5 mg qHS | Increase by 7.5 mg every 2-4 weeks | 30 mg/day [1] |
| Hemodialysis | 7.5 mg qHS | Increase by 7.5 mg every 2-4 weeks | 30 mg/day [1] |