Mirtazapine Dosing in Renal Impairment
For patients with impaired renal function, mirtazapine requires dose reduction: decrease the dose by approximately 30% in moderate renal impairment (GFR 11-39 mL/min/1.73 m²) and by 50% in severe renal impairment (GFR <10 mL/min/1.73 m²), with careful monitoring for adverse effects. 1
Renal Function-Based Dosing Algorithm
The FDA label provides clear guidance on dose adjustments based on degree of renal impairment 1:
- Moderate renal impairment (GFR 11-39 mL/min/1.73 m²): Reduce total body clearance by approximately 30% compared to normal renal function, requiring proportional dose reduction 1
- Severe renal impairment (GFR <10 mL/min/1.73 m²): Reduce total body clearance by approximately 50%, necessitating a 50% dose reduction 1
- Normal renal function (GFR >60 mL/min/1.73 m²): Standard dosing applies—start at 15 mg once daily at bedtime, with effective range of 15-45 mg/day 2, 3
Practical Dosing Recommendations
Starting dose in renal impairment: Begin with 7.5 mg once daily at bedtime for moderate impairment, or 7.5 mg every other day for severe impairment, then titrate slowly based on clinical response and tolerability 1
- The standard starting dose of 15 mg/day should be reduced proportionally to the degree of clearance reduction 1
- Titration should proceed more slowly than in patients with normal renal function, allowing adequate time to assess tolerability 1
- Maximum doses should be proportionally reduced: 30 mg/day for moderate impairment and 22.5 mg/day for severe impairment 1
Critical Pharmacokinetic Considerations
Mirtazapine's renal elimination makes dose adjustment essential 1, 4:
- Approximately 75% of mirtazapine and its metabolites are eliminated via urine, with only 15% in feces 1, 4
- The elimination half-life of 20-40 hours allows once-daily dosing but also means accumulation occurs over 4-6 days to reach steady state 2, 4
- Plasma protein binding (85%) is nonspecific and reversible, but reduced renal clearance increases systemic exposure 4
Monitoring Requirements
Close monitoring for adverse effects is mandatory in renal impairment 1:
- Assess for excessive sedation, which is the most common adverse effect and may be more pronounced with reduced clearance 2, 3
- Monitor for orthostatic hypotension, particularly in elderly patients who often have concurrent renal impairment 1
- Watch for increased appetite and weight gain, which occur more frequently than with placebo (11% vs 2% and 10% vs 1%, respectively) 5
- Evaluate for dry mouth (25% vs 16% with placebo), though anticholinergic effects are generally minimal 5
Special Considerations in Elderly Patients with Renal Impairment
The combination of age and renal impairment requires particular caution 1:
- Elderly patients have 40% lower oral clearance in males and 10% lower in elderly females compared to younger patients 1
- Females exhibit significantly longer elimination half-lives (mean 37 hours) compared to males (mean 26 hours) across all ages 1
- Sedating drugs like mirtazapine may cause confusion and over-sedation in the elderly, and elderly patients are at greater risk of hyponatremia 1
- Start at the lowest possible dose (7.5 mg or less) in elderly patients with renal impairment 1
Common Pitfalls to Avoid
- Never use standard dosing without assessing renal function—this is the most critical error, as reduced clearance leads to drug accumulation and increased adverse effects 1
- Do not assume hemodialysis significantly removes mirtazapine—it contributes minimally to drug clearance, so post-dialysis supplementation is not required 1
- Avoid combining renal impairment with hepatic impairment without further dose reduction, as hepatic impairment alone decreases clearance by 30% 1
- Do not overlook the 4-6 day period to reach steady state when assessing efficacy or tolerability—premature dose escalation increases risk of adverse effects 4
Drug Interactions Affecting Clearance
Be aware of medications that may further compromise mirtazapine clearance 1, 4: