Phenergan (Promethazine) Renal Dosing
No specific dose adjustment is required for promethazine in renal impairment, as it is primarily metabolized hepatically with minimal renal elimination; however, use with caution in severe renal dysfunction (CrCl <30 mL/min) and consider reducing doses or extending intervals to minimize risk of metabolite accumulation and enhanced sedative effects.
Primary Metabolism and Elimination
- Promethazine undergoes extensive hepatic metabolism via sulfoxidation and demethylation, with renal excretion playing a minor role in elimination of parent drug 1, 2.
- Unlike renally-cleared medications that require systematic dose reduction based on GFR, promethazine's pharmacokinetics are not significantly altered by mild to moderate renal impairment 3.
Practical Dosing Approach by Renal Function
Mild to Moderate Renal Impairment (CrCl 30-89 mL/min)
- Standard dosing can be maintained without adjustment, as hepatic clearance remains the primary elimination pathway 2, 3.
- Monitor for enhanced sedation, as uremia may increase sensitivity to CNS depressants 1.
Severe Renal Impairment (CrCl <30 mL/min)
- Consider reducing individual doses by 25-50% OR extending dosing intervals (e.g., every 8-12 hours instead of every 4-6 hours) 1, 3.
- This conservative approach accounts for potential accumulation of minor metabolites and altered protein binding in uremia 2.
- Start with lower doses (e.g., 12.5 mg instead of 25 mg) and titrate based on clinical response 1.
End-Stage Renal Disease (ESRD) and Dialysis
- Use the lowest effective dose with extended intervals, as promethazine is not significantly removed by hemodialysis due to high protein binding and large volume of distribution 1, 2.
- Timing relative to dialysis sessions is not critical, unlike water-soluble drugs 1.
Critical Safety Considerations
- Avoid combining with other CNS depressants (opioids, benzodiazepines) in renal impairment, as uremia enhances sedative effects and increases fall risk 1.
- Monitor for anticholinergic toxicity (confusion, urinary retention, constipation), which is amplified in elderly patients with renal dysfunction 1.
- Reassess renal function regularly (every 2-3 days in hospitalized patients) to adjust dosing if kidney function deteriorates 4, 3.
Common Pitfalls to Avoid
- Do not assume all antihistamines require renal dose adjustment—promethazine's hepatic metabolism distinguishes it from renally-cleared alternatives 2, 3.
- Avoid using standard GFR-based dosing algorithms designed for renally-eliminated drugs, as these do not apply to promethazine 3.
- Be cautious in elderly patients (>65 years), who often have both reduced renal function and increased sensitivity to anticholinergic effects 5, 1.
- Do not overlook reduced protein binding in uremia, which may increase free drug concentrations and enhance pharmacologic effects even without dose adjustment 2.
Alternative Considerations
- For patients with severe renal impairment requiring antiemetic therapy, consider ondansetron (no renal adjustment needed) or metoclopramide (requires dose reduction in CrCl <40 mL/min) as alternatives with more predictable pharmacokinetics 3.