Is hydralazine removed by dialysis?

Hydralazine Removal During Dialysis

Hydralazine is not significantly removed by dialysis, and therefore no dose adjustment or supplemental dosing is required after dialysis sessions. 1

Pharmacokinetics of Hydralazine in Dialysis

Hydralazine is primarily metabolized by the liver through acetylation and oxidative pathways, with minimal renal excretion of unchanged drug. This pharmacokinetic profile explains why dialysis has limited impact on hydralazine clearance:

• Unlike medications that are primarily cleared by the kidneys, hydralazine undergoes extensive hepatic metabolism
• The K/DOQI clinical practice guidelines do not list hydralazine among medications that require supplemental dosing after hemodialysis 1
• In contrast to medications like midodrine which are "effectively cleared by HD" with half-life reduced to 1.4 hours during dialysis, hydralazine maintains its pharmacokinetic profile during dialysis sessions 1

Comparison with Other Medications in Dialysis

The American Thoracic Society/CDC/IDSA guidelines provide a useful comparison by categorizing medications based on their dialyzability:

• Medications that are dialyzable: atenolol, nadolol, practolol, sotalol
• Medications that are NOT dialyzable: betaxolol, carvedilol, labetalol, propranolol, timolol 1

Hydralazine belongs to the category of medications that are not significantly removed by dialysis due to its:

• Extensive hepatic metabolism
• Complex metabolic pathways dependent on acetylator status
• Limited renal excretion of unchanged drug 2

Clinical Implications

For patients receiving hydralazine who are on dialysis:

1. No supplemental dosing needed: Unlike some medications that require post-dialysis supplementation, hydralazine does not need additional dosing after dialysis sessions 1

2. Dose adjustment for renal function: While not significantly removed by dialysis, hydralazine does show altered pharmacokinetics in renal impairment:

   • Serum half-life increases as GFR decreases (r=-0.69; p<0.01)
   • Patients with GFR <30 ml/min show significant drug accumulation 3

3. Monitoring considerations:

   • Patients with severe renal impairment may require lower doses due to slower elimination
   • The ratio between minimum steady-state drug concentration and daily dose increases as GFR decreases 3

Dosing Considerations

When prescribing hydralazine to dialysis patients:

• Standard dosing can be maintained without post-dialysis supplementation
• Consider potential for drug accumulation in patients with severely reduced GFR
• Monitor for side effects which may be more common due to altered pharmacokinetics
• For heart failure patients on dialysis, the standard dosing of isosorbide dinitrate and hydralazine (20-40 mg isosorbide dinitrate and 37.5-75 mg hydralazine three times daily) can be maintained 1

Conclusion

Hydralazine undergoes extensive hepatic metabolism with minimal renal clearance of unchanged drug, making it a medication that is not significantly removed by dialysis. Therefore, no supplemental dosing is required after dialysis sessions, though dose adjustments may be needed based on the patient's overall renal function due to altered pharmacokinetics in renal impairment.