What is the appropriate Hydroxyurea dose adjustment for a patient with impaired renal function (CrCl of 28) currently taking 500mg every 2 days?

Hydroxyurea Dose Adjustment for Impaired Renal Function

For a patient with CrCl of 28 mL/min currently taking hydroxyurea 500mg every 2 days, the dose should be reduced to 250mg every 2 days (50% of current dose) due to impaired renal function. 1

Rationale for Dose Adjustment

• The FDA drug label specifically recommends reducing the dose of hydroxyurea by 50% in patients with measured creatinine clearance of less than 60 mL/min 1
• With a CrCl of 28 mL/min, this patient falls well below this threshold and requires dose adjustment 1
• Systemic exposure to hydroxyurea increases and urinary recovery decreases as the degree of renal insufficiency worsens 2

Pharmacokinetic Considerations

• Hydroxyurea is primarily eliminated through renal clearance, making dose adjustment essential in renal impairment 2
• Research shows that patients with renal impairment have higher systemic exposure to hydroxyurea, which increases risk of toxicity 2
• The recommended initial dosing regimen for patients with CrCl <60 mL/min is 7.5 mg/kg/day (compared to 15 mg/kg/day in patients with normal renal function) 2

Monitoring Recommendations

• Close monitoring of hematologic parameters is advised in patients with renal impairment receiving hydroxyurea 1
• Monitor for signs of myelosuppression, which is the most common adverse effect of hydroxyurea 1
• Leukopenia is generally the first and most common manifestation of bone marrow suppression, followed by thrombocytopenia and anemia 1

Administration Considerations

• If the patient is on dialysis, hydroxyurea should be administered following hemodialysis sessions 1
• The capsules should be swallowed whole and not opened, broken, or chewed as hydroxyurea is a cytotoxic drug 1
• Prophylactic administration of folic acid is recommended during hydroxyurea therapy 1

Toxicity Management

• Monitor blood counts at least once weekly during hydroxyurea therapy 1
• Consider further dose modifications or temporary discontinuation if severe myelosuppression occurs 1
• Recovery from myelosuppression is usually rapid when therapy is interrupted 1

By following these recommendations, you can help minimize the risk of toxicity while maintaining therapeutic efficacy in this patient with impaired renal function.