What considerations should be taken when prescribing Diflucan (fluconazole) to a 78-year-old female with potential impaired renal function?

Prescribing Diflucan (Fluconazole) for a 78-Year-Old Female

Fluconazole dosing in elderly patients must be adjusted based on renal function, with a 50% dose reduction required for creatinine clearance between 30-50 mL/min and either 50% dose reduction or extended dosing intervals for CrCl <30 mL/min. 1, 2

Critical First Step: Assess Renal Function

• Calculate creatinine clearance using the Cockcroft-Gault equation rather than relying on serum creatinine alone, as serum creatinine is unreliable in elderly patients 3
• For a 78-year-old female, use the formula: 0.85 × [Weight (kg) × (140 - age)] / [72 × serum creatinine (mg/dL)] 2
• Be aware that glomerular filtration rate declines approximately 10 mL/min every 10 years after age 40, making renal impairment highly likely in this age group 3

Dosing Algorithm Based on Renal Function

For CrCl >50 mL/min (Normal Function)

• Administer standard dosing without adjustment 2
• Loading dose: 50-400 mg depending on indication 2
• Maintenance: Full dose according to infection type 2

For CrCl 30-50 mL/min (Moderate Impairment)

• Give initial loading dose as normal (50-400 mg based on indication) 2
• Reduce maintenance dose by 50% of the standard daily dose 1, 2
• Example: If standard dose is 400 mg daily, give 200 mg daily 2

For CrCl <30 mL/min (Severe Impairment)

• Give initial loading dose as normal 2
• Either reduce dose by 50% OR extend dosing interval 1, 2
• This flexibility allows clinical judgment based on infection severity 2

For Hemodialysis Patients

• Administer 100% of recommended dose after each hemodialysis session 2
• On non-dialysis days, dose according to creatinine clearance 2
• Hemodialysis removes approximately 50% of fluconazole over 3 hours 2

Pharmacokinetic Considerations in the Elderly

• Fluconazole half-life extends to 46.2 hours in elderly patients (versus 30 hours in younger adults), increasing drug accumulation risk 2
• Renal clearance decreases significantly in elderly patients (0.124 mL/min/kg versus higher values in younger patients) 2
• 80% of fluconazole is excreted unchanged in urine, making renal function the primary determinant of drug clearance 2, 4
• The terminal elimination half-life correlates inversely with creatinine clearance 2

Drug Interaction Monitoring

• Review all concurrent medications as fluconazole inhibits CYP3A4 and can increase levels of warfarin, oral hypoglycemics, phenytoin, and cyclosporine 4
• Tacrolimus levels can increase 1.33-2.45 times when combined with fluconazole, even at low fluconazole doses in patients with renal impairment 5
• Rifampin decreases fluconazole clearance and should be avoided if possible 4

Monitoring Requirements

• Baseline assessment: Obtain creatinine clearance, liver function tests, and complete medication list 2, 3
• Ongoing monitoring: Check renal function periodically, especially if using nephrotoxic medications concurrently 3
• For drug interactions: Monitor therapeutic drug levels of interacting medications (e.g., tacrolimus, warfarin) more frequently 5

Common Pitfalls to Avoid

• Do not rely on serum creatinine alone - it underestimates renal impairment in elderly patients with reduced muscle mass 3
• Do not skip the loading dose - even with renal impairment, the initial loading dose should be given to achieve therapeutic levels quickly 2
• Do not assume single-dose therapy needs adjustment - vaginal candidiasis treatment with a single dose requires no renal adjustment 2
• Do not forget that even low-dose fluconazole (100 mg every other day IV) can cause significant drug interactions in patients with pre-existing renal impairment 5

Practical Dosing Examples

For oropharyngeal candidiasis with CrCl 35 mL/min:

• Day 1: 200 mg loading dose 2
• Day 2 onward: 100 mg daily (50% reduction) 1, 2
• Duration: Minimum 2 weeks 2

For systemic candidiasis with CrCl 25 mL/min:

• Day 1: 400 mg loading dose 2
• Day 2 onward: Either 200 mg daily OR 400 mg every 48 hours 1, 2
• Adjust based on clinical response and tolerance 2