Modafinil Dosing in End-Stage Renal Disease (ESRD)
For patients with ESRD, the recommended dose of modafinil (Provigil) should be reduced to 200 mg once daily. While there are limited specific guidelines for modafinil in ESRD, this recommendation is based on pharmacokinetic principles and available evidence on medication dosing in renal impairment.
Pharmacokinetic Considerations in ESRD
- Modafinil is primarily eliminated via metabolism in the liver, with subsequent excretion of metabolites in the urine 1
- Less than 10% of modafinil is excreted unchanged in the urine, but elimination processes can be significantly slowed in patients with renal impairment 1
- In patients with renal insufficiency, there are substantial increases in levels of modafinil acid (a metabolite), necessitating caution with dosing 2
Dosing Recommendations
- Initial dose: 200 mg once daily in the morning 3
- Avoid dose escalation to 400 mg daily (which would be standard in patients with normal renal function) 3
- Timing: Administer in the morning to minimize potential sleep disruption 3
- For patients on hemodialysis: Administer after dialysis sessions on dialysis days 4
Monitoring Recommendations
- Monitor for excessive CNS stimulation, insomnia, headache, and cardiovascular effects (especially hypertension) 2
- ESRD patients are at increased risk of adverse drug reactions and drug-drug interactions due to altered pharmacokinetics 5
- Pay particular attention to potential drug interactions as modafinil can induce or inhibit several cytochrome P450 enzymes 1
Special Considerations
- Patients with ESRD often take multiple medications, increasing the risk of drug-drug interactions 5
- Modafinil may affect the pharmacokinetics of other drugs metabolized by certain CYP enzymes, particularly CYP3A4, CYP1A2, CYP2B6, and CYP2C19 1
- Common adverse events to monitor include insomnia, headache, nausea, nervousness, and hypertension 2
Clinical Pearls
- The elimination half-life of modafinil (normally 12-15 hours) may be prolonged in ESRD patients 1
- Dose adjustments should be conservative, starting with the lower recommended dose and titrating based on clinical response and tolerability 2
- While specific ESRD dosing guidelines for modafinil are limited, the approach follows general principles for medication dosing in renal impairment 4
Remember that ESRD patients are particularly vulnerable to adverse drug reactions due to altered drug metabolism and elimination, as well as the presence of multiple comorbidities and concomitant medications 5.