Nintedanib Dosage in Chronic Kidney Disease
No dose adjustment of nintedanib is required for patients with mild to moderate chronic kidney disease (CrCl ≥30 mL/min), but the drug is contraindicated in severe renal impairment (CrCl <30 mL/min) due to lack of safety and efficacy data. 1
Standard Dosing and Renal Function Considerations
The standard dose of nintedanib is 150 mg twice daily for idiopathic pulmonary fibrosis, with dose reductions to 100 mg twice daily available for managing adverse effects 1
Renal function has no clinically significant influence on nintedanib pharmacokinetics in mild to moderate CKD, as nintedanib undergoes primarily hepatic metabolism via hydrolytic ester cleavage followed by glucuronidation, with less than 1% of drug-related radioactivity eliminated in urine 1
The terminal elimination half-life remains approximately 10-15 hours regardless of renal function in patients with CrCl ≥30 mL/min, and accumulation after repeated twice-daily dosing is negligible 1
Contraindications and Warnings
Nintedanib is contraindicated in patients with severe renal impairment (CrCl <30 mL/min) because safety, efficacy, and pharmacokinetics have not been studied in this population 2, 1
No formal dosage adjustment guidelines exist for patients on hemodialysis or peritoneal dialysis, as these patients were excluded from clinical trials 2
Emerging Evidence in Severe CKD
A single case report from 2024 described successful use of nintedanib 150 mg twice daily in a patient who progressed to stage 3/4 CKD and eventually required hemodialysis, with good tolerability, sporadic diarrhea as the only adverse effect, and no toxic effects observed during dialysis 2
This case demonstrated stable pulmonary function and improved 6-minute walk test results despite concurrent severe renal impairment, though renal biopsy showed no correlation between nintedanib use and kidney disease 2
However, this represents only anecdotal evidence from a single patient, and more studies are necessary before recommending nintedanib in severe CKD or dialysis patients 2
Monitoring Recommendations
Careful monitoring of both liver and kidney function is essential when using nintedanib in any patient with CKD, particularly those approaching the CrCl threshold of 30 mL/min 2
Creatinine clearance should be calculated using the Cockcroft-Gault formula to determine eligibility for nintedanib therapy, as this is the standard method for drug dosing adjustments in renal impairment 3, 4, 5
Clinical Decision Algorithm
For patients with CKD considering nintedanib:
CrCl ≥30 mL/min: Use standard dose of 150 mg twice daily without adjustment; monitor renal function regularly 1
CrCl <30 mL/min (not on dialysis): Nintedanib is contraindicated; consider alternative therapies 1
End-stage renal disease on dialysis: Nintedanib is contraindicated per current evidence, though exceptional use with intensive monitoring may be considered in consultation with nephrology if no alternatives exist and potential benefits outweigh unknown risks 2, 1
Important Caveats
The lack of renal elimination does not eliminate the need for caution in severe CKD, as chronic kidney disease can affect drug metabolism, protein binding, and drug transporter activity beyond simple renal excretion 3, 5
Concomitant use of P-glycoprotein inhibitors or inducers can affect nintedanib pharmacokinetics and should be avoided or used with caution, particularly in patients with any degree of renal impairment 1