What is the recommended dosage of nintedanib (BIBF 1120) in patients with Chronic Kidney Disease (CKD)?

Nintedanib Dosing in Patients with Chronic Kidney Disease

For patients with chronic kidney disease (CKD), nintedanib does not require dose adjustment regardless of renal function severity, as the drug is primarily eliminated via hepatic metabolism with less than 1% excreted in urine. 1

Pharmacokinetic Rationale

Nintedanib's pharmacokinetic profile supports its use without dose modification in CKD patients:

• Less than 1% of drug-related radioactivity is eliminated in urine 1
• Metabolism occurs primarily via hydrolytic ester cleavage, resulting in formation of the free acid moiety that is subsequently glucuronidated and excreted in feces 1
• Renal function has no significant influence on nintedanib pharmacokinetics 1

Dosing Recommendations

The standard dosing for nintedanib should be maintained in CKD patients:

• 150 mg twice daily is the typical starting dose
• No adjustment needed based on CKD stage or eGFR

Important Monitoring Considerations

While renal dose adjustment is not required, patients with CKD require careful monitoring:

1. Hepatic function: Monitor liver enzymes regularly as nintedanib is primarily metabolized by the liver 1

   • Administration in patients with moderate or severe hepatic impairment is not recommended
   • Patients with mild hepatic impairment should be monitored closely with dose adjustment if needed

2. Drug interactions: Be aware of potential interactions with medications commonly used in CKD patients

   • Concomitant treatment with potent inhibitors or inducers of P-glycoprotein transporters can affect nintedanib pharmacokinetics 1
   • Nintedanib has low potential for interactions with drugs metabolized by cytochrome P450 enzymes

3. Adverse effects: Monitor for common side effects, particularly:

   • Diarrhea (reported in up to 75.7% of patients) 2
   • Decreased appetite and nausea 3
   • Hepatic function abnormalities (reported in 14.4% of patients) 3

Special Considerations

1. Rare renal complications: Though uncommon, cases of renal thrombotic microangiopathy have been reported with nintedanib use 4. Monitor for:

   • Development of proteinuria
   • Changes in renal function
   • Hypertension

2. Discontinuation considerations: In real-world studies, discontinuation rates can be high (64.8% at 24 months), primarily due to adverse events 3. Have a plan for managing side effects to improve medication adherence.

Clinical Approach

1. Initiate nintedanib at standard dose of 150 mg twice daily
2. Monitor hepatic function closely, especially in early treatment
3. Implement proactive management strategies for gastrointestinal side effects
4. No specific renal function monitoring required beyond standard CKD care
5. Consider drug interactions with other medications in the patient's regimen

Remember that while nintedanib doesn't require renal dose adjustment, the overall medication regimen for CKD patients should be carefully evaluated to minimize polypharmacy and drug interaction risks.