What are the contraindications to resuming Ofev (nintedanib) as an inpatient?

Contraindications to Resuming Ofev (Nintedanib) as an Inpatient

Nintedanib should not be resumed in inpatients with severe hepatic impairment, active liver injury with AST/ALT >3x upper limit of normal with symptoms (or >5x without symptoms), severe renal impairment (creatinine clearance <30 mL/min), or active bleeding complications. 1, 2, 3

Absolute Contraindications

Hepatic Impairment

• Do not resume nintedanib if liver enzymes are elevated >3x upper limit of normal with symptoms or >5x upper limit of normal without symptoms 1, 2
• Moderate to severe hepatic impairment is a contraindication to use 1, 3
• Active cholestatic jaundice or hepatic dysfunction requires permanent discontinuation 1

Severe Renal Impairment

• Nintedanib is contraindicated in patients with creatinine clearance <30 mL/min 4, 5
• While one case report showed tolerability in a dialysis patient, this represents off-label use with insufficient safety data 5
• For creatinine clearance 30-60 mL/min, consider dose reduction to 100 mg twice daily with close monitoring 4

Relative Contraindications Requiring Dose Hold

Gastrointestinal Toxicity

• Hold nintedanib for severe (Grade 3-4) diarrhea, nausea, vomiting, or abdominal pain until symptoms improve to Grade 1 or better 2, 6
• Resume at reduced dose of 100 mg twice daily after resolution 4, 2
• Persistent Grade 2 symptoms despite anti-diarrheal management warrant temporary discontinuation 6

Bleeding Risk

• Active bleeding or high bleeding risk situations require careful assessment before resuming 6
• While bleeding events are rarely reported in real-world data, nintedanib's mechanism (VEGF inhibition) carries theoretical bleeding risk 3, 6

Cardiovascular Events

• Acute cardiovascular events should prompt temporary hold until stabilized 6
• Though cardiovascular adverse events are rarely reported, they warrant caution in the inpatient setting 6

Clinical Algorithm for Resumption Decision

Step 1: Check liver function tests

• If AST/ALT >3x ULN with symptoms OR >5x ULN without symptoms → Do not resume 1, 2
• If AST/ALT 1-3x ULN → May resume with close monitoring 1
• If normal → Proceed to Step 2 1

Step 2: Assess renal function

• If CrCl <30 mL/min → Do not resume 4, 5
• If CrCl 30-60 mL/min → Resume at 100 mg twice daily 4
• If CrCl >60 mL/min → Proceed to Step 3 4

Step 3: Evaluate gastrointestinal symptoms

• If Grade 3-4 symptoms present → Hold until Grade ≤1, then resume at 100 mg twice daily 2, 6
• If Grade 1-2 symptoms → May resume with anti-diarrheal prophylaxis 6
• If no symptoms → Resume at previous tolerated dose 2

Step 4: Screen for active bleeding or acute cardiovascular events

• If present → Hold until resolved 6
• If absent → Safe to resume 6

Important Monitoring Requirements Upon Resumption

• Liver function tests should be checked monthly for the first 3 months, then every 3 months thereafter 1
• Monitor for diarrhea (occurs in 62-67% of patients) and have anti-diarrheal medications readily available 2, 6, 7
• Assess for nausea (50% incidence), vomiting, and weight loss 4, 7

Common Pitfalls to Avoid

• Do not resume at full dose (150 mg twice daily) after a treatment interruption for adverse events - always consider starting at 100 mg twice daily 4, 2
• Do not overlook baseline liver function - hepatotoxicity is a significant risk requiring proactive monitoring 1, 6
• Do not assume renal safety in severe CKD - despite one case report, safety data are insufficient for CrCl <30 mL/min 5
• Do not withhold anti-diarrheal prophylaxis - proactive management improves tolerability and reduces discontinuation rates 6