What are the considerations for starting nintedanib (Ofev) on a patient already taking Tegretol (carbamazepine)?

Nintedanib and Carbamazepine Interaction Considerations

Caution is warranted when starting nintedanib (Ofev) in a patient taking carbamazepine (Tegretol) due to potential drug interactions that may reduce nintedanib effectiveness, as carbamazepine is a strong CYP3A4 inducer that can decrease nintedanib plasma concentrations. 1

Drug Interaction Mechanism

• Carbamazepine is a strong CYP3A4 inducer that can significantly decrease nintedanib plasma concentrations, potentially reducing its therapeutic efficacy 1
• For patients in whom CYP3A4 inducers like carbamazepine are indicated, alternative agents with less enzyme-induction potential should be considered whenever possible 1
• If nintedanib must be administered with carbamazepine, a dose adjustment of nintedanib may be necessary to maintain therapeutic levels 1

Monitoring Recommendations

• Liver function tests (LFTs) should be monitored monthly for the first 3 months of nintedanib therapy, then every 3 months thereafter 1
• Close monitoring for reduced efficacy of nintedanib is essential when co-administered with carbamazepine 1
• Monitor for diarrhea and weight loss, which are common adverse effects of nintedanib 1
• The standard starting dose of nintedanib is 100-150 mg PO every 12 hours, but this may need adjustment based on the interaction with carbamazepine 1

Clinical Considerations for Specific Patient Populations

For Systemic Sclerosis-Associated ILD (SSc-ILD)

• Nintedanib is conditionally recommended as a first-line ILD treatment option in SSc-ILD 1
• The potential reduction in nintedanib efficacy due to carbamazepine interaction is particularly concerning in SSc-ILD patients, where nintedanib has demonstrated benefit 1
• Consider whether alternative anticonvulsants with less CYP3A4 induction could be substituted for carbamazepine in these patients 1

For Other SARD-ILD Types

• For SjD-ILD, IIM-ILD, and MCTD-ILD, nintedanib is conditionally recommended against as a first-line treatment option 1
• For RA-ILD, there is no consensus on whether to recommend nintedanib as a first-line treatment option 1
• The drug interaction with carbamazepine may be less clinically significant in conditions where nintedanib is not a first-line recommendation 1

Management Strategies

• If possible, consider alternative anticonvulsants with less enzyme-induction potential than carbamazepine 1
• If carbamazepine cannot be discontinued or substituted:
  • Consider increasing the nintedanib dose, though this should be done cautiously with close monitoring for adverse effects 1
  • Monitor LFTs more frequently to assess for both potential hepatotoxicity and to ensure adequate therapeutic effect 1
  • Be vigilant for signs of reduced nintedanib efficacy, such as worsening pulmonary symptoms or decline in pulmonary function tests 2

Safety Considerations

• Nintedanib is associated with hepatotoxicity, diarrhea, increased risk of cardiovascular events, and potential increased risk of bleeding 1
• Carbamazepine itself has problematic side effects and requires regular monitoring of complete blood cell count and liver enzyme levels 1
• The combination may lead to reduced efficacy of nintedanib rather than increased toxicity 1
• No significant bleeding episodes have been reported in patients taking nintedanib with anticoagulant therapy, suggesting some drug combinations can be managed safely 2

Practical Recommendations

• Establish baseline pulmonary function tests before starting nintedanib to better assess any changes in efficacy 3
• Consider more frequent monitoring of FVC and DLCO to detect any accelerated decline that might indicate reduced nintedanib efficacy 2
• Educate the patient about potential gastrointestinal side effects, which are the most common reason for nintedanib discontinuation 2
• If diarrhea occurs, prompt management is essential to maintain adherence to therapy 2