From the Guidelines
Nintedanib is recommended for idiopathic pulmonary fibrosis (IPF) at a standard dose of 150 mg taken orally twice daily with food, approximately 12 hours apart. This recommendation is based on the results of the INPULSIS-1 and INPULSIS-2 trials, which demonstrated that nintedanib slows disease progression by reducing the decline in forced vital capacity (FVC) 1. The medication should be taken consistently long-term as it does not cure IPF, but rather slows its progression.
Key considerations for the use of nintedanib in IPF include:
- Dose reduction to 100 mg twice daily may be necessary if patients experience adverse effects, particularly gastrointestinal symptoms like diarrhea, nausea, or abdominal pain, which were commonly reported in the INPULSIS trials 1.
- Liver function tests should be monitored regularly, with testing recommended before treatment initiation, monthly for three months, then quarterly thereafter, due to the potential for nintedanib to cause liver injury.
- Nintedanib works by inhibiting multiple tyrosine kinases involved in fibrotic processes, thereby slowing the decline in lung function, as evidenced by the significant reduction in FVC decline in patients treated with nintedanib compared to placebo 1.
- The medication should be used as part of a comprehensive treatment approach that may include pulmonary rehabilitation, oxygen therapy if needed, and management of comorbidities.
- Patients should be advised to avoid pregnancy while taking nintedanib and to report any unusual bleeding, as the drug can increase bleeding risk, although the INPULSIS trials did not show a significant increase in serious adverse events, including bleeding 1.
- Treatment should be temporarily suspended before major surgeries due to the bleeding risk and in cases of acute liver injury or severe diarrhea that doesn't respond to antidiarrheal medications.
From the Research
Treatment Regimen for Idiopathic Pulmonary Fibrosis (IPF) with Nintedanib
The recommended treatment regimen for IPF with Nintedanib is as follows:
- Nintedanib is administered orally at a dose of 150 mg twice daily 2
- The treatment has been shown to slow the decline in forced vital capacity (FVC) in patients with IPF 2
- Nintedanib has a manageable safety and tolerability profile, with the most common adverse events being diarrhea, hepatic function abnormal, and decreased appetite 2, 3
Key Considerations
- Patients with IPF should be closely monitored for adverse events, particularly hepatic disorders and diarrhea 3
- Nintedanib can be used in combination with pirfenidone, but the safety and efficacy of this combination require further research 4
- The treatment sequence of pirfenidone followed by nintedanib may be associated with a higher incidence of early termination of nintedanib due to anorexia and weight loss 5
Pharmacokinetics and Pharmacodynamics
- Nintedanib has time-independent pharmacokinetic characteristics, with maximum plasma concentrations reached approximately 2-4 hours after oral administration 6
- The terminal elimination half-life of nintedanib is about 10-15 hours, with negligible accumulation after repeated twice-daily dosing 6
- Nintedanib has a low potential for drug-drug interactions, but concomitant treatment with potent inhibitors or inducers of the P-glycoprotein transporter can affect its pharmacokinetics 6