Practical Considerations in the Pharmacologic Treatment of Idiopathic Pulmonary Fibrosis

Christopher S. King; Steven D. Nathan


Curr Opin Pulm Med. 2015;21(5):479-489. 

In This Article

Abstract and Introduction


Purpose of review Idiopathic pulmonary fibrosis (IPF) is a progressive and deadly disease. The US Food and Drug Administration recently approved two medications for the treatment of IPF – pirfenidone and nintedanib. Given the limited clinical experience with these agents, a number of questions remain regarding their use.

Recent findings Both pirfenidone and nintedanib were demonstrated to reduce the rate of decline in forced vital capacity in independent large, double-blind, randomized controlled clinical trials.

The successful implementation of both agents in clinical practice is dependent on many factors, including which patients to prescribe them in and managing patient expectations regarding efficacy and side effects. Pirfenidone is frequently associated with gastrointestinal upset, malaise, and rash. Nintedanib often causes diarrhea. Both drugs may cause elevations in liver-associated enzymes and require serial monitoring. Despite the side effects mentioned, these drugs are generally well tolerated in the long term. It should be emphasized to patients that these drugs do not represent a 'cure' for IPF and that the goal of therapy is stabilization of their disease.

Summary Currently many questions remain regarding the use of pirfenidone and nintedanib in IPF, including which drug to prescribe, the optimal patient population to treat, the duration of therapy, and how to define treatment success or failure. It also remains to be seen whether combination therapy with both agents will result in improved outcomes. Hopefully, future randomized controlled trials will address these issues.


Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown cause characterized by a progressive and often fatal course. In October 2014, the US Food and Drug Administration (FDA) approved two medications – pirfenidone and nintedanib – for the treatment of IPF.[1] The approval of pharmacologic therapies with efficacy demonstrated in multiple randomized controlled trials (RCTs) represents a major step forward in the battle against this deadly disease.[2–5] While the approval of these medications has been greeted with enthusiasm by the pulmonary community, it has also resulted in some confusion and controversy. Common questions raised include the optimal patient population for treatment, the duration of therapy, and the mitigation of possible side effects. In this review, we summarize the current understanding of the pathogenesis of IPF and the mechanism by which pirfenidone and nintedanib are thought to act. We then review the RCT data supporting the efficacy of these agents, as well as the pharmacokinetics, side effects, and recommended monitoring of both drugs. Finally, we present commonly encountered questions regarding the use of these agents and attempt to answer them using the existing data or the experience from our center when data are lacking.