Common side effects of nintedanib

In the field of interstitial lung diseases, nintedanib is considered to be an antifibrotic drug. Its action is to slow down the progression of the fibrosis (scarring) of the lungs, even though it does not reverse it.

Initially approved for idiopathic pulmonary fibrosis (IPF), it can now also be prescribed for patients with any progressive fibrotic lung disease (which fits certain criteria) and also for a condition called systemic sclerosis associated ILD. (SSc-ILD)

It is normally prescribed as one 150mg tablet twice per day, although if a dose reduction is required, a 100mg tablet is also available.

Most patients are actually able to tolerate nintedanib quite well, despite all the possible adverse effects mentioned in the package insert. A listing of side effects does not mean that each patient will experience all of them or any of them in a significant degree. It can vary greatly from person to person.

The side effects I discuss in this post are some of the more common ones and do not represent a comprehensive list. It is a commentary of the most common ones that I have seen in clinical practice. For a full listing of the side effects I would recommend consulting the package leaflet and the patient-oriented information documents provided by your healthcare team. Another great resource for detailed side-effect profiles is to consult a document called the SmPC (summary of product characteristics), which is available online in all the EU languages (as it is a requirement to publish this freely in Europe). You can use a search engine looking for “nintedanib summary of product characteristics” or the translation of this phrase to locate the right version in your preferred language. The link for the English UK version is here.

Diarrhoea and loose stools

The most notable expected adverse effect is diarrhoea or loose stools. When this occurs, it can happen in varying degrees, ranging from very mild (requiring no treatment), to more serious, where anti-diarrhoeal medication needs to be given daily or the dose of the drug needs to be reduced. In rare cases, the drug needs to be stopped completely as the impact on quality-of-life is too great.

Managing diarrhoea can be difficult, but usually can be controlled relatively well to allow for a normal quality of life. Taking the medication with food can help.

If there are many episodes of loose stools per day, an anti-diarrhoeal medication such as loperamide (Imodium) is prescribed to be taken as required. There can be better and worse days. Most patients do not actually need to take loperamide every day, just as needed, when the episodes are increasing in frequency.

Each person’s diet is also different and there may be unpredictable interactions which worsen the diarrhoea. It is quite hard to advise in a general manner which diet would be the best, because every person is different. It may be a case of trying out different meals to understand if there is something that improves or worsens the digestive issues. Developing this awareness of your body, coming up with meal plans according to how you feel is probably a very important step.

In some cases however, despite dietary changes and loperamide, the dose of nintedanib needs to be reduced, or a break in treatment needs to be considered. This is required to allow the body to recover electrolyte levels and allow for proper nutrition. Quality of life can be affected significantly and needs to be considered in the risk-benefit discussion, as there is no point in pushing through with a treatment that would make you feel very unwell or lead to severe complications. Such decisions to permanently discontinue nintedanib should be made after a good discussion with the healthcare team, to make sure that all options to manage side effects have been explored.

Other digestive side effects

In addition to the diarrhoea, nausea and vomiting can also occur. Appetite may also be reduced, which can be difficult to tolerate in the context of chronic lung disease because of the need to have adequate nutrition to cope with the respiratory impairment. Having an increased work of breathing because of the fibrosis and hardening of the lungs means that the body may use a lot of energy to cope with mundane tasks. Weight loss can be an issue in this context and should be monitored regularly.

Just as with diarrhoea, if these side effects become significant, an interruption in treatment may be required and a good break can sometimes allow you to continue the medication in the long run.

Many patients are worried about interrupting treatment and how this will affect the efficacy of the medication. Short gaps in treatment should not have a major effect on the long term prognosis of the fibrosis – nintedanib should be thought of as a very long term treatment that slows down progression, while unfortunately not reversing the lung scarring. The benefits are gauged by the reduction in the rate of lung function decline over several years.

If the side effects improve during this break in treatment, a lower dose may be resumed, at 100mg twice daily instead of the full standard dose of 150mg twice daily. Unfortunately, if the 100mg dose is not tolerated, nintedanib treatment should not be continued, as the risks likely will outweigh the benefits.

Liver test abnormalities

Nintedanib treatment needs to be monitored with routine blood tests, done every month at the beginning and then roughly every 3 months. Local policies may differ regarding the monitoring schedule. The reason for performing these tests is that nintedanib can sometimes affect the liver and this can be picked up if there are elevations in liver function tests. The risk of liver function abnormalities seems to be higher in women, people with low body weight and those of Asian ethnicity. The main measurements checked are liver transaminases – ALT or AST. In some countries, ALT is also known as TGP, and AST as TGO.  If any of these increase to values higher than 3 times the upper limit of normal, treatment is interrupted. After the values return to normal, resuming treatment at the lower dose (100mg twice daily) can be considered with close monitoring, and if no further issues sometimes it may be possible to return to the full dose.