Nintedanib is used for the treatment of idiopathic pulmonary fibrosis. It has been shown to slow down decrease in forced vital capacity, and it also improves people's quality of life. Nintedanib does not improve survival in people with IPF.NICE recommends nintedanib in cases of IPF where the FVC is 50-80% of predicted. NICE recommends discontinuation of therapy if a person's FVC decreases by 10% or more in a 12 month period, indicating disease progression despite treatment.
It is also used in combination with docetaxel as a second-line treatment for adult patients with locally advanced, metastatic, or locally recurring non-small cell lung cancer of adenocarcinoma histology. It is unclear how this combination compares to other second line agents as the comparisons have not been done as of 2014.
Nintedanib is contraindicated in patients with known hypersensitivity to nintedanib, peanut or soya. Nintedanib has not been tested in patients with moderate to severe impairment of liver function. Given that the drug is metabolised in the liver, it may not be safe in such patients. Nintedanib can be used in geriatric population without any dose modifications. It has not been studied in paediatric populations and hence cannot be given in patients below 18 years of age. It is also contraindicated in pregnancy
Only a small percentage of orally taken nintedanib is absorbed in the gut, partially due to transport proteins (such as P-glycoprotein) moving the substance back into the lumen. Combined with a high first-pass effect, this results in an oral bioavailability of about 4.7% with a 100mg tablet. The drug reaches peak plasma levels in 2 to 4 hours after oral intake in the form of a soft gelatin capsule.
Nintedanib is a substrate of the transporter P-glycoprotein which moves the absorbed substance back into the gut's lumen. The P-glycoprotein inhibitor ketoconazole is known to increase blood plasma levels of nintedanib by a factor of 1.8; other inhibitors such as erythromycin or ciclosporin are expected to have a similar effect. On the other hand, the P-glycoprotein inducer rifampicin cuts nintedanib plasma levels in half; other inducers such as carbamazepine, phenytoin or St. John's Wort probably lower plasma levels as well.
The drug is used in form of its salt with ethanesulfonic acid. This salt, nintedanib esliate, is a yellow, crystalline solid that melts at 244 °C (471 °F) to 251 °C (484 °F). It has poor solubility in water, and somewhat better solubility in dimethyl sulfoxide at 25 g/l.
Idiopathic pulmonary fibrosis
Nintedanib was approved for idiopathic pulmonary fibrosis on 15 October 2014 by the United States Food and Drug Administration (FDA), and received a positive opinion from the European Medicines Agency on 20 November 2014, being approved in the EU in January 2015. It is also approved in Canada, Japan, Switzerland, and other countries.
The drug was approved by the FDA on 6 September 2019 to slow the rate of decline in pulmonary function in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD).
Nintedanib was approved for combination therapy of non-small-cell lung cancer in the European Union in 2014, and is now approved for this indication in other parts of the world.
Society and culture
A review, which assumed the price of nintebanib was 39,300 pounds a year found that it was not cost effective.
Boehringer is using the brand name Ofev for marketing nintedanib for idiopathic pulmonary fibrosis and Vargatef for marketing the medication for lung cancer.
Nintedanib is being tested in several phase I to III clinical trials for cancer. Angiogenesis inhibitors such as nintedanib may be effective in a range of solid tumour types including lung, ovarian, metastatic bowel, liver and brain cancer.
Current phase II trials are investigating the effect of nintedanib in patients with bladder cancer, metastatic bowel cancer, liver cancer and the brain tumour glioblastoma multiforme.
Phase III trials are investigating the use of nintedanib in combination with carboplatin and paclitaxel as a first line treatment for patients with ovarian cancer.
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