Drug Interactions between dexamethasone and nintedanib

MONITOR: Coadministration of corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of gastrointestinal (GI) perforation that can occasionally occur with the use of nintedanib. Overall, premarketing clinical data reveal no increased risk of GI perforation in nintedanib-treated patients. There were no reports of GI perforation in patients receiving nintedanib in the phase III clinical studies cited by the prescribing information for the treatment of systemic sclerosis-associated interstitial lung disease and chronic fibrosing interstitial lung diseases with a progressive phenotype. GI perforation occurred in 0.3% of patients (2 cases, both serious) receiving nintedanib compared to 0 cases in placebo-treated patients in the clinical studies for idiopathic pulmonary fibrosis. In the phase III LUME-Lung1 study comparing treatment with nintedanib plus docetaxel against placebo plus docetaxel in patients with locally advanced, metastatic, or recurrent non-small cell lung cancer after first-line chemotherapy, the frequency of GI perforation was comparable between the treatment arms. However, cases of GI perforation and ischemic colitis, including some with fatal outcome, have been reported in the postmarketing period. Although a definitive causal relationship to nintedanib has not been established, the association is possible based on nintedanib's mechanism of action. Additional risk factors for GI perforation include recent abdominal surgery or hollow organ perforation, a prior history of peptic ulceration, or diverticular disease.

MANAGEMENT: Caution is recommended when using nintedanib in combination with other drugs associated with an increased risk of GI perforation, such as corticosteroids and NSAIDs, and in patients with other risk factors such as recent abdominal surgery or hollow organ perforation, a prior history of peptic ulceration, or diverticular disease. Nintedanib should only be used if the anticipated benefit outweighs the potential risk. Some authorities recommend waiting at least 4 weeks after abdominal surgery before initiating nintedanib. Patients should be advised to contact their healthcare provider if they experience signs and symptoms of GI perforation such as severe abdominal pain, fever, chills, nausea, or vomiting. Therapy with nintedanib should be permanently discontinued in patients who develop GI perforation.