Ceritinib‐associated hyperglycemia in the Japanese Adverse Drug Event Report Database

Abstract

Genetic rearrangements of anaplastic lymphoma kinase contribute to the pathogenesis of non-small-cell lung cancer; the anaplastic lymphoma kinase inhibitor, ceritinib, is widely used, as it is effective even in patients with non-small-cell lung cancer resistant to other anaplastic lymphoma kinase inhibitors. Although a case of possible ceritinib-induced hyperglycemia was reported, the association of ceritinib with hyperglycemia remains to be investigated. Disproportionality analysis was carried out using the Japanese Adverse Drug Event Report database, which contains all pharmacovigilance data based on spontaneous reports of adverse events between April 2004 and November 2018 to the Pharmaceuticals and Medical Devices Agency. The reporting odds ratio of ceritinib for hyperglycemia was 2.25 (95% confidence interval [CI] 1.24-4.08], whereas those of crizotinib and alectinib were 0.07 (95% CI 0.01-0.40) and 0.94 (95% CI 0.30-2.94), respectively. Among reported events without antidiabetes agent use, the reporting odds ratio of ceritinib was still 2.54 (95% CI 1.27-5.12). Thus, the possibility of hyperglycemia should be carefully monitored in patients receiving ceritinib. † These authors contributed equally to this work.

Recurrent hyperglycemic hyperosmolar state after re-administration of dose-reduced ceritinib, an anaplastic lymphoma kinase inhibitor

“…According to the revised attachment, it was initially 2.3%, but is now reported to be 2.9%. Some reports of hyperglycemia due to ceritinib have been reported [14,15]. The frequency of worsening glycemic control in patients with diabetes mellitus due to the administration of ceritinib has not been clarified.…”

“…The frequency of worsening glycemic control in patients with diabetes mellitus due to the administration of ceritinib has not been clarified. A study that analyzed the relationship between ALK inhibitors and hyperglycemia or diabetes mellitus in March 2019 [14] showed that the odds ratio for hyperglycemia-associated side effects was significantly high after the administration of ceritinib. Insulin is frequently used in hyperglycemic cases, and the side effects due to hyperglycemia are likely to occur in patients with decreased insulin secretion [14,15].…”

“…A study that analyzed the relationship between ALK inhibitors and hyperglycemia or diabetes mellitus in March 2019 [14] showed that the odds ratio for hyperglycemia-associated side effects was significantly high after the administration of ceritinib. Insulin is frequently used in hyperglycemic cases, and the side effects due to hyperglycemia are likely to occur in patients with decreased insulin secretion [14,15]. Although a previous report also included a history of steroid use, our patient had no history of steroid use, and no other factors increasing the blood sugar levels were evident.…”

Organizing pneumonia in ALK+ lung adenocarcinoma treated with ceritinib

“…Ceritinib exhibits marked antitumor activity against ALK+ NSCLC, as well as brain metastases; however, it is associated with a number of adverse events including diarrhea, nausea, prolonged QT interval, and fatal pneumonitis [7] . Organizing pneumonitis (OP) is a very rare adverse event, and usual is commonly misdiagnosed infectious pneumonia, metastases, or cancer progression [8–10] . A diagnosis of OP should be suspected when there is no response to multiple antibiotics, and blood and sputum cultures are negative.…”

“…[7] Organizing pneumonitis (OP) is a very rare adverse event, and usual is commonly misdiagnosed infectious pneumonia, metastases, or cancer progression. [8][9][10] A diagnosis of OP should be suspected when there is no response to multiple antibiotics, and blood and sputum cultures are negative. It affects the patient prognosis, and its treatment is different than pneumonia and cancer progression; thus, a prompt and accurate diagnosis is very important.…”