Sitagliptin-Associated Drug Allergy: Review of Spontaneous Adverse Event Reports

Januvia; Merck and Co Inc, White- house Station, New Jersey) was the first dipeptidyl peptidase-4 inhibitor (DPP-4) to gain approval from the Food and Drug Administration (FDA) in October 2006 for the treatment of type 2 diabetes mellitus. 1In October 2007, approved labeling for sitagliptin was updated to note the appearance of spontaneous adverse event reports of hypersensitivity reactions (ie, anaphylaxis, angioedema, serious skin reactions) and noted that most reported events occurred within the first 3 months after initiation of treatment, including some following the first dose. 1 The objective of our study was to construct a case series of sitagliptin-associated allergic reactions within an empirical model for the assessment of events consistent with drug allergy.Methods.The Adverse Event Reports System (AERS) database of the FDA was searched for all reports of potential drug allergy (including domestic and foreign reporters) with outcomes of (1) death, (2) life-threatening conditions, (3) disability, (4) hospitalization, or (5) intervention required to prevent permanent impairment.Reports of drug allergy occurring within 6 weeks following the initiation of sitagliptin therapy that suggested at least a possible causal relationship between the adverse event and sitagliptin use, as described in the World Health Organization (WHO) criteria, 2 were retained as cases.Previously published criteria were modified for classification of cases into 1 of the following 4 categories to build case definitions suitable for examination of spontaneous adverse event reports, which frequently have partial or limited information.Explicit inclusion and exclusion criteria for each category are outlined as follows:•Anaphylaxis: We defined anaphylaxis as any unexplained episode of hypotension or respiratory compromise with or without angioedema or a clinical diagnosis by a health care professional.Reports that were confounded by a major concurrent illness were excluded.•Angioedema Without Upper Airway Obstruction/ Symptomatology: Patients who rapidly developed unexplained swelling of skin or mucosa without any signs of respiratory compromise were included under this category.We excluded reports of anaphylaxis and angioedema that were confounded by concomitant use of antibiotics or in which therapy with an angiotensinconverting enzyme inhibitor or angiotensin receptor blocker was started within 1 month of onset of the hypersensitivity reaction, since these drugs most commonly cause angioedema during this period.•Serious Skin Reactions: Reports of Stevens-Johnson syndrome or toxic epidermal necrolysis diagnosed by a health