American Journal of Therapeutics 23, e972–e973 (2016)

Canagliflozin-Associated Acute Pancreatitis Rajanshu Verma, MD*

Canagliflozin is a new drug in class of sodium–glucose cotransporter 2 inhibitors used for treatment of type 2 diabetes mellitus. We describe a patient who developed moderately severe acute pancreatitis as an untoward consequence after being initiated on this drug. To the best of our knowledge, this is the first reported case of canagliflozin-associated acute pancreatitis in clinical literature. Keywords: canagliflozin, acute pancreatitis, Invokana

CASE REPORT A 46-year-old white woman presented to our hospital with a 4-day history of nausea, vomiting, and severe abdominal pain. She tried taking acetaminophen for her abdominal pain; however, it did not help. In the emergency department, she was found to have hypotension with blood pressure of 80/60 mm Hg. She was given pain medicines and fluid resuscitated with 3 L of normal saline. Her serum chemistries showed a white blood cell count of 15.6 3 103/mm3 with 65% neutrophils (normal, 4.5–11 3 103/mm3), glucose of 348 mg/dL (normal, ,140 mg/dL), blood urea nitrogen of 23 mg/dL (normal, 8–20 mg/dL), creatinine 1.1 mg/dL (normal, 0.7–1.3 mg/dL), lactic acid 3.2 mmol/L (normal, 0.67– 1.8 mmol/L), lipase 388 IU/L (normal, , 95 IU/L), and normal liver enzymes. Urinalysis, electrocardiogram, and chest x-ray were unremarkable. A computerized tomography scan of abdomen and pelvis was obtained for her abdominal pain and showed evidence of acute pancreatitis with peripancreatic fat stranding around the head of pancreas (Figure 1). As her blood pressure did not improve despite aggressive fluid resuscitation, she was started on dopamine infusion and was given piperacillin–tazobactam by emergency department staff

Department of Hospital Medicine (UHS), United Hospital, Allina Health, St. Paul, MN. The author has no conflicts of interest to declare. *Address for correspondence: Allina Health, United Hospitalist Service, 333 N Smith Avenue, St. Paul, MN 55102. E-mail: [email protected]

and sent to intensive care unit for treatment of acute pancreatitis. She had never had acute pancreatitis before. She denied any history of drinking alcohol, was not currently smoking cigarettes, and had not had any history of gallstones. She denied any trauma to the abdomen or insect bite. Patient had a history of diabetes mellitus, obstructive sleep apnea, obesity, dyslipidemia, depression, and chronic neuropathic pain. Her cholesterol and triglycerides had been well controlled with the help of cholesterol-lowering drugs. She did not have any autoimmune conditions or any family history of pancreatitis. On obtaining further history, patient mentioned that 3 weeks ago, she was prescribed canagliflozin by her primary care physician for controlling her diabetes mellitus. Her other prescription medications that she had been taking for several years included lisinopril, metformin, estradiol, lovastatin, calcium citrate, citalopram, cranberry capsule, cyclobenzaprine, gabapentin, insulin glargine, and oxybutynin. In intensive care unit, piperacillin–tazobactam was continued; however, dopamine was switched to norepinephrine and intravenous hydrocortisone, and albumin was given to support her blood pressure. Her condition improved over the next 36 hours, and so vasopressors were discontinued. Her procalcitonin, blood, and urine cultures came back negative and so piperacillin–tazobactam was discontinued. She was discharged home on hospital day 3 on a low-fat diet and was advised to discontinue her canagliflozin. Given the chronology of her presentation in relation to initiation of canagliflozin and noncontributory workup

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Canagliflozin-Associated Acute Pancreatitis

e973

the kidney thus increasing glucose excretion. Most common side effects from this drug include vulvovaginal candidiasis, urinary tract infection, and orthostatic hypotension. It can also result in renal impairment, hyperkalemia, hypoglycemia, and hypersensitivity reactions. Per prescribing drug information, the incidence rate of acute or chronic pancreatitis was 2.7 per 1000 patient-years.3 To the best of our knowledge, our case is the first in clinical literature reporting this untoward side effect of this drug.

CONCLUSIONS

FIGURE 1. Computerized tomography of the abdomen showing acute pancreatitis around head of pancreas (arrow).

for other causes, a diagnosis of moderately severe acute pancreatitis due to canagliflozin as per modified Atlanta criteria was made.1

DISCUSSION Canagliflozin (US brand name: Invokana) is the first in the new class of diabetes drugs known as sodium–glucose cotransporter 2 inhibitors. It was approved by the US Food and Drug Administration in March 2013 for treatment of type 2 diabetes mellitus.2 Canagliflozin works by blocking the reabsorption of glucose by

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Our case emphasizes the importance of being aware of newer drugs (canaglifllozin) for treatment of diabetes mellitus and their untoward side effects (acute pancreatitis).

REFERENCES 1. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013; 62:102–111. 2. FDA approves Invokana to treat type 2 diabetes: FDA news release [FDA approval webpage]. Available at: http://www. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm345848.htm. Accessed June 4, 2014. 3. Invokana (Canagliflozin) Prescribing Drug Information [Webpage]. New Brunswick, NJ: Janssen Pharmaceuticals: Division of Johnson & Johnson. Available at: http://www. invokanahcp.com/prescribing-information.pdf. Accessed June 4, 2014.

American Journal of Therapeutics (2016) 23(3)

Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.