Clopidogrel/repaglinide interaction

Abstract

Hypoglycaemia following medication error: case report An 81-year-old woman developed hypoglycaemia secondary to pharmacokinetic interaction between repaglinide and clopidogrel. It was later noted that concomitant use of repaglinide and clopidogrel was contraindicated [not all routes stated]. The woman was diagnosed with type 2 diabetes mellitus at the age of 50 years and was treated with oral hypoglycaemic agents. Later, she developed hypertension, atrial fibrillation, dyslipidaemia, peripheral artery disease, cardiovascular disease and adrenal insufficiency owing to approximately five years of unspecified glucocorticoid therapy for autoimmune hepatitis. Her renal function deteriorated gradually [aetiology not stated]. Subsequently, she was admitted to Osaka Police Hospital, Japan at the age of 81 years for the treatment of acute coronary artery dissection. Upon admission, she was prescribed with teneligliptin, oral repaglinide 1.5 mg/day for type 2 diabetes mellitus, febuxostat, pravastatin, carvedilol, azelnidipine, verapamil, cilostazol, aspirin, edoxaban, propafenone, vonoprazan and hydrocortisone. Thereafter, she underwent percutaneous coronary intervention due to the dissection and aspirin was then switched to clopidogrel 75 mg/day as an antiplatelet therapy. At that time, she was taking teneligliptin and repaglinide 0.5mg three times a day and was following diabetic diet. She subsequently exhibited gradual decrease in the fasting plasma glucose level. She developed hypoglycaemia three days after initiation of clopidogrel. Therefore, the dose of teneligliptin decreased. Her hypoglycaemia persisted. Nine days after initiation of clopidogrel, she was referred to the another department for further evaluation and treatment of the recurrent hypoglycaemia. She had had no obvious symptoms of hypoglycaemia apart form decreased pre-breakfast plasma glucose level. Based on her clinical course, it was considered that the hypoglycaemia was secondary to drug-drug interaction due to concomitant use of clopidogrel and repaglinide. It was also identified that she had been prescribed clopidogrel and repaglinide concomitantly, despite being contraindicated. The woman’s therapy with repaglinide was therefore suspended, and she underwent testing that showed fasting plasma glucose level at 85 mg/dL, fasting C-peptide 2.71 ng/mL and immunoreactive insulin level 3.7 μU/mL. Her renal function was found to be impaired (underlying). After discontinuation of repaglinide, her fasting plasma glucose level improved. Two days before discontinuation of repaglinide, her fasting C-peptide level and C-peptide index were high and glucose level was low. Her C-peptide index decreased after discontinuation of repaglinide. She started taking mitiglinide and was discharged form hospital without hypoglycaemia. Afterwards, teneligliptin and mitiglinide were continued for diabetes and clopidogrel was also continued. At the four month follow-up visit, no hypoglycaemia was detected. It was concluded that the hypoglycaemia was due to concomitant treatment with repaglinide and clopidogrel, which was contraindicated [not all durations of treatments to reactions onsets stated].