Repaglinide 500microgram tablets

AbstractAims/IntroductionGlinides are antidiabetic drugs that enhance the early phase of insulin secretion, but have been considered to be less effective at lowering blood glucose than sulfonylureas. However, glinides show a lower risk of hypoglycemia and a greater effect on postprandial hyperglycemia, and are particularly recommended for use in elderly patients with type 2 diabetes. We investigated the efficacy and safety of repaglinide compared with sulfonylurea for the treatment of elderly patients.Materials and MethodsIn the present multicenter, prospective, randomized, open‐label, controlled trial, 57 elderly lean patients with type 2 diabetes who were being treated with sulfonylureas were studied. They were either switched to repaglinide (Repa group) or continued a sulfonylurea (SU group) for 12 weeks. The primary outcome comprised the change in glycemic control, and among the secondary outcomes was the presence of hypoglycemia and drug compliance.ResultsAlthough glycated hemoglobin (HbA1c) was not significantly different between the two groups (SU +0.02% vs Repa −0.07%), greater improvements in the glycated albumin (GA) and GA to HbA1c ratio (GA/HbA1c) were observed in the Repa group (ΔGA, SU +0.12% vs Repa −1.15%; ΔGA/HbA1c, SU +0.01 vs Repa −0.13; each P < 0.01) without increasing hypoglycemia. When the Repa group was subdivided according to whether GA improved, the SU dose before switching to repaglinide was significantly smaller and the homeostatic model assessment of β‐cell function was significantly higher in the GA improvement subgroup.ConclusionsSwitching from SU to Repa improved GA and GA/HbA1c, and had favorable effects on glucose fluctuation in elderly patients with type 2 diabetes.

Abstract licence: CC BY-NC 4.0

Background/objectivesIndex substrates are used to understand the processes involved in pharmacokinetic (PK) drug-drug interactions (DDIs). The aim of this analysis is to review metabolite measurement in clinical DDI studies, focusing on index substrates for cytochrome P450 (CYP) enzymes, including CYP1A2 (caffeine), CYP2B6 (bupropion), CYP2C8 (repaglinide), CYP2C9 ((S)-warfarin, flurbiprofen), CYP2C19 (omeprazole), CYP2D6 (desipramine, dextromethorphan, nebivolol), and CYP3A (midazolam, triazolam).MethodsAll data used in this evaluation were obtained from the Certara Drug Interaction Database. Clinical index substrate DDI studies with PK data for at least one metabolite, available from literature and recent new drug application reviews, were reviewed. Further, for positive DDI studies, a correlation analysis was performed between changes in plasma exposure of index substrates and their marker metabolites.ResultsA total of 3261 individual index DDI studies were available, with 45% measuring at least one metabolite. The occurrence of metabolite measurement in clinical DDI studies varied widely between index substrates and enzymes.Discussion and conclusionsFor substrates such as caffeine, bupropion, omeprazole, and dextromethorphan, the use of the metabolite/parent area under the curve ratio can provide greater sensitivity to DDI or reduce intrasubject variability. In some cases (e.g., omeprazole, repaglinide), the inclusion of metabolite measurement can provide mechanistic insights to understand complex interactions.

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Abstract Background The prevention of cytomegalovirus (CMV) infection after kidney transplantation (KTx) is important. Letermovir (LTV), a drug used for CMV prophylaxis, has various drug–drug interactions. Repaglinide (RPG), an anti-diabetic drug administered after KTx, is a substrate for CYP2C8, which may interact with LTV. We report the first case of a KTx recipient with prolonged severe hypoglycemia due to the enhanced effects of RPG caused by CYP2C8 inhibition by LTV. Case presentation The patient was a woman in 60s who underwent living-donor KTx. RPG (0.5 mg three times a day immediately before each meal) was started on day 27 post-KTx. Although renal function did not improve sufficiently owing to the development of acute tubular necrosis and thrombotic microangiopathy, the patient was weaned off hemodialysis and discharged on day 36 post-KTx (creatinine, 3.57 mg/dL; estimated glomerular filtration rate, 10.8 mL/min/1.73 m2). On the day of discharge (day 0), 480 mg LTV was administered once daily for CMV prophylaxis. The patient was brought to the emergency room because she lost consciousness at home at approximately 4 PM on day 2. The blood glucose level (BGL) at the time of transport was 33 mg/dL, indicating severe hypoglycemia. Therefore, RPG was discontinued immediately before lunch on day 2, and 40 mL of 50% glucose was administered. After transportation, 500 mL of 10% glucose was administered intravenously in parallel. However, the BGL decreased to 32 mg/dL at 9 PM. Hypoglycemia caused by short-acting RPGs usually does not persist for several hours. We considered the possibility of prolonged severe hypoglycemia due to the interaction of LTV and RPG, and LTV was suspended on day 3. No hypoglycemia occurred after 9 AM on day 3. LTV administration was resumed on day 6, and the patient was discharged on day 7 without further hypoglycemic events. Conclusions Delayed elimination owing to severe renal dysfunction and CYP2C8 inhibition by LTV potentiated the effects of RPG and caused prolonged severe hypoglycemia. When LTV is used for CMV prophylaxis in KTx patients, close attention should be paid to interactions with non-immunosuppressive drugs.

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