Symptomatic hypoglycemia associated with trimethoprim/sulfamethoxazole and repaglinide in a diabetic patient.
OBJECTIVE
To report a case of clinically significant hypoglycemia attributed to the concomitant use of trimethoprim/sulfamethoxazole (TMP/SMX) and repaglinide by a diabetic patient.


METHODS
A 76-year-old diabetic patient with impaired renal function and no history of hypoglycemia was receiving treatment with repaglinide 1 mg 3 times daily. Five days after TMP/SMX therapy was started for a urinary tract infection, the man developed symptomatic hypoglycemia. Repaglinide and TMP/SMX were stopped and intravenous D-glucose was administered to normalize glucose levels. Repaglinide, but not TMP/SMX, was reintroduced 5 days later and no other hypoglycemic episode occurred. Objective causality assessments revealed that the interaction was probable (World Health Organization-Uppsala Monitoring Centre) or possible (Horn Drug Interaction Probability Scale).


CONCLUSIONS
This interaction between TMP/SMX and repaglinide was predictable according to available pharmacokinetic data in healthy subjects. Trimethoprim induced CYP2C8 inhibition, thus increasing the plasma concentration of repaglinide. This interaction is mentioned in the repaglinide product information. To our knowledge, however, no case of symptomatic hypoglycemia associated with a combination of repaglinide and trimethoprim has been described before. This discrepancy may be explained by the subtherapeutic dosage used in the pharmacokinetic study. Moreover, our patient had impaired renal function, which may have led to trimethoprim accumulation and potentiated its interaction with repaglinide. A direct lowering of blood glucose levels due to sulfamethoxazole, also potentiated by renal failure, could also be involved in triggering hypoglycemia.


CONCLUSIONS
This interaction between TMP/SMX and repaglinide may have involved inhibition of CYP2C8 by trimethoprim. Clinicians should be aware that this association may lead to symptomatic hypoglycemia, particularly in patients with renal dysfunction.
Roustit
Matthieu
M
Department of Public Health, Grenoble University Hospital, Grenoble, France.
Blondel
Emeline
E
Villier
Céline
C
Fonrose
Xavier
X
Mallaret
Michel P
MP
D000368:Aged; D000892:Anti-Infective Agents, Urinary / Q000009:adverse effects*; D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000009:adverse effects*; D048909:Diabetes Complications / Q000139:chemically induced*; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000150:complications; D004347:Drug Interactions; D002149:Energy Intake; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D010880:Piperidines / Q000009:adverse effects*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*; D014552:Urinary Tract Infections / Q000188:drug therapy
D000892:Anti-Infective Agents, Urinary; D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide; D015662:Trimethoprim, Sulfamethoxazole Drug Combination