There are no direct interactions between the antidiabetic drug repaglinide (Novonorm) and cimetidine, digoxin or theophylline, report Dr Vibeke Hatorp and Dr Mikael Thomsen (Novo Nordisk, Denmark). They conclude that these pairs of drugs may be co-prescribed without any change in dosage (Journal of Clinical Pharmacology 2000;40:184).
The researchers conducted three open-label, cross-over studies of 14 healthy volunteers. Cimetidine caused no significant change in plasma repaglinide levels. Co-administered repaglinide and digoxin did not influence the safety profile of digoxin.
While a direct metabolic interaction between repaglinide and theophylline was unlikely, a reduction in steady-state trough concentration of theophylline was seen. This was most likely to have been due to repaglinide causing hypoglycaemia, resulting in faster gastric emptying, Dr Hatorp says, and may have no clinical significance for co-prescribing of the two drugs.
The area under the curve and half-life of theophylline were not affected by repaglinide.
In another study by Dr Hatorp, published in the same journal, the clearance of repaglinide was found to be significantly reduced in patients with hepatic impairment (Journal of Clinical Pharmacology 2000;40:142). The researchers recommend that the agent should be used with caution in such patients, for example, with longer intervals between dose adjustments. (The SPC currently recommends that repaglinide is avoided in severe liver disease.)
Reporting the results of a pharmacokinetic study of 24 patients (12 with moderate to severe liver disease), Dr Hatorp says that maximum serum concentrations of repaglinide were nearly 2.5-fold higher in patients with chronic liver disease. In addition, values for area under the curve were lower in healthy subjects and the half-life of repaglinide was prolonged in the patients with liver disease.