Lack of Pharmacokinetic Interaction between Tiagabine and Erythromycin

Abstract

This study was conducted to investigate the effects on the pharmacokinetics of tiagabine at steady state when coadministered with therapeutic doses of erythromycin. Tiagabine doses of 4 mg twice daily and erythromycin doses of 500 mg twice daily were administered for 4 days in an open-label, crossover, two-period interaction trial in 13 healthy volunteers. No statistically significant differences in maximum plasma concentration (Cmax), area under the concentration-time curve (AUC tau), or half-life (t1/2) of tiagabine were observed when tiagabine was administered alone or in combination with erythromycin. A statistically significant treatment effect was observed for time to maximum concentration (tmax; 0.72 after tiagabine alone versus 0.56 hours after administration with erythromycin). No statistically significant differences were seen between men and women except in tmax and t1/2; these differences were thought to be of no clinical significance. The decrease in tmax seen in women in this study is interpreted as a differential effect of erythromycin on gastric emptying of females and not as an interaction between tiagabine and erythromycin. No changes in laboratory parameters or vital signs were attributable to trial medication. The most common treatment-emergent adverse events that were possibly related to trial medication were central nervous system effects (e.g., headache, dizziness); all adverse events were transient, the majority were rated mild in severity, and did not require additional action. Coadministration of erythromycin in healthy subjects does not significantly affect the pharmacokinetics of tiagabine at the doses tested.

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

“…Finally, several studies found that ERY exhibited no effect on the co-administered agents oxcarbazepine [227], phenytoine [228], or tiagabin [229]. …”

The Importance of Drug Interactions in Epilepsy Therapy

“…Patients should be closely monitored and the CBZ dosage adjusted if necessary. Two small studies of healthy volunteers demon-strated that the second-generation AEDs, OXC and TGB, were not affected by coadministration with erythromycin (139,140).…”

Perspectives on interactions between antiepileptic drugs (AEDs) and antimicrobial agents

“…The author has come across one such case with severe CNS toxicity induced by an interaction between erythromycin and valproate. Oxcarbazepine, tiagabine, felbamate, topiramate, and levetiracetam appear not to be affected by the concomitant administration of erythromycin (Keranen et al, 1992; Thomsen et al, 1998).…”