Pharmacokinetic interactions between topiramate and diltiazem, hydrochlorothiazide, or propranolol

Abstract

Drug-drug interactions between topiramate and diltiazem, hydrochlorothiazide, or propranolol were evaluated along with safety/tolerability in three open-label studies. Healthy participants (aged 18-45 years) received topiramate 75 mg every 12 hours (q12h) and diltiazem 240 mg/day (study 1); topiramate 96 mg q12h and hydrochlorothiazide 25 mg/day (study 2); topiramate 100 mg q12h and propranolol 40-80 mg q12h (study 3). The pharmacokinetic parameters for topiramate, diltiazem (and active metabolites, desacetyldiltiazem [DEA], N-demethyl diltiazem [DEM]), hydrochlorothiazide, and propranolol (and its active metabolite) were assessed at steady state. Results showed no effect of diltiazem on topiramate pharmacokinetics. However, a modest reduction in systemic exposures of diltiazem and DEA (10-27%) occurred during coadministration with topiramate. Systemic exposure of DEM was unaffected. Furthermore, oral and renal clearance of topiramate decreased (22-30%) significantly (P < 0.05) during coadministration with hydrochlorothiazide, while systemic exposure increased by 27-29%. Topiramate had no effect on hydrochlorothiazide pharmacokinetics. The results demonstrated lack of pharmacokinetic interaction between topiramate and propranolol. Overall, no new safety concerns emerged when topiramate was coadministered with diltiazem, hydrochlorothiazide, or propranolol.

Effects of Lasmiditan on Cardiovascular Parameters and Pharmacokinetics in Healthy Subjects Receiving Oral Doses of Propranolol

“…[20][21][22] The dose of propranolol (80 mg bid) was selected because it is within the recommended dose for migraine and has been shown to be tolerated by healthy subjects in previous PK and pharmacodynamic (PD) studies. [20][21][22][23][24][25] As shown in Figure 1, screening occurred up to 28 days before enrollment, and subjects were admitted to the clinical research unit on day -2, 2 days prior to their first dose of study drug. On day 1 subjects received a single dose of 200 mg lasmiditan.…”

Low-dose topiramate and hydrochlorothiazide-associated early acute myopia and angle narrowing: A case report

“…In contrast, our case was of a low dose and in a short time. Besides, plasma topiramate concentrations can be increased by coadministration of hydrochlorothiazide ( 11 ). In addition, thiazide diuretics are one of the possible risk factors for aACG when they are in combination with topiramate ( 9 ).…”