Isradipine drug interactions

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-525-6884

Important Drug Interactions

Hydrochlorothiazide: A study in normal healthy volunteers has shown that concomitant administration of Isradipine and hydrochlorothiazide does not result in altered pharmacokinetics of either drug. In a study in hypertensive patients, addition of Isradipine to existing hydrochlorothiazide therapy did not result in any unexpected adverse effects, and Isradipine had an additional antihypertensive effect.

Propranolol: In a single dose study in normal volunteers, co-administration of propranolol had a small effect on the rate but no effect on the extent of Isradipine bioavailability. Significant increases in AUC (27%) and Cmax (58%) and decreases in tmax (23%) of propranolol were noted in this study. However, concomitant administration of 5 mg b.i.d. Isradipine and 40 mg b.i.d. propranolol to healthy volunteers under steady-state conditions had no relevant effect on either drug’s bioavailability. AUC and Cmax differences were <20% between Isradipine given singly and in combination with propranolol, and between propranolol given singly and in combination with Isradipine.

Cimetidine: In a study in healthy volunteers, a one-week course of cimetidine at 400 mg b.i.d. with a single 5 mg dose of Isradipine on the sixth day showed an increase in Isradipine mean peak plasma concentrations (36%) and significant increase in area under the curve (50%). If Isradipine therapy is initiated in a patient currently receiving cimetidine, careful monitoring for adverse reactions is advised and downward dose adjustment may be required.

Rifampicin: In a study in healthy volunteers, a six-day course of rifampicin at 600 mg/day followed by a single 5 mg dose of Isradipine resulted in a reduction in Isradipine levels to below detectable limits. If rifampicin therapy is required, Isradipine concentrations and therapeutic effects are likely to be markedly reduced or abolished as a consequence of increased metabolism and higher clearance of Isradipine.

Warfarin: In a study in healthy volunteers, no clinically relevant pharmacokinetic or pharmacodynamic interaction between Isradipine and racemic warfarin was seen when two single oral doses of warfarin (0.7 mg/kg body weight) were administered during 11 days of multiple-dose treatment with 5 mg b.i.d. Isradipine. Neither racemic warfarin nor Isradipine binding to plasma proteins in vitro was altered by the addition of the other drug.

Digoxin: The concomitant administration of Isradipine and digoxin in a single-dose pharmacokinetic study did not affect renal, nonrenal and total body clearance of digoxin.

Fentanyl Anesthesia: Severe hypotension has been reported during fentanyl anesthesia with concomitant use of a beta blocker and a calcium channel blocker. Even though such interactions have not been seen in clinical studies with Isradipine, an increased volume of circulating fluids might be required if such an interaction were to occur.