Dynacirc CR (Isradipine) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug Interactions

Nitroglycerin: Immediate-release DynaCirc^® (isradipine) has been safely coadministered with nitroglycerin.

Hydrochlorothiazide: A study in normal healthy volunteers has shown that concomitant administration of immediate-release DynaCirc^® (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 using immediate-release DynaCirc^® (isradipine), 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 C_max (58%) and decreases in t_max (23%) of propranolol were noted in this study.

Digoxin: The concomitant administration of immediate-release DynaCirc^® (isradipine) and digoxin in a single-dose pharmacokinetic study did not affect renal, non-renal 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. An increased volume of circulating fluids might be required if such an interaction were to occur.

OVERDOSAGE

Although there is no well documented experience with DynaCirc^® (isradipine) overdosage, available data suggest that, as with other dihydropyridines, gross overdosage would result in excessive peripheral vasodilation with subsequent marked and probably prolonged systemic hypotension. Clinically significant hypotension overdosage calls for active cardiovascular support including monitoring of cardiac and respiratory function, elevation of lower extremities and attention to circulating fluid volume and urine output. A vasoconstrictor (such as epinephrine, norepinephrine, or levarterenol) may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Since isradipine is highly protein bound, dialysis is not likely to be of benefit.

Significant lethality was observed in mice given oral doses of over 200 mg/kg and rabbits given about 50 mg/kg of isradipine. Rats tolerated doses of over 2000 mg/kg without effects on survival.

CONTRAINDICATIONS

DynaCirc CR^® (isradipine) is contraindicated in individuals who have shown hypersensitivity to any of the ingredients in the formulation.