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Active ingredient: Isradipine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Calcium Channel Blockers
  • Vasodilator Agents
  • Antihypertensive Agents

Dosage Forms

  • Capsules (2.5 mg or 5 mg)

Brands / Synonyms

(+-)-Isradipine; (+/-)-Isradipine; Clivoten; Dynacirc; DynaCirc (TN); Dynacirc CR; DynaCire; DynaCire CR; Dynacrine; Esradin; Isradipin; Isradipine (USP); Isradipine [USAN:BAN:INN]; Isradipino [Spanish]; Isradipinum [Latin]; Isrodipine; Lomir; Prescal; Rebriden

Indications

For the management of hypertension. It may be used alone or concurrently with thiazide-type diuretics.

Pharmacology

Isradipine, the most potent calcium-channel blocking agent of the dihydropyridine class, is similar to nifedipine, amlodipine, and felodipine. It binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and smooth muscle. The effects observed in mechanistic experiments in vitro and studied in intact animals and man are compatible with this mechanism of action and are typical of the class.

Mechanism of Action

Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, isradipine inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.

Absorption

Isradipine is 90%-95% absorbed and is subject to extensive first-pass metabolism, resulting in a bioavailability of about 15%-24%.

Toxicity

Symptoms of overdose include lethargy, sinus tachycardia, and transient hypotension. 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.

Biotrnasformation / Drug Metabolism

Hepatic. Completely metabolized prior to excretion and no unchanged drug is detected in the urine.

Contraindications

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

Drug Interactions

Nitroglycerin: DynaCirc® (isradipine) has been safely coadministered with nitroglycerin.

Hydrochlorothiazide: A study in normal healthy volunteers has shown that concomitant administration of DynaCirc® (isradipine) and hydrochlorothiazide does not result in altered pharmacoktnetics 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, coadministration 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 drugís 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 multipledose 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 DynaCirc® (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 DynaCirc® (isradipine), an increased volume of circulating fluids might be required if such an interaction were to occur.

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