Isradipine is a second generation calcium channel blocker that is used to treat hypertension. Isradipine is associated with a low rate of serum enzyme elevations during therapy, but has not been linked convincingly to instances of clinically apparent liver injury.
Isradipine (is rad' i peen) is an antihypertensive medication that belongs to the dihydropyridine class of calcium channel blockers. Like other calcium channel blockers, isradipine acts by blocking the influx of calcium ions into smooth muscle and cardiac cells using depolarization. This inhibition leads to vasodilation and decrease in cardiac work and oxygen consumption. Isradipine was approved in the United States in 1990 and its current sole indication is for hypertension. Isradipine is available in extended release capsules of 2.5, 5 and 10 mg generically and formerly under the commercial name DynaCirc. The recommended dose in adults is 5 to 10 mg in one or two divided doses daily. Like other calcium channel blockers, isradipine is generally well tolerated. Side effects are largely due to its vasodilating activities and include headache, dizziness, flushing, fatigue, nausea, peripheral edema and rash.
Hepatotoxicity, Outcome and Management
Isradipine is reported to be associated with mild elevations in serum aminotransferase levels during therapy that are usually transient, asymptomatic and resolve even with continued therapy. Cases of idiosyncratic liver injury attributed to isradipine have not been published. Large trials of isradipine have not mentioned liver injury, persistent serum aminotransferase elevations or discontinuation of drug because of hepatic adverse events. Liver injury has been reported with other calcium channel blockers such as verapamil, diltiazem, amlodipine and nifedipine, but only as isolated case reports and the injury was generally mild and self-limiting in outcome. Thus, clinically apparent liver injury due to isradipine must be rare, if it occurs at all.
Likelihood score: E (Unlikely cause of clinically apparent liver injury).
The reason why some calcium channel blockers are associated with liver injury while others are not is unclear. Isradipine is metabolized by the hepatic P450 system, predominantly by CYP 3A4 and is susceptible to drug-drug interactions with agents that induce or inhibit the microsomal enzyme.
REPRESENTATIVE TRADE NAMES
Isradipine – Generic, DynaCirc®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 11 January 2017
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Nelson EB, Pool JL, Taylor AA. Antihypertensive activity of isradipine in humans: a new dihydropyridine calcium channel antagonist. Clin Pharmacol Ther 1986; 40: 694-7. PubMed Citation (Controlled trial of isradipine in 24 patients with hypertension for 3 weeks; there were no significant changes in ALT or AST values during treatment).
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Citation (Systematic review
of literature of drug induced liver injury in Latin American countries published
from 1996 to 2012 identified 176 cases; one case was attributed to verapamil,
but none were linked to isradipine or other calcium channel
N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.;
United States Drug Induced Liver Injury Network. Features and outcomes of 899
patients with drug-induced liver injury: The DILIN Prospective Study.
Gastroenterology 2015; 148: 1340-52.e7. PubMed Citation (Among
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between 2004 and 2013, 39 [4%] were due to antihypertensive agents including 4
due to calcium channel blockers [amlodipine in 1 and verapamil in 3
instances], but none to isradipine).