Nisoldipine is a second generation calcium channel blocker and commonly used antihypertensive agent. Nisoldipine therapy is associated with a low rate of serum enzyme elevations, but has not been specifically linked to instances of clinical apparent acute liver injury.
Nisoldipine (nye sol' di peen) belongs to the dihydropyridine class of calcium channel blockers (similar to amlopdine, felodipine and nifedipine) and is used predominantly for hypertension. Like other calcium channel blockers, nisoldipine acts by blocking the influx of calcium ions into cardiac and vascular smooth muscle cells during membrane depolarization. This action causes relaxation of arterial smooth muscle cells, resulting in arterial vasodilation and a decrease in cardiac work and oxygen consumption. Nisoldipine was approved in the United States in 1995 and current indications are for treatment of hypertension. It is available as extended release tablets of 8.5, 17, 25.5 and 34 mg generically and under the commerical name Sular. The recommended dose in adults is 17 mg once daily, adjusting to 17 to 34 mg per day based upon clinical effects and tolerance. Like other calcium channel blockers, nisoldipine is generally well tolerated, but side effects can include headache, flushing, dizziness, fatigue, nausea, diarrhea, palpitations, peripheral edema and skin rash.
Hepatotoxicity and Outcome and Management
Nisoldipine has been associated with a low rate of serum aminotransferase or alkaline phosphatase elevations during long term therapy, but the elevations are usually asymptomatic, mild, transient and resolve even with continuation of treatment. Cases of idiosyncratic liver injury due to nisoldipine have not been published. Large trials of nisoldipine have not mentioned liver injury, serum aminotransferase elevations or discontinuation of drug because of hepatic adverse events. Thus, liver injury from nisoldipine 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 (such as amlodipine, diltiazem and nifedipine) cause idiosyncratic liver injury while others (such as nisoldipine) do not, is not known. Because liver injury from calcium channel blockers is rare, there may have been inadequate exposures to the uncommonly used agents to lead to clinically manifest cases. Nisoldipine like many calcium channel blockers is metabolized in the liver by CYP 3A4 and is susceptible to drug-drug interactions with substrates, inhibitors and induces of CYP 3A4.
REPRESENTATIVE TRADE NAMES
Nisoldipine – Generic, Sular®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 11 January 2017
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