Livertox

DRUG RECORD

 

RIVASTIGMINE

 

Introduction

Rivastigmine is an oral acetylcholinesterase inhibitor used for therapy of Alzheimer disease.  Rivastigmine is associated with a minimal rate of serum enzyme elevations during therapy and is a rare cause of clinically apparent liver injury.

 

Background

Rivastigmine (riv" a stig' meen) is a selective acetylcholinesterase inhibitor which acts by inhibition of the metabolism of acetylcholine in the postsynaptic clefts, thus enhancing cholinergic neurotransmission.  Rivastigmine has selective activity for acetylcholinesterase in the central nervous system with little effect on the enzyme in peripheral tissue.  The increase in concentration of acetylcholine is associated with improvement in cognitive function in patients with Alzheimer disease who typically have relative cholinergic deficiency in the cerebral cortex.  Rivastigmine was approved for use in the United States in 2007 for treatment of mild-to-moderate dementia in Alzheimer and Parkinson disease.  Rivastigmine is available generically and under the brand name Exelon in capsules of 1.5, 3, 4.5 and 6 mg, as an oral solution of 2 mg/mL, and a transdermal patch of 14.6 and 9.5 mg applied every 24 hours.  The usual dose regimen is 3 to 6 mg twice daily.  Common side effects include diarrhea, nausea, vomiting, dizziness, fatigue, insomnia, vivid dreams, anxiety, restlessness, blurred vision, dry mouth and pruritus, symptoms common to cholinergic stimulation.

 

Hepatotoxicity

In large placebo controlled trials, rivastigmine therapy was not associated with an increased rate of serum enzyme elevations compared to placebo treatment and no instances of clinically apparent liver injury with jaundice were reported.  Nevertheless, since its introduction into clinical use, rivastigmine (administered by transdermal patch) has been implicated in at least one report of clinically apparent hepatotoxicity with mild jaundice.  The time to onset was 2 months and the serum enzyme elevations had a mildly hepatocellular pattern.  Mild rash and eosinophilia were also present, but autoimmune features were not.  Recovery was complete within 5 weeks of drug discontinuation. 

 

Likelihood score: D (possible, rare cause of clinically apparent drug-induced liver injury). 

 

Mechanism of Injury

Rivastigmine differs from the other acetylcholinesterase inhibitors in not having major hepatic metabolism.  The mechanism of potential hepatotoxicity of rivastigmine is not known, but is likely to be immunological idiosyncracy.

 

Outcome and Management

Cases of hepatotoxicity from rivastigmine have been too few to characterize clinically.  There have been no published reports of acute liver failure, chronic hepatitis or vanishing bile duct syndrome attributed to rivastigmine.  There is no information on the possible cross sensitivity to liver injury among the various acetylcholinesterase inhibitors.

References regarding the safety and potential hepatotoxicity of the drugs used for Alzheimer disease are provided together after the Overview section of Alzheimer Disease Agents (updated June 2018).

 

Drug Class:  Alzheimer Disease Agents

Top of page

 

REPRESENTATIVE TRADE NAMES
Rivastigmine – Generic, Exelon®

 

DRUG CLASS
Alzheimer Disease Agents

 

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

 

Top of page

DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Rivastigmine	123441-03-2	C14-H22-N2-O2

Top of page

 

 

1. Recent References on Rivastigmine

2. Trials on Rivastigmine

Top of page