Galantamine is an oral acetylcholinesterase inhibitor used for therapy of Alzheimer disease. Galantamine is associated with a minimal rate of serum enzyme elevations during therapy and has not been implicated as a cause of clinically apparent liver injury.
Galantamine (ga lan' ta meen) is a selective acetylcholinesterase inhibitor which acts by inhibition of the metabolism of acetylcholine in the postsynaptic clefts, thus enhancing cholinergic neurotransmission. Alzheimer disease is associated with a cholinergic deficiency in the cerebral cortex, and the increase in concentration of acetylcholine with acetylcholinesterase inhibition is associated with improvement in cognitive function in affected patients. Galantamine has selective activity for acetylcholinesterase in the central nervous system with little effect on the enzyme in peripheral tissue. Galantamine was approved for use in the United States in 2001, and current indications include mild-to-moderate dementia of the Alzheimer disease type. Galantamine is available generically and under the brand name of Razadyne in tablets of 4, 8 and 12 mg and as sustained release capsules of 8, 16 and 24 mg. It is also available as an oral solution (4 mg/mL). The usual maintenance dose is 16 to 24 mg daily in two divided doses. Common side effects include nausea, vomiting, diarrhea, abdominal pain, dizziness, fatigue, insomnia, vivid dreams, anxiety, restlessness, blurred vision, dry mouth and pruritus, symptoms common to cholinergic stimulation.
In several large placebo controlled clinical trials, there was no increase in the rate of serum enzyme elevations in patients treated with galantamine compared to those on placebo and no reports of hepatotoxicity. No individual case reports of clinically apparent hepatotoxicity have been published, although cases of liver enzyme elevations and hepatitis attributed to galantamine have been reported to the sponsor. With the exception of tacrine, the acetylcholinesterase inhibitors used for Alzheimer disease have only rarely been linked to instances of clinically apparent, acute liver injury.
Mechanism of Injury
Galantamine is extensively metabolized by the hepatic cytochrome P450 system (CYP 2D6 and 3A4) followed by glucuronidation. Hepatotoxicity might occur as a result of its idiosyncratic metabolism to a toxic or immunogenic intermediate.
Outcome and Management
Galantamine has not been associated with published cases of clinically apparent hepatotoxicity, acute liver failure, chronic hepatitis or vanishing bile duct syndrome. There is no information on the possible cross sensitivity to liver injury among the various acetylcholinesterase inhibitors.
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