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Title: Drug Interactions with Cholinesterase Inhibitors: a Review

URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
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CNS Drugs 2003;17:13:947-63. "Clinically significant drug interactions with cholinesterase inhibitors : a guide for neurologists"
10/23/2003 11:00:00 AM
By Keely S. Solomon, PhD

Cholinesterase inhibitors (ChEIs) are the therapeutic strategy of choice for the treatment of Alzheimer's disease. However, the probability of an adverse drug-drug interaction increases as the elderly population receiving ChEIs continues to grow. In a recent review, Daniele Bentue-Ferrer, with the Laboratoire de Pharmacologie, Faculte de Medecine, Rennes, France, and colleagues described known drug interactions with the 4 available ChEIs, tacrine, donepezil, rivastigmine and galantamine. Adverse effects most commonly observed with ChEIs result from combined overactivation of central and peripheral cholinergic receptors. Common peripheral effects include gastrointestinal, cardiovascular, and neuromuscular symptoms, whereas central effects include insomnia, nightmares, agitation and a panic-like state. Most adverse interactions have been observed with tacrine, such that the manufacturer now advises against prescribing new tacrine regimens. Drugs known to interact with tacrine include fluvoxamine, cimetidine, estradiol, theophylline, and tobacco smoking. In addition, tacrine can cause major elevation of liver transaminase levels and hepatoxicity, so transaminase levels should be carefully monitored in all patients receiving this treatment. Some adverse interactions have been observed between ChEIs and antipsychotic drugs. It is thought that the co-prescription of ChEIs and dopamine D2 receptor blockers may induce an acetylcholine/dopamine imbalance in the striatum, producing an extrapyramidal syndrome. Such interactions have been reported for tacrine with haloperidol, and for donepezil with tiapride and risperidone. The bioavailability of galantamine was reported to be increased when coadministered with paroxetine, ketoconazole or erythromycin. Thus, coprescription with these drugs may necessitate a decrease in the dosage of galantamine. Rivastigmine is poorly bound to plasma protein and its metabolism is mediated predominately by esterases rather than hepatic microsomal enzymes, making clinically relevant drug interactions unlikely for this treatment. "Despite their use in an elderly population at risk of drug interactions and adverse effects, ChEIs are generally well tolerated," the reviewers conclude. However, they caution that, "the apparently general excellent tolerability of ChEIs does not diminish in any way the need for careful monitoring when these drugs are prescribed."

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=R
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