Drug Interactions between cimetidine and tacrine

GENERALLY AVOID: Cimetidine has been shown to possess clinically significant anticholinergic activity and may negate the already small pharmacologic benefits of acetylcholinesterase inhibitors in the treatment of dementia. Agents with anticholinergic properties may also adversely affect elderly patients in general. Clinically significant mental status changes associated with anticholinergic agents can range from mild cognitive impairment to delirium, and patients with Alzheimer's disease and other dementia are especially sensitive.

MONITOR: Coadministration with cimetidine may increase the bioavailability and plasma concentrations of tacrine. The proposed mechanism is cimetidine inhibition of the first-pass (presystemic) hepatic extraction of tacrine by cytochrome P450 enzymes. In 12 healthy elderly subjects, pretreatment with cimetidine (300 mg orally four times a day for 3 days) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tacrine (40 mg single oral dose) by 36% and 39%, respectively, compared to administration of tacrine alone. The combination was generally well tolerated, but nausea and vomiting occurred in one patient and led to withdrawal from the study.

MANAGEMENT: Drugs that possess anticholinergic activity such as cimetidine should generally be avoided in patients with Alzheimer's disease or other cognitive impairment, regardless of whether they are receiving an acetylcholinesterase inhibitor. Famotidine or nizatidine may be suitable alternatives if an H2-receptor antagonist is necessary. In patients who are already receiving an acetylcholinesterase inhibitor with cimetidine, every attempt should be made to discontinue the latter. Caution is required, however, since anticholinergic withdrawal may occur. Seizures have been reported following abrupt discontinuation of anticholinergics during acetylcholinesterase inhibitor therapy.

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