Tacrine Side Effects
Applies to tacrine: oral capsule
Elevations in LFTs (liver function tests) have been reported in as many as 50% of patients started on tacrine therapy. LFTs should be closely monitored while patients are treated with tacrine, particularly when therapy is initiated and when dosages are altered.
Specific recommendations for LFT monitoring are as follows:
Every-other-week monitoring of LFTs, particularly ALT, is recommended during the first sixteen weeks of tacrine therapy.
If modest elevations of up to two times the ULN (upper limit of normal) occur, continued every-other-week LFTs are recommended.
If elevations of up to three times ULN occur, weekly LFT monitoring is recommended until LFTs return to normal.
If elevations of up to five times ULN occur, a daily dosage reduction of 40 mg and weekly LFT monitoring is recommended until LFTs return to normal.
If elevations greater than five times ULN occur, discontinuation of tacrine therapy is recommended until LFTs return to normal.
Rechallenge may be attempted in patients who have discontinued tacrine therapy as a result of elevated LFTs (but rechallenge is contraindicated in patients with a history tacrine-induced jaundice). Rechallenge should only proceed once LFTs have returned to normal. A daily dose of 40 mg may be attempted. LFTs should be monitored weekly during rechallenge. Limited experience is available concerning rechallenge in patients with a history of tacrine-induced LFT elevations greater than 10 times ULN.[Ref]
Twenty-five percent of patients may experience a rise in ALT to three times normal. Seven percent may experience a rise in ALT to 10 times normal. Large rises in LFTs have been associated with hepatocellular injury rarely. Pathologic findings associated with tacrine-induced hepatotoxicity include granulomatous changes and hepatocellular necrosis.[Ref]
Cholinergic adverse effects occur in as many as 68% of treated patients and include nausea, vomiting, diarrhea, dyspepsia, anorexia, restlessness, tremors, myalgia, arthralgia, excessive sweating, rash and frequent micturition. Hypotension, hypertension, bradycardia, syncope, ataxia and confusion have also been reported less frequently.[Ref]
The cholinomimetic effects of tacrine may result in an increase in gastric acid secretion and may therefore increase the risk of gastric ulceration in some patients.
Because of the potential vagotonic effects of cholinomimetic therapy, use in patients with "sick sinus syndrome" should be undertaken, if at all, with caution.[Ref]
A case of exacerbation of parkinsonism has been reported. Some clinicians have also reported vertigo and paresthesias as nervous system effects. Six cases of generalized tonic or tonic-clonic seizures have also been reported.[Ref]
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7. Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW "Hepatotoxic effects of tacrine administration in patients with alzheimers disease." JAMA 271 (1994): 992-8
8. Forsyth DR, Surmon DJ, Morgan RA, Wilcock GK "Clinical experience with and side-effects of tacrine hydrochloride in Alzheimer's disease: a pilot study." Age Ageing 18 (1989): 223-9
9. Wilcock GK, Surmon D, Forsyth D, Morgan R "Cholinergic side-effects of tetrahydroaminoacridine." Lancet 2 (1988): 1305
10. "Product Information. Cognex (tacrine)." Parke-Davis, Morris Plains, NJ.
11. Ott BR, Lannon MC "Exacerbation of parkinsonism by tacrine." Clin Neuropharmacol 15 (1992): 322-5
Medically reviewed by Drugs.com. Last updated on July 27, 2020.
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