Tacrine dosing

Recommended Tacrine Dose and Monitoring Regimen Modification in Response to Transaminase Eievations ... 

Almkvist, O., Jelic, V., Amberla, K., Hellstrom-Lindahl, E., MeurUng, L., Nordberg, A. (2001) Responder characteristics to a single oral dose of cholinesterase inhibitor a doubleblind placebo-controlled study with tacrine in Alzheimer patients. Dement. Geriatr. Cogn. Disord., 12, 22-32. 

Although tacrine is longer-lasting than its predecessor physostigmine, it is by today s standards a short-acting medication. It must be taken four times per day with the total daily dose ranging from 80 to 160mg/day. 

The rate of dose escalation may be slowed if a patient is intolerant to the recommended titration schedule. However, it is not advisable to accelerate the dose incrementation plan. Following initiation of therapy, or any dosage increase, observe patients carefully for adverse effects. Take between meals whenever possible however, if minor Gl upset occurs, take with meals to improve tolerability. Taking tacrine with meals can be expected to reduce plasma levels approximately 30% to 40%. 

Initiation of treatment The initial dose of tacrine is 40 mg/day (10 mg 4 times/day). Maintain this dose for 4 weeks or more with every other week monitoring of transaminase levels beginning at week 4 of therapy. It is important that the dose not be increased during this period because of the potential for delayed onset of transaminase elevations. 

Cognitive function - Worsening of cognitive function has been reported following abrupt discontinuation of tacrine or after a large reduction in total daily dose (80 mg/day or more). 

Knapp MJ, Knoppman DS, Solomon PR, et al A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer s disease. JAMA 271 985-991, 1994... 

Wilson MA, Dwyer KD, Roy EJ Direct effects of ovarian hormones on antidepressant binding sites. Brain Res Bull 22 181-185, 1989 Winblad B, Adolfsson R, Carlsson A, et al Biogenic amines in brains with Alzheimer s disease, in Alzheimer s Disease A Report of Progress (Ageing, Vol 19). Edited by Corkin S, Davis KL, Growdon JH, et al. New York, Raven, 1982, pp 25-33 Winker MA Tacrine for Alzheimer s disease. Which patient, what dose JAMA 271 1023-1024, 1994... 

Tacrine Cognex Administer 10 mg po qid for 4 weeks, dien 20 mg qid for 4 weeks, then 30 mg qid for 4 weeks, and dien 40 mg qid. Titration is based on tolerability and serum transaminase levels. Refer to current product labeling for guidelines on dose adjustments, monitoring, and rechallenging. 10-, 20-, 30-, 40-mg capsules... 

Tacrine 55% 2-4 CYP 1A2 substrate CYP 1A2 inhibitor Rarely used in current clinical practice Risk for hepatotoxicity Multiple doses daily Requires close hepatic monitoring... 

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