Memantine does not appear to attenuate anticholinesterase effects of donepezil, galantamine, or tacrine, nor affect pharmacokinetics of galantamine or donepezil.
Clinical evidence,mechanism, importance and management
An in vitro study in rats suggested that memantine does not attenuate anticholinesterase effects of donepezil at therapeutic concentrations (See reference number 1). In a later study 19 healthy subjects were given memantine 10mg before and on last day of taking donepezil (5 mg daily for 7 days then 10mg daily for 22 days). The pharmacokinetics of both drugs were not significantly affected by concurrent use, and effects of donepezil on anticholinesterase were also unaffected (See reference number 2). Furthermore, an efficacy and safety study of one year’s duration has reported that combination is well tolerated and beneficial (See reference number 3).
An in vitro study in rats suggested that memantine does not attenuate anticholinesterase effects of galantamine at therapeutic concentrations (See reference number 1). A study in 15 healthy subjects found that concurrent use of extended-release galantamine 16mg daily with memantine 10mg twice daily for 12 days did not affect pharmacokinetics of galantamine and generally did not increase incidence of adverse effects, although dizziness may have been more common (See reference number 4).
Furthermore, a review of efficacy studies suggested that effects of galantamine on anticholinesterase are unaffected, that combination is safe and generally well tolerated (See reference number 5).
An in vitro study in rats suggested that memantine does not attenuate anticholinesterase effects of tacrine at therapeutic concentrations (See reference number 1)
Wenk GL,Quack G, Moebius H-J, Danysz W. No interaction of memantine with anticholinesterase inhibitors approved for clinical use. Life Sci (2000) 66, 1079–83.
Periclou AP,Ventura D, Sherman T, Rao N, Abramowitz WT. Lack of pharmacokinetic or pharmacodynamic interaction between memantine and donepezil. Ann Pharmacother (2004) 38, 1389–94.
Tariot PN,Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, for the Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer Disease already receiving donepezil: a randomized controlled trial. JAMA (2004) 291, 317–24.
Yao C,Raoufinia A, Gold M, Nye JS, Ramael S, Padmanabhan M, Walschap Y, Verhaeghe T, Zhao Q. Steady-state pharmacokinetics of galantamine are not affected by addition of memantine in healthy subjects. J Clin Pharmacol (2005) 45, 519–28.
Grossberg GT,Edwards KR, Zhao Q. Rationale for combination therapy with galantamine and memantine in Alzheimer’s disease. J Clin Pharmacol (2006) 46, 17S–26S.