Can you combine memantine and donepezil?/nA patient at the pharmacy has been prescribed memantine (

Fråga: Can you combine memantine and donepezil?

A patient at the pharmacy has been prescribed memantine (Ebixa) 10 mg x2 and donepezil (Aricept) 5 mg x1 by two different physicians. The pharmacist wonders if there is any documentation of the combination of these two drugs.

Sammanfattning: The combination of memantine and donepezil seems to be safe and well tolerated in patients with Alzheimer´s disease. No pharmacodynamic or pharmacokinetic interactions are expected.

Svar: This question has previously been answered in Drugline (1). At that time, only one in vitro study with the combination of memantine and cholinesterase inhibitors had been published. An updated search revealed two new human studies.

Memantine is an NMDA-receptor antagonist and donepezil is a cholinesterase inhibitor, both used in the treatment of Alzheimer´s disease (2). Preclinical studies have shown that memantine does not affect the inhibition of acetylcholinesterase, nor does it bind to muscarinic receptors (3).

In a prospective randomized placebo-controlled study with 404 patients, the combination of memantine and donepezil was studied. The addition of memantine, 20 mg/d, to patients already receiving donepezil was safe and well tolerated. The incidence of adverse events was similar in both groups. The efficacy was significantly better when combining memantine with donepezil than with placebo (3). A previous prospective 4-month study with 158 patients, taking memantine (5-60 mg/d) and a cholinesterase inhibitor has been done. Onehundred and thirtytwo of the patients received donepezil (2.5-10 mg/d). No severe adverse reactions were reported and the combination was well tolerated by the patients (4).

No pharmacokinetic interactions between donepezil and memantine have been found. Donepezil is a cytochrome P-450 CYP3A4 and CYP2D6 substrate (5). Memantine is not metabolised by the CYP-system and has not shown any inhibitory effects of the CYP-enzymes in vitro (2). Drugline no 18958 (year 2002) FASS 2003 (The Swedish catalogue of approved medical products) Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil. A randomized controlled trial. JAMA 2004;291(3):317-24. Hartmann S, Mobius HJ. Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy. Int Clin Psychopharmacol 2003;18:81-5. Bentue-Ferrer D, Tribut O, Polard E; Allain H. Clinically significant drug interactions with cholinesterase inhibitors. A guide for neurologists. CNS Drugs 2003;17(13):947-63.