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Classification: A

Drug products: Aricept, Aricept Evess 5 mg, Aricept®, Azepezil, Donepezil Accord, Donepezil Actavis, Donepezil Aurobindo, Donepezil bluefish, Donepezil Ebb, Donepezil Jubilant, Donepezil Krka, Donepezil Mylan, Donepezil Navamedic, Donepezil Orifarm, Donepezil Orion, Donepezil Paranova, Donepezil Sandoz, Donepezil STADA, Donepezil Teva

ATC code: N06DA02

Substances: donepezil, donepezil hydrochloride, donepezil hydrochloride monohydrate


Most studies show no differences between men and women in effect of cholinesterase inhibitors. There are some studies on donepezil where women had a better response than men on the mini mental scale. The risk of anorexia and weight drop seems to be higher in women while anxiety and aggression may be more common in men. According to some observations, the risk of premature death associated to donepezil treatment could be slightly higher in men than in women.

Additional information

A systematic review of 33 RCTs on cholinesterase inhibitors (in all: 6868 men, 9103 women) concludes an almost complete lack of sex-specific reporting of data in clinical trials for dementia drug therapies, and no sex-specific reporting of adverse events [1]. Another review identified 48 RCTs of which two had taken patient’s sex into account when evaluating Alzheimer dementia (AD) treatment efficacy [2].

Pharmacokinetics and dosing

Pharmacokinetic studies of donepezil do not indicate sex differences regarding plasma concentration or clearance of donepezil [8]. Higher doses of donepezil (23 mg vs. 10 mg daily) have a better effect in both men and women [9] .


The effect of donepezil measured by GBS (Gottfries-Bråne-Steen) and mini mental state examination (MMSE) at week 52 was studied in a randomized placebo controlled trial of patients with Alzheimer Dementia (AD) (102 men, 184 women). No sex difference in effect was found [10]. In a 36-week open-label trial of patients with mild to moderate AD (35 men, 82 women) response to donepezil (5-10 mg/d) was not affected by APOE genotype, patient’s sex, or both factors combined [11].

In contrast, some studies report different treatment effects regarding sex. In a Japanese cohort Okayama Late Dementia Study (OLDS) of older patients with AD (19 men, 36 women) men, but not women, had worse MMSE at 12 months compared to  baseline [12]. A similar pattern was noted in an Italian sample of patients with late onset AD (26 men, 70 women). Women, but not men, responded to treatment with donepezil with improved MMSE compared to a control group [13]. In an open-label, retrospective cohort 2-year study (107 men, 229 women) in patients with AD treated with donepezil (mean dose 0f 8.1 mg/d), women had lower mortality rates than men (10% and 20%, respectively). The study reported that male sex was one of several variables associated with a higher mortality [14].

 It has been noted that women seems to be overrepresented in populations of patients with AD but have similar prevalence in MCI populations indicating a faster  transition from MCI to AD in women [3]. The increased risk for disease progression from MCI to AD in women  has also been linked to certain genetic variants (e.g. butyrylcholineesterase wild type genotype) as suggested by a publication based on data from the InDDEX trial [4].In a review of 14 studies (in all 1820 men, 2942 women) the evidence relating to patient functioning as an outcome measure in the treatment with donepezil, galantamine, rivastigmine or memantine for AD was evaluated and showed that the pooled effect size was not significantly affected by patient's sex [5].In addition, a review of seven double-blind, open-label clinical trials and 13 case studies of donepezil, galantamine and rivastigmine did not produced support of an association between treatment outcomes and patient's sex [6].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

An American retrospective data analysis investigated the relationship between adherence to oral AD therapy (rivastigmine, donepezil, galantamine or memantine) and other variables. Male AD patients were approximately 18% more likely to be adherent to index oral AD therapy than female patients [7].

Updated: 2020-08-28

Date of litterature search: 2018-04-16


  1. Mehta N, Rodrigues C, Lamba M, Wu W, Bronskill SE, Herrmann N et al. Systematic Review of Sex-Specific Reporting of Data: Cholinesterase Inhibitor Example. J Am Geriatr Soc. 2017;65(10):2213-2219. PubMed
  2. Canevelli M, Quarata F, Remiddi F, Lucchini F, Lacorte E, Vanacore N et al. Sex and gender differences in the treatment of Alzheimer's disease: A systematic review of randomized controlled trials. Pharmacol Res. 2017;115:218-223. PubMed
  3. Ferris S, Lane R, Sfikas N, Winblad B, Farlow M, Feldman HH. Effects of gender on response to treatment with rivastigmine in mild cognitive impairment: A post hoc statistical modeling approach. Gend Med. 2009;6:345-55. PubMed
  4. Ferris S, Nordberg A, Soininen H, Darreh-Shori T, Lane R. Progression from mild cognitive impairment to Alzheimer's disease: effects of sex, butyrylcholinesterase genotype, and rivastigmine treatment. Pharmacogenet Genomics. 2009;19(8):635-46. PubMed
  5. Hansen RA, Gartlehner G, Lohr KN, Kaufer DI. Functional outcomes of drug treatment in Alzheimer's disease: A systematic review and meta-analysis. Drugs Aging. 2007;24:155-67. PubMed
  6. Haywood WM, Mukaetova-Ladinska EB. Sex influences on cholinesterase inhibitor treatment in elderly individuals with Alzheimer's disease. Am J Geriatr Pharmacother. 2006;4:273-86. PubMed
  7. Borah B, Sacco P, Zarotsky V. Predictors of adherence among Alzheimer's disease patients receiving oral therapy. Curr Med Res Opin. 2010;26:1957-65. PubMed
  8. Aricept (donepezil). Summary of Product Characteristics. Medical Products Agency - Sweden; 2014.
  9. Sabbagh M, Cummings J, Christensen D, Doody R, Farlow M, Liu L et al. Evaluating the cognitive effects of donepezil 23 mg/d in moderate and severe Alzheimer's disease: analysis of effects of baseline features on treatment response. BMC Geriatr. 2013;13:56. PubMed
  10. Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A et al. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology. 2001;57(3):489-95. PubMed
  11. Rigaud AS, Traykov L, Latour F, Couderc R, Moulin F, Forette F. Presence or absence of at least one epsilon 4 allele and gender are not predictive for the response to donepezil treatment in Alzheimer's disease. Pharmacogenetics. 2002;12(5):415-20. PubMed
  12. Matsuzono K, Yamashita T, Ohta Y, Hishikawa N, Sato K, Kono S et al. Clinical Benefits for Older Alzheimer's Disease Patients: Okayama Late Dementia Study (OLDS). J Alzheimers Dis. 2015;46(3):687-93. PubMed
  13. Scacchi R, Gambina G, Broggio E, Corbo RM. Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigmine in patients with Alzheimer's disease. Int J Geriatr Psychiatry. 2014;29:610-5. PubMed
  14. López-Pousa S, Olmo JG, Franch JV, Estrada AT, Cors OS, Nierga IP et al. Comparative analysis of mortality in patients with Alzheimer's disease treated with donepezil or galantamine. Age Ageing. 2006;35:365-71. PubMed
  15. Farlow M, Veloso F, Moline M, Yardley J, Brand-Schieber E, Bibbiani F et al. Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer's disease. BMC Neurol. 2011;11:57. PubMed
  16. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2017 [cited 2018-04-17.] länk

Authors: Carl-Olav Stiller, Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson