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Classification: A

Drug products: Exelon, Exelon®, Nimvastid®, Orivast, Prometax, Prometax®, Rigmin, Rivastigmin Abacus Medicine, Rivastigmin Ebb, Rivastigmin Orifarm, Rivastigmin Orion, Rivastigmin Stada, Rivastigmin STADA, Rivastigmine Actavis, Rivastigmine Sandoz, Rivastor

ATC code: N06DA03

Substances: rivastigmine, rivastigmine tartrate


Most clinical studies show no differences between men and women in effect of cholinesterase inhibitors. However, the post hoc analysis of a large controlled clinical study of patients with mild cognitive impairment found the risk of developing Alzheimer’s Disease (AD) to be lower in women, but not in men, treated with rivastigmine.

Additional information

Swedish patients diagnosed with dementia by a specialist (and not by a general practitioner), are diagnosed with Alzheimer’s disease (AD) in 2/3 of the cases. The prevalence of dementia is higher in women, especially among the oldest patients [1]. The incidence of AD in Europe is significantly higher in women than in men (13.25 vs 7.02  per 1000 person-years); these rates increased with age [2].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 [3]. Another review identified 48 RCTs of which two had taken patient’s sex into account when evaluating AD treatment efficacy [4].

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding the pharmacokinetics of rivastigmine have been found. The dose is titrated based on tolerability and the manufacturer does not recommend different doses in men and women [5]. In a randomized placebo-controlled trial (486 men, 532 women), the InDDEx trial [6], the mean daily doses of rivastigmine were 5.84 mg/day in men and 3.93 mg/day in women to achieve effect.


A small clinical study (13 men, 48 women) reported a positive response to rivastigmine in women, but not in men with AD [7]. With so few men included in the study and thus a low statistical power it is hard to draw any conclusions regarding sex differences and treatment outcome. A Japanese cohort study, the Okayama Late Dementia Study OLDS included patients with AD treated with rivastigmine (20 men, 43 women) [8] reported stable Mini-Mental State examination (MMSE) with rivastigmine in both men and women with no significant sex differences.

A post hoc analysis of a randomized placebo-controlled trial (486 men, 532 women) the InDDEx trial [6], evaluated the effect of patient's sex on treatment response of rivastigmine 3- to 12 mg/day capsules in patients with mild cognitive impairment (MCI) [9]. The mean daily doses of rivastigmine were 5.84 mg/day in men and 3.93 mg/day in women. In women, rivastigmine decreased the rate of progression from MCI to AD from 24.8% in the placebo group to 17.4% in the treatment group. The disease progression in men was similar in the placebo group but not affected by rivastigmine treatment [9].

Adverse effects

In the post hoc analysis of the RCT InDDEx trial mentioned above (486 men, 532 women), the prevalence of serious adverse events in the rivastigmine groups were 27.0% in women and 29.0% in men [9].

Reproductive health issues

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

Other information

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 [10]. 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 [11].

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 [12]. 

A German study (4883 men, 8027 women) found that younger men (45-60 years) and patients with private health insurance had a lower risk of discontinuation of AD treatment with memantine, donepezil, galantamine, and rivastigmine [13].

Updated: 2022-06-13

Date of litterature search: 2018-04-13


  1. Nationella riktlinjer – Utvärdering 2018 Vård och omsorg vid demenssjukdom 2018 Indikatorer och underlag för bedömningar. Socialstyrelsen [www]. [updated 2018-01-01, cited 2022-01-22]. länk
  2. Niu H, Álvarez-Álvarez I, Guillén-Grima F, Aguinaga-Ontoso I. Prevalence and incidence of Alzheimer's disease in Europe: A meta-analysis. Neurologia. 2017;32(8):523-532. PubMed
  3. 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
  4. 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
  5. Exelon (rivastigmine). Summary of Product Characteristics. European Medicines Agency (EMA); 2018.
  6. Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y et al. Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study. Lancet Neurol. 2007;6:501-12. PubMed
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. Bohlken J, Weber S, Rapp MA, Kostev K. Continuous treatment with antidementia drugs in Germany 2003-2013: a retrospective database analysis. Int Psychogeriatr. 2015;27(8):1335-42. PubMed
  14. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2017 [cited 2018-04-17.] länk

Authors: Carl-Olav Stiller, Linnéa Karlsson Lind

Reviewed by: Diana Rydberg

Approved by: Karin Schenck-Gustafsson