Memantine

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 review identified 48 RCTs of which two had taken patient’s sex into account when evaluating AD treatment efficacy [3].

Pharmacokinetics and dosing

Following a multiple dose administration of memantine 20 mg twice a day, Cmax and AUC in women were approximately 45% higher than in men. However, there were no differences in Cmax or AUC when adjusting for body weight [4]. In another pharmacokinetic study (34 men, 74 women), men had higher oral clearance (CL/F) [5]. Despite the pharmacokinetic differences of memantine, the clinical studies have shown effect with similar doses in men and women, and no sex differentiation in dosing has been suggested [6].

Effects

A Japanese cohort study including AD patients treated with memantine (11 men, 22 women), reported significant improvement of the Abe’s Behavior and Psychological Symptom of Dementia Score (ABS) at 12 months in women. However, these results are not considered clinically relevant due to the low number of patients [7]. No studies with a clinically relevant sex analysis regarding the effects of memantine have been found.

Adverse effects

No studies with a clinically relevant sex analysis regarding adverse effects of memantine have been found.

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 [8].

An American retrospective data analysis (1100 men, 1991 women) investigated the relationship between adherence to oral AD therapy (rivastigmine, donepezil, galantamine or memantine) and other variables. Men with AD were approximately 18% more likely to be adherent to index oral AD therapy than women [9].

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 [10].