Galantamin

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

Population pharmacokinetic modelling with galantamine has shown that the patient characteristics affecting clearance are age, sex, and bodyweight [8]. In an analysis of data from 15 clinical trials (539 men, 550 women) the galantamine clearance in women was on average 20% lower than in men. Creatinine clearance and weight were lower and mean age was higher in women [9]. These results are in line with data from a Swedish cohort with mild to moderate AD patients, SATS (24 men, 60 women), reporting 21% lower mean galantamine plasma concentration in men despite similar doses [10]. Despite the pharmacokinetic differences of galantamine, the clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested [11].

Effects

Two Japanese cohort studies, the Okayama Galantamine Study OGS (109 men, 170 women) [12] and the Okayama Late Dementia Study OLDS (83 men, 139 women) [13], reported similar results regarding Mini-Mental State examinations (MMSE) in men and women. However, regarding the Hasegawa Dementia Rating Scale-revised (HDS-R) women worsened over time. Women in the OGS study had higher HDS-R at baseline and a deterioration was only seen in women at 12 and 24 months [12]. Also in the OLDS study a deterioration of HDS-R at 12 months was only noted in women [13]. A worsening of the Abe’s BPSD score (ABS) in women treated with galantamine, was observed. The OLDS study reports worsening in women (increased ABS 3.0±7.4) at 12 months. ABS scores for men were preserved in the galantamine group until 12 months [13]. Also in the OGS study ABS-score had deteriorated in women at 24 months while no change was detected in men [12].

 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].

Adverse events

Results from a Dutch cohort of patients with AD and treated with galantamine (112 men, 191 women) report that galantamine has no effect on weight [14]. This is in contrast to donepezil where weight-loss is a known adverse event more common in women [15].

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].