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Galantamin

Klassificering: A

Preparat: Galantamin Abacus Medicine, Galantamin Actavis, Galantamin Ebb, Galantamin Krka, Galantamin Mylan, Galantamin Orion, Galantamin Sandoz, Galantamin STADA, Galantamin Teva, Galantamine Medical Valley, Indukolin, Reminyl, Reminyl®

ATC kod: N06DA04

Substanser: galantamin, galantaminhydrobromid

Sammanfattning

De flesta studier visar inga könsskillnader i effekt eller biverkningar.

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

Population pharmacokinetic modelling with galantamine has shown that the patient characteristics affecting clearance are age, sex, and bodyweight [5]. 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 [6]. 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 [7]. 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 [8].

Effects

Two Japanese cohort studies, the Okayama Galantamine Study OGS (109 men, 170 women) [9] and the Okayama Late Dementia Study OLDS (83 men, 139 women) [10], 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 [9]. Also in the OLDS study a deterioration of HDS-R at 12 months was only noted in women [10]. 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 [10]. Also in the OGS study ABS-score had deteriorated in women at 24 months while no change was detected in men [9].

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 [11]. This is in contrast to donepezil where weight-loss is a known adverse event more common in women [12].

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 [13]. 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 [14].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 [15].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 [16].

Försäljning på recept

Fler kvinnor än män hämtade ut galantamin (ATC-kod N06DA04) på recept i Sverige år 2017, totalt 3 304 kvinnor och 2 091 män. Det motsvarar 0,7 respektive 0,4 patienter per tusen invånare. Andelen som hämtat ut läkemedlet var högst i åldersgruppen 85 år och äldre. I genomsnitt var galantamin 1,3 gånger vanligare hos kvinnor [17].

Uppdaterat: 2022-06-07

Litteratursökningsdatum: 2018-04-13

Referenser

  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. Farlow MR. Clinical pharmacokinetics of galantamine. Clin Pharmacokinet. 2003;42(15):1383-92. PubMed
  6. Piotrovsky V, Van Peer A, Van Osselaer N, Armstrong M, Aerssens J. Galantamine population pharmacokinetics in patients with Alzheimer's disease: modeling and simulations. J Clin Pharmacol 2003 May;43(5):514-23 PubMed
  7. Wattmo C, Jedenius E, Blennow K, Wallin AK. Dose and plasma concentration of galantamine in Alzheimer's disease - clinical application. Alzheimers Res Ther. 2013;5(1):2. PubMed
  8. Reminyl (galantamin). Summary of Product Characteristics. Medical Products Agency - Sweden; 2015.
  9. Nakano Y, Matsuzono K, Yamashita T, Ohta Y, Hishikawa N, Sato K et al. Long-Term Efficacy of Galantamine in Alzheimer's Disease: The Okayama Galantamine Study (OGS). J Alzheimers Dis. 2015;47(3):609-17. PubMed
  10. 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
  11. Droogsma E, van Asselt DZ, van Steijn JH, Schuur T, Huinink EJ. Effect of long-term treatment with galantamine on weight of patients with Alzheimer's dementia. J Nutr Health Aging. 2013;17(5):461-5. PubMed
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2017 [cited 2018-04-17.] länk

Författare: Carl-Olav Stiller, Linnéa Karlsson Lind

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson