Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Akamprosat

Klassificering: A

Preparat: Aotal, Campral

ATC kod: N07BB03

Substanser: akamprosat, akamprosatkalcium

Sammanfattning

En metaanalys av kliniska studier av akamprosat visar god effekt hos både kvinnor och män även om kvinnor rapporterade mer biverkningar. Akamprosat utsöndras långsammare hos personer med lägre njurfunktion vilket är vanligare hos kvinnor, fler kvinnor exponeras därför för högre doser vilket ökar risken för dosberoende biverkningar.
 
Vår bedömning är att nuvarande kunskapsunderlag inte motiverar skillnad i dosering eller behandling mellan kvinnor och män.

Additional information

The risk of alcohol use according to the Global Burden of Disease Study 2010, was ranked as number three in men and number twelve in women. Disability-adjusted life years were three times higher in men than in women and alcohol related deaths were twice as common in men as in women [1].

In Sweden, hospital care due to alcohol related diagnoses were twice as common in men compared to women in 2012 and alcohol related deaths were more common in men than in women [2].In a meta-analysis of 22 randomized controlled trials of patients treated with acamprosate (4794 men, 1317 women), 22% of the participants in the trials were females although one-third of alcohol dependent individuals are women [3].

Pharmacokinetics and dosing

After a single oral dose of 666 mg acamprosate in healthy volunteers (12 men, 12 women) pharmacokinetic parameters were similar in men and women [4, 5]. Acamprosate is excreted renally with linearity between creatinine clearance and clearance of acamprosate [6] . Despite a higher renal function in men than in women [7] the clinical studies have shown good effect with similar doses in men and women and no sex differentiation in dosing has therefore  been suggested by the manufacturer [5].

Effects

A meta-analysis including 22 randomized controlled trials ( 4794 men, 1317 women) of treatment with acamprosate during 3 to 12 months (mean 6 months) found similar effects in men and women. Outcome was measured in the percentage of abstinent days, rate of complete abstinence, percentage of no heavy drinking days, and rate of no heavy drinking [3]. A pooled analysis of the cumulative abstinence duration of seven of the randomized controlled trials included in the meta-analysis (1175 men, 310 women, in all), found that outcome of 3-6 months treatment was similar in men and women [8]. Similar results were shown in a single-blind, placebo-controlled 12 week study (31 men, 19 women) [9]. Also, in a retrospective study of consecutively acamprosate treated chronic alcoholics (19 men, 22 women), drinking was reduced equally in men and women [10]. A small observational study including very few women showed conflicting results [11].

Adverse effects

A meta-analysis of 22 randomized controlled trials of patients treated with acamprosate (in total 4794 men, 1317 women) during 3-12 months (mean 6 months) showed that women reported moderate to severe adverse events  more often than men (28% vs 20%), although there was no difference in the rate of discontinuation due to adverse events [3].

Reproductive health issues

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

Other information

In a placebo controlled study of patients with alcohol dependence (955 men, 428 women) randomized to naltrexone, acamprosate or naltrexone + acamprosate, with or without supportive counseling during 16 weeks showed a similar medication adherence in men and women [12].

A US study based on data from Veterans Health Administration (VHA) of treatment of alcohol misuse (270 774 men, 9 319 women) showed that women were more likely than men to receive a prescription of acamprosate (1% vs 0.6%), naltrexone (2.9% vs 1.6%), disulfiram (1.8% vs 1.1%), or any medication (5.2% vs 3%). The odds ratio for receiving any of these medications was 1.58 in women compared to men [13].

Försäljning på recept

Fler män än kvinnor hämtade ut tabletter innehållande akamprosat (ATC-kod N07BB03) på recept i Sverige år 2015, totalt 4 791 män och 2 591 kvinnor. Det motsvarar 1,0 respektive 0,5 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 50-64 år hos båda könen. I genomsnitt var tabletter innehållande akamprosat 2,2 gånger vanligare hos män [14].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2016-04-19

Referenser

  1. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224-60. PubMed
  2. Folkhälsan i Sverige Årsrapport 2014. Folkhalsomyndigheten [www]. [updated 2015-12-28, cited 2016-04-19]. Länk
  3. Mason BJ, Lehert P. Acamprosate for alcohol dependence: a sex-specific meta-analysis based on individual patient data. Alcohol Clin Exp Res. 2012;36:497-508. PubMed
  4. Saivin S, Hulot T, Chabac S, Potgieter A, Durbin P, Houin G. Clinical pharmacokinetics of acamprosate. Clin Pharmacokinet 1998 Nov;35(5):331-45 PubMed
  5. Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - CAMPRAL (acamprosate). US Food and Drug Administration [www]. [updated 2004-07-29, cited 2016-04-01]. länk
  6. Produktresumé Campral (akamprosat) (SPC) Merck Santé
  7. Läkemedelsboken 2015. Upplaga 19. Uppsala: Läkemedelsverket; 2015. Länk
  8. Verheul R, Lehert P, Geerlings PJ, Koeter MW, van den Brink W. Predictors of acamprosate efficacy: results from a pooled analysis of seven European trials including 1485 alcohol-dependent patients. Psychopharmacology (Berl). 2005;178:167-73. PubMed
  9. Gross CM, Spiegelhalder K, Mercak J, Feige B, Langosch JM. Predictability of alcohol relapse by hippocampal volumetry and psychometric variables. Psychiatry Res. 2013;212:14-8. PubMed
  10. Icro Maremmani AG, Bacciardi S, Rovai L, Rugani F, Massimetti E, Gazzarrini D et al. Six-month outcome in bipolar spectrum alcoholics treated with acamprosate after detoxification: a retrospective study. Int J Environ Res Public Health. 2014;11:12983-96. PubMed
  11. Aguiar P, Neto D, Lambaz R, Chick J, Ferrinho P. Prognostic factors during outpatient treatment for alcohol dependence: cohort study with 6 months of treatment follow-up. Alcohol Alcohol. 2012;47:702-10. PubMed
  12. Greenfield SF, Pettinati HM, O'Malley S, Randall PK, Randall CL. Gender differences in alcohol treatment: an analysis of outcome from the COMBINE study. Alcohol Clin Exp Res. 2010;34:1803-12. PubMed
  13. Harris AH, Kivlahan DR, Bowe T, Humphreys KN. Pharmacotherapy of alcohol use disorders in the Veterans Health Administration. Psychiatr Serv. 2010;61:392-8. PubMed
  14. Socialstyrelsens statistikdatabas . Stockholm: Socialstyrelsen. 2014 [cited 2016-02-17.] Socialstyrelsens statistikdatabas

Författare: Maria Enghag

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson