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Simvastatin

Klassificering: A

Preparat: Ezetimib/Simvastatin Krka, Inegy®, Lipcut, Simidon, Simvastatin ACO, Simvastatin Actavis, Simvastatin Alpharma, Simvastatin Alternova, Simvastatin Arrow, Simvastatin Bluefish, Simvastatin Brown, Simvastatin Ebb, Simvastatin Gevita, Simvastatin IVAX, Simvastatin Krka, Simvastatin Mylan, Simvastatin Nycomed, Simvastatin Orifarm, Simvastatin Orion, Simvastatin Pensa, Simvastatin Ranbaxy, Simvastatin ratiopharm, Simvastatin Sandoz, Simvastatin STADA®, Simvastatin Teva, Vabadin, Zocor, Zocord®

ATC kod: C10AA01, C10BA02

Substanser: simvastatin

Sammanfattning

Studier har visat att simvastatin vid sekundärprevention minskar dödlighet och sjuklighet på ett likvärdigt sätt hos kvinnor och män.

I en studie på japanska patienter med hyperkolesterolemi fick kvinnor en större kolesterolsänkande effekt av 5 mg simvastatin jämfört med män. Det saknas studier avseende könsskillnader för en europeisk population.

En stor studie har visat att män har större risk att drabbas av måttliga till svåra muskelbiverkningar av simvastatin.
 
Vår bedömning är att de beskrivna skillnaderna inte motiverar olika dosering eller behandling hos kvinnor och män.

Additional information

Pharmacokinetics and dosing

The influence of sex on the plasma profile of simvastatin (40 mg/day) has been investigated following multiple doses in young (9 men, 9 women) and elderly patients (7 men, 9 women) with hypercholesterolemia. Mean steady-state plasma concentrations of active and total simvastatin were 20-50% higher in women than in men [2]. However, an open-label single-dose study in healthy Chinese patients (6 men, 6 women) found no sex difference in the pharmacokinetics of simvastatin when evaluated as an ezetimibe/simvastatin combination tablet [3]. Although sex differences in pharmacokinetics of simvastatin have been described, no dosage adjustment based on sex is considered necessary [2, 4].

Effects

Simvastatin is used for cardiovascular prevention and treatment of hypercholesterolemia.

The effect of simvastatin on cholesterol was evaluated in an open multicenter study (342 men, 253 women). Patients with hypercholesterolemia received simvastatin 10-40 mg once daily for 18 weeks. The reduction in LDL cholesterol was similar in women and men [5]. However, in a study in Japanese patients (71 men, 191 women), simvastatin 5 mg/day (the initial dose in Japan) was given to patients with hypercholesterolemia for 12 months. The percentage changes in TC (total cholesterol) and LDL-C (low-density lipoprotein cholesterol) levels were greater in women than in men. These results suggest that the rate of decrease in TC and LDL-C levels might be higher in women, irrespective of the baseline level, and that the response to simvastatin treatment might be greater in women [6]. Another Japanese study (12575 men, 27013 women) showed that among hypercholesterolemic patients taking simvastatin, the incidence of coronary events was 60% lower in women than in men. An observation in this study is that 44% of the men were smokers compared to 4% of the women. The relationship of serum TC and LDL-C concentrations to coronary events was similar in men and women [7].

Secondary preventionIn patients with atherosclerotic coronary disease, risk reductions with simvastatin have shown to be consistent in men and women [8]. The 4S study (3617 men, 827 women) showed that simvastatin reduced the risk of major coronary events in women to about the same extent as it did in men [9]. Also, the HPS trial (15454 men, 5082 women) showed a substantial benefit of adding 40 mg simvastatin daily to existing treatment in patients with coronary disease, other arterial disease or diabetes, in women as well as men. In the HPS study, differences between sexes was a primary outcome and pre-specified power calculations were performed [10]. In most other studies sex differences were assessed in subgroup analyses.

Adverse effects

In a large register-based cohort study (121 148 men, 104 744 women), the risk of moderate to serious myopathy was higher in men than in women for lipophilic statins such as simvastatin and atorvastatin. However, for the hydrophilic statins such as rosuvastatin and pravastatin there were no sex differences in the risk of myopathy. Adjusted hazard ratio for simvastatin-induced myopathy was 6.14 in men vs. 3.03 in women [11].

Reproductive health issues

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

Other information

Studies of adherence to statin therapy show conflicting results depending on study population. In a study from the U.S. (93006 men, 90594 women), female patients were more likely to be non-adherent to their prescribed statin [1].However, in a Korean study (368 men, 651 women), persistence of therapy was higher in women than in men, but the difference was not significant in the multivariate analysis [12].

Försäljning på recept

Fler män än kvinnor hämtade ut tabletter innehållande simvastatin (ATC-kod C10AA01) på recept i Sverige år 2015, totalt 298 182 män och 234 704 kvinnor. Det motsvarar 61 respektive 48 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70 år och äldre hos båda könen. I genomsnitt var tabletter innehållande simvastatin 1,7 gånger vanligare hos män [13].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2014-04-14

Referenser

  1. Foody JM, Joyce AT, Rudolph AE, Liu LZ, Benner JS. Persistence of atorvastatin and simvastatin among patients with and without prior cardiovascular diseases: a US managed care study. Curr Med Res Opin. 2008;24:1987-2000. PubMed
  2. Cheng H, Rogers JD, Sweany AE, Dobrinska MR, Stein EA, Tate AC et al. Influence of age and gender on the plasma profiles of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity following multiple doses of lovastatin and simvastatin. Pharm Res. 1992;9:1629-33. PubMed
  3. Chu NN, Chen WL, Xu HR, Li XN. Pharmacokinetics and safety of ezetimibe/simvastatin combination tablet: an open-label, single-dose study in healthy Chinese subjects. Clin Drug Investig. 2012;32:791-8. PubMed
  4. García MJ, Reinoso RF, Sánchez Navarro A, Prous JR. Clinical pharmacokinetics of statins. Methods Find Exp Clin Pharmacol. 2003;25:457-81. PubMed
  5. Simons LA. Simvastatin in severe primary hypercholesterolemia: efficacy, safety, and tolerability in 595 patients over 18 weeks The Principal Investigators. Clin Cardiol. 1993;16:317-22. PubMed
  6. Nakajima K. Sex-related differences in response of plasma lipids to simvastatin: the Saitama Postmenopausal Lipid Intervention Study S-POLIS Group. Clin Ther. 1999;21:2047-57. PubMed
  7. Sasaki J, Kita T, Mabuchi H, Matsuzaki M, Matsuzawa Y, Nakaya N et al. Gender difference in coronary events in relation to risk factors in Japanese hypercholesterolemic patients treated with low-dose simvastatin. Circ J. 2006;70:810-4. PubMed
  8. Zocor (simvastatin). DailyMed [www]. US National Library of Medicine. [updated 2014-02-01, cited 2014-04-14]. länk
  9. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-1389.
  10. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22. PubMed
  11. Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010;340:c2197. PubMed
  12. Kim YS, Sunwoo S, Lee HR, Lee KM, Park YW, Shin HC et al. Determinants of non-compliance with lipid-lowering therapy in hyperlipidemic patients. Pharmacoepidemiol Drug Saf. 2002;11:593-600. PubMed
  13. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler, Expertrådet för hjärt-kärlsjukdomar

Godkänt av: Karin Schenck-Gustafsson