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Pravastatin

Klassificering: A

Preparat: Pravachol, Pravachol®, Pravastatin Actavis, Pravastatin Nycomed, Pravastatin Omnia, Pravastatin Ranbaxy, Pravastatin Sandoz, Pravastatin Teva

ATC kod: C10AA03

Substanser: pravastatin, pravastatinnatrium

Sammanfattning

Studier har visat att pravastatin vid sekundärprevention minskar dödlighet och sjuklighet på ett likvärdigt sätt hos kvinnor och män.
En stor registerstudie har visat att kvinnor och män har lika stor risk att drabbas av måttliga till svåra muskelbiverkningar av pravastatin.
 
Kunskapsunderlaget avseende skillnader mellan kvinnor och män är begränsat och motiverar inte olika dosering eller behandling.

Additional information

Pharmacokinetics and dosing

Only small differences in the pharmacokinetic profile of pravastatin in young and elderly men and women have been demonstrated [1, 2]. Pravastatin is a substrate of the hepatic uptake transporter OATP1B1. The effect of gene polymorphism on the pharmacokinetics of pravastatin was studied in a Finnish study (18 men, 14 women). Cmax and AUC of pravastatin were markedly higher in women with the c.521TT genotype than in men with the same genotype [3]. Based on the findings in pravastatin pharmacokinetics [1, 2], dosage modification in elderly men or women are not considered necessary.

Effects

Primary/secondary preventionThe large ALLHAT-LLT trial (5304 men, 5051 women) compared pravastatin 40 mg/day with “usual care” in hypercholesterolemic, hypertensive patients with at least one additional CHD risk factor. All-cause mortality did not differ between the pravastatin and usual care treatment groups, and the results were similar in men and women [4].Results from the Japanese MEGA study (2476 men, 5356 women; mean age 59.7 years in women, 55.2 years in men) show that treatment with pravastatin 10-20 mg/day in women with elevated cholesterol but without previous cardiovascular disease provides a benefit similar to that seen in men. The incidence of cardiovascular events was lower in women than in men, probably due to lower percentage of smokers among women [5].The effect of pravastatin on hsCRP levels was evaluated in the PRINCE trial (1764 men, 1120 women), including a primary prevention cohort and a secondary prevention cohort. Pravastatin 40 mg/day reduced hsCRP levels at 24 weeks in both cohorts. Compared to placebo, the effect of pravastatin on hsCRP levels was significant in both men and women. The median change in hsCRP was similar in men and women [6].In the double-blind placebo-controlled CARE trial (3577 men, 582 women), patients with myocardial infarction and average cholesterol levels were treated with pravastatin 40 mg/day for 5 years. The beneficial effect of pravastatin on major coronary events was greater among women than men [7].The LIPID trial (7498 men, 1516 women) was a double-blind, randomized trial, comparing pravastatin 40 mg/day with placebo in patients with coronary heart disease and a broad range of cholesterol levels. The mortality risk reduction with pravastatin was consistent in men and women [8].

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 HR for pravastatin-induced myopathy was 4.8 in men [95%CI 2.9-8.2] vs. 2.6 in women [95%CI 1.3-5.4] [9].Most large pivotal studies, even recent ones, have not performed relevant sex-analyses of side effects [10]. In the LIPID study [9] no sex differences in adverse events were reported.

Reproductive health issues

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

Other information

A meta-analysis  of three large-scale clinical trials (in total 7082 men, 6642 women) studied the influence of pravastatin therapy on cancer morbidity and mortality in Japanese patients. No increased risk for cancer incidence and cancer death following administration of pravastatin was detected in either men or women [11].

Försäljning på recept

Nästan lika många män och kvinnor hämtade ut tabletter innehållande pravastatin (ATC-kod C10AA03) på recept i Sverige år 2015, totalt 7 346 män och 7 334 kvinnor. Det motsvarar 1,5 respektive 1,5 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 pravastatin 1,4 gånger vanligare hos män [12].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2014-06-09

Referenser

  1. Pan HY, Waclawski AP, Funke PT, Whigan D. Pharmacokinetics of pravastatin in elderly versus young men and women. Ann Pharmacother. 1993;27:1029-33. PubMed
  2. Hatanaka T. Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events. Clin Pharmacokinet. 2000;39:397-412. PubMed
  3. Niemi M, Pasanen MK, Neuvonen PJ. SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin. Clin Pharmacol Ther. 2006;80:356-66. PubMed
  4. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288:2998-3007. PubMed
  5. Mizuno K, Nakaya N, Ohashi Y, Tajima N, Kushiro T, Teramoto T et al. Usefulness of pravastatin in primary prevention of cardiovascular events in women: analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA study). Circulation. 2008;117:494-502. PubMed
  6. Albert MA, Danielson E, Rifai N, Ridker PM, PRINCE Investigators. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA. 2001;286:64-70. PubMed
  7. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001-9. PubMed
  8. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The New England Journal of Medicine. 1998;339(19):1349-1357.
  9. 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
  10. Finegold JA, Manisty CH, Goldacre B, Barron AJ, Francis DP. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Prev Cardiol. 2014;21:464-74. PubMed
  11. Matsushita Y, Sugihara M, Kaburagi J, Ozawa M, Iwashita M, Yoshida S et al. Pravastatin use and cancer risk: a meta-analysis of individual patient data from long-term prospective controlled trials in Japan. Pharmacoepidemiol Drug Saf. 2010;19:196-202. PubMed
  12. 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