Drug products: Pravachol, Pravachol®, Pravastatin Actavis, Pravastatin Nycomed, Pravastatin Omnia, Pravastatin Ranbaxy, Pravastatin Sandoz, Pravastatin Teva
ATC code: C10AA03
Substances: pravastatin, pravastatin sodium
Studies have shown that pravastatin as secondary prevention reduces mortality and morbidity equally in men and women.
A large registry-based study has men and women to have similar risk of moderate to severe adverse muscle effects.
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.
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 . Based on the findings in pravastatin pharmacokinetics [1, 2], dosage modification in elderly men or women are not considered necessary.
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 .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 .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 .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 .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 .
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] .Most large pivotal studies, even recent ones, have not performed relevant sex-analyses of side effects . In the LIPID study  no sex differences in adverse events were reported.
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
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 .
Date of litterature search: 2014-06-09
Reviewed by: Mia von Euler, Expertrådet för hjärt-kärlsjukdomar
Approved by: Karin Schenck-Gustafsson