Drug products: Clexane, Klexane, Klexane®, Klexane® (med konserveringsmedel)
ATC code: B01AB05
Substances: enoxaparin, enoxaparin sodium
The risk of bleeding with enoxaparin is similar in men and women. Women using enoxaparin has been shown to have a higher risk of bleeding than women using unfractionated heparin.
Women with mechanical heart valve prosthesis may have a higher risk of thromboembolism during pregnancy and have a higher frequency of spontaneous abortions, premature delivery, and miscarriages due to still birth with use of enoxaparin. Pregnant women should therefore be monitored for Factor Xa-levels and may need dose adjustment.
Patients with low body weight (women <45 kg, men <57 kg) and patients older than 65 years (mainly women) may benefit from dose adjustment due to body weight to reduce the risk of bleeding.
Following a single subcutaneous administration (40 mg and 60 mg, not weight adjusted), men had slightly higher values of apparent clearance and maximal anti-Factor Xa activities than women. The explanation behind this sex difference has not been conclusively identified, but body weight may be a contributing factor .
An increased exposure of enoxaparin with prophylactic non-weight adjusted dosages has been observed in patients with low body weight (women <45 kg, men <57 kg), which may result in higher risk of bleeding [1, 2].
A study comparing the pharmacokinetics of enoxaparin (i.v. 1.5 mg/kg, single dose) in healthy obese adults and in healthy non-obese adults (24 men, 24 women) report that patient’s sex did not have any impact on the pharmacokinetic parameters, except for non-weight-adjusted clearance and volume of distribution .
An open-label, cross-over study compared the pharmacokinetics of two formulations of enoxaparin (s.c. 1.5 mg/kg for 5 days in 1 shot vs. 2 shots, versus s.c. 1.5 mg/kg for 5 days in double concentrations) in healthy men and women. Women had longer extent of absorption and lower exposure. No sex difference in aPTT was observed .
In a cohort study (31 men, 66 women), women older than 65 years appeared to achieve more benefit from body weight adjusted dosing of enoxaparin than men. Women had more frequent therapeutic anti-Xa levels, fewer supra-therapeutic anti-Xa levels and no anti-Xa activity > 1.5 IU/ml. Men had comparable serum anti-Xa levels in both study and control groups. These sex differences may be explained by differences in body composition, with women having generally more fat and less lean muscle mass than men, lower blood volume and therefore a smaller volume of distribution, all of which favor weight-adjusted dosing .
In a clinical trial of enoxaparin as VTE prophylaxis after surgical procedures (49 men, 44 women), female sex was one factor predicting peak anti-factor Xa levels .
A randomized controlled trial found that women with myocardial infarction and treated with enoxaparin had a similar relative risk reduction as men (14%). Women had a higher baseline mortality risk than men and achieved a greater absolute benefit than men (2.6% vs.1.6% absolute risk reduction) when treated with enoxaparin .
The rate of major bleeding with enoxaparin has been shown to be similar among women and men (2.3% vs 2.0%). Compared to unfractionated heparin, major and minor bleeding was more frequent among women receiving enoxaparin .
The use of enoxaparin sodium injection for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic heart valves given enoxaparin (1 mg/kg twice daily), two of eight women developed clots resulting in blockage of the valve leading to maternal and fetal death. However, no causal relationship has been established. There have also been post-marketing reports of valve thrombosis in pregnant women with mechanical prosthetic heart valves while receiving enoxaparin for thromboprophylaxis. Women with mechanical prosthetic heart valves may be at higher risk for thromboembolism during pregnancy and have higher rate of fetal loss from spontaneous abortion, premature delivery and fetal loss from stillbirth. Frequent monitoring of peak and trough anti-Factor Xa levels, and adjusting of dosage may be needed .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2019-01-30
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson