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Enoxaparin

Klassificering: C

Preparat: Clexane, Klexane, Klexane®, Klexane® (med konserveringsmedel)

ATC kod: B01AB05

Substanser: enoxaparin, enoxaparinnatrium

Sammanfattning

Blödningsrisken av enoxaparin är likartad hos både kvinnor och män. Kvinnor som får enoxaparin har högre blödningsrisk än kvinnor som får ofraktionerat heparin.

Kvinnor med mekaniska hjärtklaffsproteser kan löpa högre risk för tromboembolism under graviditet och har en högre frekvens av spontanabort, förtidig förlossning och missfall från dödfödsel vid medicinering med enoxaparin. Gravida kvinnor bör därför genomgå täta kontroller av antifaktor Xa-nivåer och kan behöva en dosjustering.

Personer med låg vikt (kvinnor <45 kg, män <57 kg) och personer över 65 år (framförallt kvinnor) kan ha nytta av att dosen justeras för kroppsvikt för att minska risken för blödning.

Additional information

Pharmacokinetics and dosing

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 [1].

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 [3].

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 [4].

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 [5].

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 [6].

Effects

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 [7].

Adverse effects

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 [7].

Reproductive health issues

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 [1].

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

Försäljning på recept

Fler kvinnor än män hämtade ut injektionsvätska innehållande enoxaparin (ATC-kod B01AB05) på recept i Sverige år 2017, totalt 5 843 kvinnor och 4 613 män. Det motsvarar 1,2 respektive 0,9 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 75 år och äldre hos båda könen. I åldersgruppen yngre än 64 år var injektionsvätska innehållande enoxaparin i genomsnitt 2,4 gånger vanligare hos kvinnor medan i åldersgruppen 60 år och äldre var det i genomsnitt 1,3 gånger vanligare hos män [8].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2019-01-30

Referenser

  1. Lovenox (enoxaparin). DailyMed [www]. US National Library of Medicine. [updated 2018-12-21, cited 2019-01-30]. länk
  2. Klexane (enoxaparin). Summary of Product Characteristics. Swedish Medical Products Agency. [updated 2018-06-13, cited 2019-01-30]
  3. Sanderink GJ, Le Liboux A, Jariwala N, Harding N, Ozoux ML, Shukla U et al. The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers. Clin Pharmacol Ther. 2002;72(3):308-18. PubMed
  4. Food and Drug Administration (FDA) . Clinical Pharmacology and Biopharmaceutics Review - LOVENOX (enoxaparin sodium). Drugs@FDA [www]. [updated 1998-01-30, cited 2019-01-30]. länk
  5. Leri F, Voyce SJ, Scialla S, Glavich W, Dzielak E, Smego RA et al. Enoxaparin dosing in the elderly using adjusted body weight. J Thromb Thrombolysis. 2009;28:348-53. PubMed
  6. Pannucci CJ, Fleming KI, Holoyda K, Moulton L, Prazak AM, Varghese TK. Enoxaparin 40 mg per Day Is Inadequate for Venous Thromboembolism Prophylaxis After Thoracic Surgical Procedure. Ann Thorac Surg. 2018;106(2):404-411. PubMed
  7. Mega JL, Morrow DA, Ostör E, Dorobantu M, Qin J, Antman EM et al. Outcomes and optimal antithrombotic therapy in women undergoing fibrinolysis for ST-elevation myocardial infarction. Circulation. 2007;115:2822-8. PubMed
  8. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2017 [cited 2019-01-30.] länk

Författare: Linnéa Karlsson Lind

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson