Lepirudin in the management of patients with heparin-induced thrombocytopenia

Petros, Sirak

doi:10.2147/btt.s3415

Cited by 16 publications

(16 citation statements)

References 82 publications

(120 reference statements)

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“…The anticoagulant drug lepirudin is excreted by the kidney with systemic clearance in women about 25% lower than in men (NDA 020807 [31]). But PK variables do not translate linearly into phenotypes; thus, in women lepirudin is detectible in the circulation for up to 48 h, compared to just 2 h in men, which greatly increases the potential for undesired bleeding [32]; indeed, in this example, low molecular weight heparin-induced thrombocytopenia is a clinically important ADR which occurs more frequently in women than men [33], a difference that corresponded to much higher drug exposure as indicated by female-bias in multiple PK measures.…”

Section: Reasons Why Men and Women Respond Differently To Drugsmentioning

confidence: 99%

Sex differences in pharmacokinetics predict adverse drug reactions in women

2020

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Background: Women experience adverse drug reactions, ADRs, nearly twice as often as men, yet the role of sex as a biological factor in the generation of ADRs is poorly understood. Most drugs currently in use were approved based on clinical trials conducted on men, so women may be overmedicated. We determined whether sex differences in drug pharmacokinetics, PKs, predict sex differences in ADRs. Methods: Searches of the ISI Web of Science and PubMed databases were conducted with combinations of the terms: drugs, sex or gender, pharmacokinetics, pharmacodynamics, drug safety, drug dose, and adverse drug reaction, which yielded over 5000 articles with considerable overlap. We obtained information from each relevant article on significant sex differences in PK measures, predominantly area under the curve, peak/maximum concentrations, and clearance/elimination rates. ADRs were identified from every relevant article and recorded categorically as female-biased, male-biased, or not sex-biased. Results: For most of the FDA-approved drugs examined, elevated blood concentrations and longer elimination times were manifested by women, and these PKs were strongly linked to sex differences in ADRs. Of the 86 drugs evaluated, 76 had higher PK values in women; for 59 drugs with clinically identifiable ADRs, sex-biased PKs predicted the direction of sex-biased ADRs in 88% of cases. Ninety-six percent of drugs with female-biased PK values were associated with a higher incidence of ADRs in women than men, but only 29% of male-biased PKs predicted male-biased ADRs. Accessible PK information is available for only a small fraction of all drugs Conclusions: Sex differences in pharmacokinetics strongly predict sex-specific ADRs for women but not men. This sex difference was not explained by sex differences in body weight. The absence of sex-stratified PK information in public records for hundreds of drugs raises the concern that sex differences in PK values are widespread and of clinical significance. The common practice of prescribing equal drug doses to women and men neglects sex differences in pharmacokinetics and dimorphisms in body weight, risks overmedication of women, and contributes to female-biased adverse drug reactions. We recommend evidence-based dose reductions for women to counteract this sex bias.

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Section: Reasons Why Men and Women Respond Differently To Drugsmentioning

confidence: 99%

Sex differences in pharmacokinetics predict adverse drug reactions in women

2020

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“…Peak plasma concentration occurs after 3-4 hours. Ninety percent of the administered dose of lepirudin is excreted through the kidneys [123].…”

Section: Lepirudinmentioning

confidence: 99%

Emerging Anticoagulants

Kennedy¹,

Gargoum²,

Kennedy³

et al. 2012

curr med chem

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Warfarin, heparin and their derivatives have been the traditional anticoagulants used for prophylaxis and treatment of venous thromboembolism. While the modern clinician is familiar with the efficacy and pharmacokinetics of these agents, their adverse effects have provided the impetus for the development of newer anticoagulants with improved safety, ease of administration, more predictable pharmacodynamics and comparable efficacy. Research into haemostasis and the coagulation cascade has made the development of these newer anticoagulants possible. These drugs include the factor Xa inhibitors and IIa (thrombin) inhibitors. Direct and indirect factor Xa inhibitors are being developed with a relative rapid onset of action and stable pharmacokinetic profiles negating the need for close monitoring; this potentially makes them a more attractive option than heparin or warfarin. Examples of direct factor Xa inhibitors include apixaban, rivaroxaban, otamixaban, betrixaban and edoxaban. Examples of indirect factor Xa inhibitors include fondaparinux, idraparinux and idrabiotaparinux. Direct thrombin inhibitors (factor IIa inhibitors) were developed with the limitations of standard heparin and warfarin in mind. Examples include recombinant hirudin (lepirudin), bivalirudin, ximelagatran, argatroban, and dabigatran etexilate. This review will discuss emerging novel anticoagulants and their use for the prophylaxis and management of venous thromboembolism, for stroke prevention in nonvalvular atrial fibrillation and for coronary artery disease.

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“…In the absence of a known antidote or drug to reverse its effect, hemofiltration has been used to enhance the elimination of lepirudin at the end of CPB. 18 , 19 Although clinical trials have demonstrated its efficacy to provide anticoagulation, allergic reactions ranging from urticaria to hemodynamic instability have been reported. 20 , 21 These anaphylactoid reactions may occur regardless of previous exposure, although reexposure to lepirudin is associated with a greater risk when compared with first exposure.…”

Section: Discussionmentioning

confidence: 99%

Perioperative care in an adolescent patient with heparin-induced thrombocytopenia for placement of a cardiac assist device and heart transplantation: case report and literature review

Sebastian¹,

McConnell²,

Gómez³

et al. 2017

IMCRJ

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Heparin-induced thrombocytopenia (HIT) can cause life-threatening complications following the administration of heparin. Discontinuation of all sources of heparin exposure and the use of alternative agents for anticoagulation are necessary when HIT is suspected or diagnosed. We present the successful use of bivalirudin anticoagulation in an adolescent patient during cardiopulmonary bypass who underwent both placement of a left ventricular assist device and subsequent heart transplantation within a 36-hour period. The pathophysiology and diagnosis of HIT are reviewed, previous reports of the use of direct thrombin inhibitors for cardiac surgery are presented, and potential dosing regimens for bivalirudin are discussed.

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Lepirudin in the management of patients with heparin-induced thrombocytopenia

Cited by 16 publications

References 82 publications

Sex differences in pharmacokinetics predict adverse drug reactions in women

Sex differences in pharmacokinetics predict adverse drug reactions in women

Emerging Anticoagulants

Perioperative care in an adolescent patient with heparin-induced thrombocytopenia for placement of a cardiac assist device and heart transplantation: case report and literature review

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