The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

Letter to the Editor

Editor, – Boehringer Ingelheim suggests an alternative title for the feature about dabigatran (Aust Prescr 2012;35:64-5) – Medicinal mishap: Always read the product information before prescribing.

Given the case history of the elderly woman with nephropathy (creatinine clearance (CrCl) 29 mL/min), she should clearly not have been prescribed dabigatran. This serves to reinforce the need for appropriate patient selection consistent with the approved product information which includes the contraindication ‘severe renal impairment (CrCl<30 mL/min)’.

Prescribers should always read the product information before prescribing, regardless of whether a drug is new or old. As the sponsor for dabigatran, we are concerned the authors of this article did not include the dabigatran product information as a reference. The product information provides information pertinent to many of the issues raised in this case history.

On presentation to hospital, the patient was reported as having an INR of 2.5. As the authors mention later in the article, interpretation of an INR 2–3 weeks after starting dabigatran is meaningless. This information is provided in the product information. Further, and very importantly, when switching from warfarin to dabigatran, prescribers should only commence dabigatran once the INR is under 2. It is not clear whether this was confirmed in this clinical scenario.

The authors quote the Queensland Health guidelines for managing patients on dabigatran who present to hospital.1 These recommendations appear broadly consistent with the product information for dabigatran. Interventions recommended for the reversal of moderate-to-severe or life-threatening bleeding by the Queensland Health document and the product information include platelets, oral charcoal, recombinant factor VIIa, activated prothrombin complex concentrates (for example, factor eight inhibitor bypassing activity FEIBA), haemodialysis and charcoal haemofiltration. These were not used in this case.

Lastly, the authors incorrectly assert ‘Currently, no assay of dabigatran’s effect on coagulation is available’. A direct thrombin inhibitor assay (Hemoclot) is commercially available in Australia for assessing the anticoagulant activity of dabigatran.2

Guy Gavagna
Medical affairs manager
Boehringer Ingelheim
North Ryde, NSW

Author's comment

Joel Iedema, one of the authors of the medicinal mishap, comments:

We thank Boehringer Ingelheim for highlighting the importance of patient selection. This principle underlies safe and effective prescribing of all medicines, but is particularly critical for medicines such as anticoagulants. This patient was not a suitable candidate for dabigatran and we reinforce the need to read the product information and other independent literature for unfamiliar medicines before prescribing.

In response to the letter, the Australian product information states that the INR is ‘too insensitive’ to be used for therapeutic monitoring. A problem with inconsistent INR results related to certain assays was described postmarketing.3 While a dabigatran assay is now available, it is provided by select pathology providers and evidence-based guidelines for rational use are lacking.

Evidence for dabigatran reversal is very limited. Inactivated prothrombin complex has no effect in dabigatran reversal4 and no human data are available for other treatments.5 Many of these treatments carry significant risks of their own and the costs are considerable. Anticoagulant reversal is critical to the management of bleeding and the current lack of specific reversal should be included in harm-benefit discussions with patients.6

These issues further reinforce the key message of our article that the real-world risk of any medicine is often not fully appreciated until considerable postmarketing experience has been gained. Regrettably, real-world risk does include inappropriately prescribed medication. Postmarketing surveillance may identify other patient groups at increased risk of adverse events, which would only reinforce the need for careful patient selection.7

References

  1. Safe and Quality Use of Medicines and the Anticoagulant Working Party. Guidelines for managing patients on dabigatran (Pradaxa) who present to hospital. Queensland Health. 2011. www.health.qld.gov.au/qhcss/mapsu/documents/ dabigatran_info.pdf [cited 2012 Jul 6]
  2. Stangier J, Feuring M. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran. Blood Coagul Fibrinolysis 2012;23:138-43.
  3. van Ryn J, Baruch L, Clemens A. Interpretation of point- of-care INR results in patients treated with dabigatran. Am J Med 2012;125:417-20.
  4. Eerenberg E, Kamphuisen P, Sijpkens M, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate. Circulation 2011;124:1573-9.
  5. Kaatz S, Kouides P, Garcia D, Spyropolous AC, Crowther M, Douketis JD, et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol 2012;87 Suppl 1:S141-5. DOI: 10.1002/ajh.23202.
  6. Cotton B, McCarthy J, Holcomb J. More on acutely injured patients receiving dabigatran [author reply]. N Engl J Med 2012;366:864.
  7. Martin JH, Coory MD. New medicines – urgent need to assess outcomes in special groups. Med J Aust 2012;196:433.