I N I T I A T I O N O F T H E R A P Y Patient-specific considerations for initiation of dabigatran therapy include the following:

Transcription

1 U N C H E A L T H C A R E G U I D E L I N E Mngement of Dbigtrn in Adults Dbigtrn is n orl nticogulnt tht cts s direct thrombin inhibitor. It is pproved s n lterntive to wrfrin for the prevention of stroke nd systemic embolism in ptients with non-vlvulr tril fibrilltion. Dbigtrn is not pproved for other indictions, such s prevention or tretment of pulmonry embolism or deep vein thrombosis. I N I T I A T I O N O F T H E R A P Y Ptient-specific considertions for initition of dbigtrn therpy include the following: Indiction for therpy. Ptients must hve non-vlvulr tril fibrilltion with risk fctors tht wrrnt therpeutic nticogultion (i.e., CHADS 2 score > 1). Renl function. A bseline serum cretinine is required for drug dosing (see tble below). Orl intke. Ptients must be ble to swllow cpsules. Dbigtrn cpsules my not be opened or crushed, s this significntly increses biovilbility nd thus risk of bleeding. Cost of therpy. Whether ptients cn fford dbigtrn must lso be considered, s costs my exceed $200 per month. TABLE 1. Initil Dbigtrn Dose Renl Function (CrCL ml/min) > < 15 Recommended Strting Dose b 150 mg BID 75 mg BID Do not use For the purpose of dbigtrn dosing, renl function should be estimted by the Cockcroft-Gult method. It is not pproprite to use the CrCL (MDRD method) utomticlly reported in the WebCIS lb section. Cockcroft-Gult eqution: CrCl= [ (140-ge) x weight (kg) ] / (SCr x 72) (x 0.85 if femle) b The medin weight of ptients treted with dbigtrn in RE-LY ws 82.5±19.4 kg. No informtion is vilble on its sfety nd efficcy in overweight or obese ptients nd nti-x levels re not useful for guiding drug dosing. C O N V E R S I O N T O D A B I G A T R A N TABLE 2. Converting to Dbigtrn Agent Heprin Enoxprin Conversion Instructions Strt dbigtrn t the time the heprin infusion is turned off. Strt dbigtrn t the time the next dose of enoxprin ws to be dministered (my overlp by up to 2 hours). If enoxprin ws djusted for renl function, dbigtrn my lso require dose djustment (see Tble 1 bove). Wrfrin Discontinue wrfrin nd strt dbigtrn when the INR is < 2.0. Pge 1 of 5

2 C O N V E R S I O N F R O M D A B I G A T R A N The following recommendtions re bsed on the pproved lbeling for the use of dbigtrn in ptients with tril fibrilltion. Considering the risk of stroke nd embolism in ech ptient (i.e., CHADS 2 score, crdioversion), it my be resonble to continue dbigtrn until the INR is 2 3. These guidelines do not reflect the prctice of overlpping prenterl nticogulnts nd wrfrin for 5 dys in the tretment of pulmonry embolism (PE) or deep vein thrombosis (DVT). Dbigtrn is NOT pproved t this time for the tretment of PE or DVT. Overlpping beyond the number of dys recommended below my be considered on n individul bsis ssessing the risk of embolism nd bleeding. (Jff M. Circultion. 2011;123:00.) TABLE 3. Converting Dbigtrn to Wrfrin Renl Function Conversion Instructions (CrCL ml/min) > < 15 Strt wrfrin nd overlp with dbigtrn for 3 dys. Discontinue dbigtrn on dy 4. Strt wrfrin nd overlp for 2 dys with dbigtrn. Discontinue dbigtrn on dy 3. Strt wrfrin nd overlp for 1 dy with dbigtrn. Discontinue dbigtrn on dy 2. Strt wrfrin nd overlp for 1 dy with dbigtrn. Discontinue dbigtrn on dy 2. This ptient should not resume dbigtrn therpy. b Dbigtrn my contribute to n elevted INR for up to 2 dys fter discontinution. b No dt exist in ptients with CrCL < 15 ml/min or in ptients on hemodilysis. Recommendtions re extrpolted from phrmcokinetic dt nd comprison of reltive risks nd benefits. TABLE 4. Converting Dbigtrn to Prenterl Anticogulnts (Heprin, Enoxprin) Renl Function Conversion Instructions (CrCL ml/min) > 30 Strt prenterl nticogulnt 12 hours fter lst dbigtrn dose. < 30 Strt prenterl nticogulnt 24 hours fter lst dbigtrn dose. Methods for converting dbigtrn to heprin hve not been studied nd re bsed on the phrmcokinetics of the drug. Clinicl decisions should be mde bsed on ptient-specific risk of bleeding vs. thromboembolism. Pge 2 of 5

3 P E R I O P E R A T I V E M A N A G E M E N T TABLE 5. Discontinution of Dbigtrn Prior to Inptient or Outptient Procedures Renl Function (CrCL ml/min) Hlf-life (hours), men (rnge) Timing of Discontinution Prior to Procedure (Minimum) Stndrd Risk of Bleeding High Risk of Bleedingb > (11 22) 24 hours 2 4 dys (12 34) 24 hours 2 4 dys (13 23) > 48 hours > 4 dys < (22 35) hours > 5 dys Exmples: electrophysiology procedures, crdic ctheteriztions, no dditionl ptient-specific risk fctors. b Exmples: surgery involving mjor orgns, procedures requiring complete hemostsis (e.g., spinl nesthesi), or when dditionl ptient-specific risk fctors re present. Adpted from vn Ryn, J. Thromb Hemost Jun;103(6): Bridging with Prenterl Anticogulnts for Procedures For ptients t high risk of thromboembolic events in whom invsive procedures re plnned, some clinicins my wish to bridge with prenterl nticogulnts (e.g., unfrctionted heprin, enoxprin). The necessity for this depends on ptient s risk for thromboembolism while off nticogultion, nd for bleeding if on nticogulnts. This my be performed by (1) converting dbigtrn to the desired prenterl nticogulnt s described in Tble 4, nd (2) continuing to hold dbigtrn for the minimum mount of time recommended in Tble 5, bsed on n individul ptient s renl function nd risk of bleeding. Prenterl nticogultion my then be discontinued prior to the plnned procedure ccording to usul stndrds of cre. D E N T A L P R O C E D U R E S Mny dentl procedures cn be sfely performed on full-dose dbigtrn, s the risk of complictions is considered similr to tht of therpeutic nticogultion with wrfrin. Consider the risk of bleeding versus risk of thromboembolism when deciding to hold doses of dbigtrn. Dentl procedures which require prtil or complete reversl of nticogultion with wrfrin my require temporry discontinution of dbigtrn. Pge 3 of 5

4 A D V E R S E E F F E C T S Compred to wrfrin, more ptients discontinue dbigtrn due to its dverse effects. The most common non-hemorrhgic dverse effects re GI-relted nd my include dyspepsi, nuse, upper bdominl pin, nd dirrhe. Although overll bleeding rtes between dbigtrn nd wrfrin re similr in clinicl trils, dbigtrn is ssocited with greter risk of gstrointestinl bleeding compred to wrfrin (i.e., 1.5% per yer with dbigtrn vs. 1.1% per yer with wrfrin) (N Engl J Med. 2009; 361(12): ). Mngement of Dbigtrn-Relted Bleeding Events There is no phrmcologic ntidote for dbigtrn, so mngement of hemorrhgic complictions is primrily supportive. Dbigtrn is mostly excreted in the urine (80%), so pproprite diuresis must be mintined in order to promote dequte drug clernce. An outline for supportive mngement of dbigtrn-relted bleeding events bsed on bleeding severity is provided in Tble 6. If ptients require phrmcologic therpy to mnge hemorrhgic complictions, Hemtology/Cogultion consult is lso required. TABLE 6. Mngement of Dbigtrn-Relted Bleeding Events Bleeding Severity Mngement Recommendtions Mild Moderte Severe or Lifethretening Dely next dose or discontinue dbigtrn. Consider ny of the following bsed on bleeding severity: Symptomtic tretment Mechnicl compression Surgicl intervention Fluid replcement nd hemodynmic support Blood product trnsfusion Orl ctivted chrcol (if lst dbigtrn dose ingested within 2 hours) Dose: Liquid chrcol with sorbitol 50 g PO x 1 dose Hemodilysis Also consider in the following order (my initite while hemtology/cogultion consult is obtined): 1. Prothrombin complex concentrte (Profilnine ) 50 units/kg IV x 1 ± fresh frozen plsm (2-4 units) Hemtology/Cogultion consult must be obtined prior to the following: 2. Recombinnt fctor VII (NovoSeven ) 90 mcg/kg IV x 1 3. Fresh frozen plsm (s much s tolerted) 4. Hemodilysis To investigte potentil cuses of the bleeding event, obtin the following: serum cretinine, PT, PTT, thrombin clotting time (TCT), CBC (pltelets). Adpted from vn Ryn. Thromb Hemost Jun;103(6): ; (Author: Stephn Moll, MD) Pge 4 of 5

5 P A T I E N T E D U C A T I O N Mngement of Missed Doses If dose of dbigtrn is not tken t the scheduled time, the dose should be tken s soon s possible. If it is less thn 6 hours from the time the next dose is due, skip the dose nd resume dbigtrn with the next scheduled dose. The dose of dbigtrn should not be doubled to mke up for missed dose. Mngement of Doubled Dose If doubled dose is tken, the ptient should be dvised to skip the next scheduled dose. After skipping one scheduled dose, ptients should resume their prescribed dbigtrn dose pproximtely 12 hours from the skipped dose. Storge Instructions Dbigtrn must be stored in its originl pckging with the bottle tightly seled to ensure potency of the mediction. Do not remove dbigtrn from the originl pckging until it is time for the next scheduled dose, s the drug begins to degrde s erly s one dy. Doses left out of the mnufcturer s pckging should be discrded. Dbigtrn is only good for 60 dys fter the bulk pckging hs been opened. Any doses remining fter 60 dys from opening the pckging should be discrded long with the bulk bottle. It my be preferble tht ptients get their dbigtrn supplied in unit-dose blister pcks to void these storge issues. Pge 5 of 5