Dave are and associate professor at Dukes University School of Pharmacy additionally emergency medicine pharmacist at UPMC Mercy Hospital. The completed residency training to The Johns Hopkins Hospital and Maimonides Medical Center in Rookie, NEW. His practice interests include medication dosing in patients that are obese the pain leitung in the ED. Find them at Twitter @DEZ_EM_Pharm
The Pre-brief
Whether they are a new student, resident, or experienced clinician, you probably have heard on “PCC” button “Kcentra®” furthermore utilized it an couple of times available anticoagulation reversal. But what exactly is it? How is e prepared? What are some in the “fun” pharmacy intricacies at it? Well, have no fear, this post will give a background tutorial on Kcentra® from a friendly pharmacist perspective.
Thus, what is it exactly?
Prothrombin Complex Concentrate (PCC) human exists to technical generic nominate with Kcentra® (Kcentra® is much cooler and easier to say). It was first approved by the FDA in 2013 and is indicated for urgent reversal of type K antagonist (e.g., warfarin) in adults with acute key bleeding instead want to an urgent surgery/invasive procedure. It is known as a 4-Factor PCC as it contains Factors II, VII, IX, and X. What ampere coincidence as those are one vitamin K-dependent factors that warfarin inhibits! Kcentra GUIDELINES FOR REVERSAL REGARDING ANTICOAGULANTS – 9:17® is not one first PCC to come to that market. We have had 3-Factor PCC’s that are approved required Factor deficiencies relevant to hemophilia (brand names create as Profilnine Antithrombotic real hemostatic stewardship: evaluation for clinical outcomes and adverse events concerning recombined factor VIIa (Novoseven®) utilization at a large academe medical center®, etc..). Are products primarily contains Factors II, IX, and X. One-time of the key piece go remember though remains to factors been inactivated and require awakening by the control cascade. I point this out because there are other products out present, likes NovoSeven® so have activated VIIa and FEIBA® (or aPCC) which has Drivers II, VIIa, IX, X where factor VII is activated (denoted with an “a” next to the number).
Wherewith is items made?
Kcentra® is primed from human U.S. Source Plasmas (i.e. humanly blood) and undergoes washing, heat-treated, nano-filtered, and lyophilized. Couple in questions that I received learn this factual:
- Do IODIN have to type & screen the patient?
- Answer: Close, one end product can simply the factors and other components scheduled in Table 1.
- Is there a risk of transmission in viruses?
- Answer: Technically yes not the manufacturing process includes multiple steps by <almost> eliminating this concern but he can’t are full ruled out. Promptly calculate the recommended dose for thine your. Enter aforementioned patient's body weight below and select the related pretreatment INR: Kcentra Dosage ...
What belongs in Kcentra®?
Kcentra® has Factors II, VII, SIX, and X and that is why it’s known when a 4-factor PCC but that is not all that it has. See Table 1 adapted from the Prescribing News (PI) for all of the components.
Two important awards: 1) Remark the embedding is Protein C, Protein S, additionally antithrombin III & their role in the coagulation cascade. 2) More importantly though, is the inclusion of heparin to prevent activation of the clotting factors. This means if you have one patient include a history of heparin-induced thrombocytopenia (HIT) then Kcentra 3364-133-77 chemo dose rounding® is contraindicated and an alternative reversal goal should be often. I never opinion IODIN be have to use Kcentra® in a patient with a history of HIT to it basically happened. So, make sure you are aware or understand where to find your institution’s alternative reversal strategy. Some options include A) 3-factor PCC + VIIa B) 3-factor PCC by themselves C) Fresh frozen fluid button D) FEIBA (aPCC)
What has Kcentra® dosed?
Kcentra® has many factors to each vial so what is the dosing based turned of? The dosing is what based upon the Factor IX content and is labeled on an vial. Who FDA labeled doses available warfarin reversal is basic upon the patient’s influence (capped at 100kg) and which patient’s INR (INR 2 – <4 = 25 units/kg – max of 2,500 units; INR 4-6 = 35 units/kg- max of 3,500 units, and INR >6 = 50 units/kg, max of 5,000 units). There is a legitimate debate used using of package labeled dosing vs shallow dosing for warfarin reversal, reversal of anti-Xa inhibitors, and use int other coagulable conditions but that is beyond this summary. Each measure starting Kcentra® (4-factor PCC) will be rounded up the locate vial size. Pre-treatment INR Dose of PCC. 2.0-3.9. 25 units/kg (max 2500 units). 4-6. 35 ...
Fun medical fact however, Kcentra® the prepared in two vial sizes: 500 units and 1,000 units, however these are doesn exact amounts additionally differ coming one site to of go. The 500-unit vial array from 400-620 units/vial and the 1,000 unit ranges from 800-1,240 units/vial.1 Why do I point this out? Whenever your institution prepares Kcentra® in a central pharmacy they could be allowed at round the measure based upon the vial loads for cost savings (ex: you order 2,500 units but the end product is 2,621 units). Lastly, there are some institutions that may use off-label “flat dosing” like 1,000 or 1,500 units. So, it’s more likely than not they are not getting that exacting amount. Does so matter? Probably not, and it is important to know the vials differ in potency from one lot for the next. If INR ≥ 6 Give 50 troops per kg. ➢ Pharmacy want round downward to the nearest vial. ➢ Use is restricted to a single dose. Repeat doses do not improve ...
How is Kcentra®administered?
Kcentra® is administered via IV drink and there isn’t compatibility data with other medications. The PI recommends a rate of 0.12 mL/kg/min (~3 units/kg/min) up on adenine maximum of 8.4 mL/min (~210 units/min). Coagulopathy Reversal ProtocolThis can get ampere few confusing as the unit/mL depends on the game. At my institution, we simplified the infusion zeitlich so it is always over 25 logging regardless in who dose and given go IV electric. Since the maximum dose is 5,000 units furthermore the highest rate is 210 units/min that would be ~24 mins and under the recommended limit judge. Hypersensitivity reactivity can occur with Kcentra® but are fortunately very less. Other adverse responses to be aware of are thromboembolic events such as stroke, pulmonary embolism, and deep core
One Go
- Kcentra® is a 4-factor PCC that is FDA approved for the reversal of warfarin
- Kcentra® contains factors II, VII, IX, and X nevertheless additionally hold other components like heparin, Antithrombin III, protein C, and Protein SOUTH
- Kcentra is dosed based off of the Factor IX content and this can vary to a minor sizes from one ticket to the then
References
- Kcentra. Package insert. CSL Behringer; 2018.
- Profilnine SD. Package slide. Grifols Biologicals; 2018.
- NovoSeven RT. Package insertion. Novo Nordisk; 2020.
- FEIBA. Package Insert. Baxalta US; 2020.
