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  • March 16, 2011 2:07 PM | Brad Miller (Administrator)

    In the April WMSHP Newsletter, Juan Miretti, a PGY-1 Pharmacy Resident at Spectrum Health reviews PRE-PEN's use for penicillin allergy testing.


    PRE-PEN: A skin test for the diagnosis of penicillin allergy

    By Juan Miretti, PharmD, PGY1 Resident

    BACKGROUND

    Approximately 10% of patients report a penicillin allergy. When these individuals become ill with a serious bacterial infection, healthcare providers will often avoid using inexpensive first-line therapies over fear of a potential reaction. These patients must not only avoid penicillin antibiotics, but also the numerous other beta-lactam antibiotics available (i.e. cephalosporins, carbapenems). This forces healthcare providers to resort to other antibiotics that may limit effective antimicrobial stewardship and leads to about 30% higher costs for antibiotic treatment.

    The most common hypersensitivity reaction to penicillin is an IgE-mediated reaction. IgE-mediated reactions, also known as type I hypersensitivity reactions, are life-threatening reactions characterized by systemic manifestations of anaphylaxis, which may include but not limited to erythema, urticaria, pruritis, angioedema, bronchospasm, and hypotension. Individuals having experienced such a reaction are diagnosed as having a penicillin allergy.

    Patients may report an allergy to penicillin, but often the reaction experienced (i.e. nausea/vomiting) was an adverse drug reaction. There also exists the possibility that the reaction experienced (i.e. rash) was caused by the underlying infection and not by the penicillin. Of patients with a reported penicillin allergy, 80 to 90% do not have an IgE-mediated penicillin allergy when assessed by penicillin skin testing. Moreover, about 80% of patients that have had an IgE-mediated reaction to penicillin have negative skin tests after 10 years of avoidance. This indicates that many patients outgrow their allergy over time. It is also estimated that approximately 50% of penicillin allergic patients have outgrown their allergy after 5 years.

    PRE-PEN is the only FDA approved commercially available skin test for the diagnosis of penicillin allergy. With the recent return of PRE-PEN to the market, healthcare providers are now able to accurately determine the risk of IgE-mediated reactions to penicillin antibiotics and related beta-lactam antibiotics in patients with a reported penicillin allergy. PRE-PEN was widely used for over 30 years but in 2004 it was withdrawn from the market due to the lack of a dedicated manufacturing facility. This significantly limited a healthcare provider’s ability to evaluate for penicillin hypersensitivity. Healthcare providers turned to penicillin desensitization, which was the only way to assure safe retreatment of patients with a documented penicillin allergy. Now with the availability of PRE-PEN, many patients who have been incorrectly labeled as allergic to penicillin will be able to receive inexpensive first-line antibiotic therapies. Appropriate use of PRE-PEN can reduce hospital costs and improve antimicrobial stewardship.

    USAGE

    Candidates for PRE-PEN include any patient with a history of a reaction to a penicillin antibiotic that may have been IgE-mediated, or any patient who is currently denied access to beta-lactam antibiotics out of concern of such reactions. PRE-PEN is contraindicated in patients with clear histories of severe skin reactions (i.e. Stevens-Johnson syndrome, toxic epidermal necrolysis), patients known to be extremely hypersensitive to penicillin, and patients who have developed a systemic or marked local reaction to its previous administration.

    ADVERSE REACTIONS

    Occasionally, patients may develop an intense local inflammatory response at the skin test site. Rarely, patients will develop a systemic allergic reaction characterized by manifestations of anaphylaxis. Skin testing should be performed under direct medical supervision and treatment for an anaphylactic reaction should be available.

    THE SKIN TEST

    A proper skin test involves 4 prick/puncture skin tests, and if these tests are negative, then 5 intradermal skin tests. The 4 prick/puncture tests include tests with PRE-PEN (major determinant), Penicillin G (minor determinant), histamine (positive control), and a diluent (negative control). The 5 intradermal tests include tests with PRE-PEN in duplicate, Penicillin G in duplicate, and a diluent (negative control).

    Prick/puncture testing is performed first to decrease the risk of precipitating a systemic allergic reaction with intradermal testing. Most patients who have an IgE-mediated penicillin allergy will exhibit a negative prick/puncture skin test.

    The reasoning for performing the intradermal skin test in duplicate is to prevent healthcare providers from making the wrong diagnosis due to ambiguous results. A false positive or false negative may be observed since the changes at the test site are relatively small.

    To understand the rationale of using both major and minor determinants for the skin test, it is important to understand the immunochemistry of penicillin. When put into physiologic solution, penicillin spontaneously degrades into a number of intermediates, so called determinants. Penicillin mostly breaks down to penicilloyl, the major determinant, as well as other minor determinants that subsequently bind to host proteins. An allergic reaction occurs if the individual is sensitive to one or more of these determinants.

    PRE-PEN is benzylpenicilloyl poly-L-lysine and is the major determinant. Skin testing with PRE-PEN should be done in conjunction with Penicillin G, which is the only commercially available minor determinant. Studies have shown that skin testing with PRE-PEN along with Penicillin G identifies up to 97% of patients who have an IgE-mediated penicillin allergy.

    APPLICATION TO YOUR INSTITUTION

    An important and underappreciated aspect of penicillin allergy is the unnecessary withholding of appropriate antibiotic therapy. This can lead to less effective antimicrobial stewardship and increased medical costs in patients who are labeled as penicillin allergic. Implementing skin testing with PRE-PEN at your institution can facilitate appropriate antibiotic therapy in patients with a reported penicillin allergy. Moreover, it will demonstrate the absence of penicillin allergy in many patients, will provide cost-effective antibiotic treatment options for healthcare providers and patients, and may help avoid the development of resistance to more powerful antibiotics.

    REFERENCES

    1. Park MA, Li JTC. Diagnosis and Management of Penicillin Allergy. Mayo Clin Proc. 2005; 80(3): 405-410. 
    2. PRE-PEN® [package insert]. Round Rock, Tex: ALK-Abelló, Inc. 2009.
    3. “PRE-PEN®, Penicillin Allergy Skin Test Antigen.” Fight the Cause Newsletter. Winter 2010. 1-5. Print. 
    4. PRE-PEN®, Penicillin Allergy Skin Testing Reference. Round Rock, Tex: ALK-Abelló, Inc. 2010. 
    5. PRE-PEN®. Round Rock, Tex: ALK-Abelló, Inc. 2010. DVD.
  • February 22, 2011 2:07 PM | Brad Miller (Administrator)

    In the March WMSHP Newsletter, Sara D. Schepcoff, a PGY-1 Pharmacy Resident at Spectrum Health, reviews the new oral anticoagulant dabigatran.


    Dabigatran overview

    For approximately half a century, warfarin has been the gold standard anticoagulant for patients living with atrial fibrillation (AF).  The new oral anticoagulant, dabigatran (Pradaxa – Boehringer Ingelheim), may be a simpler option for these patients.  On October 19th, dabigatran became the first FDA-approved oral direct thrombin inhibitor in the United States.  Its sole indication is to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF.  Contrary to warfarin, dabigatran requires no monitoring of international normalized ratios (INRs), has minimal drug interactions, and comes with no known dietary restrictions. 

    Dabigatran etexilate is a prodrug which is rapidly absorbed and then converted in vivo to the active form, dabigatran, through esterase-catalyzed hydrolysis in the plasma and liver. It inhibits thrombin, thereby preventing the conversion of fibrinogen to fibrin in the coagulation cascade.  Free thrombin, clot-bound thrombin and thrombin-induced platelet aggregation are inhibited by dabigatran.

    Key studies

    The efficacy and safety of dabigatran have been evaluated in numerous clinical studies.  The pivotal trial for US approval was RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy), in which dabigatran 110 mg or 150 mg twice daily was compared to dose-adjusted warfarin in more than 18,000 patients with AF. After a median duration of 2 years, dabigatran 150 mg twice daily was associated with lower rates of stroke and systemic embolism versus warfarin.  The two drugs had similar rates of major bleeding (3.11% per year with dabigatran 150mg and 3.36% per year with warfarin).

    In a more recent analysis of RE-LY, it was noted that for all vascular events, non-hemorrhagic events, and mortality, the advantages seen with dabigatran therapy were greater at sites with poor INR control than at those with good INR control. Therefore, many experts believe that dabigatran may be a good option for patients who have difficulty maintaining their INR within range, who are troubled by dietary or drug interactions, or who experience adherence issues. However, for patients who are currently stable on warfarin therapy, there may be no benefit to switching.

     

    Dosing and therapeutic considerations

    Dabigatran (Pradaxa)

    Drug class:  Direct thrombin inhibitor

    Indication:  Reduce the risk of stroke and systemic embolism in patients with nonvalvular      atrial fibrillation (AF)

    Dosage: 

    • 150 mg twice daily, by mouth, with or without food, for patients with a creatinine clearance (CrCl) above 30 mL/min.
      • For patients with renal impairment (CrCl between 15 and 30 mL/min), the recommended dose should be reduced to 75 mg twice daily as dabigatran is primarily renally excreted (80%). 
      • No dose recommendations are available for patients with CrCl less than 15 mL/min or for patients on dialysis. 
      • Patients can be converted from warfarin to dabigatran by starting dabigatran once their INR is less than 2.0.
      • Dabigatran should be discontinued 1 to 2 days (CrCl ≥ 50 mL/min) or 3 to 5 days (CrCl < 50 mL/min) before an invasive or surgical procedure.  

    Other considerations:

    Dabigatran is contraindicated for patients with active bleeding or those with a history of serious hypersensitivity to the drug.  As with all anticoagulants, dabigatran increases the risk of bleeding, especially when used in combination with other medications that increase this risk, such as antiplatelet agents, heparin, and NSAIDs.  While dabigatran is not a substrate, inhibitor, or inducer of cytochrome P450 enzymes, it is a P-glycoprotein (P-gp) substrate and should not be used with P-gp inducers such as rifampin, as exposure to the drug will be reduced.  No dosage adjustments are required if administered with P-gp inhibitors, such as ketoconazole, verapamil, amiodarone, quinidine, or clarithromycin.

     

    Advantages and limitations

    For patients treated with dabigatran, ecarin clotting time (ECT) is considered the best assessment of bleeding risk, but is not readily available.  The aPTT test provides an approximation of dabigatran’s anticoagulant activity, but is nonlinear at higher doses.  There is no readily available reversal agent for patients who develop bleeding complications with dabigatran.  Bleeding may be managed with diuresis and dialysis to remove the drug as well as replacement with fresh frozen plasma.                

    The high rate of dyspepsia (11.5% of patients treated with dabigatran in the RE-LY trial versus 5.8% treated with warfarin) may also be a concern for clinicians and patients.  At the beginning of the study, nearly 14 % of the patients in each treatment group were taking a PPI and roughly 4% were taking an H2-receptor antagonist.  Researchers reported a 20% dropout rate by the year-2 follow-up visit. 

    Dabigatran became available in US pharmacies at a wholesale acquisition cost of $6.75 per day.  An early-release article in the Annals of Internal Medicine found that dabigatran is cost effective compared with warfarin therapy because of the associated costs of warfarin monitoring and complications. However, for patients taking dabigatran as outpatient therapy, it may come at a high co-pay cost. For these patients, and for those requiring infrequent INR monitoring, cost savings may not occur.

    Summary

    Dabigatran (Pradaxa) is a promising new oral anticoagulant indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.  It may be a good alternative for patients who have difficulty maintaining a therapeutic INR on warfarin therapy as it requires no lab monitoring, has minimal drug interactions, and no dietary limitations. 

    References

    1. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, et al, and the RE-LY Steering Committee and Investigators.  Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51.
    2. Tanzi MG. Dabigatran: Anticoag simplifies therapy. Pharmacy Today 2010:34-35.
    3. Thompson CA. First oral thrombin inhibitor enters market. Am J Health-Syst Pharm 2010;67:1974-76.
    4. Pradaxa (dabigatran etaxilate mesylate) capsules for oral use (package insert).Ridgefield, CT; Boehringer Ingelheim Pharmaceuticals, Inc.;October 2010.
    5. Freeman JV, Zhu RP, Owens DK, Garber AM, et al.  Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation. Ann Intern Med 2011;154(1):1-11. Epub 2010 Nov 1.
    6. Wallentin L, Yusuf S, Ezekowitz MD, Alings M, et al; RE-LY Investigators. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet 2010;376:975-83.
  • February 15, 2011 2:08 PM | Brad Miller (Administrator)

    The snow is finally starting to melt, and spring is hopefully right around the corner.  We have a great meeting planned for March 24th at Mangia Mangia in Kalamazoo.  The presenter is Dr. John Devlin from Northeastern University and Tufts-New England Medical Center in Boston.  He will be presenting on sedation in the intensive care unit.  Please make note that this meeting is later in the month than typical meetings.  This change was made to accommodate the presenter’s schedule.

    The following meeting will be held on April 8th.  This is the second year that we are holding a special Friday meeting in conjunction with a Grand Rapids Griffins game.  Two local residents had their presentations selected by our board members.  Dr. Todd Super will be presenting "Impact of Pharmacist Facilitated Discharge Medication Reconciliation” and Dr. Jennifer Lunger will be presenting "Comparison of Cumulative Drug Doses Administered for Sedation and Analgesia During Day and Night Shifts in Mechanically Ventilated Patients in a Medical Intensive Care Unit".

    WMSHP is still accepting applications for the annual scholarship awarded at Spring Seminar.  The application deadline is March 31, 2011.  

    The WMSHP board has a vacancy for the pharmacy technician representative.  We are currently seeking nominations for any interested technician members.  Please send an email to adamdrzewicki@borgess.com by March 1st if you are interested in being considered for this board position.

  • January 29, 2011 2:09 PM | Brad Miller (Administrator)

    We have an exciting meeting planned for February 10th at the Lacks Cancer Center on the campus of Saint Mary's in Grand Rapids. Jean Lee will be presenting on medication errors in HIV patients. Please plan on attending!

    As in years past, WMSHP is offering a scholarship for a local third year pharmacy student. Please share this information with any eligible pharmacy students that you know.

    MPA is hosting Legislative Day in Lansing on March 23rd. Legislative Day will offer 4 hours of continuing education on pain management, medical marijuana, and an important presentation on how pharmacists can protect their license. In addition, Lt. Governor Brian Calley will be speaking as well as several others from the state government. Attendees will also have an opportunity to meet with their state representative and discuss pertinent pharmacy issues. WMSHP has decided to sponsor two members and two board members to attend this meeting. More details regarding this exciting meeting can be found at http://www.michiganpharmacists.org/eventDetails.php?x=499. If you are interested in attending on behalf of WMSHP, please send me an email at adamdrzewicki@borgess.com. The board will draw names to determine who will be sponsored. In addition, there is still time to register for the MPA Annual Convention being held February 25 to 27. Please visit www.michiganpharmacists.org for more information.

  • January 05, 2011 2:10 PM | Brad Miller (Administrator)

    The holidays are officially over, and WMSHP is back from our December break. Our January meeting will be on January 13th at Borgess Medical Center in the Lawrence Educational Center. The topic will be "Health Literacy: Making Information Understandable for Healthcare Consumers" presented by Marge Kars. This should be an interesting topic that is quite different than our usual monthly offerings. Please plan on trying to make it to Kalamazoo for this exciting topic.

    You may have noticed that ballots for the WMSHP board were not sent out this year. We ended up with an extra board opening when Ben Mgboh stepped down to move to Ohio, and, therefore had an equal number of candidates to board positions. In order to save on printing and postage costs, the board elected to not send ballots out. Without further adieu, it is my pleasure to announce that Kali Shulz is the new president-elect. Andrea Goodrich, Angela Green, and Stacy Vaeth were all re-elected to new two-year terms. Dana Staat is returning to the board to finish out the final year of Ben’s term, and Becky Maynard has been newly elected to a board position. Please welcome the new and returning board members!

    Finally, we have set a date for the 2011 WMSHP Spring Seminar. Mark your calendars for May 17th, and plan on joining us at the Prince Conference Center in Grand Rapids.

  • October 23, 2010 2:10 PM | Brad Miller (Administrator)

    It is time for election season again! I am sure everyone has experienced the latest round of political ads on the radio, television, and in the newspaper. Luckily, there aren’t any campaigns for WMSHP offices, but you will be receiving an official WMSHP ballot very soon. As the process was last year, the ballot must be mailed back or brought to the November meeting. This official ballot is the only means by which you will be able to vote.

    The MSHP Annual Meeting is being held on November 5th at the Crowne Plaza in Grand Rapids. There is still time to register to attend this great meeting so close to home!

    This month's WMSHP meeting is being held in the Wege Room at St. Mary’s in Grand Rapids. The topic is “Diagnosis and Management of Pulmonary Arterial Hypertension” presented by Allan Gutierrez. We hope to see you there!

  • September 29, 2010 2:10 PM | Brad Miller (Administrator)

    Fall has officially arrived and WMSHP is back in full swing. There is still time to submit nominations for 2011-2012 WMSHP Board Members. Please talk with a current board member for more information. We are also always looking for brief articles on pharmacy related topics for the newsletter. This is a great opportunity for any pharmacists, technicians, residents, and students out there!

    This month's meeting will be on October 14th at Bronson in the Gilmore Center. The topic this month is “Ischemic Stroke: New Opportunities for Treatment” presented by our very own WMSHP secretary, Brad Miller. Our RSVP slots for our monthly meetings have been filling up quickly, so be sure to check wmshp.net often; or better yet, follow WMSHP on Twitter and Facebook for additional information.

  • August 26, 2010 2:12 PM | Brad Miller (Administrator)

    Unfortunately summer break is nearly over. Hopefully everyone has had time to enjoy the great weather that we have had over the past months. Our WMSHP meetings began their summer vacation back in May following the very successful 41st Annual WMSHP Spring Seminar. Cherie Woodhams put a lot of effort into the planning and coordination of this meeting, and deserves recognition for all her hard work. This year has been unique as far as the role of WMSHP president goes. Cherie had agreed to stay on as president for an additional 6 months, and, beginning with this newsletter, I am assuming those duties for the remainder of the year. On behalf of the WMSHP members, I would like to thank Cherie for everything she has done during her tenure as president.

    As summer comes to a close, we are resuming our monthly meetings beginning with the meeting on September 9th at St. Mary’s Hospital on the topic of “Radiation Countermeasures, What’s the Buzz” presented by Greg Pratt.

    Nominations for board positions are open for any interested members. Contact a current board member via email or at the next meeting if you are interested in being nominated for a position. Also be sure to check out www.wmshp.net and see how you can find WMSHP on Twitter and Facebook.

  • March 21, 2010 2:12 PM | Brad Miller (Administrator)

    Welcome to Spring!  We are excited about a new venue this year for our Great Lakes Residency Presentations!  We will be meeting just before a Grand Rapids Griffins Game at a different time - from 5:30-6:30PM for our CE presentation.  After that, we'll all enjoy the final game of the season together!  Please join us!

    All hockey tickets will be distributed prior to the presentation.  Any tickets not claimed by the completion of the presentation at 6:30 PM will be placed for pick-up at the box office will-call.

    Also, mark your calendars for Tuesday, May 18th, 2010.  This is the date of our Annual Spring Seminar.  Topics to be discussed include a Legislative Review, Cultural Competency in our AM session, Preceptor Development, Pharmaceutical Waste, and a 2009 H1N1 review will be discussed in our afternoon Administrative section.  In the PM clinical section, Antiplatelet medications, Pain management, and Emergency Room pearls will be reviewed.

    Happy Spring!

  • February 19, 2010 2:13 PM | Brad Miller (Administrator)

    Please join us on March 11th in Grand Rapids at the St. Mary’s Lacks Conference Center when we discuss "Current Treatment Options for Gout.” Tracy Mersfelder, PharmD, will be our speaker for the evening.

    Due to the PhRMA Standards that are now in place, it has become more challenging to obtain funding for our monthly meetings. This is why you may have seen an increase in the amount of times we have had our meetings on hospital premises in their conference rooms. When you see this venue, it most likely means that support was not received for the event and WMSHP is paying for the event from their general fund. Also, if the event is being held at a restaurant, we have a budget based on grant funding that we must adhere to. In light of this information, the WMSHP Board is respectfully asking that if you RSVP and then find out you are unable to attend, please contact us by the Monday preceding the meeting to let us know so that we can minimize waste.

    Mark your calendar for Friday, April 9th! We will be hosting our meeting on this day in conjunction with a Grand Rapids Griffin’s Hockey game as they play the Lake Erie Monster’s. Because of this alternative venue, our CE presentation will begin at 5:30PM so that we will be ready for game time of 7:00PM. Friends and family will have the opportunity to join you for the game as well. More details to follow!

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