The American Council for Pharmacy Education (ACPE) recently changed some of their standards, which will effect the way we offer our educational programs. The two changes which effect us most are: 1) continuing education (CE) presentations cannot be given while the participants are eating a meal and 2) presentations should have a different set of questions for pharmacists and technicians. To address the first change, WMSHP's Board will be surveying the membership some time in the next couple months to determine the importance of ACPE-accredited CE (Michigan Board of Pharmacy's CE standards have not changed yet), the importance of offering dinner, and reasonable meeting times. To address the second change, the Board decided to accredit our own CE credits for our technician members. Not only will this solve the issue of separate questions, but it will also save the organization some money, as we currently pay $5 per credit hour of ACPE-accredited CE per person.

Speaking of technician CE, did you know that any pharmacist can approve continuing education (CE) credits for Certified Pharmacy Technicians (CPhTs)? The Pharmacy Technician Certification Board (PTCB) will allow CPhTs to obtain up to 10 CE credits per licensure period for participating in inservices and other education activities. To obtain credit, a pharmacist must complete PTCB's Universal Continuing Education form, which can be found at their website, www.ptcb.org (click on "CE Credits" under the "CPhT Services" menu).

It is election season again. WMSHP's board has the following open positions: president-elect, treasurer, board member (4), and technician member. You will be receiving a ballot in the U.S. Mail in the next couple days. Please take the time to fill it out and return it to us. You may return the completed ballot via U.S. Mail, give it to any Board member, or take it to the November meeting. The results will be tallied and announced at the November meeting.

The November meeting will be held on November 8th at the Food Dance Cafe in Kalamazoo. Dennis Parker, Jr., Pharm.D. from Detroit Receiving Hospital will be giving a presentation on the Management of Intracerebral Hemorrhage. Due to space constraints, the meeting will be limited to the first 40 individuals who RSVP. Please be sure to select your dinner preference when you RSVP.

Help Wanted: WMSHP is seeking actively engaged members to run for a board position for 2008-2009. Openings include: president-elect, treasurer, board member (4 positions), and technician board member. Experience is not necessary. Mentoring will be provided. If you are interested in running or nominating another member to run, please contact Ryan Bickel at ryanbickel@borgess.com or (269) 226-6616 by October 11th. Elections will be held in late October/early November and the results will be announced at the November meeting.

Coming Soon: The next WMSHP meeting will be held in Grand Rapids on October 11th at Bar Divani. Dr. David Langholz will discuss hypertension and the role of Tekturna. Continuing education credits will not be offered at this meeting. Please RSVP at www.wmshp.net, if you would like to attend. Seating may be limited, so sign up now.

Announcement: The MSHP Annual Meeting will be held on Friday, November 2, 2007 at the Lansing Center. This event is open to both MSHP/MPA members and non-members. Students and residents are offered complimentary registration if they register by October 19th. To register, please visit the MPA website, http://www.michiganpharmacists.org, and go to the "Events Calendar" which is found at the "Pharmacy Professionals" link.

In this month's WMSHP Newsletter, Jeffery Tichenor Pharm.D. writes of the use of recombinant factor VII for massive hemorrhage due to traumatic injury.

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Exsanguination is a leading cause of mortality in severe trauma patients, accounting for approximately 40% of mortality.¹ This high incidence of mortality stems from the "lethal triad" of coagulopathy, hypothermia and acidosis associated with massive hemorrhage. Preventing transition to any aspect of the lethal triad is the goal of current treatment. The mainstays of massive hemorrhage management are: ligation, tamponading, or compression of the affected vessels. Other common interventions being: transfusion with fresh frozen plasma, cryoprecipitate, and/or platelet concentrates. The high mortality rate associated with massive hemorrhage bears witness to the fact that current therapeutic options often fall short of their goal in this patient population.

Recombinant activated factor VII (rFVIIa; Novoseven^®) currently has Food and Drug Administration approval for the treatment and prophylaxis of bleeding in patients with Factor VII deficiency, and those with hemophilia with inhibitors to Factors VIII and IX. Factor VII is a vitamin K dependent glycoprotein, structurally similar to human factor VII. Factor VII can exert activity via both the extrinsic and intrinsic pathways in the clotting cascade (see figure below). As predicted by these mechanisms of action, rFVIIa only induces clot formation where vascular injury is present. This ability to form clots only at sites of injury has lead to the investigation of rFVIIa for the management of massive hemorrhage secondary to traumatic injury. Other traits of rFVIIa which make it a potentially attractive agent for use in patients with massive hemorrhage are its short half life of approximately two hours, and its ability to be rapidly infused over 2-5 minutes. rFVIIa has been studied in both penetrating (gunshots and stabbings) and blunt (collisions and attacks) traumas.

The largest and best carried out of the trials using rFVIIa for the treatment of massive hemorrhage was performed by Boffard and colleagues in 8 countries and 32 hospitals.² This study included 301 patients with severe trauma. It was a parallel, randomized, placebo controlled, double-blind trial to evaluate the ability of rFVIIa to control bleeding in trauma patients experiencing extensive hemorrhage.² One arm evaluated the use of rFVIIa in patients with blunt trauma, while the other evaluated its use in patients with penetrating trauma. rFVIIa was administered in consecutive doses of 200, 100, and 100 mcg/kg as deemed necessary by the clinician. The first dose was given after transfusion of the eighth unit of red blood cells (RBCs); and subsequent doses were given after 1 and 3 hours respectively. The blunt trauma arm resulted in RBC transfusions being significantly reduced by 2.6 units (90% CI 0.7 - 4.6, p= 0.02) with rFVIIa compared to placebo.² The need for massive RBC transfusion, defined as > 20 units of RBC, was also significantly reduced from 33% in patients on placebo to 14% with rFVIIa (p= 0.03).² Similar trends were noted in the penetrating trauma group, though the results there were not statistically significant.²

Another well performed trial of rFVIIa for the management of massive hemorrhage was done by Dutton and colleagues. This was a compassionate use study performed on 81 coagulopathic patients.³ The decision to use rFVIIa went through 1 of 2 "gatekeepers" at the facility, dosing was done at 100 mcg/kg. Factor VII restored hemostasis in 75% of the patients (61 of 81), with an average of 1.23 doses.³ Despite this success, mortality at hospital discharge was still approximately 32%.³ This trial also showed that an acidic body pH tempers the effects of rFVIIa. Responders to rFVIIa (n=61) in this study had an average pH of 7.29 while non-responders (n=20) averaged 7.02 (p= 0.0016).³ The research also confirms that patients must have sufficient functional platelet counts at baseline in order for rFVIIa treatment to be effective (patients below 50,000/mcL did not form clots with rFVIIa).³ The researchers compiled a group comparable to their patients as a control (matched on: age, sex, mechanism of injury, abbreviated injury score, laboratory data, clinical outcome, and TRISS probability of survival) and were unable to associate rFVIIa with a long-term survival benefit in their patients.³

Both of these extensive studies concluded rFVIIa to be beneficial in restoring hemostasis to patients suffering traumatic massive hemorrhage, especially those due to blunt trauma. However, no overall mortality benefit was established with the use of rFVIIa in their patient populations. Though, use of rFVIIa may be beneficial in a select group of trauma patients with massive hemorrhage. Patients with the following characteristics appear to be the best served by rFVIIa therapy.

- Blunt trauma victim
- Current treatments exhausted
- Absence of negative prognosis (sepsis, major organ failure, penetrating head injury)
- pH >7.1
- Glasgow Coma Score >8
- Age >18 & <65 years
- No history of atherosclerosis or thrombosis

References

1. Sauaia A, Moore FA, Moore EE, et. al. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38:185-193.
2. Boffard KD, Riou B, Warren B, et. al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double blind clinical trials. J Trauma 2005;59:8-18.
3. Dutton RP, McCunn M, Hyder M, et. al. Factor VIIa for correction of traumatic coagulopathy. J Trauma 2004;57:709-719.

The summer is drawing to an end. The kids are heading back to school. It is also time for WMSHP to return from its summer break. The next meeting will be held in Kalamazoo on Thursday, September 13th. Check out the website, www.wmshp.net, for more details and to RSVP.

While we were on our summer recess, ASHP held the House of Delegates meeting. One of the hottest topics at this year's meeting was should residency training be required for new pharmacy graduates to provide direct patient care. After much discussion, they resolved the following:

To support the position that by the year 2020, the completion of an ASHP-accredited postgraduate-year-one residency should be a requirement for all new college of pharmacy graduates who will be providing direct patient care.

I am sure that this resolution, as well as, other new professional policies will be discussed at MSHP's annual board retreat this September. I will keep you posted on highlights.

In addition to our upcoming meeting, I would like to remind you of some other important upcoming dates. First, National Pharmacy Week this year is October 21-27. Information and planning resources can be found at the MPA website, www.michiganpharmacists.org. MSHP's annual meeting is Friday, November 2nd, at the Lansing Center. Registration forms for this meeting will be available at our September and October meetings. Finally, ASHP's 42nd Midyear Clinical Meeting will convene December 2 - 6 in Las Vegas, NV. Reserve your hotel now.

Now that April is almost upon us, we are starting to see the first signs of spring. For WMSHP, this means that we are also nearing our annual meeting, which highlights some research projects done by Western Michigan pharmacy residents. After a close vote, the Board selected the following two projects to be presented at the April meeting: "Pharmacist Interventions to Improve Adherence Among Patients with HIV/AIDS Starting Antiretroviral Therapy" by Melanie Crain, Pharm.D., and "Evaluation of Microorganisms Responsible for Early versus Late-Onset Hospital-Acquired Pneumonia in Intensive Care Unit Patients" by Sarah-Ann Brown, Pharm.D. I would like to thank all of the area residents for submitting their projects and encourage you to come to the meeting and support Melanie and Sarah-Ann.

Another spring tradition is the WMSHP Spring Seminar. This year's seminar will be held on Thursday, May 10th, at the Grand Rapids Airport Hilton. It is an excellent opportunity to earn continuing education credits and network with colleagues. Our morning sessions will focus on toxicology and advancing the pharmacy profession, while the afternoon will be broken into two tracks, Administration and Therapeutics. The Administration track will touch upon innovative technician practices, pharmacy law, and the benefits of being a preceptor. Historically, technicians have found the Administration track useful, because it fulfills their law review requirement for certification. The Therapeutics track will provide updates on HIV therapy, women's health, and glycemic control in patients with infections. Reserve the date on your calendars and watch our website, www.wmshp.net, for more information and to register.

Greetings! I just returned from MPA's Annual Convention and Exposition in Dearborn. It was nice to see many of you out there. I would like to take this opportunity to share with you some highlights from the convention.

One of the main topics which the MPA focused on this year was getting their membership involved politically to strengthen the profession of pharmacy. They suggested identifying legislators (or potential legislators) in your district that you believe in and supporting them. Support can be as simple as sending them a $10 check to support their campaign or as involved as knocking on doors for them during the campaign season. If you are not comfortable supporting a legislator, please consider supporting MPA's Political Action Coalition (PAC).

Another highlight of the meeting was finding more preceptors and sites to become involved with training pharmacy students in their P-3 and P-4 years. WMSHP will be working closely with the Michigan Colleges of Pharmacy Experiential Programs (McPEP) group to assist them in identifying preceptors and sites in our region, as well as, supporting their current preceptors and sites. WMSHP has arranged for McPEP to give a presentation at our May 10th Spring Seminar in Grand Rapids. Please mark your calendars for this event.

Finally, I would like to inform you that Jesse Hogue, Fred Schmidt, and I served as your delegates to the MPA House of Delegates session. During the session, Laura Shaw, Chairman of Michigan's Board of Pharmacy, provided the House with a special report. She reminded us that Michigan's new continuing education (CE) standards (R 338.3041) were recently signed into law. For those of who are not aware of the new standards, starting July 1, 2007, pharmacists will be required to obtain 10 hours of live CE per renewal period, will be required complete one hour of CE in pain management, and will not be permitted to obtain more than 12 hours of CE per day. The new rules can be found at www.michigan.gov/healthlicense under the "Health Professional Administrative Rules" link.

Wow! We saw record attendance at last month's meeting. Approximately 75 WMSHP members attended the 2006 ICAAC review in Grand Rapids. I want to thank Dana Staat for doing a great job facilitating the unusually large crowd and arranging for Michael Klepser to do the presentation for Michael Tiberg, who encountered a family emergency at the last minute. As a thank you for giving the presentation at such short notice, WMSHP's Board of Directors is extending an honorary lifetime membership to Michael Klepser. Thanks again, Mike!

One of my responsibilities as your president is to serve as the Regional Delegate to the Michigan Society of Health-System Pharmacists (MSHP). I attended my first MSHP board meeting and committee day on January 18th. It was a great experience meeting pharmacy leaders from around the state and providing them with a summary of our recent activities. I would like to recognize several WMSHP members, who also currently serve on MSHP's Board of Directors: Fred Schmidt, President; Jesse Hogue, Director, and Jean Lee, Director.

February is going to be a short, but busy month. On February 8th the WMSHP meeting will take place in Kalamazoo. Sandra Chase will be giving a presentation on using low molecular weight heparin in medically ill patients. Also, the MPA's Annual Convention and Exposition (ACE) meeting will take place February 23 -25th in Dearborn. More information regarding the ACE meeting can be found at MPA's website, www.michiganpharmacists.org. I hope to see you at one of the events.

Happy New Year! Hopefully, you were able to enjoy the holidays with your family and friends.

I would like to start off the year by introducing this year�s board of directors to you. Your officers include: Ryan Bickel, President; Jesse Hogue, Past President; Dana Staat, President-Elect; Ted Riley, Treasurer; and Brad Miller, Secretary. Your board members include: Jodie Bakus, Bill Kriel, Jean Lee, Kim Melgarejo, Natalie Paul, Shaun Phillips, Cindy Pollock, Jeff Van Houten, and Cheri Woodhams.

On behalf of the board, I would like to thank Jesse Hogue for all of his hard work and guidance as President. I would also like to recognize Jean Lee for her service as Past-President last year. Fortunately, she will be remaining with us as a board member. Finally, I would like to welcome our newest board member, Cindy Pollock.

I am honored to serve as your president and look forward to working with you to promote the profession of pharmacy. To assist me in serving you, please feel free to share your ideas regarding educational opportunities, topics of interest, or anything else that pertains to advancing health-system pharmacy.

Many of you are currently making New Year resolutions. I have a couple ideas that I would like to offer. If you are not currently a member of the Michigan Society of Health-System Pharmacy (MSHP) and Michigan Pharmacists Association (MPA), consider joining. If you are already a member, consider becoming involved with a committee, serving as a delegate, and/or attending the MPA's Annual Convention & Exhibition in February. More information regarding these opportunities can be found at MPA's website, http://www.michiganpharmacists.org.

In the November WMSHP Newsletter, Sakar Wahby, a pharmacy practice resident at Spectrum Health, writes about recent studies of vitamin E's potential neuroprotective effect in patients receiving chemotherapy drugs.

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Neuroprotection in Patients Receiving Chemotherapy

Sakar Wahby, Pharm.D.
Pharmacy Practice Resident
Spectrum Health, Grand Rapids, MI
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Cancer has been the leading cause of death in the United States for the population younger than 85 years of age since 1999.¹ Chemotherapeutic agents have played a big role in curative therapy for various types of cancers since their discovery in the nineteen fifties and sixties. However, these agents have the potential for causing adverse events such as nausea, vomiting, alopecia, and myelosuppression. Other side effects could be specific to some agents and cause damage to certain organs of the body such as toxicity to the gastrointestinal tract, the immune system, the kidneys, heart, and nerve tissues.²

Neurotoxicity is one of the widely known side effects for a various number of chemotherapeutic agents. Among the classes of chemotherapy known to cause neurotoxicity are the platinum compounds (cisplatin, oxaliplatin, and carboplatin), the taxanes (paclitaxel and docetaxel), vinca-alkaloids (vincristine, vinblastine, and vinorelbine), methotrexate, thalidomide, and ifosfamide. Neurotoxicity caused by vincristine, cisplatin, paclitaxel, and oxaliplatin can limit the dose of these agents that potentially can be used for treatment, thus leading to discontinuation of therapy and thereby hindering the possible full use of very effective cancer treatments.²

Currently no standard of therapy is approved for neuroprotection for cancer patients who are treated with chemotherapy. Two pilot, randomized, controlled trials (Pace et al. and Argyriou et al.) were conducted in Europe investigating the effectiveness of vitamin E as a neuroprotective agent in patients receiving cisplatin or paclitaxel.^3,4

Cisplatin is a widely used agent in the treatment of various solid tumors such as testicular, ovarian, cervical, head & neck, bladder, and lung cancer. The incidence of neuropathy is up to 100% with this agent, and the severity varies depending on cumulative doses, duration of treatment, and possible underlying diseases that can also cause neuropathy, in addition to having received previous treatments with other neurotoxic medications.^2,5 With cisplatin treatment, neurotoxicity is cumulative and signs and symptoms of neuropathy usually appear with cumulative doses of 300-500 mg/m². Patients treated with cisplatin present with sensory signs and symptoms of paresthesia and numbness. The former manifests itself as tingling, "pins-and-needles" sensation, pulling, pressure, and tightness in the limbs, most often seen in the toes and feet.^2,5

Paclitaxel is a taxane compound used in the treatment of ovarian, breast, and lung cancer.⁵ Besides myelosuppression, paclitaxel can cause neurotoxicity with severity depending on single-dose and cumulative doses administered. At doses of 135 mg/m² mild neuropathies have been observed in 50% of patients, but neurotoxicity can be dose-limiting when 175 mg/m² doses are administered. A dose greater than 200 mg/m² can cause significant neurotoxicity. The pattern of neurotoxicity from paclitaxel is manifested as paresthesia and numbness in a glove and stocking distribution in the limbs, Lhermitte’s sign (sensation similar to electrical shock) and loss of deep tendon reflexes. ^2,5

Both pilot studies have shown vitamin E to be effective in reducing the incidence and severity of neurotoxicity in patients receiving chemotherapy and vitamin E.

Pace et al. randomized 47 patients into two groups. Group one received a cisplatin regimen with vitamin E and group two received a cisplatin-only regimen serving as control. After six cycles of cisplatin administration, the incidence of neuropathy was significantly lower in the vitamin E + cisplatin group as compared to the control group (cisplatin alone). Four out of 13 patients in the vitamin E group (30.7%) and 12 out of 14 patients in the control group (85.7%) reported some sign or symptom of neuropathy (p<0.01). The relative risk of developing neurotoxicity was lower in the vitamin E group compared to the control group (RR= 0.36; 95% CI = 0.15-0.83, P<0.001).³

Argyriou et al. evaluated the neuroprotective effect of vitamin E in patients receiving cisplatin, paclitaxel, or combination of both agents. A statistically significant higher incidence of neurotoxicity were reported in the chemotherapy regimen group (16/20, 80%), versus (8/20, 40%) in the vitamin E + chemotherapy group (Yates p value= 0.023). The relative risk of developing neurotoxicity was lower in the vitamin E group compared to control (RR=0.34, 95% CI =0.14-0.84).⁴

The results of both studies have shown great potential for vitamin E in reducing the incidence of neuropathy, acting as a free radical scavenger and protecting non-tumor cells from free radical damage. However, this hypothesis raises a concern regarding the potential of vitamin E to protect cancer cells as well from free radical damage, therefore reducing the efficacy of chemotherapy.⁶

Neither study was powered enough to evaluate overall response rate and overall survival rate of those patients given vitamin E compared to placebo. Therefore, using vitamin E as a standard therapy with chemotherapeutic agents causing neurotoxicity can not be recommended at this time. Larger randomized, placebo controlled studies are warranted to further establish efficacy and safety of vitamin E in combination with chemotherapy.

 

References:

1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer Statistics, 2005. CA Cancer J Clin. 2005 Jan;55(1):10-30.
2. DeVita VT Jr., Hellman S, Rosenberg SA. CANCER: Principles & Practice of Oncology. 6th ed. Vol. 2. Philadelphia: Lippincott Williams & Wilkins; 2001.
3. Pace A, Savarese A, Picardo M, Maresca V, Pacetti U, Del Monte G et al. Neuroprotective Effect of Vitamin E Supplementation in Patients Treated With Cisplatin Chemotherapy. J Clin Oncol. 2003 Mar;21(5):927-31.
4. Argyriou AA, Chroni E, Koutras A, Ellul J, Papapetropoulos S, Katsoulas G et al. Vitamin E for Prophylaxis Against Chemotherapy-Induced Neuropathy. Neurol. 2005;64:26-31.
5. National Comprehensive cancer network [homepage on the internet]. NCCN Clinical Practice Guidelines in Oncology [updated 2005; cited 2006 Feb 26]. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp?button=I+Agre
6. Labriola D, Livingston R. Possible Interactions Between Dietary Antioxidants and Chemotherapy. Oncology. 1999 Jul;13(7):1003-8.

Don’t forget! If you have not done so already, please send in your ballot for the WMSHP Board elections. We plan to announce the results at the November 9 meeting, so ballots need to be received before then.

Hopefully every one participated in Michigan Pharmacy Week activities. Remember, if you are an MPA member please take a moment to fill out the reporting form with what you or your department did to celebrate.