HOPA Publications Committee
Bonnie Labdi, PharmD RPh, Chair
Ashley Glode, PharmD BCOP, Vice Chair
David DeRemer, PharmD BCOP, Board Liaison
Brandi Anders, PharmD BCOP Megan Bodge, PharmD
Megan Brafford, PharmD BCOP
Courtney Cavalieri, PharmD BCOP Morgan Culver, PharmD BCOP
Morgan E. Culver, PharmD BCOP
Erika Gallagher, PharmD BCOP
Lisa Lohr, PharmD BSPharm BCOP BCPS
Jennifer Kwon, PharmD BCOP
Trevor McKibbin, PharmD MS BCOP
Christan Thomas, PharmD BCOP
Board Update: Why Will Patients Ask for You... By Name?
Sarah Peters, PharmD MPH BCOP
HOPA President
In my remarks at the 12th HOPA Annual Conference, I challenged all of you to think about ways in which our patients will ask for us, their oncology pharmacists, by name. The profession has been working diligently for the last few years to seek “provider status” by amending the Social Security Act to include pharmacists in the list of providers who can bill Medicare Part B for clinical services. Members of the HOPA Board of Directors and Health Policy Committee participated in our second annual Hill Day on April 27, 2016, to advocate for H.R. 592 and S. 314, the Pharmacy and Medically Underserved Areas Enhancement Act. We also advocated for the Cancer Drug Coverage Parity Act (H.R.
2739/ S. 1566), explained the role of the hematology/oncology pharmacist, and provided updates on the new CMS Part B “demonstration project.”
HOPA is a member of the Patient Access to Pharmacists’ Care Coalition, which is a collaboration of multiple pharmacy organizations who lobby year-round to support this legislation. While the profession has aimed specifically these past few years on bills that have been gaining increasing bipartisan support, this effort is not new. In fact, when I was in pharmacy school, I remember being told that we would be entering an era of “pharmaceutical care” and pharmacists would one day “bill for cognitive services.” In addition to 47 states and the District of Columbia, California and Washington recently authorized provider status legislation allowing pharmacists to practice under collaborative drug therapy management proto- cols, many of which predate the newest provider status initiative by many years. However, I’ve met HOPA members who have shared that they never have the opportunity to meet their patients. I’ve met friends, family members, and other colleagues who had not met their oncology pharmacist during their cancer journey, and were un- aware that one was available to them.
As we continue to advocate for the opportunity to bill for these services, it is imperative that we start working toward including our most important advocate—our patients. I have yet to meet a patient who was not appreciative of the interactions that I or other pharmacists have had with them in the clinic. We all have different roles; some of us are working in very busy infusion centers and perhaps are the only pharmacist working to ensure that orders and drug therapy are written, dosed, and prepared safely. Imagine what an impact you could have if you took the time to meet just one patient—maybe that very last patient at the end of the day when you are getting orders ready for the next day—just to introduce yourself and say, “Hi Mrs. Smith. I’m Sarah Peters, and I’m your pharmacist. What questions do you have about your medications? How did that last cycle of chemo go for you? What side effects or symptoms do you have that I can help you with?”
It is incredible what you will learn from that personal interaction with your patients. These are the stories that I told legislators on the Hill in April—and these are the ones that matter. No one cares about how much education, training, or experience we have. They want to know the actual impact that we make. Describing the patient experience to legislators would pale in comparison to an actual patient writing a letter to describe how your interventions mattered to their care. We will need these stories, letters, and support to make provider status a reality, but moreover, we will need them as new payment models focusing on quality, value, outcomes, and impact rather than the quantity of services provided.
Speaking of Hill Day, we had a very successful and busy day on the Hill. We met with over 30 legislative offices from 13 states and learned within days of our visits that four legislators signed on to either the Provider Status or Oral Chemotherapy Parity bills! I asked those who attended for their thoughts on improving Hill Day for the future and one consistent message was to consider expanding participation to include more HOPA members. This is not surprising, given the standing-room only attendance at the advocacy session at this year’s annual conference and that 57 HOPA members have expressed interest in joining the Health Policy Committee through the volunteer activity center. While the board considers this suggestion and thinks of creative ways to implement it in a fiscally responsible manner, I strongly encourage you to consider meeting with your senator or representative while they are home during the summer recess (July 15–September 6 for the House of Representatives and July 18–September 5 for the Senate) on issues that matter to you. The HOPA Health Policy agenda, which includes briefs on a variety of issues with talking points and links to the actual pieces of legislation, and a link to find your senator and representative, can be found on the banner of HOPA’s current website (look for our new website in August!).
As HOPA’s new president, I am looking forward to providing leadership on a number of initiatives, some new and some that started during Scott Soefje’s term: revising the committee structure to be implemented in March 2017 to better coordinate communication among committees; revisiting the Scope of the Hematology/Oncology Pharmacist to work on “part 2”—a more granular and de- tailed version; publication of the Oral Chemotherapy Medication Therapy Management standard and development of tools, resources and perhaps even a “summit” to promote the standard and the pharmacists who provide services in this area; establishing hematology/oncology pharmacy competencies for pharmacy school graduates; enhancing our external collaborations and tangible projects with other pharmacy organizations as well as our partners in hematology/oncology medicine and nursing; implementing the selected Big Idea(s); and of course, monitoring the first year of our excellent BCOP Recertification Program involving over 50 HOPA members.
Immunotherapy for Cancer Named Advance of the Year by ASCO
Ashley E. Glode, PharmD BCOP
Assistant Professor, Department of Clinical Pharmacy
University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
Clinical Pharmacy Specialist
University of Colorado Cancer Center
Aurora, CO
Immunotherapy has been a cancer treatment strategy since the late 19th century, though not widely implemented into practice until today. In 1891, New York surgeon William Coley injected bacteria into a patient’s tumors in an attempt to elicit an immune response targeting the infection as well as the tumor.1 Several methods to harness the immune system to attack cancer cells have been investigated over the decades, including stimulating the actions of specific components within the immune system or thwarting signals made by cancer cells to suppress the immune response.2 Unfortunately using the body’s own immune system to target cancer cells is not an easy feat to master. Cancer cells may evade the immune system by concealing themselves to make it difficult for T cells to identify them, or by expressing proteins that suppress T cells in the surrounding environment.
Numerous immunotherapy treatment methods have been researched and refined leading to U.S. Food and Drug Administration (FDA) approved treatment options. Immune checkpoint modulators are agents that modulate certain proteins to limit the strength and duration of the immune response.2 By blocking these proteins, the immune system is no longer in check and can fully attack and destroy cancer cells. Ipilimumab was the first medication approved that inhibits the checkpoint CTLA4. Nivolumab and pembrolizumab are the most recently approved agents that act on a different checkpoint, PD-1.
Adoptive cell transfer (ACT) is another exciting area of immunotherapy research. One form of this treatment collects tumor-infiltrating lymphocytes (TIL) from a patient’s tumor, manipulates and grows them in the lab with cytokines, and infuses them back into the patient.2 The theory behind this approach is that the TILs have the ability to target the tumor cell, but may not be enough to kill the tumor or overcome the immune system inhibiting their activity. Administering a large amount of these cells can overcome obstacles to shrink or kill the cancer. Another approach utilizing ACT is chimeric antigen receptor (CAR)T cell therapy, which takes a patient’s own T cells and modifies them in a lab to express a protein, or CAR. These altered T cells are multiplied and then infused into the patient to attach to proteins on the surface of the cancer cell. Once the cells are bound together, the engineered T cell is activated and kills the cancer cell.
Several therapeutic antibodies have been in practice for decades, but modifications have recently been introduced. Antibodies are designed to attack specific antigens found on cancer cells and other noncancer cells and proteins in order to kill cancer cells.3 Naked monoclonal antibodies (mAb) are most commonly used and work on their own. They induce apoptosis, antibody-dependent cell-mediated cytotoxicity, and complement-dependent cytotoxicity.2 Conjugated monoclonal antibodies are mAbs that are joined to a chemotherapy agent or radioactive particle to deliver the toxic substance directly to the cancer cell.3 The newest kind of mAb is the bispecific monoclonal antibody, which combines two different mAbs allowing the drug to bind to two different proteins at the same time. Blinatumomab is an approved agent that binds to both CD19 and CD3.
Therapeutic cancer vaccines also have been an area of research for decades. The first ap- proved therapeutic vaccine was sipuleucel-T.3 To engineer this vaccine, cells are taken from the patient and treated prior to being reinfused and helping the immune system attack the cancer. Many different types of cancer vaccines (tumor cell vaccines, antigen vaccines, dendritic cell vaccines, vector-based vaccines) are currently being investigated in a variety of malignancies including brain, breast, and lung cancer. It is an exciting area of development.
The American Society of Clinical Oncology (ASCO) has named cancer immunotherapy the advance of the year due to the number of improvements made to the immunomodulary process and the clinical implementation of immunotherapy strategies into multiple disease states.3 Research is expanding the number of patients who may benefit from these strategies and developing ways to minimize adverse effects to improve tolerability.
References
1. Ledford H. The killer within. Nature. 2014. 508:24-26.
2. National Cancer Institute. Immunotherapy: using the immune system to treat cancer.
Updated: Sept 14, 2015.
3. American Cancer Society. Cancer Immunotherapy. 2015. Last revised: Nov 5, 2015.
4. ASCO Clinical Cancer Advances 2016. ASCO’s 11th Annual Report on Progress against
Cancer. Published in the J Clin Oncol online ahead of print Feb 4, 2016.
The New Oncology Pharmacy Updates Course
Christy Harris, PharmD BCOP BCPS
Associate Professor of Pharmacy Practice
MCPHS University
Boston, MA
An exciting new program is coming this summer, the Oncology Pharmacy Updates Course. This annual 2-day conference will be directed toward the advanced board certified hematology/oncology pharmacy (BCOP) practitioner. We know that our membership is very diverse and we hope that this program will fill a gap that has not yet been ad- dressed by any other BCOP recertification program.
The Oncology Pharmacy Updates Course is not designed as an introduction to the content, nor is it intended to replace a board certification preparatory review course. Each session will be literature-focused, discussing studies and results that have been published or are on- going. This course will ensure that all core topics and domains are covered, as specified by the Board of Pharmacy Specialties and the Oncology Pharmacy Specialty Council. The course curriculum will be changed and content updated yearly with all core topics covered in a 3-year cycle. The course will provide 10 BCOP continuing education (CE) and professional development hours per year.
This year there are some great topics that will be presented, including a less commonly covered disease, soft tissue sarcomas, which have had a remarkable year with one new drug approval and one added indication in the past 12 months. Other sessions will break down the new data and discuss the sequence of therapies or special circumstances in malignancies such as prostate cancer and melanoma. The speakers are knowledgeable veterans in practice and we look forward to hearing about the new literature and current developments and learning how to incorporate this new information into practice.
HOPA 12 Annual Conference Goes Beyond Expectations
Everything was sweet in "The Big Peach" during the 12th HOPA Annual Conference! A record-setting 1,040 registrants gathered in Atlanta this past March for cutting-edge education and valuable net- working. Hematology/oncology pharmacists from across the nation gathered to explore current information about new and emerging therapies for hematology/oncology patients and review recent developments in medical literature. The nation’s leading experts shared their knowledge in more than 45 educational sessions over 3.5 days. Conference attendees also took advantage of Atlanta’s beautiful weather and exciting tourist attractions.
Pulitzer Prize winner Siddhartha Mukherjee, MD PhD, delivered the John G. Kuhn Keynote Lecture. His address analyzed the role of the pharmacist in the changing landscape of cancer care. For a donation to the HOPA Research Fund, a small group of individuals had the opportunity to meet and talk with Dr. Mukherjee after the event and obtain a signed copy of his Pulitzer Prize-winning book, The Emperor of All Maladies: A Biography of Cancer.
As part of the all-new HOPA BCOP Recertification Program, HOPA offered eight specialty sessions for a total of eight (8) hours of BCOP recertification credit. Topics included haploidentical stem cell trans- plant, triple negative breast cancer, medical marijuana, and more. In case you missed these valuable sessions, they will be repeated live in Chicago on September 22 and will be available online later this yr. HOPA offered several preconference events, allowing attendees to maximize their time in Atlanta. This included a tour of the Phase 1 Clinical Trials Unit at the nearby Winship Cancer Institute of Emory University. Also new this year, attendees received complimentary professional headshots at the attendee lounge. The Attendee Lounge was the meeting place for the Big Idea project. HOPA Board Members were available to answer questions about the new Big Idea project to help HOPA achieve its strategic plan.
In addition to the eight BCOP specialty sessions and 10 breakout sessions, HOPA was pleased to offer a breadth of general session topics delivered by industry experts throughout the conference. A few of the speaker highlights were:
- Significant Papers in Hematology/Oncology
Chris Fausel, PharmD MHA BCOP; Susan Goodin, PharmD BCOP FASHP FCCP - Practice Panel: The Cost of Cancer Care
Timothy Tyler, PharmD; Michael Kolodziej, MD; Ed Li, PharmD MPH BCOP; Thomas Smith, MD FAAHPM FACP FASCO Management of Acute Lymphoblastic Leukemia in the Elderly Cindy Ippoliti, PharmD - State of the Art in Oncology Pharmacy Research
Susan Goodin, PharmD BCOP FASHP FCCP; Judith Smith, PharmD BCOP CPHQ FCCP FISOPP RPh
HOPA extends a huge thank you to the many other industry professionals who shared their insights throughout conference events!
HOPA President Scott Soefje, PharmD MBA BCOP, delivered exciting highlights from the year during his member address, including the launch of the HOPA BCOP Recertification Program, the inaugural class of Fellows of HOPA, a completely rebranded HOPA logo and look, and the success of our first annual report. Dr. Soefje commented on HOPA’s many collaborations in 2015, noting that HOPA interacted with 20 different advocacy and professional organizations on a variety of endeavors. With a renewed strategic plan under our belt, Soefje stated, “we have made great strides toward our goal of supporting the research efforts of hematology/oncology pharmacists to optimize the care of individuals affected by cancer.”
Thank you to all who attended the 2016 HOPA Annual Conference. We hope to see you next year at the 13th HOPA Annual Conference, taking place March 29–April 1, 2017, at the Disneyland® Hotel in Anaheim, CA.
NZW-Hamburg 2016
Lisa Holle, PharmD BCOP
Assistant Clinical Professor, Department of Pharmacy Practice
University of Connecticut School of Pharmacy
Storrs, CT
Following the 11th Annual HOPA meeting, I was invited by Klaus Meier, president of the German Society for Oncology Pharmacy (Duetsche Gesellschaft für Onkologische Pharmazie [DGOP]) and the European Society of Oncology Pharmacy (ESOP) to give a short greeting from HOPA to both DGOP and ESOP and to present my work on oral chemotherapy disposal (originally presented at the 11th Annual HOPA meeting) at the 24th NZW-Hamburg conference. NZW-Hamburg was held January 29–31, 2016, in Hamburg, Germany, and sponsored by the local Hamburg pharmacy association Apothekerkammer Hamburg, DGOP, and ESOP. Over 1,000 oncology pharmacists, physicians, and researchers from around the world at- tended the conference.
It was a terrific opportunity to introduce HOPA to a global pharmacy audience and to learn more about other oncology pharmacy organizations and oncology pharmacy practice in a variety of countries and settings. Similar to the Annual HOPA Meeting, the topics of the main conference were wide-ranging, including an overview of interactions of herbal medicines and oncology, the controversy of using generic tyrosine kinase inhibitors, an overview of the quality standards of the new ISO 9001, and updates on new drugs, cancer immunotherapy, end-of-life care, and oral chemotherapy. DGOP offers a certificate course for oncology pharmacists and NZW-Hamburg offered several certificate course sessions on aseptic work, clinical case reports, psycho-oncology, and risk management.
Two interesting joint professional organization endeavors were prominent during the conference. Empowering Pharmacists to Improve Healthcare for Oral Chemotherapy Patients: Establishment of a European Best Practice Model, also known as EPIC, is a joint project of the DGOP, ESOP, Slovene Chamber of Pharmacists, and Association of Estonian Hospital Pharmacists. The EPIC project conducted several seminars to display its work within specific case studies, drug information, dysphagia, and psychosocial aspects. Another joint initiative by DGOP and the German Cancer Society (DKG) is the oral cancer treatment project, aimed at optimizing oral chemotherapy by a safe, economical team-based approach that improves quality of life and minimizes drug-related problems.
ESOP hosted a short lecture session during the conference that included updates on the EPIC and Cytotoxic Drug Contamination in European Hospitals projects and presentations on the role of the pharmacist in hypothermic intraperitoneal chemotherapy (HIPEC) treatment, effect of disease state on the pharmacokinetics and efficacy of monoclonal antibodies like bevacizumab and cetuximab, disposal of oral chemotherapy drugs, and use of glutamine to prevent radiation-induced side effects. This session also included clinical pharmacy practice model examples from Japan, Egypt, and Croatia, which provided the audience with novel and innovative methods of oncology pharmacy practice. For example, Shinya Suzuki from Japan described the development of patient-friendly materials to manage adverse effects in the outpatient setting, which have become nationally accepted. Vesna Pvalica and colleagues presented on the recent creation of an oncology pharmacy team that spans community, hospital, and clinics to offer clinical oncology pharmacy services. Within 4 months of this service starting, the Croatian government approved payment for their services.
As with most conferences, the networking opportunities at NZW- Hamburg were just as important as the scientific information gained. I made connections with other oncology pharmacists and physicians from over 15 countries. I’ve encouraged them to come to a HOPA meeting some day and plan to keep in touch to foster international collaborations.
If you haven’t attended an international oncology pharmacy meeting, I would certainly encourage you to do so. It always is a treat to meet folks, collaborate, and gain so much from the great work being done around the globe. The next DGOP meeting will be NZW-Dresden on June 17–18, 2016, in Dresden, Germany, and the
next ESOP meeting will be ECOP3 in Dubrovnik, Croatia on May 19–21, 2016. For more information about NZW-Dresden visit http://www.nzw.de/nzw_ dresden.php and for ECOP3 visit https://ecop2016.wordpress.com/.
Recalls and Safety Alerts from the FDA
Jennifer Kwon, PharmD BCOP
Hematology/Oncology Clinical Pharmacy Specialist
VA Medical Center
West Palm Beach, FL
RECALLS
Baxter Recall on IV Solutions
Baxter International Inc. issued a voluntary recall on two lots of intravenous (IV) solutions due to the potential presence of particulate matter. The particulate matter has been determined to be an insect and was identified from a customer complaint. There have been no adverse events reported. For a full list of recalled products, visit http://www.fda.gov/ Safety/ Recalls/ucm479877.htm.
Downing Labs Recall in Texas
Downing Labs, LLC, in Farmers Branch, TX, voluntarily recalled all lots of sterile products compounded and packaged by Downing Labs due to concerns of sterility assurance. These products were distributed in the United States and the United Kingdom to patients and providers between April 20, 2015, and September 15, 2015. The recall does not affect any nonsterile, compounded medications prepared by Downing Labs. There have been no adverse events reported related to this recall. http://www.fda.gov/ Safety/ Recalls/ucm468215.htm
Medistat RX Recall in Alabama
Medistat RX, LLC, in Foley, AL, issued a voluntary recall of all non- expired products produced for sterile use due to possible contamination. These products were distributed between November 1, 2014, and September 3, 2015. The U.S. Food and Drug Administration (FDA) has received reports of several adverse events that are possibly associated with Medistat drug products. Healthcare professionals and patients are encouraged to report adverse reactions or quality problems experienced with the use of drug products produced by Medistat to the FDA’s MedWatch Adverse Event Reporting program. http://www.fda.gov/ Safety/ Recalls/ucm461939.htm
Medline Industries Recall on Acetaminophen
Medline Industries, Inc. announced a voluntary nationwide recall on lot #45810 of Acetaminophen tablets, 500 mg, uncoated compressed tablets. This recall was due to an error in labeling. The Acetaminophen tablets of 500 mg are incorrectly labeled as being 325 mg. The recalled lot was distributed nationwide from June 12, 2015–September 18, 2015. There have been no adverse events reported related to this recall. http://www.fda.gov/ Safety/ Recalls/ucm467049.htm
Pharmedium Recall on Norepinephrine Bitartrate
Pharmedium Services, LLC, in Lake Forest, IL, has recalled 29 lots of 4 mg norepinephrine bitartrate (16 mcg/mL) added to 0.9% sodium chloride in 250 mL Viaflex Bag and three lots of 8 mg norepinephrine bitartrate (32 mcg/mL) added to 0.9% sodium chloride in 250 mL Viaflex Bag distributed to hospitals. This recall was due to discoloration in the admixture, which could be indicative of degradation leading to decreased potency. There have been no adverse events reported related to this recall. For a full list of affected products, visit http://www.fda.gov/ Safety/ Recalls/ucm479677.htm.
Sanofi Recall on Auvi-Q®
Sanofi US issued a voluntary recall on all Auvi-Q® (epinephrine injection, USP), including all Auvi-Q® currently on the market, due to inaccurate dosage delivery. The lot numbers involved are 2081278 through 3037230 with expiration dates of October 2015 through December 2016. The recall applies to both the 0.15 mg and 0.3 mg strengths for hospitals, retailers, and consumers. As of October 26, 2015, Sanofi has received 26 reports of suspected device malfunctions in the United States and Canada, but these device malfunction reports have not yet been confirmed. No fatal outcomes have been reported in these cases. http://www.fda.gov/ Safety/ Recalls/ucm469980.htm
US Compounding, Inc. Recall in Arkansas
US Compounding, Inc. (USC) of Conway, AR, voluntarily recalled all lots of sterile products compounded and packaged by USC. This recall was due to the lack of sterility assurance. These products were distributed nationwide to patients, providers, hospitals, and clinics be- tween March 14, 2015, and September 9, 2015. The recall does not apply to any nonsterile compounded medications made by USC. http://www.fda.gov/ Safety/ Recalls/ucm464071.htm
SAFETY ALERTS
Afatinib (Gilotrif®)
The updated adverse reactions section of the drug labeling includes the incidence of nausea and vomiting seen in clinical trials experience. Reports of pancreatitis have been added to the postmarketing experience. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm480999.htm
Azacitadine (Vidaza®)
The postmarketing experience has been updated to include reported cases of necrotizing fasciitis. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm289980.htm
Bendamustine (Treanda®)
The warnings and precautions section of the package labeling for bendamustine has been revised to include the risk for reactivation of infections including hepatitis, cytomegalovirus, mycobacterium tuberculosis, and herpes zoster. Clinical and laboratory monitoring, prophylaxis, and treatment should be provided for infection and infection reactivation prior to administration of the drug. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm204021.htm
Bevacizumab (Avastin®)
Nonmandibular osteonecrosis and posterior reversible encephalopathy syndrome (PRES) are now included in the postmarketing experience section of the prescribing information. Nonmandibular osteonecrosis can be found in the pediatric use section, as well. The risk of renal injury has been added to the adverse reactions section of the drug labeling. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm275758.htm
Bortezomib (Velcade®)
The updated prescribing information for bortezomib includes use in the pediatric population. This update was based on a pediatric study, Study AALL071P1, which was a phase 2 pilot trial using bortezomib in combination with intensive reinduction therapy for children with re- lapsed acute lymphoblastic leukemia and lymphoblastic lymphoma. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ SafetyRelatedDrugLabelingChanges/ucm123444.htm
Clofarabine (Clolar®)
Hepatobiliary disorders have been added to the postmarketing experience under the adverse reactions section of the package labeling. The warnings and precautions now include the risk of hepatitis and hepatic failure. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm338244.htm
Crizotinib (Xalkori®)
The warnings and precautions section of the prescribing information for crizotinib has been updated to include a subsection for severe visual loss, inclusion of safety information across multiple clinical studies, and modifications to the embryofetal toxicity subsection. The use in specific populations has also been updated to comply with the Pregnancy and Lactation Labeling Rule (PLLR). http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm295722.htm
Deferasirox (Jadenu®)
Renal tubular necrosis and gastrointestinal perforation has been added to the postmarketing experience. In the warnings and precautions section of the prescribing information, the risk of gastrointestinal (GI) hemorrhage, and severe skin reactions are now listed. Reports have been made including deaths from GI hemorrhage, especially in elderly patients who had advanced hematologic malignancies or low plate- lets. Patients on deferasirox therapy should be monitored for signs and symptoms of GI ulceration and hemorrhage. The risk of GI hemorrhage may be increased with concurrent administration of drugs that have hemorrhagic potential, such as nonsteroidal anti-inflammatory drugs, corticosteroids, oral bisphosphonates, or anticoagulants. Rashes may occur while on deferasirox therapy. For mild to moderate rashes, deferasirox may be continued since the rash will likely resolve on its own. Severe skin reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported. If any of these serious skin reactions are suspected, deferasirox should be discontinued immediately. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm472530.htm
Docetaxel (Taxotere®)
Reported cases of permanent alopecia have been added in the post- marketing experience for docetaxel. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm212079. htm
Everolimus (Zortress®)
The risk of interstitial lung disease and noninfectious pneumonitis has been added to the warnings and precautions section of the package labeling for everolimus. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm303659.htm
Granisetron (Sancuso®)
The warnings section of the package labeling for granisetron patch has been edited to address external heat sources to the patch. A heat pad should not be applied over or near the granisetron patch as heat exposure increases the drug plasma concentrations. Application site reactions (i.e., pain, erythema, rash, irritation, urticarial) and cardiac dis- orders (i.e., bradycardia, chest pain, palpitations) have been added to the postmarketing experience under the adverse reactions section of the package labeling. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm466191.htm
Ipilimumab (Yervoy®)
Major edits were made to the following sections under the warnings and precautions part of the labeling information: immune-mediated enterocolitis, immune-mediated hepatitis, immune-mediated dermatitis, immune-mediated neuropathies, and immune-mediated endo- crinopathies. The embryo-fetal toxicity section has been added to address the risk of fetal harm ipilimumab could cause when given to pregnant women. Education should be provided to females of reproductive potential to use effective contraception during treatment with an ipilimumab-containing regimen and for 3 months after the last dose of ipilimumab. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm328023.htm
Methotrexate Injection
The boxed warning for methotrexate now has information to use the preservative-free formulation for intrathecal and high-dose therapy. There is a warning to avoid using the preserved formulation for intra- thecal or high-dose therapy because it contains benzyl alcohol. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ ucm476298.htm
Nivolumab (Opidvo®)
The prescribing information for nivolumab has been revised to update information on several immune-mediated adverse reactions. Across the clinical trial experience, 0.4% of patients with solid tumors receiving nivolumab as a single agent experienced fatal immune-mediated pneumonitis. In patients with melanoma receiving nivolumab in combination with ipilimumab, fatal immune-mediated pneumonitis occurred in 0.5% of the patients across the clinical trial experience. Immune-mediated colitis can occur when administering nivolumab in combination with ipilimumab and therapy should be held formoderate colitis. For any severe or life-threatening colitis, nivolumab should be permanently discontinued. Immune-mediated endocrinop- athies, including hypophysitis, adrenal insufficiency, and hypothyroid- ism, have occurred with nivolumab treatment. Patients should be monitored for immune-mediated rash with nivolumab therapy. Corti- costeroids should be administered for severe (Grade 3) or life-threat- ening (Grade 4) rash, or nivolumab should be held or discontinued depending on the severity of the rash. Immune-mediated encephalitis is another adverse reaction that can occur with nivolumab treatment. Patients with new-onset moderate to severe neurological signs or symptoms should undergo therapy. Nivolumab should be permanent- ly discontinued for immune-mediated encephalitis. From the clinical studies, less than 1% of the patients receiving nivolumab had encepha- litis. Other clinically significant, immune-mediated adverse reactions seen in less than 1% of patients receiving nivolumab as a single agent or in combination with ipilimumab in the clinical trials were uveitis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatic, autoimmune neuropathy, Guillain-Barre syndrome, and hypopituitarism. Infusion-related reactions (e.g., fevers, chills, rigors, flushing, rash, hy- potension), including severe and life-threatening reactions, have been reported in patients on therapy with nivolumab. Discontinue the drug for any severe or life-threatening infusion-related reactions. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ ucm472431.htm
Obinutuzumab (Gazyva®)
The warnings and precautions section of the package labeling for obinutuzumab has been revised to include the fatal cases from tumor lysis syndrome (TLS). Patients with high tumor burden, high circulat- ing lymphocyte count (>25 x 109/ L), or renal impairment are at greater risk for TLS and appropriate TLS prophylaxis should be implemented prior to administering obinutuzumab. The use in specific populations in the prescribing information has also been updated to comply with PLLR. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm404996.htm
Oxaliplatin (Eloxatin®)
The updated warnings and precautions section of the prescribing in- formation for oxaliplatin addresses severe neutropenia, cardiovascular toxicity, and rhabdomyolysis. There have been reports of sepsis, neu- tropenic sepsis, and septic shock in patients treated with oxaliplatin, including fatal outcomes. Recommendations to delay oxaliplatin until neutrophils are equal to 1.5 x 109/ L, withhold treatment for sepsis and septic shock, and dose reduce after recovery from Grade 4 neutropenia or febrile neutropenia have been added. Due to reports of QT prolongation and ventricular arrhythmias, even fatal Torsade de Pointes after oxaliplatin administration, there are recommendations to monitor the electrocardiogram in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong QT interval, and electrolyte abnormalities. Oxaliplatin should not be used in patients with congenital long QT syndrome. Reports have been made of rhab- domyolysis, including fatal cases in patients treated with oxaliplatin. Therapy should be discontinued if any signs or symptoms of rhabdo- myolysis occur. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm287508.htm
Pazopanib (Votrient®)
Interstitial lung disease (ILD)/pneumonitis is now included in the warnings and precautions section and listed in the adverse reactions section of the package labeling. ILD/pneumonitis occurred in 0.1% of patients treated with pazopanib in clinic trials. Patients should be counseled on reporting pulmonary signs or symptoms indicative of ILD or pneumonitis. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm303649.htm
Pegfilgrastim Injection (Neulasta®)
Updates have been made to the warnings and precautions section of the package insert for pegfilgrastim. The update includes the risk for glomerulonephritis, leukocytosis, and capillary leak syndrome. Glomer- ulonephritis has been diagnosed based on azotemia, hematuria, pro- teinuria, and renal biopsy. These events usually are resolved after dose reduction or discontinuation of pegfilgrastim. If glomerulonephritis is suspected due to pegfilgrastim, this medication should be discontin- ued. White blood cell counts of 100 x 109/ L or greater have been ob- served in patients receiving pegfilgrastim. Monitoring of complete blood counts during therapy is recommended. Reports of capillary leak syndrome have been made in patients getting pegfilgrastim in- jections. Patients who develop capillary leak syndrome, which can be a life-threatening condition, should receive standard symptomatic treat- ment, which may include intensive care. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm262864.htm
Ponatinib (Iclusig®)
The updated warning and precautions section of the prescribing in- formation includes vascular occlusion, arterial occlusion and throm- bosis, and hypertension. Renal artery stenosis leading to worsening or treatment-resistant hypertension has occurred in patients treated with ponatinib. Treatment should be interrupted if there is significant worsening of hypertension. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm380782.htm
Temozolomide (Temodar®)
Infections including primary and reactivated cytomegalovirus and re- activation of hepatitis B infections have been added to the postmarketing experience section of the drug labeling. http://www.fda.gov/ Safety/MedWatch/ SafetyInformation/ucm262708.htm