HOPA Publications Committee
Bonnie Labdi, PharmD RPh, Chair
Ashley Glode, PharmD BCOP, Vice Chair
Geroge Carro, RPh MS BCOP, Board Liaison
Megan Bodge, PharmD
Megan Brafford, PharmD BCOP
Christine Gegeckas, Rph BCOP
Lindsay Hladnik, PharmD BCOP
Lisa Lohr, PharmD BSPharm BCOP BCPS
Katie Long, PharmD
David Reeves, PharmD BCOP
Lisa Savage, PharmD BCOP BCPS
Alexandra Shillingburg, PharmD
Candice Wenzell, PharmD BCOP
Michael Voznial, PharmD BCOP
Happy new year! This time of year is hectic and exciting for everyone as we return to our normal routines after a busy holiday season. It also is a time when numerous “Top Events of the Year” lists are published and discussed on the radio, in press, and on social media. I figured why should HOPA be any different?
The following is my Top 10 List of HOPA Highlights for 2014 (in no particular order as they all are important):
- The HOPA 10th Annual Conference in New Orleans breaks attendance records.
- The 2nd Annual Fall Practice Management Course saw growth in the number of participants.
- HOPA held the first mini-HOPA Hill Day in September.
- HOPA’s Industry Relations Council (IRC) grew in participation and sponsorship levels.
- The Health Policy Committee introduced two new issue briefs: Pain Management and Counterfeit Drug Prevention.
- HOPA supported the passage of HR 4190!
- My mentor and friend, Moe Schwartz, won the HOPA Award of Excellence.
- HOPA published the Scope of Hematology/Oncology Pharmacy Practice document.
- HOPA published our first best practice standard, HOPA Investigational Drug Service Best Practice Standards.
- Countless number of outstanding members volunteered their time and efforts for the advancement of our profession!
Although there are numerous other highlights from the past year that were not included above, this reflection is helpful to recognize all that HOPA has accomplished in 2014. It also is a good time to look ahead and see what the organization needs to achieve this year.
HOPA’s strategic plan was last reviewed and updated in November 2012. Typically, strategic plans are updated or revised approximately every 3–5 years. In consideration of this and based on the progress HOPA has made toward fulfilling its strategic objectives, HOPA’s Board of Directors has decided to undergo strategic planning in 2015. The board of directors and key stakeholders participated in an in-per- son strategic planning session in January 2015.
HOPA has contracted Marsha Rhea, president, Signature i, LLC, to serve as HOPA’s strategic planning consultant. Signature i utilizes a methodology called forward design, which is a “systematic and creative process for exploring an organization’s current and future context, analyzing strategic issues and opportunities, inviting aspirations for design, and then using this learning to inspire an organization’s future.” Before creating Signature i, Rhea was a senior futurist with the Institute for Alternative Futures, where she honed an aptitude for environmental scanning, scenario planning, visioning, and strategy development for associations, governments, and businesses. In her career as an association executive, Rhea has held executive positions in the American Society of Association Executives (ASAE), as director of education and then executive vice president of the foundation; the National Recycling Coalition as executive director; and the American Subcontractors Association as vice president of communications and education. Signature i specializes in not for profits and associations. The board’s intention is to share the new HOPA strategic plan at the annual conference in March.
HOPA’s Collaborative Efforts
Throughout 2014, HOPA engaged and worked with numerous organizations to advance our goals and the care of oncology patients. Our collaborative efforts have spanned from working with pharmacy organizations such as the American Society of Health-System Pharmacists (ASHP) and the American College of Clinical Pharmacy to working with nonpharmacy organizations such as the American Society of Clinical Oncology and Oncology Nursing Society. In addition, our efforts have extended to organizations such as Medscape and the Institute for Safe Medication Practices. HOPA recognizes the importance of establishing partnerships with outside organizations so that we may improve cancer patient care and provide professional development opportunities for our members.
HOPA has taken steps to become a member of the Joint Com- mission of Pharmacy Practitioners (JCPP). JCPP is comprised of 11 pharmacy organizations, and their vision statement is “Pharmacists will be the healthcare professionals responsible for providing patient care that ensures optimal medication therapy outcomes.” The HOPA Board of Directors determined this organization would be a great conduit to solidify existing relationships with other pharmacy organizations and help us to form new relationships with other pharmacy organizations. HOPA has been accepted into “observation” status and is expected to attend four meetings before being reviewed for full membership. The observation status is a great opportunity for HOPA to better understand JCPP and evaluate whether it is in HOPA’s best interest to formally join, if invited. I attended their last meeting in November in Alexandria, VA. My attendance gave me a much better understanding of what other pharmacy organizations are working on and what is impacting them. It also gave me a better perspective on what opportunities there may be to collaborate with JCPP and the individual member organizations.
In other exciting news, HOPA learned in late December that our organization has been accepted into the Patient Access to Pharma- cists’ Care Coalition. The mission of the coalition “is to develop and help enact a federal policy proposal that would enable patient access to, and payment for, Medicare Part B services by state-licensed pharmacists in medically underserved communities.” Concisely, this is the coalition that is pushing for passage of HR 4190 legislation. Some notable coalition members include the American Public Health Association, ASHP, American Association of Colleges of Pharmacy, American Society of Consultant Pharmacists, and several community pharmacy companies, such as Albertsons, CVS Caremark, and Walgreens, to name a few. HOPA will partner with the coalition to see how we can help drive the passage of this legislation as we enter a new congressional year. During HOPA’s Hill Day in September, pharmacists’ provider status was one of the main topics we discussed with the congressional offices. I hope the momentum continues!
HOPA’s 11th Annual Conference
Believe it or not, HOPA’s 11th Annual Conference is a short time away! Conference registration is open. Our Program Committee has planned another outstanding conference that includes three different preconference offerings. We are excited to hold the conference in Austin, TX, and are looking forward to having a great meeting. Please check Conference Web Central at www.hoparx.org for more information.
Best wishes to everyone for a happy and healthy 2015!
USP <800>: Hazardous Drugs—Handling in Healthcare Settings
Allison R. Butts, PharmD
PGY2 Hematology/Oncology Pharmacy Resident
University of Kentucky HealthCare
Katie E. Long, PharmD
Hematology/Oncology Clinical Pharmacists
Markey Cancer Center
University of Kentucky HealthCare
What Is USP?
The United States Pharmacopeial Convention (USP) is a “scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured, distributed, and consumed worldwide.” USP publishes general chapters in the National Formulary (NF); those numbered under 1,000 contain standards that can be enforced by the U.S. Food and Drug Administration (FDA). These standards are used in more than 140 countries across the globe.1 USP issues a bimonthly online journal, the Pharmacopeial Forum (PF), in which proposed revisions to USP- NF are published for public review and comment. PF is a free, online-only resource available to the public after a one-time registration to the USP website.1
What Is USP <800>?
USP <800> is the newest chapter of the USP-NF and is designed to “guide the handling of hazardous drugs in healthcare settings.”2 USP <800> builds on previously published chapters USP <795> and USP <797>, which address sterile and nonsterile compounding practices. Although seemingly comprehensive in nature, these two chapters fail to address the growing concern of exposure to hazardous drugs. USP <800> states that “there is no acceptable level of personal exposure to hazardous drugs.”2 As such, this chapter provides guidelines for the minimization of exposure across the continuum of healthcare settings.
The chapter addresses all aspects of handling hazardous drugs, including receipt, storage, transportation, preparation, dispensing, and administration. The list of hazardous drugs can be found in the National Institute for Occupational Safety and Health (NIOSH) Alert.3
What Is Next for USP <800>?
Due to the significance of the comments received in response to the initial publication of USP <800> in the May/June 2014 issue of PF, USP announced on October 13, 2014, that the chapter would undergo revision prior to formal introduction into the NF. The updated General Chapter <800> proposal will reflect new and revised guidance documents, respond to stake- holder input, and improve clarity of General Chapter <800>. The revised proposal is tentatively projected to be published in Pharmacopeial Forum, 41(2) [Mar.–Apr. 2015].4
1. U.S. Pharmacopeial Convention. About USP. Available at: www.usp.org/about-usp. Accessed October 27, 2014.
2. U.S. Pharmacopeial Convention. General chapter <800> hazardous drugs—handling in healthcare settings. Pharmacopeial Forum. 2014;40(3):1-44.
3. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2014. Centers for Disease Control and Prevention Website. Available at: www.cdc.gov/niosh/docs/2014-138/. Accessed October 27, 2014.
4. U.S. Pharmacopeial Convention. General chapter <800> hazardous drugs—handling in healthcare settings. Available at: www.usp.org/usp-nf/notices/compounding-notice. Accessed October 27, 2014.
Highlights from Lymphoma and Myeloma 2014: An International Congress on Hematologic Malignancies
Christan M. Thomas, PharmD
Clinical Assistant Professor
St. John’s University College of Pharmacy
Clinical Pharmacist, Lymphoma/Myeloma
NewYork-Presbyterian, Weill Cornell Medical Center
New York, NY
New targets and debates on appropriate therapies came to the forefront during Lymphoma and Myeloma 2014: An International Congress on Hematologic Malignancies, which took place in New York, NY, October 23–25, 2014.
Since its inception in 2000, the conference has become one of the largest international meetings on hematologic disorders. During the course of 3 days, an interdisciplinary group of clinicians discussed basic science, new therapies, and existing data on the treatment of multiple myeloma, chronic lymphocytic leukemia (CLL), and lymphomas. The following are summaries of selected congress presentations.
Novel Agents: What Will Be Available in the Next Few Years?
Kenneth Anderson, MD, concluded that with the advent of new therapies and specific targeting of the tumor microenvironment, multiple myeloma would become a chronic illness with sustained complete responses in a significant number of patients. Anderson highlighted several new agents under investigation, including monoclonal antibodies, antibody-drug conjugates, and vaccines against multiple myeloma–specific peptides.
Elotuzumab, a monoclonal antibody directed against signaling lymphocyte activation molecule (SLAMF7 or CS1), has been well tolerated in patients during phase 1 and 2 trials. Infusion reactions have been mitigated using premedications. Early trials show overall response rates ranging from approximately 27% as a monotherapy to 84% when given in combination with lenalidomide and dexamethasone. Ongoing phase 3 trials will examine this combination for both initial therapy and in relapsed or refractory disease.
Another monoclonal antibody in development, daratumumab, targets CD38. Early, small studies show marked decreases in M-protein and positive results in overall response rates in the majority of patients. Phase 3 studies will examine daratumumab both as a monotherapy and in combination with lenalidomide/dexamethasone. Another anti-CD38 monoclonal antibody—SAR650984—also is in development.
Induction Therapies in Transplant-Eligible Patients with Multiple Myeloma
Tomer Mark, MD, discussed how to approach treatment in transplant-eligible patients with multiple myeloma in the era of novel therapies. Based on available data, Mark said combinations of novel agents lead to deeper responses pretransplant, which tend to translate into better responses posttransplant.
As a result of trials with combinations such as CyBorD (cyclophos- phamide, bortezomib, dexamethasone), BiRD (clarithromycin, lenalidomide), and VRD (bortezomib, lenalidomide, dexamethasone), Mark suggested that any three-drug combination may be an appropriate choice for initial therapy. According to Mark, the similar response over time with the various first-line treatment strategies indicate that many good induction therapies exist and that the choice should be tailored to the patient.
In addition, Mark noted that carfilzomib may enhance initial response rates and decrease minimal residual disease (MRD). Mark cited two studies in which the majority of patients were MRD negative with the addition of carfilzomib. Progression-free survival in these patients was between 89% and 91% at 3 years and 18 months, respectively. At this point, however, Mark cautioned that little is known regarding how stem cell transplant may negate initial differences in response, consequences of long-term use, or implications for subsequent therapies.
Ibrutinib: Analysis of Its Pivotal Data
Richard Furman, MD, one of the primary authors on many initial ibrutinib trials and the CLL cochair for the congress, reviewed current data on the Bruton’s tyrosine kinase (BTK) inhibitor and offered insights from his vast experience with the drug.
Furman noted that as more and more data are published, both response rate results and adverse effect profiles will continue to evolve. One take-home point from this session was that achieving best response was time dependent, and the proportion of patients with either complete or partial responses tended to increase during follow-up. The proportion of patients with a partial response with lymphocytosis also decreased as data matured.
In terms of side effects, atrial fibrillation became one notable effect during the RESONATE trial. In this trial, overall rates of atrial fibrillation were 5% with 3% reported at grade 3 or above. Furman said that additional data are needed to fully elucidate true clinical relevance— especially for the grade 3 or above reactions.
Also of concern with the administration of ibrutinib is the possible increased bleed risk. In the RESONATE trial, 44% of patients in the ibrutinib arm experienced bleeding. Grade 3 or 4 bleeds, however, occurred in only 1% of patients who experienced bleeding. The direct effect of BTK on platelets, as well as other off-target effects currently being explored, could modulate this bleed risk, Furman said.
Another particularly troublesome side effect of ibrutinib is the relatively high rate of diarrhea experienced by patients. Furman noted that this effect is reversible and generally only symptomatic when food is present in the stomach. He suggested patients take ibrutinib at night and avoid eating after ingesting the drug. A dose reduction also may be necessary, if diarrhea continues.
Idelalisib: Analysis of Its Pivotal Data
Jeff Sharman, MD, summarized available data on idelalisib, which recently received U.S. Food and Drug Administration approval, and also offered suggestions on when to use the medication in therapy.
In the United States, idelalisib is indicated for relapsed CLL in combination with rituximab in patients for whom rituximab alone would be appropriate therapy due to other comorbidities. In addition, idelalisib may be used as monotherapy in relapsed follicular lymphoma or re- lapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies. European indications also include idelalisib as first-line therapy for CLL patients with a 17p deletion or TP53 mutation and who are not suited for chemoimmunotherapy.
The drug also carries four black box warnings: fatal and/or serious hepatotoxicity, fatal and/or serious and severe diarrhea, fatal and serious pneumonitis, and fatal and serious intestinal perforation. Deaths from each of these adverse effects occurred in studies at a rate of less than 1%.
Based on indications, available data, and side effect profile, Sharman proposed several situations in which idelalisib might be a good therapeutic choice versus ibrutinib. He suggested idelalisib for CLL patients receiving rituximab and those on blood thinners with a history of atrial fibrillation, with pre-existing renal insufficiency, and possibly a 17p deletion. In contrast, Sharman recommended using ibrutinib in patients with abnormal liver function, history of bowel difficulties, lung issues, or when monotherapy is preferred.
Although not a comprehensive review, presentations from the congress are available for free download. For additional information and to download slides, visit www.imedex.com/ lymphoma-myeloma-conference. Slides may be found by clicking on the archives link from the home page.
Next year’s congress is scheduled for October 22–24, 2015, at the Waldorf Astoria Hotel in New York, NY.
A Tale of Two Residents: Exploring a PGY2 Residency
Stephanie Folan,PharmD PGY1 Resident
UMass Memorial Medical Center
Nicole Gunderson, PharmD PGY1 Resident
UMass Memorial Medical Center
Oncology pharmacy is a highly specialized field, necessitating the pursuit of PGY2 oncology pharmacy residency positions for new practitioners. The American Society of Health-System Pharmacists’ website currently lists more than 80 sites offering a PGY2 in oncology pharmacy, up 76% from 2010. Sites offering PGY2s include academic centers, community hospitals, outpatient clinics, Veterans Affairs medical centers, and others. When pursuing an oncology pharmacy residency program, residents have to consider factors such as program size, rotation structure, specialties of the practice site, and residency requirements, and make sure they coincide with their career goals.
The increase in specialized PGY2 pharmacy residency opportunities is not unique to the oncology field. In 2014, 795 PGY2 positions were available for pharmacists pursuing residency training in one of 26 specialties. With so many options, why are increasing numbers of PGY1 residents focusing on PGY2 residencies in oncology?
My exposure to oncology began in elementary school. My mom was diagnosed with stage III breast cancer at the age of 39, and I remember her being worn out and taking plenty of naps. However, I was not truly aware of the severity of her illness at the time. Looking back to- day as a healthcare professional, my perception surrounding her treatment has changed. My mom underwent a lumpectomy, mastectomy, and reconstructive surgery. She endured weeks of radiation and sever- al cycles of chemotherapy. Her healthcare team, consisting of oncologists, surgeons, nurses, and pharmacists, worked together to provide her with a treatment plan that allowed her to function in her everyday life and that has kept her cancer free for 14 years. This treatment plan not only accounted for the care my mom received, but it also included care for our family. She never seemed as sick as she truly was. When I reflect on the care my mom received, I realize the practitioners who specialize in oncology care for the whole patient as well as their family and friends.
My personal experience sparked an interest in a career in oncology that has grown with my professional experiences. As a student, I learned about oncology medications and their place in therapy during pharmacotherapeutics and pharmacology. I was surprised that much of the curriculum was focused on supportive care, and I realized pharmacists can play a large part in improving a patient’s quality of life as they receive chemotherapy. I completed an intern rotation in bone marrow transplant with a team guiding patients through high-dose chemotherapy and life-saving transplants. I was fascinated with the complexity of treatment regimens. There are many opportunities for
pharmacists to make interventions related to chemotherapy, antibiotics, and supportive care. While following the palliative care team as a resident, I interviewed many patients and their families regarding pain and symptom management. I enjoyed developing relationships with patients while helping improve their quality of life as they persevered through difficult situations. Even though oncology pharmacy is considered a specialty, I have learned that there are many different opportunities for pharmacists in the oncology field, and that is one reason why I am excited to pursue a PGY2 oncology pharmacy residency.
These experiences only scratch the surface of potential opportunities for pharmacists in oncology pharmacy. There are endless chances for pharmacists who specialize in oncology to affect the lives of patients. PGY2 programs offer rotations in inpatient oncology, outpatient oncology, infectious disease in the immunocompromised population, pediatric oncology, bone marrow transplantation, and palliative care. Because of the specialized nature of an oncology pharmacist, a PGY2 residency offers an opportunity for young pharmacists to explore the specialty and better understand the expanding roles pharmacists can play in oncology. I look forward to building on my experiences in oncology, as well as the foundation built during PGY1 pharmacy practice residency, through a PGY2 oncology pharmacy residency.
I became interested in pursuing a PGY2 in oncology pharmacy for several reasons. I first became involved in oncology while working as an oncology pharmacy technician at a Veterans Affairs medical center. My science-minded side enjoyed learning about complex chemo- therapy regimens and compounding, while my outgoing side enjoyed meeting with patients and their families. As a technician, each morning I would evaluate the infusion center schedule, review the regimens and organize my supplies, and then prepare the chemotherapy as patients arrived. I wanted to know everything and was constantly asking the pharmacists “Why?” Why this regimen? Why were there different doses? Why do we have premedications? When I delivered chemotherapy, if time permitted, I would stop and chat with patients. I loved being able to sit with patients and hear about their adventures. Throughout my experiences as an intern, and now as a pharmacy practice resident,
I continue to see oncology-related issues from different perspectives, not just from the perspective of an oncology pharmacist.
I find there are dynamic opportunities within the oncology pharmacy field. Oncology pharmacists have the possibility to work in the outpatient setting as a clinician, the inpatient setting as part of the healthcare team, or in a combination of the two. In either setting, the pharmacist has an opportunity to develop a relationship with patients and encourage them to take an active role in their health care. Some patients may feel that it is them versus the insurance company or the healthcare system as a whole. Numerous new oral chemotherapy agents have emerged on the market, creating a daunting experience for the patient when high costs and difficult dosing regimens are involved. Pharmacists can advocate for the patient, motivate patients when they are discouraged, provide alternatives and education, and act as a conduit between the doctor and insurance provider.
I’ve always loved a difficult puzzle, and I view patients with complex medical issues as a great challenge. On paper, two patients may seem very similar in their diagnosis, past medical history, and medication profile. However, their response to treatment and medication tolerance can vary greatly. Each patient’s case is like a puzzle with pieces made from their medications, response to treatment, comorbidities, insurance coverage, and personal beliefs. A clinical oncology pharmacist must be able to collaborate with the patient’s healthcare team to fit the pieces together to help provide optimal patient care.
As new agents enter the market at incredible speeds, the field of oncology pharmacy is continuously evolving. Treatments that were once considered the gold standard are being used in combination with new therapies, or in some cases, are being replaced altogether. I am excited to stay up to date on new medications, guidelines, and clinical trials published at an ever-increasing pace. I will be able to evaluate the data to determine whether study results support a change in clinical practice that would apply to my clinical setting and can take what I learn to help educate the team and patients. I continue to ask “why” to my preceptors and feel a PGY2 specializing in oncology will help me develop the skills needed to find the answers.
Each candidate has his or her own reasons for pursuing a PGY2 pharmacy residency. For me, I enjoy that oncology pharmacy is a great combination of oncology, critical care, infectious disease, internal medicine, cardiology, and more. Opportunities within the field will allow me to be an advocate for patients, a problem solver, a collaborative member of the healthcare team, and a life-long learner.
The Challenges and Rewards of Working on Behalf of Our Patients
Katie E. Long, PharmD
Hematology/Oncology Clinical Pharmacist
Markey Cancer Center
University of Kentucky HealthCare
I had been told that during the course of my career I would encounter patients who would impact me in such a way that I would never forget them and they would even transform the way I work. I was fortunate enough to meet one such individual during the first year of my first job as a clinical pharmacist in an outpatient oncology clinic. This is the story of Ms. X and how meeting her truly changed my perspective on the role of a clinical pharmacist, my passion for the care of oncology patients, and my life.
Ms. X was a delightful woman in her 60s who had a textbook case of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer: she was a healthy, lifelong nonsmoker with aggressive disease and had an impressive, but short-lived, response to initial treatment. At the time of her disease progression her physician asked me to investigate ways in which we could gain access to ceritinib, an investigational second generation ALK-inhibitor that was in phase 1 trials at the time. In my pursuit to obtain this medication for Ms. X, I contacted the drug company to apply for an individual compassionate use trial and enroll Ms. X in an expanded treatment protocol. In the midst of this process, the U.S. Food and Drug Administration approved ceritinib. The next 3 weeks included a flurry of activity as I worked tirelessly to gain access to the drug for Ms. X. I vividly remember the day I received a call from one of the many specialty pharmacies I had reached out to, informing me that they had access to the drug and would be able to ship a prescription to Ms. X the next day! I could barely contain my excitement as I called Ms. X to give her the great news. The joy I felt that day had nothing to do with me or the time I had spent working to gain access to this drug for Ms. X. The emotions I experienced—excitement, joy, and relief—were focused solely on Ms. X.
Prior to this experience, I did not fully appreciate all of the challenges surrounding the prescribing of oral chemotherapy or realize how vital the role of a pharmacist could be in the process. Providing appropriate clinical review and patient education were obvious needs, but navigating a complex network of insurance providers and specialty pharmacies were challenges I had not anticipated. As the clinical pharmacist working in the outpatient oncology clinic, I was in an ideal position to coordinate the efforts of many members of the healthcare team in the provision of oral chemotherapies. The physician looked to me to assist in procurement of this new oral chemotherapy agent. The patient and her family counted on me to answer questions and provide education about her new medication. The insurance company and specialty pharmacies valued my ability to act as a liaison for both the patient and physician.
In recent months, I have transitioned to a new position within my institution that allows me to focus my efforts on the care of patients receiving oral chemotherapy. As the oral chemotherapy clinical pharmacist, I serve as a liaison between the patient, physician, insurance company, and specialty pharmacy. This unique position provides me with the ability to counsel patients, coordinate prior authorizations and refills, and collaborate with physicians to ensure appropriate monitoring and dose adjustments of oral chemotherapy. I value the relationships I have developed with my patients and their families, and I look forward to going to work every day because I know I will significantly affect the care of my patients. My experience with Ms. X allowed me to see the need for a pharmacist devoted to oral chemotherapy management, and I count myself incredibly lucky to have been afforded the opportunity to turn my vision into a reality.
Recalls and Safety Alerts from the FDA
Lindsay Hladnik, PharmD BCOP
Clinicial Pharmacist, Hematologic Malignancies/SCT Barnes-Jewish Hospital
St. Louis, MO
Darbepoetin Alfa (Aranesp)
Recall in Non-U.S. Countries Amgen has issued a voluntary recall of darbepoetin alfa 500-mcg prefilled syringes distributed outside of the United States. This is because of the presence of visible particles that were observed in certain lots during a routine quality exam. There have been no adverse events re- ported. Darbepoetin alfa distributed in the United States has not been impacted by the recall. http://www.fda.gov/ Safety/ Recalls/ucm410011.htm
The warnings and precautions section for everolimus has been updated to include the risk of Pneumocystis jiroveci pneumonia (PJP), which may be associated with concomitant corticosteroids or other immunosuppressive agents. Consider the administration of PJP prophylaxis when these agents are used concomitantly. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm258494.htm
The package labeling for docetaxel has been updated to include information on the alcohol content of some docetaxel formulations. There have been cases of alcohol intoxication reported. Consideration on the ability to drive, operate machinery, or perform other activities that require skill and alertness should be taken into account after receiving an infusion. http://www.fda.gov/ Safety/MedWatch/SafetyInformation/ucm396551.htm
Updates have been made to the warnings and precautions—risk of infection section of the package insert for ruxolitinib. Patients should be evaluated for risk factors of tuberculosis, and those who are at high risk for latent infection should be tested prior to initiating ruxolitinib. The prescribing information within the warnings and precautions section also has been revised to include the risk of myelofibrosis symptom exacerbation following the interruption or discontinuation of ruxolitinib. Myelofibrosis symptoms may return to pretreatment levels over a time frame of approximately 1 week following interruption or discontinuation and have included respiratory distress, multiorgan failure, disseminated intravascular coagulation, hypotension, or fever. Patients may require the drug to be restarted or the dose to be increased in these instances. When possible, consideration should be made to taper the dose gradually. Patients should be educated to not interrupt or discontinue ruxolitinb therapy on their own without consulting a healthcare practitioner. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm377314.htm
Hemorrhagic events have been reported in clinical trials of ado-trastuzumab. Some of the events were fatal, and some included respiratory, central nervous system, and gastrointestinal hemorrhage. Cases occurred in patients with or without known risk factors for bleeding. Additional monitoring should be considered if concomitant anticoagulation or antiplatelet therapy is necessary.http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm409252.htm
Triptorelin (Trelstar) and Leuprolide Acetate (Lupron)
Updated warnings and precautions include the potential for androgen deprivation therapy to prolong the QT/QTc interval. Risks versus benefits should be considered in patients with congestive heart failure, congenital long QT syndrome, or frequent electrolyte abnormalities, or who are taking concomitant meds known to prolong the QT inter- val. Correct electrolyte abnormalities and consider periodic monitoring of EKGs and electrolytes. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm347049.htm
Cardiac failure was noted in 2% of patients receiving axitinib for renal cell carcinoma in a clinical trial compared with 1% in patients receiving sorafenib. Some of the cases were reported to be fatal. Patients should be monitored for signs and symptoms of cardiac failure during therapy with axitinib. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm372723.htm
Peginterferon Alfa-2b (Sylatron)
Information on dosing peginterferon alfa-2B in patients with moderate or severe renal impairment or end-stage renal disease (ESRD) has been included in the dosing and administration section of the package insert. A 25% dose reduction is recommended in patients with moderate renal impairment (CrCl 30–50 mL/min/1.73m2), and a 50% dose reduction is recommended for patients with severe renal impairment (CrCl < 30 mL/min/1.73m2) or those with ESRD on dialysis. http://www.fda.gov/Safety/MedWatch/ SafetyInformation/ucm314604.htm
The warnings and precautions have been updated to include data from cervical cancer studies. The incidence of gastrointestinal (GI) perforation in patients with persistent, recurrent, or metastatic cervical cancer occurred in 3.2% of patients treated with bevacizumab. All of the patients who developed GI perforation had previously received pelvic radiation. The incidence of GI-vaginal fistulae formation was 8.2% in cervical cancer patients who received bevacizumab, all of whom had a history of prior pelvic radiation, compared with 0.9% in control patients. The incidence of non-GI vaginal, vesical, or female genital tract fistulae was reported in 1.8% of cervical cancer patients receiving bevacizumab versus 1.4% in control patients. In addition, an increased risk of venous thromboembolic events may occur in patients with persistent, recurrent, or metastatic cervical cancer who receive bevacizumab. The incidence of ≥ grade 3 venous thromboembolism (VTE) in those receiving chemotherapy in combination with bevacizumab was 10.6% versus 5.4% in those receiving chemo alone. Bevacizumab should be permanently discontinued in patients with grade 4 VTE, including pulmonary embolism. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm287610.htm
The risk of arterial thromboembolism has been added to the black box warnings and the warnings and precautions section of the package labeling for lenalidomide. There is an increased risk of myocardial infarction and stroke in patients with multiple myeloma receiving lenalidomide with dexamethasone. Because of the increased risk of thrombotic events in patients receiving lenalidomide in combination with dexamethasone, the administration of thromboprophylaxis is recommended. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm299519.htm
5-HT3 Receptor Antagonists
The risk of serotonin syndrome has been added to the warnings and precautions section of the package inserts for all 5-HT3 receptor antagonists. Most cases have occurred concomitantly with other serotonergic agents (e.g., SNRIs, SSRIs, MAOIs, methylene blue, tramadol, lithium, mirtazapine, and fentanyl), and some cases have resulted in fatalities. Patients should be monitored for signs or symptoms of serotonin syndrome, especially when used in combination with other serotonergic drugs. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm418818.htm
The warnings and precautions section of the prescribing information for clofarabine has been updated. The update includes the risk of hemorrhage. There have been serious and fatal reports, including pulmonary, cerebral, and gastrointestinal hemorrhage, the majority of which occurred in patients with thrombocytopenia. Platelets and coagulation parameters should be monitored. The warnings and precautions section also includes the risk of enterocolitis, which has been reported most commonly within 30 days of combination therapy. Some of the cases have been serious and fatal and have included C. difficile colitis, cecitis, and neutropenic colitis. Patients should be monitored for signs or symptoms of this complication. Last, clofarabine should be discontinued if patients develop exfoliative or bullous rashes. The risk of skin reactions, including serious and fatal cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, has been reported with the drug. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm338244.htm
The drug interactions section of the prescribing information has been updated and identifies nilotinib as a moderate CYP3A4 inhibi- tor. Concomitant administration of agents that are metabolized by CYP3A4 may lead to increased concentrations. Dose adjustment of agents that CYP3A4 substrates and that have a narrow therapeutic index may be necessary.
ISMP Medication Safety Alerts
July 17, 2014 (Volume 19, Issue 14)
A recent overdose with oral lomustine was reported to the Institute for Safe Medication Practices (ISMP). The patient inadvertently took an equivalent of three cycles of lomustine at one time after thinking the pharmacy had dispensed a single dose. There have been at least five similar errors with lomustine reported by the ISMP, where more than one dose was dispensed and taken. The ISMP recommends that prescribers, pharmacists, nurses, insurers, manufacturers, and the U.S. Food and Drug Administration follow several safe practices for oral lomustine therapy, including the following:
- On the prescription, specify that only a single dose should be dispensed.
- Discuss with the patient that a single dose should be taken no sooner than every 6 weeks.
- Review and provide written instructions for the patient. Remind the patient that he or she should not assume he or she should be taking all the capsules in the bottle. The patient should compare the pre- scriber’s written instructions with the pharmacy label, and he or she needs to call if there are any questions prior to taking a dose.
- Program alerts into order entry systems to prevent errors (e.g., al- lowing only a single dose to be entered).
- Dispense only a single dose per filled prescription. Call the pre- scriber if multiple doses have been prescribed.
- Ensure patients receive counseling when picking up new prescriptions and refills for lomustine.
- Supply written drug education materials to patients that include information about dispensing only a single dose per fill. Verify the written drug education materials are consistent with the labeled instructions.
- Enhance labels with bold font or all capital letters.
- Avoid filling lomustine prescriptions via mail order or specialty pharmacies unless patient counseling can occur by phone prior to dispensing the drug.
- Reinforce education on taking only a single dose for those patients being discharged on lomustine therapy.
- Do not approve more than a single-dose supply for outpatient lomustine prescriptions.
- Enhance label warnings to dispense only enough capsules for one dose.
FDA and Manufacturer
- Require distribution of medication guides to patients receiving lomustine.