31 minute read
certification
ASHP Receives Federal Funds to Address Burnout
By Dave Doolittle
ASHP has been awarded more than $2 million to develop an educational program designed to help reduce burnout throughout the pharmacy profession and in healthcare overall.
The grant, totaling $2.3 million over three years, was provided by the Department of Health and Human Services (HHS) through the Health Resources and Services Administration (HRSA).
ASHP will use the grant to develop an educational curriculum that will allow healthcare workers, particularly those in the pharmacy profession, to implement local solutions to promote well-being and resilience, said Anna Legreid Dopp, PharmD, ASHP’s senior director of Clinical Guidelines and Quality Improvement.
The curriculum will be another key ASHP resource aimed at reducing burnout among pharmacists, pharmacy residents and students, she said.
“We know more needs to be done, and that’s why we’re so excited because this grant will allow us to do more to support the pharmacy workforce and those they work for in their practices,” Dr. Legreid Dopp said.
ASHP for decades has recognized burnout as a patient care problem and has focused on helping members build resilience and develop tools to help address burnout, Dr. Legreid Dopp said.
The problem is nationwide and complex, with at least 53% of health-system pharmacists reporting some form of emotional exhaustion, depersonalization or a low sense of accomplishment, according to a 2018 survey (Am J Health Syst Pharm 2018;75[23 Supplement 4]:S93-S100).
“Going back to the 1980s, our members have talked about the risk of burnout for those practicing in hospitals, but we have heard from members in the past 10 years that something is different in the environment,” Dr. Legreid Dopp said. “That caused our leadership to make a meaningful commitment to acknowledge there are inherent risk factors … that are causing those in the pharmacy workforce and healthcare workforce overall to burn out at a higher rate than had been [the case] previously.”
Those factors include the documentation demands of electronic health records, regulatory burdens, a feeling of diminishing autonomy and lack of time to recover from stressful events, Dr. Legreid Dopp said. The unprecedented demands of the COVID-19 pandemic have exacerbated the problem, she said.
“At its core we see burnout as a patient care problem. If your clinician is experiencing burnout, then patient care might be at risk,” Dr. Legreid Dopp said. “We’re all about caring for the patient while recognizing that the pharmacy workforce is a critical part of the interprofessional healthcare team. Siloed approaches on this are short-sighted so we need to look at this across all disciplines and to support the entire healthcare workforce.”
ASHP resources to curb burnout include a dedicated continuing education program for members and a certificate program for healthcare organizations that focuses largely on how to create cultures of well-being and resilience.
“Burnout is a local problem, and it requires local solutions,” Dr. Legreid Dopp said. “This is a systems problem, so our efforts are aimed at supporting individuals to fix their workforce.”
ASHP is among 34 organizations that received HRSA grants to develop training programs to help public safety professionals address burnout, suicide, mental health conditions and substance use disorders, the HRSA said. Ten other organizations received grants to help healthcare organizations establish, improve or expand such programs, according to HRSA.
“If you look at the awards being granted as part of this package, it speaks to the complexity of the issue and recognizes that there’s not an easy solution or one solution that can be [applied] across all sectors,” Dr. Legreid Dopp said. “It’s going to take a multifactorial response to addressing the issue. We see it as a big puzzle, and we’re excited to be a piece in that puzzle.”
The sources reported no relevant fi nancial disclosures.
New Certification Tool Highlights Practice Excellence
By David Wild
Hospitals and health systems have a new tool for honing best practices: ASHP’s Centers of Excellence certification program.
“This certification [allows] institutions to differentiate themselves from others through innovative, high-quality, safe and effective pharmacy services,” said Douglas Scheckelhoff, MS, ASHP’s senior vice president. “There has long been discussion within health-system pharmacy to create a nursing Magnet-like program that is specific to pharmacy,” and the certification program meets that need, he noted during the ASHP 2021 Midyear Clinical Meeting and Exhibition, held virtually.
One key component of the Centers of Excellence certification program is its focus on integration, according to David Warner, PharmD, ASHP’s senior director of consulting and practice. “Making sure the pharmacy department has strong relationships with other disciplines and leaders within the organization, that their services are integrated throughout the organization and that pharmacists are involved in team-based care ensures the medication expertise of pharmacists is used throughout the organization to maximize drug safety and efficacy,” Dr. Warner said at the ASHP meeting.
Achieving certification will depend on several areas, including the use of standards for leadership, management and patient care services. Surveyors also will look at quality and performance improvement initiatives as well as education, training and research programs,among other components.
Organizations pursuing certification also will need to demonstrate that they use the most rigorous processes to support safe medication use across the organization, Dr. Warner said. Surveyors will evaluate medication-use policy, formulary approval processes and medication safety best practices, including the use of information technology and automation.
According to Mr. Scheckelhoff, pharmacies that achieve certification can showcase their Centers of Excellence designation to patients as they choose where they want to receive care, as well as highlighting this certification to a range of other stakeholders. “Centers can promote this certification to their payors, much the same as is done by the nursing profession relative to Magnet status, and certification can lead to research opportunities for pharmacy practice,” he said.
Gearing Up for a Gap Analysis
Stephen Eckel, PharmD, MHA, the director of pharmacy for innovation services at UNC Medical Center and an associate professor at UNC Eshelman School of Pharmacy, in Chapel Hill, N.C., said his organization is gearing up for a gap analysis as a first step in evaluating the process of pursuing this certification. “Hospital patients want to make sure they’re getting the best care, and one pillar of optimal care is safe and appropriate medication administration utilization,” Dr. Eckel told Pharmacy Practice News. “Having a designation that the Department of Pharmacy is a Center of Excellence ensures that the public knows they’re being treated at an organization [that] follows all best practices and processes.”
Dr. Eckel cited another certification benefit: it can help pharmacy make the case for additional funding and use those funds to optimize pharmacy resources, as well as ensure operations and processes meet the most rigorous standards. “Every leader should want their pharmacy and their organization to perform at the highest level of patient care and safety,” Dr. Eckel said.
More details regarding the certification can be found at bit.ly/3HF9MkC.
UC San Diego Scores First
In mid-February, ASHP announced that the University of California San Diego Health is the first organization to be named a Certified Center of Excellence in Medication-Use Safety and Pharmacy Practice. The certification recognizes the health system’s “highperforming pharmacy department for its commitment to superior patient care,” ASHP noted in a press release.
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pharmacies that continue to thrive both clinically and financially as a result of their efforts.
But it wasn’t easy. JoAnn Stubbings, BSPharm, vividly recalls those early days of specialty pharmacy services at the University of Illinois at Chicago, where she directed specialty pharmacy for more than eight years and now serves as a clinical associate professor emerita at UIC College of Pharmacy.
“It was about a decade ago, when there were really only a handful of hospitals dabbling in the specialty space. We were small,” she said. “I started with one part-time pharmacist and one prescription, and most of the other pharmacy leadership in the hospital were just like, ‘Why don’t you see what you can do with this?’ Meanwhile, the big pharmacies like CVS were going gangbusters into the specialty market.”
What became known as “specialty” drugs had, in fact, long been the purview of hospitals and health systems. “Much of the prescription volume of the first specialty drugs originated out of the health systems. These were novel drug therapies used to manage complex, high-risk patients, such as transplant patients, cancer patients, people with multiple sclerosis and HIV and hemophilia,” said Rebekah Anguiano, PharmD, a clinical pharmacist and clinical assistant professor at UIC, whom Ms. Stubbings wooed from CVS Caremark in 2012, to help her establish UIC’s specialty pharmacy.
However, hospitals and health systems were “asleep at the wheel” in the 1990s and early 2000s, Ms. Stubbings explained, as large traditional, mailorder pharmacies were building massive specialty businesses. “While specialty pharmacy was growing, hospitals were shutting down their external pharmacies because they didn’t see any profit in dispensing generic drugs,” she said. “But they weren’t paying attention to what was really going on as new original treatments came to market for diseases like hepatitis C [HCV], multiple sclerosis and Crohn’s disease.”
Even then, these specialty drugs were very expensive—a concern for some health systems, which “weren’t excited to take that cost burden on at the time,” Dr. Anguiano said. “Also, these medications are complicated; they’re hard to get reimbursed; and many have cold chain shipping requirements, not to mention so many layers of medication management.”
Another challenge: “In general, the prescription volume was low,” Dr. Anguiano said. “Unfortunately, this resulted in specialty prescriptions being channeled to outside big specialty pharmacies, and health systems were initially shut out of the specialty niche.”
Then a few early trailblazers, including Ms. Stubbings, Dr. Anguiano and a cadre of female leaders at other institutions saw the potential. “It made no sense not to adopt specialty in the health system,” said Ms. Stubbings, whose program had generated $60 million in annual revenue when she retired in 2020. “The patient is there, the doctors are there, the clinical trials are there. You’ve got everything packaged together beautifully, but you can’t dispense the drugs they need? That’s nonsensical.”
Seeing the Future
One of the first to call attention to the importance of specialty pharmacy for hospitals was Rita Shane, PharmD, the vice president and chief pharmacy officer at Cedars-Sinai Medical Center, in Los Angeles. In 2006, she convened a panel on specialty pharmacy at the ASHP Midyear Clinical Meeting. “It had become clear to me that the future of chronic disease management was going to include biologics, that specialty pharmacy would be really important and health-system pharmacy was very well positioned to provide those services,” she said.
After the ASHP meeting, Dr. Shane published an article in the American Journal of Health-System Pharmacy (2007;64[22]:2382-2385) arguing that health-system pharmacy leaders should take ownership of specialty, including clinical guidelines, patient management, the revenue cycle and changing reimbursement models, and contracting.
Dr. Shane met with the executive leadership at Cedars-Sinai and pointed out that the institution had a growing number of patients who required specialty services. “In addition to the obvious oncology population, we had a large rare disease population and many patients with inflammatory bowel disease,” she said. “While some early adopters understood the need—solid-organ transplant [clinicians], in particular, really recognized early the quality we brought to the table—it was a challenge early on to convey why we were investing in this. Our specialty pharmacy finally opened in 2014, and although there was initial concern about the costs of building the program, the value of the program to our patients and its focus on quality and safety became evident.”
Some health systems partnered with larger outside specialty pharmacies, such as Shields or Diplomat, to build their services, but Cedars-Sinai did not. “We used Diplomat for our on-call service at one point, but other than that we insourced everything and built it all ourselves. In health systems, we have clinical pharmacists who have access to the electronic health record [EHR] along with the knowledge, skills and expertise to do comprehensive medication management,” Dr. Shane said. “In other settings, they may have accredited specialty pharmacists, but they don’t necessarily have our level of clinical expertise along with access to the [EHR] to determine that, for example, a drug that was started won’t be effective based on new biomarker data.”
Origin Stories
Debbie Duckworth, PharmD, the senior director of specialty pharmacy and infusion services at the University of Kentucky, is another pioneer of health-system specialty pharmacy. Dr. Duckworth had spent more than two decades as the owner of her own pharmacy, the Medicine Shoppe, in Harrodsburg. “I partnered with the only other female pharmacist in the county at the time. We were both young mothers working predominantly for men, and we figured we could do this together, and it would give us some flexibility and allow us to attend to the needs of our families.”
After she and her colleague decided to sell the business in 2010, Dr. Duckworth took on the position of helping to expand the University of Kentucky’s new retail pharmacy footprint. “We tasked a pharmacy fellow with the job of exploring and understanding whether or not UK should develop our own specialty pharmacy,” she said. “He came back and said yes, so he became the first director of specialty pharmacy.”
However, after the first six months, the new specialty pharmacy team was on the verge of collapse. “They were coming to my office in tears, saying if something didn’t change, they’d quit,” Dr. Duckworth said.
“We pulled our data and realized that this team had exceeded our five-year business model for specialty in less than six months. We hadn’t had time to build the necessary infrastructure underneath them. No wonder they were ready to quit. Because I had had experience in owning my own store and having gone through accreditation processes, leaders felt it made sense for me to take over specialty pharmacy, which I did in March of 2015.”
The specialty pharmacy team moved into a 5,000-square-foot space in UK’s Albert B. Chandler Hospital building—“which
Above (left to right) is the specialty pharmacy team at Children’s Hospital of Colorado: Leslie Ruppe, PharmD, Emma Osbern, CPhT, Melody Odom, PharmD, John Tipton, CPhT, Taj Laugan, CPhT, Jenny French, PharmD, and Laura Rang, BSPharm, who launched the program.
Some of the first specialty pharmacy medications were used to treat cancer, hepatitis C, HIV, multiple sclerosis and hemophilia, many of which required cold chain shipping.
‘It made no sense not to adopt specialty in the health system. The patient is there, the doctors are there, the clinical trials are there. You’ve got everything packaged together beautifully, but you can’t dispense the drugs they need? That’s nonsensical.’ —JoAnn Stubbings, BSPharm
sounded like a huge space at the time,” Dr. Duckworth said. “By August 2015, we were 20 team members strong and passed URAC accreditation with flying colors.”
Today, Kentucky’s specialty pharmacy occupies 30,000 square feet in South Lexington, about 15 minutes from the main campus. In addition, the pharmacy’s contribution to the hospital’s revenue budget grew from about $17 million in 2016 to $53 million in 2021, Dr. Duckworth said.
That Means’
Kimberly Harrison, PharmD, received her pharmacy education at one of the other early health systems to establish a beachhead in specialty pharmacy, the University of Wisconsin-Madison, where she also completed what was then a brand-new two-year residency in medication systems and operations. “It was focused on developing pharmacy managers and keeping that expertise in the operations area,” Dr. Harrison said. After completing that program in 2012, she relocated to the University of Washington, in Seattle. “They were looking for a pharmacist who could devote time to projects as they came up across the health system,” she recalled. “I focused on two things: one was standardizing the 340B [Drug Pricing] program and the other was specialty pharmacy. When they told me they were interested in specialty pharmacy, I said, ‘I don’t really know what that means, so I’ll do some research.’”
After consulting with specialty pharmacists at her alma mater for guidance, Dr. Harrison started building UW’s specialty pharmacy by developing a small call center staffed by two pharmacy technicians supporting prior authorizations (PAs). “We were originally focused on the GI [gastroenterology] clinic, trying to give those patients options for fulfilling their prescriptions with us.”
That was in 2014, when the FDA approved the first direct-acting antiviral therapy for HCV—a combination of simeprevir (Olysio, Janssen) and sofosbuvir (Sovaldi, Gilead)—revolutionizing treatment of that disease. “We then expanded our specialty pharmacy efforts into our hepatology clinic, and split one pharmacist between those two,” Dr. Harrison said. “The providers encouraged their patients to fill their prescriptions, showing them the benefits.”
The revenue from gastrointestinal and HCV medications “justified us getting a third technician,” she added. “We worked with the Epic [EHR] team to build tools for pharmacists in the specialty clinics to document their work and enable us to get access to medications.”
By the time the program expanded to include rheumatology, specialty pharmacy had taken over most of Dr. Harrison’s time. “I focused on getting feedback from patients as well,” she said. “If they had experience at other specialty pharmacies, what did they like or dislike? Our techs also took extra time with each patient to help figure out what we could do differently. For example, we learned early on that they wanted mail order and the ability to receive cold-chain medications at home, so we added that capability.”
In 2015, with enough revenue to justify bringing on a full-time specialty pharmacy manager, Dr. Harrison hired Michael Alwan, PharmD. When he was promoted to a director of pharmacy position a year later, Dr. Harrison recruited Erica Diamantides, PharmD, who still manages the program today.
HIV a Trigger for Specialty Care
Like Dr. Anguiano, Laura Rang, PharmD, got her start in specialty at CVS. “I went to pharmacy school during the HIV/AIDS pandemic; when I first graduated, that was one of my first experiences with specialty. There was such a stigma associated with those medications that we created a special pharmacy at CVS just for people with HIV,” she recalled. “I spent several years serving HIV patients who were marginalized and discriminated against, and who needed complex, expensive medications and would die without them. It turned out that other disease states like hepatitis C, oncology, multiple sclerosis and rheumatoid arthritis needed specialty pharmacy, too. So I ran specialty pharmacy for CVS for about seven years, between 2007 and 2015, and learned all about it.”
In 2015, Dr. Rang was recruited to help launch the new health-system specialty pharmacy at the University of Colorado Health, with headquarters in Aurora. “They had started filling those hepatitis C prescriptions and were making money by accident,” she said. “They realized that they needed their own specialty pharmacy.”
Dr. Rang’s role was to create UCHealth’s specialty pharmacy medication access and renewal center—essentially, its PA program. “I ended up hiring 10 pharmacists and 30 pharmacy technicians, and all we did was prior authorizations, coordination of benefits and manufacturer programs—all the behindthe-scenes work to ensure that these prescriptions got filled and delivered.”
In June 2019, she moved to Children’s Hospital of Colorado, where she launched that hospital’s specialty pharmacy. “This one, I got to plan and build from the beginning,” she said. “We now have a brick-and-mortar pharmacy and four clinical pharmacists with subspecialty PGY-2 pediatric training. These are very hard to find, and we’ve recruited from all over the country and are still recruiting more. We also have three operational pharmacists, three technicians and two interns/students.”
Building a Network
This informal cadre of health-system specialty pharmacy pioneers came together in a more organized way around 2014, under the auspices of the University Healthcare Consortium, when then–associate vice president for specialty pharmacy Kevin Colgan, RPh, reached out to leading specialty consultant Suzette DiMascio, CHE, CMCE, CPC, the founder of CSI Specialty Group. “He told me that a lot of health systems wanted to figure out specialty, and wanted me to help develop strategies,” Ms. DiMascio said. “At that time, many CEOs and CFOs [chief financial officers] still wanted nothing to do with specialty pharmacy, because all they saw were expensive drugs and pictured it as a cost center, not a revenue center. But the leaders at the consortium got the vision; they saw the difference it could make when a hospital could care for a patient all the way through their discharge to home.”
Ms. DiMascio met with Ms. Stubbings, Dr. Harrison, Dr. Rang and others. “Hospitals and health systems have traditionally been very male-oriented, and the largely female early champions of hospital specialty pharmacies were getting nowhere with the C-suite,” Ms. DiMascio said. “But gradually we started to see a change in receptivity around 2016 or 2017. We had to show them the numbers for how they could use 340B funds to successfully implement a specialty pharmacy. Leaders like JoAnn and Kim were at the forefront of showing them that there was money on the table that they were missing out on—money they could use to fund the specialty pharmacy and help patients get better care. They had meds-to-beds programs for [high] cholesterol and diabetes and so on, but not for the most critically ill patients. Why not?”
At many institutions, the real breakthrough came when the specialty pharmacy was able to demonstrate its ability to manage PAs. “That was, and continues to be, such a big burden on specialty clinics,” Dr. Anguiano said. “When we could off-load a portion of that burden and absorb it into the services we provide, with technicians and pharmacists who have specialized training in turning PAs around quickly with minimal involvement needed by the clinic, that was a huge win across the institution.”
Managing access to limited distribution medications also helped the early health-system pioneers prove their worth. “It wasn’t just a revenue opportunity, but also a true patient care opportunity—to improve access, get patients started on treatment earlier, and provide better management on an ongoing basis,” Dr. Anguiano said.
Throughout those early years, hundreds of phone calls fired back and forth between Illinois, Iowa, Washington, Kentucky and Wisconsin. “This was before everyone broke into getting accredited, and we were all just trying to figure it out,” Dr. Anguiano said. “JoAnn and I would be on the phone with Debbie or Kim and Laura. ‘How are you handling cold-chain shipping? How are you managing your call center?’ There was a lot of collaboration, and there still is.”
This collaborative approach “is one of the things that sets our model apart from traditional specialty pharmacy,” Dr. Anguiano said. “We’re not in competition with each other; we have different patient populations that are really never going to overlap. If someone has a problem they’re trying to solve, they reach out to their colleagues across the nation, formulate a solution and then share it with others. It’s a great model, and has helped to improve processes and set standards and best practices.”
For patients with cGVHD ROCK ON
INDICATION
IMPORTANT SAFETY INFORMATION
Warningsand Precautions
• Embryo-Fetal Toxicity: administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with
Adverse Reactions
• • •
Drug Interactions
• Strong CYP3A Inducers: Coadministration of REZUROCK with strong CYP3A inducers decreases belumosudil when coadministered with strong CYP3A inducers • Proton Pump Inhibitors: Coadministration of REZUROCK with proton pump inhibitors decreases belumosudil when coadministered with proton pump inhibitors
ORRa 75%
(95% CI, 63-85; P<.0001)1,4
REZUROCK achieved clinically and statistically with the 200-mg once-daily dose in a real-world demographic of patients with cGVHD.1
• 1-3 • CR was observed in all organs 5
• There was no death or new systemic therapy initiation in 62%
(95% CI, 46-74) of the responder population at 12 months1 • Clinically meaningful improvements in QOL,with CS and CNI dose reductions and discontinuations and nonresponders5
• Well tolerated1
ASSIST ™
Enroll your patients with cGVHD in Kadmon ASSIST so our Kadmon ASSIST Monday through Friday, 8 -8 ET, 1-844-KADMON1 (523-6661).
VISIT REZUROCKhcp.com TO LEARN MORE
cGVHD, chronic graft-versus-host disease; CNI, calcineurin inhibitor; CR, complete response; CS, corticosteroid; FDA, US Food and Drug Administration; NIH, National Institutes of Health; ORR, overall response rate; PR, partial response; QOL, quality of life; ROCK2, rho-associated coiled-coil–containing protein kinase-2. aProportion of patients who achieved CR or PR according to the 2014 NIH cGVHD Consensus Criteria in the 200-mg once-daily arm.1
IMPORTANT SAFETY INFORMATION (cont)
• Pregnancy: administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. Advise pregnant women and females of reproductive potential of the potential risk to the fetus • Lactation: There are no data available on the presence of belumosudil or its metabolites in human milk or the effects on after the last dose • Pediatric Use: The safety and effectiveness of REZUROCK have been established in pediatric patients 12 years and older.
The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established • Geriatric Use: clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients • Renal and Hepatic Impairment: Treatment with REZUROCK has not been studied in patients with pre-existing severe You are encouraged to report side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call
References: 1. REZUROCK. Package insert. Kadmon Pharmaceuticals, LLC; 2021. 2. Zanin-Zhorov A, Weiss JM, Nyuydzefe MS, et al.Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci USA. 2014;111(47):16814-16819.doi:10.1073/pnas.1414189111 3. Flynn R, Paz K, Du J, et al. Targeted rho associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood.2016;127(17):2144-2154. doi:10.1182/blood-2015-10-678706 4. 5. Cutler CS, Lee SJ, Arai S, et al. Belumosudil for chronic graft-versus-host disease (cGVHD) after 2 or more prior lines of therapy: the ROCKstar study. Blood. 2021;blood.2021012021. doi:10.1182/blood.2021012021
Please see Brief Summary of full Prescribing Information on adjacent pages.
REZUROCK™ (belumosudil) tablets, for oral use Initial U.S. Approval: 2021 BRIEF SUMMARY: Please see package insert for full prescribing information. 1 INDICATIONS AND USAGE
REZUROCK is indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versushost disease (chronic GVHD) after failure of at least two prior lines of systemic therapy.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS 5.1 Embryo-Fetal Toxicity
Based on findings in animals and its mechanism of action, REZUROCK can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period organogenesis caused adverse developmental outcomes including embryo-fetal mortality and malformations at maternal exposures (AUC) less than those in patients at the recommended dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1) in the full prescribing information].
6 ADVERSE REACTIONS 6.1 Clinical Trial Experience
Because clinical trials are conducted under widely variable conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice. Chronic Graft versus Host Disease In two clinical trials (Study KD025-213 and Study KD025-208), 83 adult patients with chronic GVHD were treated with REZUROCK 200 mg once daily [see Clinical Studies (14.1) in the full prescribing information]. The median duration of treatment was 9.2 months (range 0.5 to 44.7 months). Fatal adverse reaction was reported in one patient with severe nausea, vomiting, diarrhea and multi-organ failure. Permanent discontinuation of REZUROCK due to adverse reactions occurred in 18% of patients. The adverse reactions which resulted in permanent discontinuation of REZUROCK in > 3% of patients included nausea (4%). Adverse reactions leading to dose interruption occurred in 29% of patients. The adverse reactions leading to dose interruption in ≥ 2% were infections (11%), diarrhea (4%), and asthenia, dyspnea, hemorrhage, hypotension, liver function test abnormal, nausea, pyrexia, edema, and renal failure with (2% each). The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, phosphate decreased, gamma glutamyl transferase increased, lymphocytes decreased, and hypertension. Table 2 summarizes the nonlaboratory adverse reactions.
a infection with an unspecified pathogen includes acute sinusitis, device related infection, ear infection, folliculitis, gastroenteritis, gastrointestinal infection, hordeolum, infectious colitis, lung infection, skin infection, tooth infection, urinary tract infection, wound infection, upper respiratory tract infection, pneumonia, conjunctivitis, sinusitis, respiratory tract infection, bronchitis, sepsis, septic shock. b includes influenza, rhinovirus infection, gastroenteritis viral, viral upper respiratory tract infection, bronchitis viral, Epstein-Barr viremia, Epstein-Barr virus infection, parainfluenzae virus infection, Varicella zoster virus infection, viral infection. c includes cellulitis, Helicobacter infection, Staphylococcal bacteremia, catheter site cellulitis, Clostridium difficile colitis, Escherichia urinary tract infection, gastroenteritis Escherichia coli, Pseudomonas infection, urinary tract infection bacterial. d includes fatigue, asthenia, malaise. e includes edema peripheral, generalized edema, face edema, localized edema, edema. f includes nausea, vomiting. g includes abdominal pain, abdominal pain upper, abdominal pain lower. h includes dyspnea, dyspnea exertional, apnea, orthopnea, sleep apnea syndrome. i includes cough, productive cough. j includes contusion, hematoma, epistaxis, increased tendency to bruise, conjunctival hemorrhage, hematochezia, mouth hemorrhage, catheter site hemorrhage, hematuria, hemothorax, purpura. k includes pain in extremity, back pain, flank pain, limb discomfort, musculoskeletal chest pain, neck pain, musculoskeletal pain. l includes headache, migraine. m includes rash, rash maculo-papular, rash erythematous, rash generalized, dermatitis exfoliative. n includes pruritus, pruritus generalized. Table 3 summarizes the laboratory abnormalities in REZUROCK.
7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on REZUROCK
Strong CYP3A Inducers Coadministration of REZUROCK with strong CYP3A inducers decreases belumosudil exposure [see Clinical Pharmacology (12.3) in the full prescribing information], which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when coadministered with strong CYP3A inducers [see Dosage and Administration (2.3) in the full prescribing information]. Proton Pump Inhibitors Coadministration of REZUROCK with proton pump inhibitors decreases belumosudil exposure [see Clinical Pharmacology (12.3) in the full prescribing information], which may reduce the efficacy of REZUROCK. Increase the dosage of REZUROCK when coadministered with proton pump inhibitors [see Dosage and Administration (2.3) in the full prescribing information].
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy
Risk Summary Based on findings from animal studies and the mechanism of action [see Clinical Pharmacology (12.1) in the full prescribing information], REZUROCK can cause fetal harm when administered to pregnant women. There are no available human data on REZUROCK use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, administration of belumosudil to pregnant rats and rabbits during the period of organogenesis resulted in adverse developmental outcomes, including alterations to growth, embryo-fetal mortality, and embryo-fetal malformations at maternal exposures (AUC) approximately ≥ 3- (rat) and ≥ 0.07 (rabbit) times the human exposure (AUC) at the recommended dose (see Animal Data). Advise pregnant women and females of reproductive potential of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Embryo-fetal development studies were conducted in rats with administration of belumosudil to pregnant animals during the period of organogenesis at oral doses of 25, 50, 150, and 300 mg/kg/day in a pilot study and doses of 15, 50, and 150 mg/kg/day in a pivotal study. In the pilot study, maternal toxicity and embryo- fetal developmental effects were observed. Maternal toxicity (reduced body weight gain) occurred at 150 and 300 mg/kg/day doses. Increased post-implantation loss occurred at 50 and 300 mg/kg/day. Fetal-malformations were observed at ≥ 50 mg/kg/day and included absence of anus and tail, omphalocele, and dome shaped head. The exposure (AUC) at 50 mg/kg/day in rats is approximately 3 times the human exposure at the recommended dose of 200 mg. In an embryo-fetal developmental study in rabbits, pregnant animals administered oral doses of belumosudil at 50, 125, and 225 mg/kg/day during the period of organogenesis resulted in maternal toxicity and embryo-fetal developmental effects. Maternal toxicity (body weight loss and mortality) was observed at doses ≥ 125 mg/kg/day. Embryo-fetal effects were observed at doses ≥ 50 mg/kg/day and included spontaneous abortion, increased post-implantation loss, decreased percentage of live fetuses, malformations, and decreased fetal body weight. Malformations included those in the tail (short), ribs (branched, fused or deformed), sternebrae (fused), and neural arches (fused, misaligned, and deformed). The exposure (AUC) at 50 mg/kg/day in rabbits is approximately 0.07 times the human exposure at the recommended dose of 200 mg.
8.2 Lactation
Risk Summary There are no data available on the presence of belumosudil or its metabolites in human milk or the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions from belumosudil in the breastfed child, advise lactating women not to breastfeed during treatment with REZUROCK and for at least one week after the last dose.
8.3 Females and Males of Reproductive Potential
REZUROCK can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating treatment with REZUROCK.
Table 2: Nonlaboratory Adverse Reactions in ≥ 10% Patients with Chronic GVHD Treated with REZUROCK
Adverse Reaction REZUROCK 200 mg once daily (N=83) All Grades (%) Grades 3-4 (%)
Infections and infestations
Infection (pathogen not specified)a Viral infectionb Bacterial infectionc
General disorders and administration site conditions
Astheniad 53 16 19 4 16 4
46 4 Edemae 27 1 Pyrexia 18 1
Gastrointestinal
Nauseaf 42 4 Diarrhea 35 5 Abdominal paing 22 1 Dysphagia 16 0
Respiratory, thoracic and mediastinal
Dyspneah 33 5 Coughi 30 0 Nasal congestion 12 0
Vascular
Hemorrhagej 23 5 Hypertension 21 7
Musculoskeletal and connective tissue
Musculoskeletal paink 22 4 Muscle spasm 17 0 Arthralgia 15 2
Nervous system
Headachel 21 0
Metabolism and nutrition
Decreased appetite 17 1
Skin and subcutaneous
Rashm 12 0 Pruritusn 11 0
Table 3: Selected Laboratory Abnormalities in Patients with Chronic GVHD Treated with REZUROCK REZUROCK 200 mg once daily
Grade 0-1 Baseline Grade 2-4 Max Post
Grade 3-4 Max Post Parameter (N) (%) (%) Chemistry
Phosphate Decreased 76 28 7 Gamma Glutamyl Transferase Increased 47 21 11 Calcium Decreased 82 12 1 Alkaline Phosphatase Increased 80 9 0 Potassium Increased 82 7 1 Alanine Aminotransferase Increased 83 7 2 Creatinine Increased 83 4 0
Hematology
Lymphocytes Decreased 62 29 13 Hemoglobin Decreased 79 11 1 Platelets Decreased 82 10 5 Neutrophil Count Decreased 83 8 4
Contraception Females Advise females of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose of REZUROCK. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with REZUROCK and for at least one week after the last dose of REZUROCK. Infertility Females Based on findings from rats, REZUROCK may impair female fertility. The effect on fertility is reversible [see Nonclinical Toxicology (13.1) in the full prescribing information]. Males Based on findings from rats and dogs, REZUROCK may impair male fertility. The effects on fertility are reversible [see Nonclinical Toxicology (13.1) in the full prescribing information].
8.4 Pediatric Use
The safety and effectiveness of REZUROCK have been established in pediatric patients 12 years and older. Use of REZUROCK in this age group is supported by evidence from adequate and well-controlled studies of REZUROCK in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the pharmacokinetics of drug substance, that the exposure of drug substance is expected to be similar between adults and pediatric patients age 12 years and older, and that the course of disease is sufficiently similar in adult and pediatric patients to allow extrapolation of data in adults to pediatric patients. The safety and effectiveness of REZUROCK in pediatric patients less than 12 years old have not been established.
8.5 Geriatric Use
Of the 186 patients with chronic GVHD in clinical studies of REZUROCK, 26% were 65 years and older. No clinically meaningful differences in safety or effectiveness of REZUROCK were observed in comparison to younger patients.
Active ingredient made in India. Distributed and marketed by:
Kadmon Pharmaceuticals, LLC
Warrendale, PA 15086 1-877-377-7862 REZUROCK™ is a trademark of Kadmon Pharmaceuticals, LLC. © 2021 Kadmon Pharmaceuticals, LLC, Warrendale, PA 15086. All rights reserved. KAD25000266 10/21
