Pharmacy Practice News - December 2021 by McMahon Group

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POLICY

Why partering with a certifier for cleanroom testing makes sense........

A year of firsts in specialty approvals .....

Highlights of 2022 OPPS/ASC final rule sets ..................

CLINICAL

Ensuring guidelinesbased gout therapy ....

TECHNOLOGY

Replacing and upgrading ADCs: lessons learned .............

Top-Tier Results Elusive Without Benchmarking

harmacy departments contribute to the financial and clinical success of their health systems every day. But if your team isn’t documenting those outcomes and measuring performance with some type of benchmarking strategy, there may be a ceiling to those successes, experts noted during the 2021 ASHP Conference for Pharmacy Leaders, held virtually. Given the current market forces at play, benchmarking is more important than ever, noted Holly Phillips, PharmD, an acute care pharmacy manager at UCHealth University of Colorado Hospital, in Aurora. “Health care systems are facing shrinking profit margins and reduced reimbursement, which leads to more eyes on the pharmacy, making sure that we’re doing right by the resources we’re provided,” she said.

Volume 48 • Number 12 • December 2021

In the cleanroom:

Where Do You Sample For Safest Compounding?

Continued on page 22

SPECIALTY PHARMACY

ecent legislative and professional initiatives could increase access to quality nutrition care in the inpatient and outpatient settings, experts said during a webinar hosted by the American Society for Parenteral and Enteral Nutrition (ASPEN) as part of Malnutrition Awareness Week. In the United States, ASPEN has spearheaded a legislative push to expand the Medical Nutrition Therapy (MNT) Act and thus increase access to nutrition assessment and nutrition care for people at risk in the outpatient setting, Jay Mirtallo, MS, RPh, Continued on page 20

Continued on page 6

Health systems leverage data to gain specialty edge ..............

ASPEN Pushing For Nutrition as ‘A Human Right’

REVIEW ARTICLE

Harnessing Gene And Cell Therapies For Multiple Myeloma See page 17.

n September 2021, the proposed revisions to USP General Chapter <797> were finally released, with changes on beyond-use dating garnering significant attention (bit.ly/3HJ04yf-PPN). But one factor remains the same in the revised chapter: It doesn’t provide much guidance on choosing air and surface sampling locations for your environmental monitoring plan. Fortunately, by paying attention to areas most at risk, any health system can develop a safe yet streamlined sampling strategy, experts noted during the 2021 Compounding Pharmacies Grand Salon, held virtually. The first key step is to understand the stipulations of <797>. “The chapter requires you to have a sampling plan, including a diagram of sampling locations, your procedure for collecting samples, time of day and activity of compounding, and action levels,” said Abby Roth, the senior director of business operations at CriticalPoint. “Surface sampling must be done at least monthly and air sampling every six months, although monthly is best practice. But although <797> requires that you must sample in each classified space, it doesn’t dictate where within the spaces those samples must be taken.”

A patient-first approach to rare diseases ..................

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As COVID-19 cases soar …

CLINICAL

Stewardship efforts help reduce AEs during anticoagulation ...............

Muscle relaxants and pain a dangerous mix ...

POLICY

Standardization spurs better system-wide compounding .................

OPERATIONS & MGMT

Drug diversion: yet another pandemic challenge .......................... ISMP survey reveals gaps in compounding compliance ......................

TECHNOLOGY

Harnessing big data key to ADC-driven inventory control ..........

Health Systems Stay Vigilant To Rx Shortages

ro m the be g i n n i n g o f the COVID-19 pandemic, there has been a scramble to meet the soaring demand for critical medications, as infection rates, hospitalizations and deaths surged in hot spots around the country. “There were so many moving parts,” said Meryl Biksacky, PharmD, a drug information specialist at Intermountain Healthcare, in Salt Lake City. “It took a constantly vigilant team approach, with a lot of heads in the mix and a lot of ingenuity.” Those early efforts at drug shortage team building and troubleshooting at Intermountain and other health systems helped ease the impact of drug supply disruptions, even as infections began to peak again in the fall and winter.

Volume 48 • Number 2 • February 2021

Pharmacist-led Initiatives Save Millions

E N T ER A NE W WO R L D O F 72-HOUR POSTOPERATIVE PAIN RELI E F With the First and Only Extended-Release Dual-Acting Local Anesthetic (DALA)1-4 ZYNRELEF redeﬁnes postoperative pain management by providing superior pain relief for up to 72 hours, with fewer patients experiencing severe pain, and reducing or eliminating the need for opioids in many patients following surgery versus standard-of-care bupivacaine HCl solution.1-4

SYNERGISTIC MECHANISM OF ACTION1,5,a

SUPERIOR 72-HOUR PAIN RELIEF1-3,b

OPIOID REDUCTION & ELIMINATION1-3,b

NEEDLE-FREE APPLICATION1

BROAD ACCESS PRICING & FAVORABLE REIMBURSEMENT

Synergistic increases in analgesia compared with meloxicam or bupivacaine alone shown in preclinical and Phase 2 studies.1,5 Clinical ﬁndings were demonstrated in Phase 3 trials for bunionectomy with osteotomy and open inguinal herniorrhaphy comparing ZYNRELEF to both placebo and bupivacaine HCl solution.1-3

DISCOVER MORE AT ZYNRELEF.COM/PHARMA

Indication

Contraindications

ZYNRELEF is indicated in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty.

ZYNRELEF is contraindicated in patients with known hypersensitivity (eg, anaphylactic reactions and serious skin reactions) to any amide local anesthetic, NSAIDs, or other components of ZYNRELEF; with history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs (severe, sometimes fatal, anaphylactic reactions to NSAIDS have been reported in such patients); undergoing obstetrical paracervical block anesthesia; or undergoing coronary artery bypass graft (CABG) surgery.

Limitations of Use: Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. IMPORTANT SAFETY INFORMATION WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS • Nonsteroidal anti-inﬂammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. • ZYNRELEF is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. • NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/ or GI bleeding are at greater risk for serious GI events.

Warnings and Precautions Dose-Related Toxicity: Monitor cardiovascular and respiratory vital signs and patient’s state of consciousness after application of ZYNRELEF. When using ZYNRELEF with other local anesthetics, overall local anesthetic exposure must be considered through 72 hours. Hepatotoxicity: If abnormal liver tests persist or worsen, perform a clinical evaluation of the patient. Hypertension: Patients taking some antihypertensive medication may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure. Heart Failure and Edema: Avoid use of ZYNRELEF in patients with severe heart failure unless beneﬁts are expected to outweigh risk of worsening heart failure. Renal Toxicity: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Avoid use of ZYNRELEF in patients with advanced renal disease unless beneﬁts are expected to outweigh risk of worsening renal failure. Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs.

PP-HTX011-0557 | 07/21

Use in Speciﬁc Populations Methemoglobinemia: Cases have been reported with local anesthetic use. Serious Skin Reactions: NSAIDs, including meloxicam, can cause serious skin adverse reactions. If symptoms present, evaluate clinically. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): If symptoms are present, evaluate clinically. Fetal Toxicity: Due to the risk of oligohydramnios/fetal renal dysfunction and premature closure of the ductus arteriosus with NSAIDS, limit use of ZYNRELEF between about 20 to 30 weeks gestation, and avoid use after about 30 weeks. Hematologic Toxicity: Monitor hemoglobin and hematocrit in patients with any signs or symptoms of anemia. Drug Interactions Drugs That Interfere with Hemostasis: Monitor patients for bleeding who are using ZYNRELEF with drugs that interfere with hemostasis (eg, warfarin, aspirin, SSRIs/SNRIs). ACE Inhibitors, Angiotensin Receptor Blockers (ARBs), or Beta-Blockers: Use with ZYNRELEF may diminish the antihypertensive effect of these drugs. Monitor blood pressure. ACE Inhibitors and ARBs: Use with ZYNRELEF in elderly, volumedepleted, or those with renal impairment may result in deterioration of renal function. In such high-risk patients, monitor for signs of worsening renal function. Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effect.

Infertility: NSAIDs are associated with reversible infertility. Consider avoidance of ZYNRELEF in women who have difficulties conceiving. Severe Hepatic Impairment: Only use if beneﬁts are expected to outweigh risks; monitor for signs of worsening liver function. Severe Renal Impairment: Not recommended. Adverse Reactions Most common adverse reactions (incidence *10%) in controlled clinical trials with ZYNRELEF are constipation, vomiting, and headache. Report side effects to Heron at 1-844-437-6611 or to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For additional information about ZYNRELEF, please refer to the Brief Summary of Prescribing Information on adjacent page. References: 1. ZYNRELEF [package insert]. San Diego, CA: Heron Therapeutics Inc; 2021. 2. Viscusi E, Gimbel JS, Pollack RA, Hu J, Lee G-C. HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: Phase III results from the randomized EPOCH 1 study. Reg Anesth Pain Med. 2019;44(7):700-706. doi:10.1136/rapm-2019-100531. 3. Viscusi E, Minkowitz H, Winkle P, Ramamoorthy S, Hu J, Singla N. HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the Phase 3 EPOCH 2 study. Hernia. 2019;23(6):1071-1080. doi:10.1007/s10029-019-02023-6. 4. Lachiewicz PF, Lee G-C, Pollak R, Leiman D, Hu J, Sah A. HTX-011 reduced pain and opioid use after primary total knee arthroplasty: results of a randomized Phase 2b trial. J Arthroplasty. 2020;35(10):2843-2851. doi:10.1016/j.arth.2020.05.044. 5. Ottoboni T, Quart B, Pawasauskas J, Dasta JF, Pollak RA, Viscusi ER. Mechanism of action of HTX-011: a novel, extended-release, dual-acting local anesthetic formulation for postoperative pain. Reg Anesth Pain Med. 2020;45(2):117-123. doi:10.1136/rapm-2019-100714.

REDEFINE POSTOPERATIVE PAIN MANAGEMENT

ZYNRELEF™ (bupivacaine and meloxicam) extended-release solution, for soft tissue or periarticular instillation use BRIEF SUMMARY OF PRESCRIBING INFORMATION WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use • ZYNRELEF is contraindicated in the setting of coronary artery bypass graft (CABG) surgery • NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events INDICATIONS AND USAGE ZYNRELEF is indicated in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. Limitations of Use: Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. DOSAGE AND ADMINISTRATION Important Dosage and Administration Information: ZYNRELEF is intended for single-dose administration only. Avoid intravascular administration of ZYNRELEF. ZYNRELEF should be administered in a setting where trained personnel and equipment are available to promptly treat patients who show evidence of neurologic or cardiac toxicity. Avoid additional use of local anesthetics within 96 hours following administration of ZYNRELEF. The safety of concomitant administration of ZYNRELEF and other NSAID medications has not been evaluated. If additional NSAID medication is indicated in the post-operative period, monitor patients for signs and symptoms of NSAID toxicity. ZYNRELEF should only be prepared and administered with the components provided in the ZYNRELEF kit. See ZYNRELEF Instructions for Use included in the kit for complete administration instructions. ZYNRELEF is not indicated for the following routes of administration: epidural, intrathecal, intravascular or intra-articular, regional nerve blocks, pre-incisional, and pre-procedural locoregional anesthetic techniques. Administration Instructions: ZYNRELEF is applied without a needle into the surgical site using a Luer lock cone-shaped applicator attached to the syringe following final irrigation and suction of each layer and prior to suturing. Only apply ZYNRELEF to the tissue layers below the skin incision and not directly onto the subdermal layer or skin. Use only the amount necessary to coat the tissues, such that ZYNRELEF does not leak from the surgical wound after closure. Dosing Instructions: The recommended dose of ZYNRELEF (bupivacaine/meloxicam) is as follows: − Bunionectomy: up to 2.3 mL to deliver 60 mg/1.8 mg − Open inguinal herniorrhaphy: up to 10.5 mL to deliver 300 mg/9 mg − Total knee arthroplasty: up to 14 mL to deliver 400 mg/12 mg See full Prescribing Information for all important dosage and administration information, preparation instructions and compatibility considerations. CONTRAINDICATIONS ZYNRELEF is contraindicated in patients with known hypersensitivity (eg, anaphylactic reactions and serious skin reactions) to any amide local anesthetic, NSAIDs, or other components of ZYNRELEF; with history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs (severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients); undergoing obstetrical paracervical block anesthesia; or undergoing coronary artery bypass graft (CABG) surgery. WARNINGS AND PRECAUTIONS Cardiovascular (CV) Thrombotic Events with NSAID Use: To minimize the risk of CV thrombotic events, do not exceed the recommended dose. Monitor for serious CV events. Aspirin does not mitigate the risk of these thrombotic events. In patients with a recent MI, avoid the use of ZYNRELEF unless the benefits are expected to outweigh the risk, and if used, monitor patients for signs of cardiac ischemia. The risk of these events following single-dose local application of ZYNRELEF is uncertain. Gastrointestinal Bleeding, Ulceration, and Perforation with NSAID Use: To minimize the risk of GI bleeding, do not exceed the recommended dose and avoid using more than one NSAID at a time. If additional NSAID medication is indicated in the post-operative period, monitor patients for signs and symptoms of NSAID-related GI adverse reactions. In high-risk patients, evaluate if the benefit outweighs the risk of bleeding, remain alert for GI ulcerations and bleeding, and promptly evaluate and treat suspected serious GI adverse events. In patients using concomitant low-dose aspirin, monitor for GI bleeding. Dose-Related Toxicity: The toxic effect of local anesthetics are additive. When using with other local anesthetics, overall local anesthetic exposure must be considered through 72 hours. Monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity.

Risk of Use in Patients with Impaired Cardiovascular Function: Patients with impaired cardiovascular function may be less able to compensate for the prolongation of AV conduction. Monitor patients closely for blood pressure, heart rate, and ECG changes. Hepatotoxicity: Bupivacaine should be used cautiously in patients with hepatic disease because of their inability to metabolize local anesthetics normally. NSAIDs are associated with elevations of ALT or AST and rare, sometimes fatal cases of severe hepatic injury. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur, perform a clinical evaluation of the patient. The risk of these events following single-dose local application of ZYNRELEF is uncertain. Hypertension: NSAID use in patients taking ACE inhibitors, thiazide or loop diuretics may result in impaired blood pressure control. Monitor blood pressure. Heart Failure and Edema: NSAID use in patients with heart failure may increase the risk of MI, hospitalization for heart failure, and death. Additionally, fluid retention and edema have been observed with NSAIDs. Avoid use in patients with severe heart failure unless the benefit outweighs the risk of worsening heart failure; if used, monitor for signs of worsening heart failure. The risk of these events following single-dose local application of ZYNRELEF is uncertain. Renal Toxicity: NSAIDs may cause a dose-dependent reduction in renal blood flow and overt renal decompensation. Additionally, the metabolites of meloxicam are excreted by the kidney which may hasten the progression of renal dysfunction in those with renal disease. Correct dehydration and hypovolemia prior to initiating ZYNRELEF. Avoid use in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Anaphylactic Reactions: Meloxicam has been associated with anaphylactic reactions in patients with and without known hypersensitivity to meloxicam and in patients with aspirin-sensitive asthma. Seek emergency help if an anaphylactic reaction occurs. Chondrolysis with Intra-Articular Infusion: Intra-articular infusions of local anesthetics have been associated with chondrolysis. ZYNRELEF is not approved for intra-articular infusion. Methemoglobinemia: Local anesthetics have been associated with methemoglobinemia. Treat with supportive care, and if necessary, methylene blue, exchange transfusion, or hyperbaric oxygen. Exacerbation of Asthma Related to Aspirin Sensitivity: NSAIDs are contraindicated in patients with aspirin-sensitive asthma. When ZYNRELEF is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for exacerbation of asthma symptoms. Serious Skin Reactions: NSAIDs can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome, and toxic epidermal necrolysis, which can be fatal. If symptoms present, evaluate clinically. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): NSAIDs may cause DRESS. If signs or symptoms are present, evaluate the patient immediately and treat as clinically indicated. Fetal Toxicity: NSAIDs may cause fetal renal dysfunction leading to oligohydramnios at about 20 weeks gestation and premature closure of the fetal ductus arteriosus at about 30 weeks gestation or later. Limit use between about 20 to 30 weeks gestation, and avoid use after about 30 weeks. Hematologic Toxicity: NSAIDs may cause anemia due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (eg, aspirin), SSRIs and SNRIs may increase this risk. Monitor these patients’ hemoglobin and hematocrit and for signs or symtoms of anemia. Masking of Inflammation and Fever: NSAIDs reduce inflammation, and possibly fever, which may diminish detection of infections. ADVERSE REACTIONS The safety of ZYNRELEF has been evaluated in a total of 1067 patients undergoing various surgical procedures across 7 randomized, double-blind, bupivacaine- and placebo-controlled studies designed to investigate ZYNRELEF to reduce postoperative pain for 72 hours and the need for opioid analgesics. Among 504 patients who received ZYNRELEF in single doses of 60 mg/ 1.8 mg to 400 mg/12 mg via instillation into the surgical site, the most common adverse reactions (incidence greater than or equal to 10%) following ZYNRELEF administration were constipation, vomiting, and headache. The most common adverse reactions (≥ 5% and higher than placebo) in the following 3 studies were: • Bunionectomy: 157 patients received ZYNRELEF 60 mg/1.8 mg and the most common adverse reactions were dizziness, incision site edema, headache, incision site erythema, bradycardia, impaired healing, and muscle twitching. With the exception of muscle twitching, these events were also higher for bupivacaine HCl compared to placebo. A total of four subjects had delayed bone healing (assessed by X-ray on days 28 and 42), with no clinically meaningful difference between treatment groups. Additional local inflammatory adverse events observed at a higher incidence for ZYNRELEF compared to placebo or bupivacaine HCl included incision site cellulitis, wound dehiscence and incision site infection. • Herniorrhaphy: 163 patients received ZYNRELEF 300 mg/9 mg and the most common adverse reactions were headache, bradycardia, dysgeusia, and skin odor abnormal. With the exception of skin odor abnormal, these events were also higher for bupivacaine HCl compared to placebo. • Total knee arthroplasty: 58 patients received ZYNRELEF 400 mg/12 mg and the most common reactions were nausea, constipation, vomiting, hypertension, pyrexia, leukocytosis, and pruritus. With the exception of hypertension, these events were also higher for bupivacaine HCl compared to placebo.

DRUG INTERACTIONS Bupivacaine Drug Interactions: Local anesthetics: In clinical studies, other local anesthetics (including ropivacaine and lidocaine) have been administered before, during, or after application of ZYNRELEF without evidence of local anesthetic systemic toxicity. Administration of ZYNRELEF with other formulations of local anesthetics (ie, bupivacaine liposome injectable suspension) has not been studied. Drugs associated with methemoglobinemia: Bupivicane may increase risk of methemoglobinemia when concurrently used with nitrates, local anesthetics, antineoplastic agents, antibiotics, antimalarials, anticonvulsants, and other methemoglobinemia-associated drugs. Meloxicam Drug Interactions: Drugs That Interfere with Hemostasis: Meloxicam use with anticoagulants has an increased risk of serious bleeding compared to the use of either drug alone. Monitor patients with concomitant use of ZYNRELEF with anticoagulants, antiplatelet agents, SSRIs, and SNRIs for signs of bleeding. ACE Inhibitors, Angiotensin Receptor Blockers (ARBs), or Beta-Blockers: Meloxicam may diminish the antihypertensive effect of these drugs. Monitor blood pressure. ACE Inhibitors and ARBs: Meloxicam use with ACE inhibitors and ARBs in elderly, volume-depleted, or those with renal impairment may result in deterioration of renal function. In such high-risk patients, adequately hydrate and monitor for signs of worsening renal function. Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy, including antihypertensive effect. Digoxin: NSAIDs increase the serum concentration and prolong the half-life of digoxin. Monitor serum digoxin levels. Lithium: NSAIDs elevate plasma lithium levels and reductions in renal lithium clearance. Monitor for signs of lithium toxicity. Methotrexate: NSAIDs use with methotrexate may increase risk for neutropenia, thrombocytopenia, and other methotrexate-associated toxicities. Monitor for signs of methotrexate toxicities. Cyclosporine: NSAIDs use with cyclosporine may increase nephrotoxicity. Monitor for signs of worsening renal function. Pemetrexed: Meloxicam used with pemetrexed may increase myelosuppression, renal, and GI toxicities. In patient with creatinine clearance 45 to 79 mL/min, monitor for pemetrexed-associated toxicities. OVERDOSE No data are available with regard to overdose of ZYNRELEF. Management of Local Anesthetic Overdose: At the first sign of change, oxygen should be administered. The first step for convulsions, underventilation, or apnea is immediate maintenance of a patent airway and assisted or controlled ventilation capable of immediate positive airway pressure. After assuring airway and ventilation, evaluate and establish adequate circulation as indicated. Drugs that treat convulsions may depress the circulation. If convulsions persist despite adequate respiration, and if the circulation permits, small increments of an ultra-short acting barbiturate or a benzodiazepine may be administered intravenously. Supportive treatment of circulatory depression may require intravenous fluids and, when appropriate, a vasopressor. If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias, and cardiac arrest. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted. Endotracheal intubation, employing drugs, and techniques familiar to the clinician, may be indicated after initial administration of oxygen by mask if maintenance of a patent airway is inadequate or if prolonged ventilatory support is indicated. CLINICAL PHARMACOLOGY ZYNRELEF contains bupivacaine, an amide local anesthetic, and meloxicam, an NSAID. The contribution of each active ingredient in ZYNRELEF has been studied in clinical studies in herniorrhaphy or bunionectomy, utilizing ZYNRELEF and formulations of meloxicam alone or bupivacaine alone in the ZYNRELEF vehicle. Meloxicam alone provided negligible local analgesia and bupivacaine alone provided greater analgesia compared with placebo through 24 hours post surgery, despite exposure to bupivacaine for approximately 72 hours. Compared with bupivacaine alone in both studies, ZYNRELEF demonstrated greater and longer analgesia through 24, 48, and 72 hours. The instillation of ZYNRELEF into the surgical site results in significant systemic plasma levels of bupivacaine and meloxicam through 96 hours. Systemic plasma levels of bupivacaine or meloxicam following application of ZYNRELEF do not correlate with local efficacy. PATIENT COUNSELING Inform patients of the risks and mitigations for: CV thrombotic events; GI bleeding, ulceration, and perforation, including the increased risk of GI toxicity with use of NSAIDs in the postoperative period; anaphylactic reactions; serious skin reactions, including DRESS; methemoglobinemia; fetal toxicity; and temporary loss of sensation near the surgical site. This information is not comprehensive. Visit www.zynrelef.com to obtain the full Prescribing Information, including Boxed Warning. © 2021 Heron Therapeutics, Inc. All rights reserved. ZYNRELEF™ is a trademark of Heron Therapeutics, Inc.

Manufactured and marketed by: Heron Therapeutics, Inc., 4242 Campus Point Court, Suite 200, San Diego, CA, 92121, USA. PP-HTX011-0102 05/21

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6 Policy

Pharmacy Practice News • December 2021

Sterile Compounding Table. Surface Sampling Locations

Where to Sample?

Potential Sources Of Contamination

Room

Sample Location

Sample ID

Risk

continued from page 1

People, materials, touch

Buffer room/SCA

DCA PECa

High

Carta

Medium

Inside bottom of pass-throughb

Medium

High traffic, people, materials

Between worktables

S4, S5

Medium

People, materials, touch

Table (with printer) or staging table

Low

Clean cart or supply cart

Low

Although it might seem logical to let your third-party certifier choose sampling locations for you, Ms. Roth advised compounding pharmacies to conduct their own prospective risk analysis to select those locations. “Only you know where best to sample in your pharmacy, since sampling must occur in locations that, if contaminated, have a higher risk of affecting the compounded sterile preparations,” she said. “You know where your high-touch-risk and back-and-forth hightraffic areas are.” Based on those considerations, “you need to develop a rationale for your sampling locations and frequencies for each environment, and document why you chose those locations.” The sampling plan should include: • a diagram indicating where air and surface samples are collected; • some type of key to identify the sample, whether it is an air or surface sample, the number and description; • ideally, a list of locations that describes the exact area to be sampled to ensure consistency (e.g., S1-left side of staging table) and avoid

oversampling (Figure); and • one sample in the direct compounding area (DCA) in ISO Class 5 spaces. In a restricted access barrier system, Ms. Roth added, samples should be taken in the DCA in the main and transfer chambers. But in ISO Class 7 and 8 rooms, “you will probably have more choices for surface sampling than you want to think about. It can be a challenge finding those that will provide you with useful information on your microbial state of control. Some may give better information than others.” Bridget Gegorski, PharmD, a medication safety officer at University Hospitals of Cleveland, agreed that “you can’t sample every surface in your cleanroom; you have to choose strategic spaces. We always sample the direct compounding area of our ISO 5 hood, and always sample the pass-through windows,” she noted in a separate interview. “Beyond that, we focus on high-touch areas where our staff spend the most time and move the most product through the room, such as the stainless steel tables in the cleanroom

People, materials, touch People, materials, touch, high traffic, opens to unclassified

Ungarbed people, materials, touch, high traffic, sinks

Buffer room

Anteroom

There may be multiple PECs and workstations in a facility; b Applies to counter-height pass-through; fullheight pass-throughs usually are ISO 8 and treated as though they were a room. DCA, direct compounding area; PEC, primary engineering control; SCA, segregated compounding area

Source: CriticalPoint.

that are used as a staging area. The technicians place all products they are getting ready to prepare on these tables. Because all product comes through that table, it has the most opportunity to be a source of contamination.” Ms. Roth agreed with Dr. Gegorski that the best way to choose areas for

surface sampling is to watch work practices. “Look for areas at greatest risk of contamination. These can include areas of human activity during compounding, entry points from areas of lower classification to those of higher classification ingress from the anteroom into the buffer room, and areas within and around doors and pass-throughs,” Ms. Roth said (Table). “Consider the location of your equipment and how that’s going to affect the microorganisms you see. As you choose locations for sampling, make sure you stick with them for a period of time to watch trends.”

Location, Location, Location

Figure.

This schematic depicts oversampling. Too much data is overwhelming and might not be useful. Too little data does not provide an accurate picture of microbial contamination. Image courtesy of CriticalPoint.

Ms. Roth offered a few examples of optimal sampling locations: Carts and tables. “Consider how they are used,” she said. “If you have a cart that is used directly outside a primary engineering control to stage materials, then that should be sampled. In an ISO 8, if you don’t have a pass-through, you likely have a ‘dirty cart, clean cart’ system, where you bring materials into the dirty side of the line of demarcation, wipe the materials with the designated agent, and then place them on a clean cart on the clean side of the line of demarcation. A great place to take a sample is on that clean cart, so you can see what was tracked into the space after the material handling process. If you’re finding a lot of organisms there, that could be an area for improvement.” Exceeded levels on carts and tables can indicate poor sanitization during the work shift, she said. Pass-throughs. “You may have a passthrough that is going from the unclassified area into the ISO 8, and then another from the ISO 8 into the buffer room. If you have these pass-throughs, the 2019 version of <797> requires you to sample the interior of that passthrough,” Ms. Roth said. “I recommend that you go with the bottom, because that’s where materials are going to be

Policy

Pharmacy Practice News • December 2021

Sterile compounding

A Clean(room) Partnership: Working With a Certifier H

aving a strong working partnership with a certification company is critical for developing a workable cleanroom testing protocol, according to two sterile compounding veterans. Knowing the limits of your staff’s expertise in this area, coupled with an ability to troubleshoot key compliance gaps, can go a long way toward ensuring success, they noted during separate conferences on sterile compounding. The first key step is “to know that your cleanroom is in a state of control for the protection of your employees and your patients,” said Lisa Ashworth, BSPharm, RPh, a clinical pharmacist at Children’s Health System of Texas, in Dallas, during the “Cleanovators” virtual summit presented by Contec. “We’re pharmacists and pharmacy technicians; we’re not architects or engineers, and we’re not certified to perform cleanroom testing. Although I do know some hospital systems are moving toward having part of their staff certified to do that, most generally are not. We need help from our certifiers in understanding the documents used to apply testing from groups like the International Organization for Standardization, the Controlled Environment Testing Association, NSF International, the American National Standards Institute, and the American Society of Heating, Refrigerating and Air-Conditioning Engineers.” Before an inspector or accreditor even arrives at your facility, Ms. Ashworth said, you should know and understand: • your cleanrooms’ testing results; • reasons for and outcomes of any plan of action;

• how to detect any trends; and • how to troubleshoot problem areas using techniques such as smoke testing. “I like to equate my partnership with our certification company with my scuba diving equipment certifier,” Ms. Ashworth said. “I don’t want to find out when I’m 60 feet underwater that my regulator or computer isn’t working correctly. I have to have my equipment certified annually. Similarly, let’s take a ‘safety stop’ in the cleanroom and read our reports and look at all the details in them—then we don’t have to take a longer ‘safety stop’ later.” Cleanroom certification reports can take many forms, she said. “They’re unique to each company. They will have the same things in the report, but they may not be in the same place or look the same, so you have to familiarize yourself with the components, where you find them and how they are organized. “Sit down with your certifier and ask questions about these reports. Get in the cleanroom with them and ask questions,” Ms. Ashworth said. “Have them do some examples for you: How are particle count tests in the hood performed? What in those hoods can affect it? Open up a needle by the particle counter and see if that makes the counts go up. Pop the needle open inappropriately from the package and see how many more particles that makes—or does it? Tearing apart needles and different things in the hood, all of these are great examples that you can use to explain these reports and links to behavior in the cleanroom to your staff.” Certification companies should assess the following:

set, and we want to see which bugs are transferred on those materials.” Door handles of pass-throughs. That’s a “maybe” location, depending on where it is located. “The door handle of a pass-through in your ISO 8 anteroom, for example, may or may not be sampled,” she said. “If the passthrough lives on the dirty side and goes through to the unclassified space, it’s likely that people are not wearing gloves to reach in and there will be an astronomical number of bugs on that handle, which may or may not be a problem, depending on your compounding process. For a door handle on a pass-through from the ISO 8 into the buffer room, you should look at your workflow and practice. Ideally, someone passing something from your Class 8 into the buffer room is wearing gloves. If they are, sample the handle and see what’s there. If they’re not, you need to talk about material handling.” Refrigerators. “You might have a pass-through fridge that lives between

your unclassified space and the anteroom, or the anteroom and the buffer room. You need to watch work practice and see how people are utilizing this refrigerator,” Ms. Roth said. “If you have a lot of back-and-forth to it that could directly impact the sterility of the compounded sterile preparation, by all means take samples there to track the movement of microorganisms.” What about door handles in general? It depends on your setup. More and more systems have moved to hands-free doors, in which case sampling is probably unnecessary. At University Hospitals of Cleveland, the vast majority of doors are now hands-free after a 2017-2018 construction project, Dr. Gegorski said. “Those sites that updated their cleanrooms prior to getting capital for the larger project may still have manual doors. But honestly, we haven’t found door handle sampling to be all that valuable anyway, because we are also obsessively cleaning those daily.” Sinks and benches. These are another

• laminar airflow workbenches hess (hoods) and biological safety ety cabinets; • viable air and surface sampling; plin ng; • HEPA filter integrity; • nonviable airborne particlee coun counts; nts ts; and • viable air sampling. She advised reviewing room identification reports carefully and ensuring that maps on each report are drawn correctly, with proper placement of hoods, ceiling HEPA filters and lights, and negative pressure rooms, positive pressure rooms, anterooms and other areas labeled correctly, with correct and up-to-date room occupancy. “Ensure that sampling locations are identified correctly on the map and that the number of sampling locations is accurate,” Ms. Ashworth said. “There can be transcription errors in reports, and just as we put scrutiny on our prescriptions for our patients, we need to put similar scrutiny on these reports.”

A Crucial Role for Partnerships A good partnership with your certifier can identify areas where you need more viable sampling, noted Abby Roth, the senior director of business operations at CriticalPoint, during the Compounding Pharmacies Grand Salon. “Your certifier can provide you with particle counts per location, and in some areas, you may see a higher particle count than others because of the way air moves through the room and where your return grills are located.” While doing HEPA testing, certifiers can also help you determine the load on

“maybe” location. “It is difficult to sample around a freestanding sink,” Ms. Roth said. “But if you have a sink incorporated into a longer countertop, with water splashing onto that counter, and people are putting things down on the counter that will be carried into the buffer room, sampling on the sink might be valuable in the short term. But in the long term, I’d rather have you change work practices so people don’t put things next to that sink. And please don’t sample inside the sink. There will be a ton of microorganisms, even with daily cleaning. For benches, if you have staff that put things on your garbing bench that ultimately end up in the primary engineering control, you might want to sample the bench. But again, what you really want to do is change that work practice. The only thing that should be going on the bench is somebody’s backside.” Walls and floors. As for what can be skipped, “nobody should be sampling walls,” Ms. Roth said. “If your staff are touching the walls before they enter

your HEPA filters and when you may need to change them, Ms. Ashworth said. “You don’t want to find out when you’re in your biannual testing that that’s when you need filters, especially right now when there’s such a short supply of everything.” When it comes to remediation and plans of action, Ms. Ashworth said, there can be many different approaches, but certain information should always be included: • the date the report was written; • the date testing occurred; • who receives the information; • results of testing or equipment failure/replacement, including description of viable organisms and how many; • pictures, if available; and • next steps: who, when, where, what, how and why. “We can be inspected by many agencies at any time,” Ms. Ashworth said. “Be sure you know your reports, you’ve read them thoroughly and documented them, and have a great relationship with your certifier.” —Gina Shaw The sources reported no relevant financial disclosures.

the primary engineering control, you need to do some retraining, figure out why and change work practices so that is not an issue,” Ms. Roth said. “Nobody should be sampling floors. And unless you’re compounding on the floor, you can skip sampling there, especially in the anteroom. An ISO 8, in particular, and on the dirty side especially, will be loaded with microorganisms. There should be less on the clean side, but this also is why the chapter requires cleaning the floor daily to mitigate the risk of organisms present on the floor.” The point of monthly surface sampling, Dr. Gegorski said, is to paint a picture of microbial control in the space. “You want to choose locations that will help you assess how well you are behaving in the space, how well your garbing is going and how well your cleaning practices are being maintained.” —Gina Shaw The sources reported no relevant financial disclosures.

8 Policy

Pharmacy Practice News • December 2021

Finance

340B Program, PAPs Help Ensure SP Rx Success

ctively managing participation in the federal 340B Drug Pricing Program, coupled with efforts to boost financial assistance and medication access, can help maximize savings and ensure the overall success of specialty pharmacy services, a panel of experts said during the 2021 ASHP Conference for Pharmacy Leaders, held virtually. For example, when the FDA approved the pediatric cystic fibrosis

medication elexacaftor-tezacaftorivacaftor (Trikafta, Vertex) in June, the specialty pharmacy team at Atrium Health Wake Forest Baptist, in WinstonSalem, N.C., worked with eligible patients and their families to ensure they were completing necessary lab tests and education counseling during clinic visits leading up to the approval so patients would be ready, said Regina Schomberg, PharmD, BCPS, the system

director of pharmacy, retail and specialty pharmacy services. With the help of a medication access specialist, they were able to obtain prior approval for 19 patients within one week of the FDA approval, and all patients were able to have their prescriptions sent either to the hospital’s internal specialty pharmacy or another specialty pharmacy within the first week. Dr. Schomberg and her colleagues

also were able to use 340B savings to support pharmacy staff to continue providing personalized care to this vulnerable population.

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Solid-organ transplant patients also can benefit from ongoing specialty pharmacy care and 340B funding. “Financial assistance continues to be the largest barrier these patients experience,” Dr. Schomberg said. “You can imagine the severity of a patient being overwhelmed with the desire to continue with their newly transplanted organ, and then also have to grapple with the need for finance assistance.” During a patient outreach call, one of her pharmacy technicians discovered that a patient had lost their job two months before, was at risk for losing insurance coverage, and had been paying out of pocket for the medication. The patient shared they were a few days from being out of medication and didn’t have the funds to pay for the new script. The pharmacy technician found a patient assistance program (PAP) and contacted the manufacturer for approval within a few days. Year to date, Dr. Schomberg and her colleagues’ work on PAPs has garnered millions of dollars of medication savings. They also use a computerized system that allows searching for PAP, foundation or grant funding, and they keep track of the paperwork to assist patients. Their efforts to maximize 340B savings also have paid off. But Dr. Schomberg stressed that the program doesn’t just benefit patients; at her institution, 340B savings also are invested in staff, including two designated medication access specialists fully devoted to PAPs. —Karen Blum Dr. Schomberg reported no relevant financial disclosures.

Web Exclusive For UC Davis Health System’s approach to helping transplant patients access affordable medications, see expanded version of this article at www. pharmacypracticenews.com.

Q&A

Pharmacy Practice News • December 2021

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10 Policy

Pharmacy Practice News • December 2021

FDA Watch

Spending ekes out a win over traditional meds

Specialty Drug Approvals: A Year of Firsts Aurora, Colo.—Two of the most notable new drug approvals in 2021 were not technically new; they were new indications, but they should have a significant effect on the specialty market. Two biosimilars became the first interchangeable biologics approved by the FDA. Just more than one year after it was approved, insulin glargine-yfgn (Semglee, Viatris/Biocon Biologics) was granted interchangeable status with its reference product Lantus (Sanofi) in July 2021. It can be automatically substituted with the reference product by a pharmacist, similar to the substitutions made for traditional generics. On Oct. 20, Express Scripts listed insulin glargine-yfgn as a preferred insulin on its National Preferred Formulary, due to take effect in January 2022. “Semglee currently costs about half as much as Lantus,” explained Aimee Tharaldson, PharmD, at the 2021 AMCP Nexus meeting. “This could save clients $20 million next year due to this decision,” added Dr. Tharaldson, a senior clinical pharmacist of Emerging Therapeutics at Express Scripts. The second biosimilar to be designated as interchangeable is adalimumabadbm (Cyltezo, Boehringer Ingelheim), a biosimilar to Humira (AbbVie). Adalimumab-adbm, which was originally approved in August 2017, was made interchangeable on Oct. 18. Unlike insulin glargine-yfgn, however, adalimumabadbm will not launch immediately due to patent settlement agreements with AbbVie. It will launch in 2023, along with five other biosimilars to adalimumab, but only adalimumab-adbm has interchangeability at this point. Another biosimilar approved this year, ranibizumab-nuna (Byooviz, Samsung Bioepis/Biogen), a biosimilar to Lucentis (Genentech), is the first ophthalmic biosimilar. The anti–vascular endothelial growth factor therapy was approved to treat several eye conditions, including neovascular age-related macular degeneration, the leading cause of blindness in those 65 years of age and older. Bevacizumab (Biothera), a biosimilar to Avastin (Genentech) for several cancer types, and another adalimumab biosimilar by Coherus were expecting approvals before the end of the year. “So far, FDA has approved 31 biosimilars to 11 biologics. And 21 biosimilars to 8 biologics are currently available on the market,” Dr. Tharaldson explained. “These biosimilars have combined sales of about $4 billion.” Specialty spending, which has been creeping up each year, has overtaken the traditional drug spend, Dr. Tharaldson

noted. “Fifty-one percent of per member per year drug spend under the pharmacy benefit is for specialty drugs,” she said, but only about 2% of the patients covered take specialty medications.

More Firsts

and an AURORA clinical trial investigator, said in a press release announcing the approval (bit.ly/30ekHkz). “About 10% of these patients with lupus nephritis develop end-stage renal disease,” Dr. Tharaldson said.

Long-Acting HIV Medication

Genetic Disorders

ViiV Healthcare kicked off the year with the approval of the first long-acting HIV medication. Cabotegravir-rilpivirine injectable (CAB/RPV; Cabenuva) is an alternative to oral treatment for adults with low viral loads who are on a current stable regimen and no history of treatment failure, she explained. Dosed monthly, CAB/RPV comes as a copack with two injectable medications, ViiV’s cabotegravir and Janssen’s rilpivirine.

Casimersen (Amondys 45, Sarepta Therapeutics) is the first drug approved to treat Duchenne muscular dystrophy (DMD) with a mutation amenable to exon 45 skipping. About 10,000 boys and young men have DMD, but only about 8% have this genetic mutation, according to Dr. Tharaldson. Casimersen is an antisense oligonucleotide that skips over exon 45 to enable a partially functioning dystrophin protein. The medication is

(HIF-2alpha) inhibitor, is the first treatment for von Hippel-Lindau (VHL) syndrome, a rare genetic disorder that leads to the development of cancerous and noncancerous tumors. Seventy percent of people with this condition develop renal cell carcinoma, Dr. Tharaldson explained. Belzutifan reduces transcription and expression of HIF-2alpha target genes associated with cellular proliferation, angiogenesis and tumor growth. “In Study 004, nearly half of all patients with VHL-associated renal cell carcinoma, as well as the majority of patients with VHL-associated central nervous system hemangioblastomas or pancreatic neuroendocrine tumors, who were treated with Welireg experienced a reduction of their respective tumor size,” explained Ramaprasad Srinivasan, MD, PhD, the head of the Molecular Cancer Therapeutics Section, National Cancer Institute.

Cancer Drugs Approved Non-Small Cell Lung Cancer

Voclosporin (Lupkynis, Aurinia), the first therapy for adults with active lupus nephritis (LN), was approved in January. LN, a common complication of systemic lupus erythematosus, causes irreversible kidney damage and significantly increases the risk for kidney failure, cardiac events and death.

The approval was based on the phase 3 ATLAS and FLAIR studies that included more than 1,100 patients from 16 countries. Prior to initiating treatment, oral dosing of CAB and RPV are given to assess tolerability with therapies. The first therapy for adults with active lupus nephritis was also approved in January. Lupus nephritis, a common complication of systemic lupus erythematosus, causes irreversible kidney damage and significantly increases the risk for kidney failure, cardiac events and death. Voclosporin (Lupkynis, Aurinia), an oral therapy used with a background immunosuppressive regimen, is a calcineurin inhibitor. In the pivotal AURORA trials, patients treated with voclosporin with immunosuppressives were more than twice as likely to achieve renal response and experience a decline in the urine protein to creatinine ratio. “For years, treating patients with lupus nephritis has been challenging. We have had a very limited number of therapeutic options, and these have been only modestly effective but highly toxic,” Brad H. Rovin, MD, the director of the Division of Nephrology at The Ohio State University Wexner Medical Center, in Columbus,

given as a weekly infusion. The new indication is based on a statistically significant increase in dystrophin production in skeletal muscle observed in patients treated with casimersen, which is reasonably likely to predict clinical benefit. Fosdenopterin (Nulibry, BridgeBio/ Origin Biosciences) is the first drug for patients with molybdenum cofactor deficiency (MoCD) type A, which affects fewer than 150 infants and young children worldwide. MoCD type A is an autosomal recessive, inborn error of metabolism caused by mutations in the molybdenum cofactor synthesis 1 gene and characterized by a deficiency in molybdenum cofactor production and enzyme activity. The lack of activity leads to a buildup of sulfite and secondary metabolites in the brain, which causes irreversible, progressive neurologic damage. “Nulibry allows the production of a missing enzyme that reduces the buildup of the harmful substances in the brain. It’s administered as a daily IV infusion,” Dr. Tharaldson said. Small studies showed improved overall survival (OS) compared with an untreated cohort. Belzutifan (Welireg, Merck), an oral hypoxia-inducible factor-2 alpha

Non-small cell lung cancer (NSCLC) patients also benefited from several approvals. Although lung cancer rates are decreasing in the United States, 235,760 adults still are diagnosed each year, and 85% with NSCLC, according to the American Society of Clinical Oncology. • Sotorasib (Lumakras, Amgen) is the first targeted treatment for KRAS G12C–mutated locally advanced or metastatic NSCLC. About 13% of NSCLC patients have this “previously elusive mutation,” according to David M. Reese, MD, the executive vice president of Research and Development at Amgen. A phase 2 study found a 37% objective response rate. • Mobocertinib (Exkivity, Takeda) is the first medication to target epidermal growth factor receptor (EGFR) exon 20 insertion mutations, and is indicated for locally advanced or metastatic disease. “EGFR exon 20 insertion plus NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs [tyrosine kinase inhibitors],” said Pasi A. Jänne, MD, PhD, of the Dana Farber Cancer Institute, in Boston. • Amivantamab-vmjw (Rybrevant, Janssen), an EGFR exon 20–directed and mesenchymal–epithelial transition (MET) receptor–directed antibody, was approved to treat patients with NSCLC with EGFR exon 20 insertion mutations. “This [NSCLC variant] is pretty rare,” Dr. Tharaldson said. “Only about 1% to 2% of patients with NSCLC have these exon 20 insersee NEW DRUGS, page 12

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12 Policy

Pharmacy Practice News • December 2021

FDA Watch

NEW DRUGS continued from page 10

tion mutations. It’s more common in Asian populations and is associated with lower survival rates.” • Tepotinib (Tepmetko, EMD Serono), a second oral MET inhibitor, is indicated for adults with NSCLC that has metastasized and has MET exon 14 alterations, which affects about 3% to 4% of patients with NSCLC. • Trilaciclib (Cosela, G1 Therapeutics/ Boehringer Ingelheim), a cyclin-

dependent kinase 4 and 6 inhibitor, was approved to reduce chemotherapy-induced myelosuppression in extensive-stage small cell lung cancer. The IV infusion is given four hours before chemotherapy to reduce the duration and severity of neutropenia. Lymphomas

Lymphomas also benefited from new options in 2021. • Loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics) is the first CD19directed antibody and alkylating agent

conjugate approved for diffuse large B-cell lymphoma (DLBCL) and indicated in the third-line setting. DLBCL affects about 10% of patients. • Lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb [BMS]), a chimeric antigen receptor (CAR) T-cell agent, was approved for the third-line treatment of adults with relapsed/ refractory DLBCL. It is given as a onetime infusion. • Umbralisib (Ukoniq, TG Therapeutics) is an oral phosphoinositide 3-kinase delta and casein kinase 1 epsilon

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COMPLIANT? WE’VE GOT YOU COVERED

inhibitor approved for adults with relapsed/refractory marginal zone or follicular lymphoma. Marginal zone lymphoma is diagnosed in about 7,500 U.S. patients and follicular lymphoma in about 15,000. Both are slow-growing forms of non-Hodgkin lymphoma, Dr. Tharaldson explained. Multiple Myeloma

Two specialty medications were approved for multiple myeloma (MM), both for relapsed/refractory disease: melphalan flufenamide (Pepaxto, Oncopeptides), a peptide–drug conjugate alkylating drug used in combination with dexamethasone, and idecabtagene vicleucel (Abecma, BMS/bluebird bio), a B-cell maturation antigen-directed CAR T-cell therapy. However, Oncopeptides is withdrawing melphalan flufenamide after results from the OCEAN study (ClinicalTrials.gov Identifier: NCT03151811) showed the OS of patients who received the injection with dexamethasone was lower than those who were treated with pomalidomide (Pomalyst, BMS) and dexamethasone, as reported in Pharmacy Practice News (bit.ly/3oh6xHO). Collaborating with the FDA, Oncopeptides will ensure that patients who need to keep using melphalan flufenamide will have access to it. (For more information, contact OnCourse Patient Support Services at 1-844-300-6626.) “Even though there are a lot of drugs to treat MM, most patients wind up relapsing,” Dr. Tharaldson said. Advanced Renal Cell Carcinoma

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The FDA approved tivozanib (Fotivda, Aveo Oncology), a new oral angiogenesis inhibitor, for third-line treatment of adults with advanced renal cell carcinoma. “About of 76,000 new cases of kidney cancer are diagnosed each year, and about 90% are renal cell carcinoma, which typically does not respond well to chemotherapy,” she explained. Cholangiocarcinoma

Infigratinib (Truseltiq, BridgeBio/ Helsinn) is an oral fibroblast growth factor 2 TKI indicated for cholangiocarcinoma that is inoperable. About 8,000 cases of cholangiocarcinoma are diagnosed each year. It’s typically difficult to diagnose, and the average survival rate is less than 10%. About 50% of cases involved an FGFR2 mutation. Leukemias

Asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze, Jazz Pharmaceuticals) is a new asparaginespecific enzyme product used with other chemotherapy drugs to treat acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) for patients 1 month of age and older. “These are rare cancer types that primarily affect

Policy

Pharmacy Practice News • December 2021

FDA Watch children,” Dr. Tharaldson said. Clinical data from an ongoing pivotal phase 2/3, dose-confirmation study evaluating pediatric and adult patients with ALL or LBL demonstrated the achievement and maintenance of nadir serum asparaginase activity (NSAA) greater than or equal to 0.1 U/mL at 48 hours using intramuscular 25-mg/m2 doses of asparaginase erwinia-rywn. The proportion of patients maintaining NSAA of at least 0.1 U/mL at 48 hours after a dose of asparaginase erwinia-rywn was 93.6% (95% CI, 92.6%-94.6%). Asciminib (Scemblix, Novartis) was approved to treat Philadelphia chromosome–positive myeloid leukemia chronic phase (Ph+ CML-CP) previously treated with two or more TKIs, and Ph+ CMLCP with the a T315I mutation. Asciminib is the first FDA-approved CML treatment that works by binding to the ABL myristoyl pocket.

Orphan and Other Conditions Belumosudil (Rezurock, Kadmon Holdings) is an oral graft inhibitor for patients 12 years of age and older with chronic graft-versus-host disease (cGVHD), a common complication after hematopoietic stem cell transplant. In ROCKstar, a randomized, openlabel, multicenter pivotal trial of belumosudil, patients with cGVHD who had received two to five prior lines of systemic therapy achieved an overall response rate of 75% through cycle 7 on day 1 of treatment, with 6% achieving a complete response and 69% achieving a partial response. The median time to first response was 1.8 months. “Patients receiving Rezurock reported significant improvements in cGVHD symptoms, showing that not only did treatment result in organ responses, but it also made people feel better. This is so important for a chronic disease with a high symptom burden,” Stephanie Lee, MD, MPH, a professor at the Fred Hutchinson Cancer Research Center, in Seattle, said in a Kadmon Holdings press release (bit.ly/3qyeH1m). Other notable approvals include two ileal bile acid transporter inhibitors: odevixibat (Bylvay, Albireo Pharma) and maralixibat (Livmarli, Mirum). Odevixibat is indicated for the once-daily oral treatment of pruritus associated with progressive familial intrahepatic cholestasis patients 3 months of age and older. Maralixibat is approved for cholestatic pruritus caused by Alagille syndrome. Pegcetacoplan (Empaveli, Apellis Pharmaceuticals) is the first C3 complement inhibitor used to treat paroxysmal nocturnal hemoglobinuria, a rare life-threatening blood disorder affecting about 6,000 patients in the United States. The approval of pegcetacoplan is based on results from the head-to-head phase 3 PEGASUS study, which demonstrated

Dr. Tharaldson said. “Two phase 3 trials were actually stopped early because they didn’t look like they’re going to be effective. But a reanalysis of one of the studies found that those treated longer term with a higher dose responded to therapy.” —Marie Rosenthal

Graft-versus-host disease can occur in response to hematopoietic stem cell transplants.

superiority to eculizumab (Soliris, Alexion) for the change from baseline in hemoglobin level at week 16, with an adjusted mean increase of 3.84 g/dL of hemoglobin (P<0.0001). Eighty-five percent of pegcetacoplan patients were transfusion-free over 16 weeks versus 15%

of those treated with eculizumab. Aducanumab (Aduhelm, Biogen/ Eisai), an amyloid beta–directed antibody indicated to treat Alzheimer’s disease, was probably one of the most controversial approvals (bit.ly/3bWL3du-PPN). “The results of clinical trials are mixed,”

Dr. Tharaldson reported no relevant financial disclosures. In addition to her presentation at AMCP Nexus, company and FDA press materials were used to develop this article. This is not a comprehensive list of all specialty drugs approved in 2021.

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14 Policy

Pharmacy Practice News • December 2021

Reimbursement Matters

Highlights of the 2022 OPPS/ASC Final Rule Sets T

he final CY 2022 rule sets have been released by CMS, with payment rates for Medicare Part B drugs and biologicals essentially remaining the same as they were last year: ASP+6% for SI G and SI K products for non-340B facilities, and ASP+6% for SI G and ASP-22.5% for 340B facilities. The payment threshold differentiating SI K from SI N remains at $130 per day based on ASP. However, the hold on the minus 2% sequestration due to the pandemic expires Dec. 31, 2021. Once again, 2% will be deducted from 80% of CMS payments; the 20% copay is not affected. Addendum B is the key to knowing which SIs apply to which drugs. SI N covers products either below the threshold cutoff ($130 per day based on ASP)

or products that are bundled because of statute. In either case, there is no separate payment for the products; they are paid as part of the bundle. Note that per CMS instructions, all bundled products must be separately billed to account for their use even though they won’t appear as separate line-item payment. SI K covers separately payable products above the $130-per-day threshold and often is the category where drugs land once their pass-through status

expires. Note that this is the only category of products affected by the 340B payment reduction of ASP-22.5%. SI G is the pass-through category, which is one of the most interesting ones this year. Since 1999, the passthrough payment provision requires additional payments to hospitals for: • current orphan drugs, as designated under Section 526 of the Federal Food, Drug, and Cosmetic Act; • current drugs and biologicals and

“Reimbursement Matters” is a tool for maintaining your health system’s fiscal health. Please email the author at bonniekirschenbaum@ gmail.com with suggestions on reimbursement issues that you would like to see covered.

Bonnie Kirschenbaum, MS, FASHP, FCSHP

A Reimbursement Lexicon ASC, ambulatory surgery center; ASP, average sales price; CMS, Centers for Medicare & Medicaid Services; CY, calendar year; HCPCS, Healthcare Common Procedure Coding System; IPPS, Inpatient Prospective Payment System; NTAP, new technology add-on payment; OPPS, Outpatient Prospective Payment System; P&T, Pharmacy and Therapeutics; SI, Status Indicator

Table 1. 27 Drugs With Expiring Pass-Through Status That Will Receive an Extension of Separate Payment in 2022

CY 2022 LONG DESCRIPTOR

Pass-Through Payment End Date

Extension Of Separate Payment (# Quarters)

Iodine i-131 iobenguane, therapeutic, 1 millicurie

12/31/2021

J0222

Injection, Patisiran, 0.1 mg

12/31/2021

J0291

Injection, plazomicin, 5 mg

12/31/2021

J1943

Injection, aripiprazole lauroxil, (aristada initio), 1 mg

12/31/2021

J2798

Injection, risperidone, (perseris), 0.5 mg

12/31/2021

J9204

Injection, mogamulizumab-kpkc, 1 mg

12/31/2021

J7169

Injection, coagulation factor Xa (recombinant), inactivated (andexxa), 10 mg

03/31/2022

C9046

Cocaine hydrochloride nasal solution for topical administration, 1 mg

03/31/2022

J0642

Injection, levoleucovorin (khapzory), 0.5 mg

03/31/2022

J1095

Injection, dexamethasone 9 percent, intraocular, 1 microgram

03/31/2022

J3031

Injection, fremanezumab-vfrm, 1 mg (code may be used for Medicare when drug administered under the direct supervision of a physician, not for use when drug is self-administered)

03/31/2022

J3245

Injection, tildrakizumab, 1 mg

03/31/2022

J7208

Injection, factor viii, (antihemophilic factor, recombinant), pegylated-aucl (jivi) 1 i.u.

03/31/2022

J9119

Injection, cemiplimab-rwlc, 1 mg

03/31/2022

J9313

Injection, moxetumomab pasudotox-tdfk, 0.01 mg

03/31/2022

Q5108

Injection, pegfilgrastim-jmdb, biosimilar, (fulphila), 0.5 mg

03/31/2022

Q5110

Injection, filgrastim-aafi, biosimilar, (nivestym), 1 microgram

03/31/2022

Q5111

Injection, Pegfilgrastim-cbqv, biosimilar, (udenyca), 0.5 mg

03/31/2022

C9047

Injection, caplacizumab-yhdp, 1 mg

06/30/2022

J0121

Injection, omadacycline, 1 mg

06/30/2022

J1096

Dexamethasone, lacrimal ophthalmic insert, 0.1 mg

06/30/2022

J1303

Injection, ravulizumab-cwvz, 10 mg

06/30/2022

J9036

Injection, bendamustine hydrochloride, (belrapzo/bendamustine), 1 mg

06/30/2022

J9210

Injection, emapalumab-lzsg, 1 mg

06/30/2022

J9269

Injection, tagraxofusp-erzs, 10 micrograms

06/30/2022

J3111

Injection, romosozumab-aqqg, 1 mg

09/30/2022

J9356

Injection, trastuzumab, 10 mg and hyaluronidase-oysk

09/30/2022

CY 2022 HCPCS CODE A9590

CY, calendar year; HCPCS, Healthcare Common Procedure Coding System

Policy

Pharmacy Practice News • December 2021

Reimbursement Matters

Table 2. New Drug NTAPs Approved for FY 2022

Product

ICD-10-PCS Code

Maximum NTAP Payment In FY 2022, $

Abecma (idecabtagene vicleucel)

XW033K7 or XW043K7

272,675.00

Cosela (trilaciclib)

XW03377 or XW04377

5,526.30

Fetroja (cefiderocol) (HABP/VABP indication)

XW033A6 or XW043A6 in combination with Y95 and one of the following: J14.0, J15.0, J15.1, J15.5, J15.6, J15.8 OR XW033A6 or XW043A6 in combination with J95.851 and one of the following: B96.1, B96.20, B96.21, B96.22, B96.23, B96.29, B96.3, B96.5, B96.89

8,579.84

Recarbrio (imipenem, cilastatin, and relebactam)

XW033U5 or XW043U5 in combination with Y95 and one of the following: J14.0, J15.0, J15.1, J15.5, J15.6, or J15.8 OR XW033U5 or XW043U5 in combination with J95.851 and one of the following: B96.1, B96.20, B96.21, B96.22, B96.23, B96.29, B96.3, B96.5, B96.89

9,576.51

Rybrevant (amivantamab-vmjw)

XW033B7 or XW043B7

6,405.89

Stratagraft

XHRPXF7

44,200.00

Tecartus (brexucabtagene autoleucel)

XW033M7 or XW043M7

259,350.00

Veklury (remdesivir)

XW033E5 or XW043E5

2,028.00

Zepzelca (lurbinectedin)

XW03387 or XW04387

8,622.90

FY, fiscal year; HABP, hospital-acquired bacterial pneumonia; ICD-10-PCS, International Classification of Diseases, 10th Revision, Procedure Coding System; NTAP, new technology add-on payment; VABP, ventilator-associated bacterial pneumonia

Table 3. Drug NTAPs Continuing in FY 2022

Product

ICD-10-PCS Code

Maximum NTAP Payment In FY 2022, $

Andexxa (coagulation factor Xa)

XW03372 or XW04372

18,281.25

Azedra (iobenguane I 131)

XW033S5 or XW043S5

98,150.00

Balversa (erdafitinib)

XW0DXL5

3,563.23

Cablivi (caplacizumab)

XW013W5 or XW033W5 or XW043W5

33,215.00

Fetroja (cefiderocol) (cUTI indication)

XW033A6 or XW043A6

7,919.86

Elzonris (tagraxofusp-erzs)

XW033Q5 or XW043Q5

144,116.04

Imfinzi (durvalumab)

XW03336 or XW04336

6,875.90

JAKAFI (ruxolitinib)

XW0DXT5

4,096.21

Nuzyra (omadacycline) for injection

XW033B6 or XW043B6

1,552.50

Recarbrio (imipenem, cilastatin, and relebactam)

XW033U5 or XW043U5

3,532.78

Soliris (eculizumab)

XW033C6 or XW043C6

21,199.75

Spravato (esketamine)

XW097M5

1,014.79

Tecentriq (atezolizumab)

XW033D6 or XW043D6

6,875.90

Xenleta (lefamulin)

XW03366 or XW04366 or XW0DX66

1,275.75

Xospata (gilteritinib)

XW0DXV5

7,312.50

Zemdri (plazomicin)

XW033G4 or XW043G4

4,083.75

Zerbaxa (ceftolozane/tazobactam)

XW03396 or XW04396

1,836.98

cUTI, complicated urinary tract infection; FY, fiscal year; ICD-10-PCS, International Classification of Diseases, 10th Revision, Procedure Coding System; NTAP, new technology add-on payment

brachytherapy sources used in cancer therapy; and • current radiopharmaceutical drugs and biologicals. “Current” refers to those types of drugs or biologicals that are hospital outpatient services under Medicare Part B. Payment is provided for certain “new” drugs and

biologicals not being paid for as a hospital outpatient department service as of Dec. 31, 1996, and whose costs are “not insignificant” in relation to OPPS payments for the procedures or services associated with the new drugs or biologicals. For passthrough payment purposes, radiopharmaceuticals are included as “drugs.” This

period lasts at least two but not more than three years, with products being added and expiring on a quarterly basis. Due to the pandemic, 27 products (Table 1) have been given an extended additional one to four quarters of SI eligibility—a significant win for 340B facilities. Pass-through eligibility remains for 65 drugs. Since it’s

not uncommon for CMS to change the HCPCS codes for these products, it’s essential to ensure your charge description master and pharmacy drug master are up-to-date with the correct codes. Note: Who’s responsible at your site? Is your IT department on it? An initial and rapid file build is critical. Any drug being used needs an immediate accurate file build regardless of its formulary status or while under P&T Committee review. Remember that new payment technology for inpatients paid under IPPS can be separately payable as well, if it has been submitted to CMS for extensive review and is approved as an NTAP. This review continues on an annual basis, so the product listing is fluid. See Tables 2 and 3 for 2022. (For more information on antibiotic NTAPs, see “Act Now to Get Paid for Novel ABx Under NTAP” at bit. ly/3nkVAWt. For a Table of 65 additional drugs with continuing pass-through status, see expanded version of this column at www.pharmacypracticenews.com.) ■

One Burning Question Q Podcast What is involved in getting paid for Medicare Part B drugs and their administration? Access discussion between Keith Streckenbach and Bonnie Kirschenbaum at bit.ly/30UVyvN

16 Clinical

Pharmacy Practice News • December 2021

Inflammatory Disorders

Pharmacists Drive Guidelines-Based Gout Therapy

pharmacist-driven educational initiative to alert primary care providers about potential risks of febuxostat (Uloric, Takeda) in gout patients with cardiovascular disease has led to increased use of guideline-based therapy and a significant drop-off in febuxostat prescribing, according to a study by pharmacists at Cone Health, in North Carolina. To understand why the researchers undertook the study, it is important to

review the debate over the safety of febuxostat, which was spurred in part by a boxed warning about an increased risk for death in gout patients taking the medication (bit.ly/3FFj2nA). It also is important to understand the mechanisms underpinning gout flares. Because gout is caused by accumulation of urate crystals in the joints, especially in the big toes, “the goal is to reduce the serum urate level in the

THE DISTINCTION IN

COMPOUNDING

blood to below the point at which urate can crystallize,” said Tuhina Neogi, MD, PhD, a professor of medicine at Boston University School of Medicine. Although Dr. Neogi was not involved in the Cone Health study, she is well versed in the issues surrounding optimal gout management, having been a co-author of the “2020 American College of Rheumatology [ACR] Guideline for the Management of Gout” (Arthritis

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Care Res 2020;72[6]:744-760). The 2020 ACR guideline recommends allopurinol as the first-line urate-lowering therapy (ULT) of choice for the management of all patients with gout, given its efficacy, tolerability, safety and cost, Dr. Neogi noted. Historically, providers have sometimes chosen febuxostat over allopurinol in patients with renal insufficiency, who are at increased risk for allopurinol hypersensitivity syndrome, she said. “But in our new guideline, allopurinol is preferred even in those with moderate to severe renal insufficiency.” In addition, due to uncertainty about the risk of febuxostat in patients with a history of cardiovascular disease (CVD) or a new cardiovascular event, the guideline conditionally recommends that patients taking febuxostat switch “to an alternative ULT agent,” provided the switch is consistent with other recommendations in the guideline, she explained. Concern over febuxostat stems in part from results of the CARES trial, which evaluated the cardiovascular safety of febuxostat and allopurinol (N Engl J Med 2018;378[13]:1200-1210). Although the CARES investigators found that overall rates of major cardiovascular events were similar among patients with gout and CVD treated with the two drugs, allcause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio [HR] for death from any cause, 1.22 [95% CI, 1.01-1.47]; HR for cardiovascular death, 1.34 [95% CI, 1.03-1.73]). Although the CARES trial led to the FDA’s black box warning, which was added in 2019, Dr. Neogi cautioned that the trial was not conclusive. “There was a lot of discontinuation of therapy and a lot of participants lost to follow-up,” she said. “And in the primary composite cardiovascular end point, there was no difference between the two arms of the trial. Febuxostat was associated with a higher risk of cardiovascular death and all-cause mortality than allopurinol, but 85% of deaths occurred after participants stopped ULT. Also, there was no untreated arm. It’s very challenging to say definitively that there is an issue with cardiovascular risk associated with febuxostat.” But, as noted, the data were enough to prompt the FDA to require the addition of the febuxostat boxed warning, stating that “health care professionals see GOUT GUIDELINES, page 21

Clinical

Pharmacy Practice News • December 2021

Review Article

Gene Therapy Series

Harnessing the Potential of Multiple Myeloma Therapy RHONDA LETWIN, RN, BSN, OCN Clinical Program Manager

MARCIE MORRIS, PHARMD, CSP Clinical Program Manager AllianceRx Walgreens Prime, Pittsburgh, Pennsylvania

Gene and Cell Therapy Defined

ultiple myeloma (MM), which develops in plasma cells, can result in low blood counts and weakening of the immune system.1

According to the National Cancer Institute, MM accounted for approximately 1.8% of new cancer cases in the United States in 2020.2 The cause of MM is unknown, and there is no cure. Less than half of Americans diagnosed with MM die within 5 years.3

Despite advances in treatment over the last 20 years,4 MM remains an incurable disease characterized by periods of remission and relapse. Studies show that patients with relapsed or refractory MM who have been treated with the 3 major drug classes (immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) generally have low response rates (20%-30%), a short duration of response (2-4 months), and poor survival.5-8

Current Cell Therapies: CAR T-Cell Therapy Chimeric antigen receptor (CAR) T-cell therapy has been a major breakthrough in the treatment of specific types of leukemia and lymphoma, and now is approved for the treatment of relapsed or refractory MM. T cells collected from a patient’s blood are genetically modified to have CARs on their surface, giving the T cells the ability to bind to a specific protein expressed on a tumor cell, which, in turn, activates the immune system to destroy the tumors. After the new T cells multiply and reach a certain number in the laboratory (usually hundreds of millions to billions), they are sent back for infusion into the patient. The process is detailed in the Figure.9-11 B-cell maturation antigen (BCMA)

is a major target for CAR T-cell therapies. The targeted tumor cell protein normally is not expressed in healthy cells; thus, the CAR T cells bind to and destroy only tumor cells. Shortly before the CAR T-cell therapy infusion, a patient receives preparatory lymphodepleting chemotherapy to allow the new “superpotent” T cells to establish themselves. The infused cells then circulate throughout the body, attacking the patient’s cancer cells.10 CAR T-cell therapy is a one-time treatment, and if all goes well, the patient will achieve a complete remission and the CAR T cells will continue to proliferate and persist in the patient’s body. Like all treatments, CAR T-cell therapy carries risks. Approximately onethird of patients experience serious adverse effects (AEs) that require acute management in the hospital, occasionally in intensive care.10 Cytokine release syndrome (CRS) is the most frequent serious acute CAR T-cell–related toxicity, with an absolute incidence of 30% to 100% (10%30% for CRS grade ≥3).12,13 CRS causes shortness of breath, malaise, high fever, and a drop in blood pressure and oxygenation, among other symptoms. The inflammatory response also can cause neurotoxicity, resulting in difficulty speaking, drowsiness,

Gene and cell therapy (GCT) is an exciting new area of medicine offering the potential to treat, or even cure, diseases that previously may have had limited or no treatment options. These therapies treat or cure disease by introducing cells or DNA to address the underlying cause of a disease. Cell therapy involves removal of cells from either the patient (autologous) or a donor (allogeneic), modification of those cells outside the body, and reinfusion of the modified cells back into the patient to treat the disease.1 The type of cell used depends on the specific treatment. Gene therapy is the delivery of genetic material via a vector, usually viral in origin, to replace, deactivate, or repair faulty DNA that is causing a disease.1 Use of a viral vector allows the new genetic material to be inserted directly into a patient’s own DNA, thereby enabling proper protein production to lessen the effects of or completely cure a disease. This article is part of a series describing the potential of gene therapy for various disease states. 1. American Society of Gene and Cell Therapy. Gene and cell therapy FAQs. Accessed November 22, 2021. https://www.asgct.org/education/more-resources/gene-and-cell-therapy-faqs

disorientation, and even coma. Most patients will experience some AEs within the first 2 to 4 weeks of treatment, and the majority will completely recover. Due to the potential for serious AEs, CAR T-cell therapy is administered only in specialized centers and is reserved for patients who have no other options.10 BCMA-TARGETED CAR T-CELL THERAPY FOR MM One CAR T-cell therapy—idecabtagene vicleucel, or ide-cel (Abecma, Bristol Myers Squibb/bluebird bio)— is approved by the FDA for the treatment of MM. It is approved as a one-time infusion for the treatment of adults with relapsed or refractory MM after 4 or more lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.5,14,15 The safety and efficacy of idecel were established in a multicenter study of 127 patients with relapsed or refractory MM who received at least 3 prior lines of therapy.15 Overall, 72% of the patients partially or completely responded to the treatment; 28% showed a complete response (CR) to ide-cel, and 65% of this group had a CR lasting at least 12 months.15 Treatment with ide-cel has the potential to cause severe AEs.

The labeling for ide-cel has a boxed warning about CRS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life-threatening.14 Because of the risk for CRS and neurologic toxicities, ide-cel is approved with a Risk Evaluation and Mitigation Strategy. The FDA also requires that hospitals and their associated clinics dispensing ide-cel be specially certified and that staff involved in prescribing, dispensing, or administering ide-cel be trained to recognize and manage CRS, nervous system toxicities, and other AEs associated with ide-cel. In addition, clinicians must inform patients about the potential for serious AEs and of the importance of promptly seeking treatment if AEs develop.15

Future Cell and Gene Therapies BCMA-BASED CELL THERAPIES Additional BCMA-targeted CAR T-cell therapies in development include JNJ-4528 (Janssen), which showed strong and durable responses in patients with relapsed or refractory disease in a phase 1b/2 trial,16 and bb21217, which uses the bb2121 CAR molecule with an additional see MYELOMA, page 18

18 Clinical

Pharmacy Practice News • December 2021

Review Article

MYELOMA

limited-distribution medications, including any relevant reporting, purchasing, or dispensing requirements, may offer manufacturers added confidence as these products are given to patients. Research is seeking to uncover the next generation of CAR T-cell therapies, which are hoped to be off-theshelf treatments that can be mass manufactured from a healthy donor’s cells and used for multiple patients. As CAR T-cell therapy enters mainstream cancer immunotherapy, pharmacists can play a fundamental role in the comprehensive care of patients receiving these treatments.

continued from page 17

manufacturing process.17 It is cultured with the PI3K inhibitor bb007 to improve CAR T-cell functional persistence. Overall, CAR T cells targeting BCMA on MM cells have shown high response rates.17 However, the question still remains whether these responses will be durable. Data released from a phase 1 study of bb21217 demonstrated that 6 of the 15 patients who achieved complete responses relapsed.18 Median progression-free survival among all patients was approximately 1 year.18

Source: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy.

CD229-BASED CELL THERAPIES Future approaches will have the goal of producing more durable responses. One such approach uses CD229, which is prevalent on the surface of both MM cells and stem cells, which can produce treatment-resistant tumor cells. A preclinical study found that CD229-targeted treatment produced a significant reduction in MM-propagating cells compared with the BCMA-targeted CAR T-cell therapies.19 The next step for researchers is to determine whether the CD229targeted cells will be safe to use in human clinical trials. DUAL-TARGETED CAR T-CELL THERAPY BM38 CAR T cells are the first dualtarget CAR T cells that contain antiBCMA and anti-CD38 in tandem for the treatment of MM. In a phase 1 trial, more than 90% of patients with relapsed or refractory MM responded to therapy with a bispecific CAR T-cell

References 1.

therapy targeting the CD38 protein and BCMA on myeloma cells.9 CRISPR EDITING–COMBINED GENE AND CELL THERAPY An approach that uses the geneediting technique CRISPR has identified several pathways that MM cells use to evade immunotherapy, with the goal of enhancing the effectiveness of CAR T-cell therapy. The results could lead to therapeutic improvements, such as supplementing BCMA-targeted immunotherapy to reduce resistance and potential relapses.20 GENE INHIBITION Many patients with MM develop resistance to treatment due to the formation of cancer stem cells, which drive the disease. Some researchers are working to silence the IRF4 gene, which allows MM stem cells and tumor cells to proliferate and survive.

They are using an engineered piece of DNA specifically designed to bind the genetic material coding for IRF4, causing it to degrade.21

The Pharmacist’s Role Although CAR T-cell therapy is a medication, neither specialty nor hospital pharmacists dispense this treatment. Due to the specialized nature of manufacturing and administering CAR T-cell therapy, these products are available only at certified treatment centers, where CAR T-cell therapy is treated in a similar manner as a stem cell infusion and less like traditional therapy. However, due to its potentially life-threatening risks and monitoring requirements, it is critical that pharmacists be knowledgeable about the process of CAR T-cell therapy and toxicity management.22 Specialty pharmacists’ expertise and ability to manage

Mayo Clinic. Multiple myeloma. Accessed October 22, 2021. www.mayoclinic.org/ diseases-conditions/multiple-myeloma/ symptoms-causes/syc-20353378

2. National Cancer Institute. Surveillance, Epidemiology and End Results Program. Cancer stat facts: myeloma. Accessed October 22, 2021. seer.cancer.gov/statfacts/ html/mulmy.html 3. American Cancer Society. Survival rates by stage for multiple myeloma. Accessed October 22, 2021. www.cancer.org/cancer/ multiple-myeloma/detection-diagnosisstaging/survival-rates.html 4. Kumar S. Treatment of newly diagnosed multiple myeloma in transplanteligible patients. Curr Hematol Malig Rep. 2011;6(2):104-112. 5. U.S. Food and Drug Administration approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the ﬁrst anti-BCMA CAR T cell therapy for relapsed or refractory multiple myeloma [press release]. Bristol Myers Squibb; March 26, 2021. Accessed October 22, 2021. bit.ly/3nmHQsO 6. Gandhi UH, Cornell RF, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD38targeted monoclonal antibody therapy. Leukemia. 2019;33(9):2266-2275. 7. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21(2):207-221. 8. Jagannath S, Lin Y, Goldschmidt H, et al. KarMMa-RW: a study of real-world treatment patterns in heavily pretreated patients with relapsed and refractory multiple myeloma (RRMM) and comparison of outcomes to KarMMa. J Clin Oncol. 2020;38(15 suppl): abstract 8525. 9. Weaver CH. CAR-T cell therapy - advances in the management of multiple myeloma. Cancer Connect. Updated June 8, 2021. Accessed October 22, 2021. bit.ly/3pp5EPC 10. NewYork-Presbyterian. CAR T-cell therapy, a breakthrough treatment for cancer patients. Health Matters. Accessed October 22, 2021. bit.ly/3C8jJnZ 11. National Cancer Institute. CAR T-cell therapy. Accessed October 22, 2021. bit. ly/3Gaj1Jt 12. Frontiers in Oncology. CAR T-cells in multiple myeloma: state of the art and future directions. Accessed October 22, 2021. www.ncbi.nlm.nih.gov/pmc/articles/ PMC7399644/ 13. Frey N, Porter D. Cytokine release syndrome with chimeric antigen receptor T cell therapy. Biol Blood Marrow Transplant. 2019;25(4):e123-e127.

Clinical

Pharmacy Practice News • December 2021

Oncology

Propylene Glycol–Free Melphalan Passes Safety Test C

oncerns have been raised about the potential toxicity of propylene glycol (PG)-free melphalan treatment in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplant (auto-HSCT). But new data suggest those concerns may be unfounded. Generic melphalan contains PG as one solvent. After the FDA approved PG-free melphalan (Evomela, Acrotech) in 2016, contradictory reports emerged about its toxicity, said Ko Maung, MD, of Duke Cancer Institute in Durham, N.C. “At Duke, we used PG-free melphalan since May 2017, but switched to generic melphalan in November 2017 due to the concern for increased toxicity. We hypothesized that PG-free melphalan is associated with more toxicity than generic melphalan,” he said. Dr. Maung and his colleagues evaluated outcomes among patients with multiple myeloma undergoing their first auto-HSCT between May 2017 and September 2018, comparing those treated with PG-free melphalan with those given generic melphalan (J Natl Compr Canc Netw 2020 Mar 20. doi.org/10.6004/ jnccn.2019.7412). Of the 63 patients in the overall study population, 27 received PGfree melphalan and 36 received generic melphalan. All patients received outpatient auto-HSCT and were admitted if acute issues arose. The analysis showed no statistically significant differences in time to count recovery, toxicities or resource utilization between groups. The rate of treatment response also was similar: 33% with PG-free melphalan and 39% with generic melphalan (P=0.0655), Dr. Maung reported. “Our auto-transplant data for

14. ABECMA [prescribing information]. Bristol Myers Squibb; March 2021. Accessed October 22, 2021. packageinserts.bms.com/ pi/pi_abecma.pdf

myeloma did not show significant difference in toxicities between PG-free melphalan and generic melphalan,” he said. “Generic melphalan seemed to be associated with a higher early treatment response, but, again, this was not statistically significant.” Despite the findings, Dr. Maung said the Duke bone marrow transplant program “decided to keep using generic melphalan.” He added that “PG-free melphalan is convenient because it is stable, without crystallization at room temperature. But we did not have evidence that one is better than the other in terms of efficacy or toxicity, and, at least at Duke, PG-free melphalan is much more expensive. Considering everything, we didn’t feel it’s reasonable to use PG-free melphalan.”

Waste Another Factor “This retrospective report adds to those previously published demonstrating similar efficacy and toxicity between the PG-free and PG-containing melphalan,” David Frame, PharmD, a clinical assistant professor of pharmacy and clinical pharmacist at Michigan Medicine in Ann Arbor, told Pharmacy Practice News. “The largest report, also retrospective, was from the Mayo clinic evaluating 416 myeloma patients [Bone Marrow Transplant 2019;54(4):587-594], most of whom were also outpatient transplants with similar outcomes as reported here. “At the University of Michigan, we switched to the PG-free melphalan in early 2017 due the significantly extended stability time of four hours versus one hour for the PG-containing product,” Dr. Frame said. “It can be very challenging” to make melphalan and deliver and

Table. Transplant Outcomes With PG-Free And PG-Containing Melphalan Outcome

PG-Free Melphalan PG Melphalan P (n=27) (n=36) Value

Average ANC recovery, days

12.0

12.2

0.727

Average platelet recovery, days

18.3

21.3

0.115

Total transplant stay, days

17.7

18.4

0.549

Admission rate, %

0.691

Average length of stay, days

3.2

3.4

0.837

Mucositis, %

0.938

Febrile neutropenia, %

0.619

ANC, absolute neutrophil count; PG, propylene glycol

infuse it before it expires, he added, noting that this resulted in waste of “many bags of drug, which was quite costly.” He said “this waste was virtually eliminated with the PG-free product.” Dr. Frame also noted that additional generic PG-containing melphalan products have been approved over the last few years, decreasing the cost “significantly,”

19. Radhakrishnam SV, Leutkens T, Scherer SD, et al. CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. Nat Commun. 2020;11(798). doi.org/10.1038/s41467-02014619-z13

16. Johnson & Johnson. Janssen’s BCMA CAR-T therapy JNJ-4528 showed early, deep and durable responses in heavily pretreated patients with multiple myeloma. Accessed October 22, 2021. bit. ly/2XCgRAX

20. Figueiredo M. CRISPR-edited T-cells safely, effectively target cancer cells in myeloma patients, early phase 1 data suggests. Myeloma Research News. November 13, 2019. Accessed October 22, 2021. bit. ly/3C85fVi

17. bluebird bio and Celgene Corporation present Initial data from ongoing phase 1 clinical study of next-generation anti-BCMA CAR T cell therapy bb21217 in patients with relapsed/refractory multiple myeloma at ASH annual meeting [press release]. bluebird bio; December 2, 2018. Accessed October 22, 2021. investor.bluebirdbio. com/news-releases/news-release-details/ bluebird-bio-and-celgene-corporationpresent-initial-data

21. Designer DNA therapeutic wipes out cancer stem cells, treats multiple myeloma in mice. Science Daily. January 20, 2021. Accessed October 22, 2021. bit.ly/3jsZrOS 22. Shaw G. Pharmacy’s role in managing CAR-T therapy. Specialty Pharmacy Continuum. October 21, 2021. www. specialtypharmacycontinuum.com/ Clinical/Article/07-18/Pharmacy-s-Role-inManaging-CAR-T-Therapy/52309

—Caroline Helwick and Sarah Tilyou Drs. Frame and Maung reported no relevant financial disclosures.

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18. Weintraub A. Celgene reports ‘durable’ responses to multiple myeloma CAR-T in early trial despite relapses. Fierce Biotech. May 3, 2019. Accessed October 22, 2021. bit.ly/3B15dNr

15. FDA. FDA approves ﬁrst cell-based gene therapy for adult patients with multiple myeloma. Accessed October 22, 2021. www.fda.gov/news-events/ press-announcements/fda-approves-ﬁrstcell-based-gene-therapy-adult-patientsmultiple-myeloma

but he underscored that the factors influencing the decision about which melphalan product to use “need to be evaluated in each institution.”

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20 Clinical

Pharmacy Practice News • December 2021

Nutrition

Nutrition a ‘Human Right’ continued from page 1

a clinical practice specialist at ASPEN, told webinar attendees. He believes the expansion “could have real importance in connecting individuals with training to diagnose and assess malnutrition with the people most at risk of poor nutrition.” Those U.S. efforts are being undertaken in the context of a global commitment by World Health Organization member states to eliminate malnutrition as part of the UN Decade of Action on Nutrition (www.unscn.org).

A Medicare Part B Benefit The MNT Act provides individualized nutrition assessment and therapy, as well as support for behavioral and lifestyle changes, to Medicare Part B recipients with renal disease or diabetes, noted Mr. Mirtallo, a professor emeritus at The Ohio State University in Delaware, Ohio. As specified in the act, MNT has to be provided by a registered dietitian and is limited to three hours of MNT in the first

year and two hours in the second year, with additional hours allowable if there is a change in the patient’s diagnosis, medical condition or treatment regimen. Since its passage in 2000, the MNT Act has been amended to allow for MNT services to be provided via telehealth, and the 20% copay specified in the original act was removed. Despite those amendments, MNT services still do not reach many of those who need it, Mr. Mirtallo said. “One of the obstacles to utilization of MNT is that a patient needs a referral by a physician,” he said. However, meeting that challenge can be difficult, he noted, because physicians may not be aware of the availability of MNT services or able

to find a registered dietitian in their area. To address these awareness and provider gaps, the proposed MNT expansion would add nurse practitioners, physician assistants, clinical nurse specialists and psychologists to the list of professionals who can refer patients for MNT, Mr. Mirtallo explained. “We need more providers and others in the community to be able to identify patients at risk [for poor nutrition] and refer them. Nutrition screening followed by assessment and a nutritional care plan developed by a dietitian is essential to [establishing] nutrition care as a human right.” Another barrier to MNT access that the proposed expansion is meant to address is that while only patients with renal disease and diabetes are eligible to receive these services, many other patient groups could benefit from MNT, Mr. Mirtallo said. In 2020, he and his colleagues screened 221 consecutive individuals seen at a charitable community

broad range of conditions apart from renal disease and diabetes, including those with prediabetes, obesity, cancer, high blood pressure, high cholesterol, malnutrition, eating disorders, celiac disease, HIV/ AIDS, cardiovascular disease and any other condition/disease that causes unintentional weight loss. The amendment also would provide the Secretary of Health with the authority to add other diseases based on medical necessity. “Hopefully, Medicare will set a standard that private insurers will pick up on and use to expand their own coverage of MNT,” said Mr. Mirtallo, urging webinar attendees to contact their U.S. representatives to support the MNT Act expansion.

Standardization Up North

While ASPEN has been working to legislate expanded access to nutrition care, in Canada, Leah Gramlich, MD, a professor of medicine at the University of Alberta, in Edmonton, and her colleagues on the Canadian Malnutrition Task Force, which she co-chairs, are standardizing the way nutrition care is provided in the hospital setting. She told webinar attendees that treating mal5 Key MNT Act nutrition isn’t just a human Provisions right in the community; it’s also one that needs to be hon1. Medicare Part B recipients with renal disease or diabetes are given ored in hospitalized patients, individualized nutrition assessment with interventions guided by and therapy, and support for evidence-based MNT, includbehavioral and lifestyle changes. ing artificial nutrition and 2. The nutrition support has to be hydration. This is a particuprovided by a registered dietitian and larly important goal, given the is limited to three hours in the first fact that malnutrition is assoyear and two hours in the second year. ciated with worse disease out3. Additional hours are allowed if there comes and as many as 45% of is a change in the patient’s diagnosis, hospitalized patients require medical condition or treatment nutrition care (Nutr Clin Pract regimen. 2021;36[3]:534-544). 4. MNT services can be provided via “The human right to bentelehealth. efit from nutrition care means 5. A 20% copay specified in the that every patient also has the original act has been removed. right to be screened for malnutrition, diagnosed with malMNT, Medical Nutrition Therapy. nutrition and to receive nutrition care to obviate the impact pharmacy catering to an underserved of that malnutrition,” Dr. Gramlich said. community and found that 63% were at To help standardize hospital-based risk for poor nutrition, either because nutrition, she and others on the Canadiof food insecurity, malnutrition risk or an Malnutrition Task Force have develboth (J Health Care Poor Underserved oped an Integrated Nutrition Pathway 2021;32[3]:1493-1513). for Acute Care (INPAC), which covers “Unlike the CMS [Centers for the gamut of hospital-based nutrition Medicare & Medicaid Services] criteria care, from screening to nutrition provifor MNT, the population at risk for poor sion, patient monitoring and promotion nutrition in our study predominantly of food intake (bit.ly/2ZY71KL). consisted of people with hypertension, as The INPAC protocol also is part of well as a few patients with diabetes, and a Malnutrition Prevention, Detection, others with mental health conditions, and Treatment Standard for use in hyperlipidemia and pulmonary condi- hospitals (standard available through tions,” Mr. Mirtallo said. store.healthstandards.org). According If passed, the MNT Act expansion to Dr. Gramlich, the standard identifies would provide Medicare Part B coverage key steps that hospital staff can folof outpatient MNT to individuals with a low to ensure that adequate nutrition

care is given. For example, it specifies that all patients should be screened for nutrition risk within 48 hours of hospital admission and that those with a positive screen be assessed further within 72 hours of admission. The standard also defines the types of nutrition care—including standard, advanced and specialized nutrition—and it emphasizes the need for repeated nutrition assessments to document the impact of treatment and highlight the need to focus on transitions of care. “Standardizing practices is not only an effective way of making sure hospitalized patients with malnutrition are recognized and treated; it can also serve as the foundation for accreditation criteria and public policy,” Dr. Gramlich said, noting that a subset of the standard’s criteria will serve as the foundation for voluntary accreditation for hospitals in Canada seeking to optimize their nutrition care practices. “Organizations that take part in this accreditation program choose to do so because they have firsthand knowledge of the contribution accreditation makes in improving quality, reducing risk and strengthening accountability for best nutrition care.” Angela Bingham, PharmD, the director of the PGY-2 Critical Care Residency Program, Philadelphia College of Pharmacy and Science, University of the Sciences, said Dr. Gramlich’s efforts “shine a light on the truth that nutritional care must be considered a human right. The bottom line is that nutrition screening, diagnosis and assessment of malnutrition, and appropriate nutrition care plans can improve outcomes in hospitalized patients.” (Dr. Bingham was not involved in the webinar.) She also praised ASPEN’s legislative efforts for “advancing clinical nutrition public policies,” adding that the MNT Act expansion “would importantly widen Medicare Part B coverage for outpatient medical nutrition therapy and allow referrals from a broader array of health care professionals.” Dr. Bingham encouraged health-system pharmacists to help improve access to nutrition care by joining or building a multidisciplinary team to focus on the issue. “Additionally, during interprofessional rounds, pharmacists can ensure a nutrition care plan is discussed,” she said. “They also can develop standardized institutional processes and engage in education, research and quality improvement initiatives to advance clinical nutrition in their institution and beyond.” —David Wild Dr. Bingham reported no relevant financial disclosures. Dr. Gramlich reported serving as a speaker for and consultant to Abbott, Baxter, Fresenius Kabi and Takeda. Mr. Mirtallo reported serving as a speaker for and consultant to Fresenius Kabi.

Clinical

Pharmacy Practice News • December 2021

Inflammatory Disease

GOUT GUIDELINES continued from page 16

should reserve [febuxostat] for use only in patients who have failed or do not tolerate allopurinol.”

Cone Health Responds The addition of the boxed warning prompted the team at Cone Health to assess how many of their patients were taking febuxostat. An electronic health record (EHR) review showed that 226 (4.9%) of 4,616 patients with gout were taking febuxostat; 152 (3.3%) had cardiovascular disease, said Jennifer Kim, PharmD, an associate professor of clinical education at UNC Eshelman School of Pharmacy, in Chapel Hill, N.C. Dr. Kim and her colleagues sent a general email about the FDA warning to all of Cone Health’s primary care providers; then, they sent individual EHR messages to providers who had prescribed febuxostat to patients with CVD, “providing our recommendations on alternative management—usually a switch to allopurinol,” she said. After the intervention, the percentage of gout patients taking febuxostat declined from 4.9% to 3.7% (P<0.001), and the percentage of patients with CVD taking the drug declined from 3.3% to 1.45% (P<0.001). No serious adverse events were reported among patients who were switched to another ULT or discontinued ULT. In the three-month period after the intervention, four patients experienced gout exacerbations that resolved without reinitiation of febuxostat. “There were some cases where the patient could not tolerate the allopurinol or had a reaction to it, but we were able to give auxiliary recommendations for patients who had to stay on, like switching to the antihypertensive losartan, which also has benefits for gout,” Dr. Kim said.

A New Agent In addition to allopurinol and febuxostat, there is a newer specialty agent, pegloticase (Krystexxa, Savient), indicated for gout, but Dr. Neogi noted that it is not recommended as first-line therapy in the new guidelines. “We don’t yet have enough studies to say exactly what its place should be in [ULT] after failure of a first-line agent,” she said. Although pegloticase is effective in reducing sodium urate and decreasing flares, it is delivered by IV infusion, requiring visits to an infusion center. “At this point, it is primarily recommended for patients in whom other ULTs have failed to lower sodium urate levels, and who are still experiencing active disease, meaning frequent flares, which is defined as two or more per year, or nonresolving tophi,” she said.

As for other treatment choices when managing gout flares, there are several options. Dr. Neogi noted that the ACR guideline recommends the use of antiinflammatory agents such as colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) and/or steroids such as prednisone/prednisolone. What is not recommended, Dr. Neogi stressed, is opioids. “Gout is an intensely inflammatory process; opioids don’t affect inflammation,” she said. And yet clinicians persist in prescribing the painkillers for gout. A recent study

presented at an American College of Clinical Pharmacy Virtual Poster Symposium, for example, found that among patients who presented to the emergency department with gout flares, opioids (28%) were used second only to NSAIDs (41.6%). Upon discharge, opioids (23.9%) were the third most common medication prescribed, after NSAIDs (37%) and corticosteroids (34.6%). Thus, education about more appropriate treatments for gout flares is needed, she stressed. “There also is a need for additional options in managing flares, particularly

in patients who have multiple comorbidities, such as congestive heart failure [CHF] and renal insufficiency, where we would want to avoid NSAIDs, potentially colchicine depending on their other medications, and even steroids since they can exacerbate CHF,” Dr. Neogi said. “We might use off-label IL-1 [interleukin-1] inhibitors, such as anakinra [Kineret, Amgen], in these patients.” —Gina Shaw Dr. Neogi reported no relevant financial disclosures.

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22 Operations & Management

Pharmacy Practice News • December 2021

Quality Improvement

Benchmarking Benefits

that you’re being fiscally responsible with your resources and gives you the ability to show the impact of additional resources.”

continued from page 1

Where Are the Standards?

Dr. Gutierrez cited several other benchmarking benefits. “You can cite positive benchmarking data when you’re submitting for new projects and proposals and seeking new staffing,” she noted. “It gives you justification for your existing services and expansion of services. Benchmarking also allows pharmacy leaders to speak at the [same level as] the CEO and the C-suite; it proves to them

“Benchmarking is very important in the C-suite,” agreed Amy Gutierrez, PharmD, UCHealth’s vice president of pharmacy and chief pharmacy officer. “I oversee a number of pharmacies and hospitals in our system, and it’s essential to have the ability to track key performance indicators to see how we’re performing internally and externally, and to foster innovation and creativity.”

But there’s a challenge: No industry standard has been identified for benchmarking productivity in the inpatient pharmacy setting, which leaves it up to each system to decide what metrics they should use. “I can’t tell each and every one of you what metrics to use for your dashboard, because you have unique organizations,” Dr. Phillips said.

However, all health-system pharmacies should consider several questions. The first: Will you use external or internal benchmarking, or both? With external benchmarking, you’re measuring your pharmacy’s metrics against those of other leading health-system pharmacies; internal benchmarking measures your own progress over time. “Ideally, you will want to be doing both,” she suggested. “If you’re not looking externally as well as internally, you may be missing key important elements about what other people are doing.

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A powerful COVID-19 partnership ......................

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he dispute between drugmakers and covered entities under the 340B Drug Pricing Program has ramped up, as a number of hospital and pharmacy associations are suing the Department of Health and Human Services to undo manufacturer limitations on 340B discounts. Their efforts have paid off: On Dec. 30, HHS issued an advisory opinion stating that drug manufacturers are required to deliver 340B discounts on covered outpatient drugs when contract pharmacies are acting as agents of 340B covered entities. Although advisory opinions do not carry the force of law, “they set out the agency’s current views on issues,” HHS said in a statement. “Those views may be reflected in the ... enforcement and oversight powers the federal government has to run the 340B Program.”

Volume 48 • Number 1 • January 2021

Coping tips shared during ASHP, ACCP annual meetings

Longer storage times now permitted if testing performed

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Pharmacy Shines nes Amid COVID Darkness

Pandemic spurs nutrition gap in ICUs ..... 6 HOPA: When to stop ABx for febrile neutropenia ........................

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Volume 48 • Number 2 • February 2021

U Releases USP Newly Proposed N <797> Revisions <

Volume 48 • Number 11 • November 2021

$80 million recovered at just one health system

Replacing Lost Revenue e During the Pandemic

fter almost two years of anticipation, USP has issued its new pro proposed revisions to Chapter <797>, “Ph “Pharmaceutical Compounding— Ste Sterile Preparations.” What does this me mean for sterile compounding in you your pharmacy? F For most hospitals, which already had prepared to comply with the origina inal <797> revisions, the temptation is to answer, probably “not much.” But com complacency is not advisable, experts wa warned. They stressed that the release stil still provides an important opportunity tto check compliance with key provisio sions, and to become familiar with an imp important and much-awaited decision on beyond-use dating (BUD). A After the original publication

Continued on page 32

ith normal revenues severely constricted by the influx tals of critical COVID-19 patients, health systems and hospitals across the country have had to find other ways to replace vanished income streams. nu“One of the biggest challenges with COVID-19 has been the continuing downward pressure on the financials,” said James Jorgenson, MS, RPh, the CEO of Visante, a pharmacy consulting firm. “Operating margins for the average hospital right now are somewhere in the 1% to 3% range.”

Continued on page 24

Continued on page 34