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Muscle relaxants and pain a dangerous mix
Muscle Relaxants and Chronic Pain a Dangerous Mix
In what can be seen as a sign of a distressing trend considering current prescribing guidelines and the shortage of data on efficacy, the long-term use of skeletal muscle relaxants (SMRs) to treat pain appears to be on the rise.
More concerning is that repeat prescriptions in older adults (over 65 years)— a patient population for whom guidelines advise against prescribing this class of drugs—nearly tripled in the last decade.
The findings emerged from a study of 300 million U.S. ambulatory care office visits. More than 30 million of those visits during 2005-2016 resulted in a prescription for an SMR for the first time or as part of ongoing therapy. Overall, the researchers wrote, “Office visits with a prescribed SMR nearly doubled, from 15.5 million in 2005 to 30.7 million in 2016” (JAMA Netw Open 2020;3[6]:e207664).
Although initial prescriptions of an SMR remained somewhat stable over that period, the team found that repeat prescriptions accounted for much of the increase, nearly tripling in all age groups (8.5 million in 2005; 24.7 million in 2016). “Given that there are minimal data on long-term safety and effectiveness, and these drugs are not indicated for use beyond a couple of weeks of therapy, it starts to raise [a] red flag,” said Charles Leonard, PharmD, an assistant professor of epidemiology at the University of Pennsylvania’s Perelman School of Medicine, in Philadelphia, and senior author of the paper.
Possibly the most concerning aspect of this study is that adults 65 years and older account for nearly one-fourth (22.2%) of the office visits. The increase in SMR use occurred despite the fact that these drugs have known adverse effects in older patients and are never the recommended course of action to treat pain in this patient population.
“Muscle relaxers can cause confusion at all ages, but [that effect is heightened] in the elderly,” said Kimberly Croley, PharmD, a clinical pharmacist at Laurel Senior Living Community, in London, Ky. However, her concern for her patients goes beyond increased risks for falls and fractures or motor vehicle accidents, pointing out that SMRs are not pain relievers at all, since they don’t treat a patient's pain or reduce inflammation. Instead, relief often comes from the sedative properties of these drugs. A sleeping patient, by definition, is a patient free from pain, she noted.
A frequent source of pain in patients of this age group is procedures such as reconstructive hip or knee surgery, and proper recovery requires physical and occupational therapy to normalize a patient’s mobility levels. “But how do you rehab someone who sleeps all the time?” Croley asked. Her answer, simply, is “You don't.” As a result, “[patients] don’t get the benefit of the surgery. In some instances, the joint can almost become frozen.”
Digging Deeper
Why is SMR use increasing? Leonard cited the fact that “treatment of persistent pain is incredibly challenging, and can be complicated by medical, psychological, social and environmental factors. As providers may hesitate to prescribe opioids, there are few pharmacologic treatment options available beyond acetaminophen or nonsteroidal anti-inflammatory drugs.”
Croley said focusing on SMRs isn’t the answer. More than anything else, she feels that greater provider involvement, including a treatment plan, education of patient and caregivers, and messaging, are vital in addressing patients’ pain. “I’m a pharmacist. I should want people to take pills, but that’s not always the answer. Part of medical care should be not just chemistry, but a lifestyle,” she said. “When we have an acute illness, we will only treat the acute illness in the short term, as necessary, to get past it. Then we go back to focusing on wellness.” —W. Harry Fortuna
HyperRAB®
Rabies Immune Globulin (Human)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use HYPERRAB® safely and effectively. See full prescribing information for HYPERRAB. HYPERRAB [rabies immune globulin (human)] solution for infiltration and intramuscular injection Initial U.S. Approval: 1974
HYPERRAB is a human rabies immune globulin indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies. Limitations of Use Persons previously immunized with rabies vaccine that have a confirmed adequate rabies antibody titer should receive only vaccine. For unvaccinated persons, the combination of HYPERRAB and vaccine is recommended for both bite and nonbite exposures regardless of the time interval between exposure and initiation of postexposure prophylaxis. Beyond 7 days (after the first vaccine dose), HYPERRAB is not indicated since an antibody response to vaccine is presumed to have occurred.
--------------DOSAGE AND ADMINISTRATION------------For infiltration and intramuscular use only. Administer HYPERRAB within 7 days after the first dose of rabies vaccine.
Postexposure prophylaxis, along with rabies vaccine, after suspected exposure to rabies HYPERRAB 20 IU/kg body weight OR 0.0665 mL/kg body weight Single dose • Administer as soon as possible after exposure, preferably at the time of the first rabies vaccine dose. • Infiltrate the full dose of HYPERRAB thoroughly in the area around and into the wound(s), if anatomically feasible. • Inject the remainder, if any, intramuscularly.
-----------DOSAGE FORMS AND STRENGTHS----------
300 IU/mL solution for injection supplied in 1 mL, 3 mL and 5 mL single-dose vials.
--------------------CONTRAINDICATIONS---------------------
None.
• Severe hypersensitivity reactions, including anaphylaxis, may occur with HYPERRAB. Have epinephrine available immediately to treat any acute severe hypersensitivity reactions. • HYPERRAB is made from human blood; it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
The most common adverse reactions in >5% of subjects in clinical trials were injection site pain, headache, injection site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain.
To report SUSPECTED ADVERSE REACTIONS, contact Grifols Therapeutics LLC at 1-800-520-2807 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
• Repeated dosing after administration of rabies vaccine may suppress the immune response to the vaccine. • Defer live vaccine (measles, mumps, rubella) administration for 4 months.
Although most drug shortages result from increased demand or lack of active pharmaceutical ingredients, a shortage of the thyroid disease agent teprotumumab-trbw occurred after Operation Warp Speed officials ordered the drug’s contract manufacturer to halt production and begin bolstering supplies of COVID-19 vaccine.
Photo credit: The International Society for Pharmaceutical Engineering.
COVID-19 Rx Shortages
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Today, most health systems are in better shape to cope with COVID-19–related shortages than they were in early March. They got there because “as a community of health-system organizations, we had been working on different strategies to improve drug supply,” said Eric Tichy, PharmD, MBA, the vice chair of supply chain management for Mayo Clinic in Rochester, Minn.
One example, he said, was the membership that many health systems shared in Civica Rx, the nonprofit generic drug manufacturer, which began distributing medications at the beginning of 2020, several months before the threat of a pandemic became evident to all but a handful of epidemiologists.
Intermountain also benefited from Civica’s paid-access model, which supplies generic drugs to health-system members that contract to buy stipulated quantities on a yearly basis. “Dexamethasone is one product that we were able to obtain through Civica that helped ease the shortage impact,” Biksacky told Pharmacy Practice News.
The corticosteroid is listed on the ASHP’s Current Drug Shortages database, which is maintained in partnership with the University of Utah Drug Information Service (bit.ly/3nzBCnJ). The shortage is being driven by increased demand for the treatment of hospitalized COVID-19 patients with severe inflammatory lung disease.
Tichy also noted initiatives that Mayo Clinic’s group purchasing organization, Vizient, has implemented to improve critical drug supplies. (In December, Vizient launched an updated COVID-19 Surge Demand Calculator; bit.ly/3nA3nwq.)
5 Agents Under Close Watch
Intermountain has five agents under close surveillance due to COVID-19, Biksacky said. They are the neuromuscular blocker cisatracurium, the proton pump inhibitor pantoprazole (injection), the sedative-hypnotic agent propofol, the nutrition supplement Proteinex 15 (Llorens Pharmaceutical) and the thyroid eye disease agent teprotumumab-trbw (Tepezza, Horizon Therapeutics).
Although propofol remains on the ASHP/University of Utah drug shortage list, Biksacky said that supplies of the sed-
ative-hypnotic agent recently had eased when Intermountain was able to obtain larger vials from Pfizer. “Thankfully, the 100-mL vials have been adequately filling our needs recently,” she said. Biksacky added, however, that “if push comes to shove,” and propofol supplies begin to evaporate again, the drug shortages team has a last-resort mitigation strategy: a recipe for a 100-mL pooled bag that can be called into service. The recipe has been approved by the health system’s executive compounding committee, she said.
Although most shortages result from increased demand, manufacturing interruptions or lack of active pharmaceutical ingredients, the teprotumumab-trbw shortage represents a different scenario. In December, manufacture of the insulinlike growth factor-1 receptor inhibitor was temporarily set aside, when the federal government’s Operation Warp Speed program, acting under the Defense Production Act of 1950, ordered Horizon’s contract manufacturer, Catalent, to halt production and begin bolstering supplies of COVID-19 vaccine. Horizon reported that the shortage was expected to last only through the first quarter of this year. Teprotumumab-trbw has no therapeutic equivalent for treating the rare, progressive thyroid eye disease.
An important goal for health systems has been to build safety stocks of critical medications facing depletion as COVID-19 patients needing mechanical ventilation for respiratory distress flooded critical care units. At Mayo Clinic, Tichy said shutting down elective procedures for several weeks not only helped conserve dwindling stocks
of personal protective equipment, it also preserved critical medication supplies.
Months of dealing with drug shortages have had a lasting impact. “We’ve learned we have to be very agile,” Tichy said. “From day to day, things are going to have to change quickly, and we have to be able to move our operations in an agile fashion. We also have to be able to communicate with federal agencies and manufacturers quickly.”
Stretching Pfizer Vaccine ‘A Christmas Miracle’
Rapid communication paid off when the first supplies of the Pfizer/ BioNTech vaccine arrived in December. As reported in Pharmacy Practice News in January (bit.ly/2XJcv7f), “we found that we could get an extra dose or two out of every vial,” Tichy said. “That was a huge bonus. It meant the equivalent of an additional 20% of vaccine for every five-dose vaccine vial. That was very significant because for every 1,000 doses we were getting an extra 200. I was telling people that was like our Christmas miracle.” (For more details on safe vaccine dilution practices, see pages 20-21.)
Because health systems communicated the potential benefit among themselves, he said, “it got escalated up to the FDA. And within three days of the vaccine’s shipment,” he noted, the agency gave the go-ahead to use the extra doses.
Avoiding Waste
Communication has continued to play a large part in helping health systems to mitigate shortages. “We raised awareness in the organization about the need to avoid product waste,” Tichy said. “And as a practice community, we quickly made sure we had the right evidence and didn’t rush into using things that were unnecessary. Hydroxychloroquine was a good example.”
At Intermountain, communicating about drug shortages is part of the daily routine. “Near the start of the pandemic,” Biksacky said, “the shortage team implemented daily brief shortage huddles, where we have key leaders call in every day and chat for 15 minutes at most, bringing up supply issues and trying to find solutions.” The virtual chats not only involve the team leader, Conor Hanrahan, PharmD, the director of Medication, Policy, Outcomes and Stewardship, and her fellow drug information specialists— Renee Pitt, PharmD, Shannon Inglet, PharmD, and Sarah Yost, PharmD—but also critical pharmacy technicians and central purchasing stakeholders.
The team also maintains a list of shortages updated in real time by the health system’s Drug Shortages Advisory Group. “It’s transparent to all and available on our intranet,” Biksacky said. “It provides a single source of truth to what our approaches are to given shortages. The list includes links to many conservation strategy documents that provide our staff and our caregivers with the most up-todate information.”
—Meryl Biksacky, PharmD
—Bruce Buckley
