My elderly patients always remark on my ability to communicate with them. They tell me that I speak loudly and clearly and enunciate, that I never mumble.

My grandpa, a blacksmith, was “stone deaf.” I remember speaking, loudly and clearly, into his Beltone hearing aid that he kept in his shirt pocket, the wires running up to his left ear. I learned that if I wanted Grandpa to understand me, I had to speak and enunciate. I’ve applied this tactic when counseling many of my elderly patients, and it has never failed me—except for 1 patient.

“Dave,” a 75-year-old, longtime patient with type 2 diabetes, is hearing impaired. He came into my pharmacy after his wife, also hearing impaired, called me about issues concerning her husband’s insulin injections. We had recently switched him from the expensive brand-name pen needles to a generic. We discussed the need for such cost savings; she said it was not the needles but the pens. Insulin glargine (Lantus Solostar) pens have been around for years, and I thought I’d misunderstood. Dave and his wife lived a mere 2 blocks from the pharmacy, so I asked whether I could speak with her husband in person.

Dave visited the pharmacy, his box of Lantus Solostar pens in tow. Keeping an 8-ft distance between me and himself, Dave requested that I take off my mask so he’d be able to read my lips. I complied, and he then explained that he was struggling with his new devices and that he wanted the “old” insulin pens he had used previously. After analyzing his file, I found an order for insulin degludec (Tresiba FlexTouch) pens that were formulary last year. Dave’s dexterity issues made the Solostar pens problematic, but he was able to work the Tresiba FlexTouch and get accurate dosing. Mystery solved! I called his physician’s office to explain what Dave needed.

The office sent a new order for Tresiba, which needed a prior authorization from the insurance company. I provided the details and even a script of what to say, and the officesent a prescription for Toujeo (glargine)—the same device. Five days later, I was notified that Dave’s prescription hadn’t been authorized. He has 2 insurance providers for Medicare D, both of which had not given permission to fill insulin. Concerned, I called both providers, and they informed me that the physician’s office hadn’t responded to them. As I left another message with the physician’s office, my patience was wearing thin. “For God’s sake, he needs insulin, not some monoclonal antibody,” I remember muttering.

I called the secondary insurance, PACE, a state prescription assistance program funded by the Pennsylvania Lottery. PACE told me that the primary must pay first. Frustrated and concerned for my patient, I pleaded my case for Dave. The provider gave me the perfunctory apology but no action.

Two days later, I received a call from PACE, asking for Pete. Dave’s wife, who’d just called the PACE representative, instructed her to ask for me. Again, I described Dave’s situation.

“I get it, you have rules. But how can I be the only person here [who cares about their patients]? The primary insurance doesn’t care, the physician’s office doesn’t care, and your organization doesn’t seem to care either,” I told her.

I suggested that a PACE representative visit my pharmacy to witness the desperation felt by our patients when insurance companies and pharmacy benefit managers (PBMs) deny the medications they need. Seemingly convinced, she told me she would consult the next level of PACE management.

About 1 hour later, the PACE rep called and assured me that she’d secured authorization for a 1-year approval of Dave’s insulin. I immediately filled Tresiba for a 90-day supply, barely breaking even, but Dave’s ear-to-ear smile and thumbs-up were compensation enough for me. I just hope that pharmacists’ judgment can soon be a contributing factor in pharmacotherapy decisions made by PBMs and insurance companies. For now, it was just nice to win one.

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“I just hope that pharmacists’ judgment can soon be a contributing factor in pharmacotherapy decisions made by PBMs and insurance companies.”

Go to Bat for Patients in Need

Since Governor Charlie Baker of Massachusetts issued a stay-at-home advisory in response to the coronavirus disease 2019 (COVID-19) pandemic, UMass Memorial Health Care in Worcester, Massachusetts, has dispensed more than 5000 medications to patients and employees using its curbside prescription service.

The top 3 medications filled are those for blood pressure, cholesterol, and acid reflux, said Jackie Breeds, PharmD, RPh, pharmacy supervisor at the health system.

UMass Memorial offers the service at 2 separate locations, both in downtown Worcester. Patients and employees start the pickup process by entering an order in the patient portal or calling the pharmacy team, said Breeds. In either case, they are prompted to call the pharmacy team to schedule a pickup and discuss paying co-pays by credit card or cash.

A pharmacy order takes approximately 2 hours to fill, although the turnaround time can depend on the current volume of prescription requests; Mondays are the busiest days, Breeds said. Patients park in 1 of 2 designated parking spots at each location, and a sign instructs them to call the pharmacy. The pharmacy staffer captures information about the make, model, and color of the patient’s or employees’ car, which makes identifying them easier. The staffer also verifies their birthdate to ensure the individual is getting the correct medication. The staffer typically brings out the medications within 3 to 5 minutes.

“[Staffers] stay far back from the car window,” said Breeds. “They don’t want to sneak up on people. They wait until [the person] unrolls their window.” Staffers are required to wear masks, she added, and they use hand sanitizer upon reentering the building.

When a medication order is generated, a pharmacy staffer bills insurance and determines the patient co-pay. If they come across any formulary issues, they call the patient’s doctor to make changes or ask questions.

Some of UMass Memorial’s pharmacy techs have been furloughed. The staffers bringing medications to patients’ cars are typically recent nursing school graduates and medical assistants from clinics with reduced patient volume, said Neil Gilchrist, PharmD, BCPS, DPLA, senior director of pharmacy services. Nonpharmacy tech employees can serve in these roles during the state of emergency declared by Governor Baker on March 10. For opioid-based medications, the prescribing physician sends the order to UMass Memorial electronically, said a health-system spokesperson. The pharmacy staffer tells the patient that they’ll need to show photo identification at pickup. During pickup, the staffer verifies the patient’s birth date and photo to ensure the correct individual receives the medication.

Because of the positive response from patients and employees, many of whom have been working remotely during the pandemic, UMass Memorial is considering continuing the program when the health system returns to steady-state operations.

An inside look at the process from prescription to dispensing.

UMass Memorial Provides Model for Curbside Medication Delivery

On May 8, 2020, the FDA granted accelerated approval to selpercatinib (Retevmo; Eli Lilly and Company).

 Selpercatinib is now indicated for (1) adults with metastatic RET fusion–positive non–small cell lung cancer (NSCLC), (2) adults and pediatric patients 12 years or older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and (3) adults and pediatric patients 12 years and older with advanced or metastatic RET-fusion MTC who require systemic therapy and who are refractory to radioactive iodine. Selpercatinib inhibits wild-type RET and multiple mutated forms of RET as well as VEGFR1/3 to ultimately inhibit tumor cell proliferation promoted by these pathways.

Accelerated approval of selpercatinib stemmed from results of the multicenter phase 1/2 LIBRETTO-001 trial (NCT03157128), which evaluated selpercatinib in patients with RET-driven cancer.

 The trial enrolled both treatment-naïve and heavily treated patients with solid tumors, including those with RET fusion–positive NSCLC (n=144) and MTC (n=27) and RET-mutant MTC (n=143). The primary end point of overall response rate (ORR; complete and partial responses) was 85% (95% CI, 70-94) of patients with treatment-naïve RET fusion–positive NSCLC; in treatment-experienced patients, the ORR 

was 64% (95% CI, 54-73). The ORR was 73% (95% CI, 62-82) in treatment-naïve patients with RET-mutant MTC versus 69% (95% CI, 55-81) in treatment-experienced patients. In those with RET fusion–positive MTC, the ORR was 100% (95% CI, 63-100) in treatmentnaïve patients and 79% (95% CI, 54-94) in experienced patients. The median duration of response has not yet been reached for most of these patients. Selpercatinib is also effective in patients with RET fusion–positive NSCLC and measurable brain metastases, with a reported central nervous system ORR of 91% and a duration of response of 6 months or longer.

The most common adverse reactions (≥25%) were dry mouth, diarrhea, hypertension, fatigue, edema, rash, and constipation. Common laboratory value abnormalities (≥25%) included level increases in aspartate aminotransferase, alanine aminotransferase, glucose, alkaline phosphatase, cholesterol, and creatinine and decreases in leukocytes, albumin, calcium, platelets, and sodium.

 Because of these adverse events, routine monitoring of liver function enzymes at baseline, every 2 weeks during the first 3 months, and then monthly thereafter, and monitoring of 

blood pressure at baseline, after week 1, and monthly thereafter are recommended. Patients are also at risk for QTc prolongation, so monitoring of electrolyte and thyroid stimulating function levels at baseline and periodically is also recommended. Additionally, because selpercatinib can inhibit VEGFR, hemorrhage and impaired wound healing can occur. Drug-drug interactions can occur with acid-reducing drugs, strong and moderate cytochrome P450 (CYP) 3A4 inhibitors and inducers, and CYP2C8 and CYP3A substrates. Practitioners should avoid each of these if possible; otherwise, they may need to dose-adjust.

Dosing is based on weight; for patients 50 kg or greater, the dose is 160 mg by mouth daily. For those less than 50 kg, the dose is 120 mg by mouth daily.

Patients may take selpercatinib with or without food. Dose adjustments are recommended for severe hepatic impairment, adverse drug reactions, and some drug interactions.

A 40-mg capsule costs $137.33, and an 80-mg capsule costs $206.

1. FDA approves selpercatinib for lung and thyroid cancers with RET gene mutations or fusions. News release. FDA. May 8, 2020. Updated May 11, 2020. Accessed June 2, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-selpercatinib-lung-and-thyroid-cancers-ret-gene-mutationsor-fusions 

2. Retevmo. Package insert. Eli Lilly and Company; 2020. Accessed June 2, 2020. https://www.accessdata.fda. gov/drugsatfda_docs/label/2020/213246s000lbl.pdf 

3. Lilly receives U.S. FDA approval for Retevmo (selpercatinib), the rst therapy specically for patients with advanced RET-driven lung and thyroid cancers. News release. Eli Lilly and Co. May 8, 2020. Accessed June 2, 2020. http://lilly.mediaroom.com/index. php?s=9042&item=138045 

4. Wolters Kluwer-Health Inc. Lexicomp. Lexi-Drugs/ Selpercatinib. Accessed June 2, 2020.

Selpercatinib for NSCLC and Thyroid Cancer With RET Mutations or Fusions 

Why are some individuals prone to developing certain health conditions? Why do some have a more robust immune system than do others? These are only 2 of the many questions that research into the microbiome—the complex community of bacteria, fungi, and viruses that live in and on the human body—may answer.

Microbiome studies, the latest wave of health research, explore the role of the microbiome in a host of chronic conditions and examine how it affects metabolism, regulates the immune system, and protects against pathogens. "Over 2000 years ago, Hippocrates, the father of medicine, said that all disease begins in the gut," said Suzanne Keyes, PharmD, IFMCP, FACA, of Keyes Com-pounding and 180 Wellness in Elk City, Oklahoma. “Now, with advances in med-ical technology, in testing and analysis, we can see that link clearly.”

Currently hundreds of pharmabiotics companies are engaged in more than 650 active research programs. At least 3 companies have microbiome-related treatments in the trial phase. The first microbiome-targeted products likely to win FDA approval are expected to be treatments for skin or gastrointes-tinal (GI) conditions.

“Emerging therapeutics are following the path of least resistance in terms of access to the therapeutic area and the regulatory path,” said Sandrine Miller-Montgomery, PharmD, PhD, executive director of the Center for Microbiome Innovation and professor of practice, bioengineering, at the Jacobs School of Engineering, University of California, San Diego. “In terms of therapeutic areas, skin diseases have quite a significant amount of product in development; the same is true for GI diseases. What will likely lag behind in reaching the market are therapeutics targeting organs. The notable exception will likely be in the cancer field, as it is starting to be well documented that microbes play a significant role in the effectiveness [of and] responsiveness to chemotherapy.” Research suggests that modulating the gut microbiome may help boost the immune system in patients with cancer and also reduce the adverse effects of some cancer treatments.

The balance of the microbiome is vulnerable to a variety of factors, including medication and environmental exposure. One example is overexposure to antibiotics. “According to the latest statistics in 2017, the average 2-year-old has had 3 rounds of antibiotics,” said Keyes. “By the time a child is 17, they’ve had 21 rounds of antibiotics.”

Prolonged or frequent antibiotic use can lead to an increase in the number of antibiotic-resistant microbes. Individuals who frequently take antibiotics for an underlying condition are often prone to recurrent 

infections, which damage the lining of the large intestine, causing diarrhea. Such infections affect half a million Americans every year.

A proposed donor stool therapeutic uses microbes to help restore a healthy microbiome balance, enabling the gut to fight the infection. Ferring Pharmaceuticals’ nonantibiotic therapeutic RBX2660 is currently in phase 3 clinical development for the prevention of recurrent 

 infections. Fecal transplants may one day also play a role in correcting the microbiome imbalance, which has been suggested as a possible link to obesity and diabetes.

Although patients may ask pharmacists to recommend a probiotic supplement, it’s not a 1-size-fits-all remedy. Probiotic products sold as dietary supplements don’t require FDA approval, so quality may vary. Products also contain different strains, the most common being Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus.

“Make sure to stock probiotics that you trust are stable and have data to show that they are still active once they get to the small intestine and the colon,” said Melody Hartzler, PharmD, PhD associate professor of pharmacy practice at Cedarville University School of Pharmacy in Ohio.

“There are some commercial products that have been shown in multiple clinical trials to have benefits. Find those products that you know are backed by good research and are strain specific to conditions you would recommend them for.

“The other thing you need to think about when you talk about probiotics is prebiotics. Prebiotics are the food that grows the good bacteria, so if we take probiotics and we don’t eat any fiber, it’s not going to be as helpful to our microbiome as [also] eating prebiotic fibers in our diet. People who don’t get enough in their diet...may need a prebiotic supplement. Some probiotics are mixed with prebiotics.” However, the effects of probiotics are usually not permanent. “When you take a probiotic, you take them every day,” said Suzanne Keyes, of Keyes Compounding and 180 Wellness. “The growth that is happening is very short lived.”

Studies investigating soil microbes suggest the effect of these microbes may last longer, said Hartzler. The effects of fecal microbe transplants may also be permanent. “Fecal transplants are definitely a big area of research, but there are 2...high-dose probiotics that are already available for doctors to prescribe: VSL#3 and Visbiome,” said Hartzler.

Although pharmacists may not yet encounter a slew of mi- crobiota-targeted medications, they can help patients achieve and maintain a healthier microbiome by exercising antibiotic stewardship, recommending probiotics, and encouraging a healthier lifestyle.

“Diversity of your microbiome is key, and commercially available probiotics usually [comprise] only a few strains,” said Sandrine Miller-Montgomery, of the Center for Microbiome Innovation. “So it will always remain crucial to eat a diverse diet and include a large variety of fermented food as well. Although pharmacists—and I am one by training—are always looking forward to providing a miracle pill to their patients, they need to keep in mind that having a healthy microbiome at the individual level starts with advising patients to have a good quality of life: a diverse and nutritious diet, quality sleep, appropriate amount of exercise, and a stress reduction practice.”

In the past 2 decades, microbiome research has accelerated thanks to less invasive sampling techniques and more efficient means of analysis. But development of microbiome-based treatments remains complicated. Not only is an individual’s microbiome unique, but it also features trillions of organisms, making the determination of cause-and-effect relationships difficult. Sequencing an individual’s microbiome as a diagnostic tool has become increasingly popular, but it may not always provide useful information.

“Although there are some companies that have taken advantage of this market need, they are still not off ering true insights, as we are still in the observation phase when it comes to understanding the microbiome,” said Miller-Montgomery. “Sure, we have made humongous leaps in better understanding at the population scale the diversity of a microbiome profile, but translating this into something that works at the individual level despite the claims of some service providers—we are surely not there yet.”

1. Gosálbez L. The microbiome biotech landscape: an analysis of the pharmaceutical pipeline. Microbiome Times. March 26, 2020. Accessed May 17, 2020. 

https://www.microbiometimes.com/the-microbiome-biotech-landscape-an-analysis-of-the-pharmaceutical-pipeline/

2. Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A

, Wargo JA. The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. 

. 2018;33(4):570‐580. doi:10.1016/j.ccell.2018.03.015

3. Institute of Medicine (US) Food Forum. 

4. Haiser HJ, Gootenberg DB, Chatman K, Sirasani G, Balskus EP, Turnbaugh PJ

. Predicting and manipulating cardiac drug inactivation by the human gut bacterium 

 2013;341(6143):295‐298. doi:10.1126/science.1235872

5. National Institutes of Health. Probiotics: fact sheet for health professionals. Updated June 3, 2020. Accessed May 18, 2020. 

https://ods.od.nih.gov/factsheets/Probiotics-HealthProfessional/

Prepare to counsel patients on microbiome-related products.

Microbiome Research Calls  for Due Diligence in Pharmacy

Are you testing for coronavirus disease 2019 (COVID-19)? A recent National Community Pharmacists Association (NCPA) survey found that most pharmacists want to be part of the testing process, but few pharmacies offer sample collection or onsite testing.

“There are so many different barriers. One thing gets cleared, and then there’s another step and then another,” said pharmacy owner and California Pharmacists Association President Ken Thai, PharmD. “Especially if you are an independent pharmacy wanting to do testing, you have to find your own channels to get it going. And then it comes down to economics. Billing mechanisms seem to be in place, but they aren’t necessarily functional. There are still a lot of ques- tions before we can start widespread testing in pharmacies.”

Some pharmacists have opted not to test. In the Atlanta suburb of Johns Creek, Good Neighbor Pharmacy affiliate Lily’s Pharmacy focused on existing patients and the flood of discharge patients as Emory Johns Creek Hospital cleared its wards.

“The pandemic hit hard and fast,” said co-owner Jennifer Shannon, PharmD, BCPS. “Our volume went sky-high for the first 6 weeks of [COVID-19]—really sick patients who needed a lot of pharmacist attention. We started curbside pickup, ramped up delivery, and set up new protocols as hospitals and doctors closed. Relationships with our providers have been strengthened, and we are caring for patients at a higher level than just a few months ago. I’m amazed at how many people are coming by to say they never realized how much they needed a local pharmacy.”

Other pharmacists built their own testing programs. In rural Surgoinsville, Tennessee, Beth Bryan, PharmD, was the first pharmacist in the state and one of the first in the country to offer COVID-19 testing. Her Surgoinsville Pharmacy began offering appointment-only, drive-up testing in mid-April 2020. Pharmacy staff collected nasopharyngeal swabs and sent them to a lab for processing. Bryan said there are clear public health, community service, and professional advancement arguments for providing COVID-19 testing. And she didn’t have to worry about the business case. Her pharmacy partnered with the state health department to obtain sample collection kits, the local fire department to acquire hazmat suits, and a local welder for face masks. Community members donated N95 masks.

“Without community support, we would not have been able to obtain test kits or PPE [personal protective equipment],” Bryan said. “There is no good pathway to reimbursement. We’re working on it, [the US Department of Health & Human Services (HHS)] is working on it. There is a learning curve for all of us, just like there was with immunizations. But if somebody is looking for a big moneymaker, COVID-19 testing isn’t it.”

In West Sacramento, California, Capitol Pharmacy is building relationships, not profits. The Health Mart pharmacy has yet to be reimbursed for testing. Health Mart, part of McKesson, was part of an HHS pilot program to test community pharmacies as sample collection sites for molecular testing. The test manufacturer provided sample collection kits, McKesson provided PPE and supplies, and pharmacies provided space and personnel.

“We’re not paying for testing supplies,” said Capitol Pharmacy owner Thomas Bui, PharmD. “When we agreed to be a testing site, we got supplies overnight, but we didn’t have time to prepare, to communicate to the community that we would be offering COVID-19 testing. We’re just trying to give back to the community. It’s the right thing to do.” Economics made a huge difference at the University of Southern California (USC), said Richard Dang, PharmD, RPh,BCACP,assistantprofessorofclinical pharmacy. Plans to test the entire USC community—students, faculty, and staff—went on hold when the university saw cost estimates for test kits, PPE, and supplies. “They were not expecting the budgetary impact of testing,” said Dang, a California Pharmacists Association COVID-19 Taskforce chair and speaker. “They had sticker shock.”

And then there is the murky question of regulatory authority.

On April 8, HHS authorized licensed pharmacists to order and administer FDA-authorized COVID-19 tests, including serology tests. By mid-May, about two-thirds of states were allowing pharmacists to play a role in testing.

On May 19, the agency issued an advisory opinion (20-02) declaring that states and localities may not establish, enforce, or continue in effect any legal requirements that prohibit licensed pharmacists from ordering and administering FDA-authorized COVID-19 tests. HHS cited the Public Readiness and Emergency Preparedness Act as preempting state licensing laws that restrict pharmacists from ordering and administering COVID-19 tests.

By early June, some 40 states had cleared the way for pharmacists to test. California, New York, and Pennsylvania were notable exceptions. New York had announced plans for a pilot program with independent pharmacies to provide COVID-19 testing. However, the rollout was delayed.

In California, lawmakers thought they had the testing problem solved. The state conferred provider status on pharmacists in 2014 and allowed pharmacists to provide point-of-care testing. But point-of-care serology testing is limited to blood glucose, glycated hemoglobin A1c, and cholesterol, Dang noted. The FDA has issued Emergency Use Authorizations for 4 point-of-care COVID-19 tests, but the state is not allowing pharmacists to use them without first getting a Clinical Laboratory Improvement Amendments (CLIA) certificate of waiver from the state health department.

“We are seeing disagreement with HHS from the state,” Dang said. “Our department of health is indicating there are no changes to their requirements regarding CLIA certificates of waiver. The ultimate issue is that pharmacists are unable to obtain a waiver without having a qualified laboratory direction, whose definition does not include a pharmacist.”

CLIA waivers are also a barrier in Pennsylvania, said Patricia A. Epple, CAE, CEO of the Pennsylvania Pharmacists Association. The state’s Bureau of Laboratories, part of the health department, requires a lab director with a doctorate in science and at least 2 years of hands-on experience that is acceptable to the bureau.

“A PharmD would qualify, but the bureau is requiring experience in a clinical lab, which excludes most pharmacists,” Epple said. “Pennsylvania has the lowest percentage of pharmacies with CLIA waivers in the country, around 2.8% of our pharmacists. We have been working for 10 years trying to get changes and have not gotten any result.”

The reliability of existing tests is another consideration. The FDA released independent evaluations of 5 COVID- 19 serological tests in early June, including 1 that had been voluntarily withdrawn from the market. Among the marketed tests, positive predictive values ranged from 100% to 63.7%. Negative predictive values ranged from 100% to 99.5%. AmerisourceBergen is not distributing any of them.

“We just haven’t been comfortable with the accuracy of tests that have been FDA approved, so we are not distributing them,” said Rich Tremonte, executive vice president and president of community and specialty pharmacy at AmerisourceBergen. “We know that some of our independent pharmacy customers are administering tests and some of our chain customers are doing testing. They are focusing on molecular tests where you collect samples and send them to a lab for processing. Many independent pharmacies just don’t have the resources to do that.” The need for pharmacy testing is clear, especially as flu season approaches. Influenza and COVID-19 share multiple signs and symptoms. Pharmacists cannot practically identify one for treatment without ruling out the other. Respiratory syncytial virus is another potential confounder.

“The diseases are so similar in presentation that you want to be able to test for all 3 to advise the best course of action,” said Hannah Fish, PharmD, CPHQ, associate director for strategic initiatives at the NCPA. “We are seeing some of that preparation already taking place in pharmacies. We need clarification on pharmacists’ ability to offer testing and to bill for tests.”

Preparation taking place in some pharmacies, but clarification is still needed.

COVID-19 Testing Is Not an Automatic Choice for Pharmacists

An estimated 32 million individuals 12 years and older used psychedelic medicine in the United States in 2010, according to a US population survey. As the opioid epidemic has eclipsed concerns about illegal drugs in recent years, the medical community and the federal government alike have begun reexamining certain illicit drugs as potential alternatives to opiates in pain management.

Perhaps no other "illicit" substance has played a greater role in turning the tides recently than medical cannabis. Its slow but steady serial legalization and decriminalization at the state levels to treat a variety of complaints, including pain, have helped bring cannabis, cannabis products, and other stigmatized  drugs to the forefront.

"It is most surprising that even though cannabis has been used for a number of ailments for thousands of years—even dating back to the 28th century BC—it is now being recognized as a valid treatment option," said Swathi Varanasi, PharmD, an integrative health pharmacist and medical cannabis consultant in Los Angeles, California. "However, because of the way cannabis has been criminalized, it hasn't been integrated into standard treatment algorithms.'

Regulatory measures aside, pharmacists and other members of the medical profession often wrestle with safety when assisting patients who use cannabis for medicinal purposes. Cannabis has been studied extensively for numerous uses, including its potential benefits in neuropathic pain, chronic pain, and inflammation. A 2014 study found that most patients cited relief from chronic pain as the most common reason for their medicinal use of cannabis. Yet the plant's psychoactive properties continue to draw concerns regarding abuse potential, owing to the effects of 1 phytochemical, Delta-9-tetrahydrocannabinol, known for its psychoactive properties.

However, these are not the only challenges pharmacists face when it comes to assisting patients. "The biggest pitfall in advising patients on cannabis is that dosing is so difficult to standardize," Victoria Starr, RPh, a cannabis pharmacist at SageLife, LLC, in Portland, Oregon, told 

Cannabis for medicinal purposes is highly complex, largely because of its high number of phytochemicals, called constituents. To date, the plant has been found to contain more than 560 constituents. When individuals consume these as the whole plant, the chemicals ofery synergistic and therapeutic benefits while mitigating potential toxicities, what's known as the entourage effect. Synthetic cannabis typically contains only 1 active ingredient and lacks additional chemicals that can help regulate undesirable effects. However, customizing cannabis dosing to even the individual patient is no small feat.

"Besides attaching medical benefits to each of these components, the combination of synergistic benefits needs to be determined, along with the proper ratio and dose," Starr explained. "So unlike Western medicine, in cannabis, there exists a multitude of different medications—with a wide range of potencies, targeting a vast array of medical conditions—made up of varied combinations of cannabinoids, terpenes, and flavonoids.

Psilocybin, the primary ingredient found in mushrooms that produce psychoactive effects, in enjoying an increased share of popularity and renewed exploratory use.

It’s exciting that patients are starting to ask their pharmacist about psilocybin,” said Emily Kulpa, PharmD, an integrative health pharmacist and psychedelic medicine consultant based in Milwaukee, Wisconsin.

Although psychedelic mushrooms have been used for millennia, they gained popularity in the United States for recreational use during the 1960s and had spawned some academic interests as well. From 1960 to 1962, psilocybin, along with psychedelic relatives lysergic acid diethylamide (LSD) and mescaline, became the focus of a series of trials known as the Harvard Psilocybin Project. At the time, these drugs were legal. Criminalization of these drugs would later erupt in the following decade as safety concerns grew.

Fast-forward to the new millennium. Psilocybin sparked some interest in its potential analgesic effects in cluster headaches and migraines. Psilocybin agonizes the 5-hydroxytryptamine receptor and may interact with nociceptive and antinociceptive processing. The results from one 2016 retrospective study Googling the keywords “cluster headache discussion forums” and “migraine discussion forums” found that patients who self-treated themselves with psychedelic tryptamines such as psilocybin and LSD reportedly experienced a reduction in cluster frequency and severity.

Although these claims may warrant clinical study in pain management, research has focused on the role of psilocybin in mood disorders. Kulpa credits events in popular culturwith helping bring psilocybin into the mainstream. In the fall of 2019, Johns Hopkins announced the opening of the Center for Psychedelic & Consciousness Research, the first institution in the United States devoted exclusively to psychedelic research.

Indigenous to Thailand, Malaysia, Myanmar, and other regions of Southeast Asia, kratom (Mitragyna speciosa) belongs to the coffee family and also exhibits dose-dependent sedative and stimulatory effects. The plant is typically consumed in pill, capsular, or extract form, although some individuals brew dried or powdered leaves as a tea. Others may chew, smoke, or consume the leaves in food. However, because of kratom’s harmful adverse effects and abuse potential, the FDA warns individuals against using the substance.

Kratom contains mitragynine, an alkaloid bearing a tryptaminelike structure that exhibits µ- and ∂-opioid receptor agonist activity that results in dose-dependent stimulatory and analgesic effects. In lower doses, mitragynine produces stimulatory effects, whereas higher doses result in opioid-like activity. However, its metabolite, 7-α-hydroxymitragynine, exhibits significantly stronger µ-opioid receptor agonist behavior.

Although kratom is not an opioid, the CDC found an association between kratom use and overdose deaths, also involving opioid and nonopioid use, in the State Unintentional Drug Overdose Reporting System. Moreover, based on toxicology results, medical examiners or coroners determined kratom as the culprit in deaths in 11 states from July 2016 to June 2017 and 27 states during the last 6 months of 2017.

“There is no legitimate medical use for kratom in the [United States],” the Drug Enforcement Administration (DEA) wrote in a report on its website.8 On August 16, 2016, the DEA announced its intent to classify kratom as a Schedule I controlled substance, noting that the plant had been “abused for its ability to produce opioidlike effects” and “was often marketed as a legal alternative to controlled substances.”

Pharmacists should be aware of the substance so they can educate patients about the potential harms.

Varanasi believes the importance of cannabis in pain management will only continue to grow. “Preliminary evidence demonstrates cannabis’ ability to provide significant pain relief as well as [to help individuals] taper off opioids [particularly in the setting of addiction],” she said. “Though the research is inconclusive, patient anecdotes support the continued use of cannabis in pain management.”

In Oregon, the Oregon Psilocybin Program Initiative will appear on ballots in November 2020. “If passed, it would [be] the first state-sanctioned program for the administration of psilocybin services between a certified practitioner and a patient,” Varanasi said. “This would not only set the standard for other states but also support published studies reporting that a strong patient-practitioner relationship improves overall health outcomes.”

In the meantime, patients and practitioners alike will have wait to see how these and other psychedelics will alter integrative medicine and the world of health care.

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Whelan A, Johnson MI. Lysergic acid diethylamide and psilocybin for the management of patients with persistent pain: a potential role? 

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Andersson M, Persson M, Kjellgren A. psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches. 

 2017;14(1):60. doi:10.1186/s12954-017-0186-6

About. Johns Hopkins Center for Psychedelic & Consciousness Research. Accessed June 1, 2020. 

). Drug Enforcement Administration. November 2019. 

https://www.deadiversion.usdoj.gov/drug_chem_info/kratom.pdf. 

What is kratom? National Institute on Drug Abuse. April 2019. 

https://www.drugabuse.gov/publications/drugfacts/kratom

FDA and Kratom. FDA. Updated September 11, 2019. Accessed June 4, 2020. 

https://www.fda.gov/news-events/public-health-focus/fda-and-kratom

Olsen EO, O’Donnell J, Mattson CL, Schier JG, Wilson N. Notes from the field: unintentional drug overdose deaths with kratom detected — 27 states, July 2016–December 2017. 

Kruegel AC, Uprety R, Grinnell SG, et al. 7-Hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects. 

DEA announces intent to schedule kratom. News release. Drug Enforcement Administration. August 30, 2016. https://www.dea.gov/press-releases/2016/08/30/dea-announces-intent-schedule-kratom

Once largely stigmatized, illicit substances are breaking into the field of pain management. 

Psychedelic Medicines for Pain Go Mainstream

Although community pharmacies are the ideal locations to provide a vaccine for coronavirus disease 2019 (COVID-19) after it is developed, they must overcome barriers that include state regulations and patient objections. One recent survey found that only 3 in 4 Americans would choose to receive the COVID-19 vaccine when it becomes available.

"Vaccine hesitancy is a major barrier to vaccine uptake and the achievement of herd immunity, which is required to protect the most vulnerable populations,” wrote the authors of a recent 

 article. “Given that certain individuals will be ineligible for COVID-19 vaccination because of age, immunocompromised status, and other preexisting medical conditions, a vaccine refusal rate greater than 10% could significantly impede attainment of this goal.”

However, experts with the National Association of Chain Drug Stores (NACDS) and the National Community Pharmacists Association (NCPA) believe demand for the COVID-19 vaccine will be significant and that pharmacies should prepare now to administer it. “We are operating under the assumption that the demand for a COVID-19 vaccine will be high, when available,” said Kathleen Jaeger, RPh, senior vice president of pharmacy care and patient advocacy for NACDS. NACDS’ recent poll conducted by Morning Consult found that 86% of Americans say pharmacists should be allowed to provide a COVID-19 vaccine. “This, combined with the tremendous trust that patients place in pharmacists, suggests that Americans will continue to look to these highly educated health professionals for reliable information,” Jaeger said.

Pharmacists are in a “great position” to administer the vaccine, according to John Beckner, RPh, senior director of strategic initiatives at NCPA. “If you want to mass-immunize the population, you want to use pharmacists,” he told 

. It is not too early to begin educating patients about the vaccine, which practitioners can do now while providing other routine vaccinations, Beckner said.

However, Beckner acknowledged that some patients will have concerns. “Like anything new, there is probably going to be some pushback. There are going to be antivaxxers, and there are always going to be folks thinking they can get the flu from the vaccine, for example. It is really important to educate them,” Beckner said.

Community pharmacies need to work with their state associations, who will partner with local and state health departments, to break down barriers to pharmacists’ vaccinations in certain states—and to communicate that they are set up to administer the new vaccine. Some states have age restrictions on pharmacists who can administer vaccines. “NCPA has been pushing for pharmacists to administer all American Council on Immunization Practices–approved vaccines,” Beckner added.

NACDS is advocating for the federal and state governments to take “swift action” to ensure the population can rely on pharmacies and pharmacists for the COVID-19 vaccine, Jaeger said. The organization has engaged with the Trump administration’s Operation Warp Speed to make the case for pharmacy’s role, based in large part on the industry’s proven track record during the H1N1 pandemic.

Despite some anticipated hesitancy, demand for the novel coronavirus vaccine will be significant when it becomes available.

Pharmacies Must Prepare for a COVID-19 Vaccine

Pharmacists can play an important role in helping patients with asthma manage their disease through drug therapy assessment and education.

Asthma Pharmacotherapy and Counseling Pearls 

Pharmacists should ensure that patients have a written asthma action plan that includes their medications with directions, steps to take if symptoms worsen, and means of accessing medical care. Pediatric patients will generally need nebulizers, pressurized metered dose inhalers, or face masks attached to a metered dose inhaler, depending on age, to ensure the correct dose of medication is delivered into the lungs. Patients should continue taking their current asthma medications and discuss any concerns with their pharmacist and other health care providers during the COVID-19 pandemic.

Pharmacists can also help ensure that patients have an adequate supply of medications. The Global Initiative for Asthma recommends that all adults and adolescents with asthma receive inhaled corticosteroids (ICSs) as long-term control medications; experts consider these the most effective anti-inflammatory drugs because they reduce the risk of exacerbations, hospitalizations, and death.

 Examples include fluticasone (Flovent HFA), budesonide (Pulmicort Flexhaler), and beclomethasone (Qvar RediHaler), and they have a low risk of adverse effects (AEs).

 Local AEs may include oral candidiasis and dysphonia (hoarse voice), which patients can minimize by using a spacer and rinsing with water and spitting out after inhalation.

 agonists (LABAs) are bronchodilators that practitioners can add to an ICS if patietns require combination therapy.

Combination ICS-LABA inhalers include fluticasone-salmeterol (Advair Diskus), budesonide-formoterol (Symbicort), and formoter- olmometasone (Dulera). Importantly, patients must always use LABAs with ICSs because evidence shows that LABAs used alone may increase the risk of a severe asthma attack.

 AEs associated with LABAs include tachycardia, headache, and cramps.

Leukotriene receptor antagonists such as montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo) are another option for controller therapy, specifically in children.

The FDA recently issued a drug safety communication about the addition of a boxed warning for montelukast because of the risk of serious mental health AEs, including suicidal thoughts or actions.

 Practitioners should weigh the benefits and risks before prescribing montelukast for patients with asthma. Patients taking montelukast should discontinue the medication and contact their pharmacist and other health care providers immediately if they experience any behavior- or mood-related changes.

Rescue medications provide rapid, short-term symptom relief during an asthma attack.

 agonist bronchodilators (SABAs) such as albuterol (ProAir HFA, Ventolin HFA) and leval-buterol (Xopenex) only as needed and at the lowest dose, and SABAs should not be used without an ICS.

 Patients may experience tremor and tachycardia with initial use of SABAs, but tolerance develops with regular use.

 Ipratropium (Atrovent) is a short-acting anticholinergic inhaler that is less effective than SABAs as a rescue medication, with dry mouth as a common AE.

 Practitioners should prescribe systemic corticosteroids (eg, prednisone, methylprednisolone) only short term to treat severe asthma symptoms, as long-term use can cause serious AEs, including diabetes, hypertension, osteoporosis, and cataracts.

 Corticosteroid use should be tapered if the treatment duration is longer than 2 weeks. Short-term use of corticosteroids may cause hyperglycemia, insomnia, increased appetite, and mood changes.

May is asthma awareness month. CDC. Updated May 4, 2020. Accessed May 18, 2020. 

https://www.cdc.gov/asthma/world_asthma_day.htm

2. Coronavirus disease 2019 (COVID-19): people with moderate to severe asthma. CDC. Updated April 2, 2020. Accessed May 20, 2020. 

https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/asthma.html

3. Asthma associated with longer time on ventilators for younger COVID-19 patients. News release. Rush University Medical Center. May 15, 2020. Accessed May 21, 2020. 

https://www.rush.edu/news/press-releases/asthma-associated-longer-time-ventilators-younger-covid-19-patients

4. COVID-19 and asthma: what patients need to know. American Academy of Allergy, Asthma & Immunology. Updated April 23, 2020. Accessed May 22, 2020. 

https://www.aaaai.org/conditions-and-treatments/library/asthma-library/covid-asthma

5. Pocket guide for asthma management and prevention for adults and children older than 5 years. Global Initiative for Asthma. April 3, 2020. Accessed May 22, 2020. 

https://ginasthma.org/wp-content/uploads/2020/04/Main-pocket-guide_2020_04_03-final-wms.pdf

6. Asthma. Mayo Clinic. September 13, 2018. Accessed May 24, 2020. 

https://www.mayoclinic.org/diseases-conditions/asthma/symptoms-causes/syc-20369653

7. FDA requires stronger warning about risk of neuropsychiatric events associated with asthma and allergy medication Singulair and generic montelukast. News release. FDA. March 4, 2020. Accessed May 23, 2020. 

https://www.fda.gov/news-events/press-announcements/fda-requires-stronger-warning-about-risk-neuropsychiatric-events-associated-asthma-and-allergy

8. Biologics for the management of severe asthma. American Academy of Allergy Asthma & Immunology. Updated March 22, 2019. Accessed May 24, 2020. 

https://www.aaaai.org/conditions-and-treatments/library/asthma-library/biologics-asthma

“Pharmacists should ensure that patients have a written asthma action plan.”

Pharmacists Are Key Players in Asthma Management

Nonmedical issues are requiring pharmacists’ attention in increasingly urgent ways, especially in light of the coronavirus disease 2019 (COVID-19) pandemic. A greater focus on social determinants of health (SDOH) may lead to a much more comprehensive approach to treating patients in the pharmacy and ultimately drive improved outcomes. Overall health is often determined by social and economic issues, and understanding how these factors affect patients is key to identifying and addressing SDOH in the pharmacy setting.

The World Health Organization (WHO) defines SDOH as the conditions in which individuals are born, grow, live, work, and age. The WHO definition also states that these circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels. SDOH can be directly related to health inequities contributing to unfair and avoidable differences in health status. However, the health care community is now addressing these issues in a much more formal way, with the COVID-19 pandemic placing even greater urgency on pharmacists to adopt models of SDOH.

Hannah Fish, PharmD, associate director of strategic initiatives at the National Community Pharmacists Association in Washington, DC, said pharmacists are one of the most accessible health care providers and are often the first point of care for many patients. “Pharmacists are intimately familiar with the lives of the patients in their community and often are aware of nonmedical-related concerns such as transportation, housing, and food security," she told 

Fish added that because many independent pharmacies deliver medications, they can see firsthand many of the SDOH affecting their patients. Pharmacies across the country are starting to train their pharmacy technicians as community health workers. “Pharmacists have been leveraged informally as the eyes and ears of the care team, documenting what they see in their pharmacy management systems or simply just knowing their community so well. Now we’re starting to see some formality,” she said.

The CDC has recognized the importance of SDOH to public health and has established programs that partner with communities to provide a greater health impact. The CDC programs include the National Program to Eliminate Diabetes-Related Disparities in Vulnerable Populations, which helps 6 organizations plan, develop, implement, and evaluate multisector, community-based interventions.

Fish said some community health workers can assist with screening and assessing patients adversely affected by SDOH. These health workers can serve as a referral source to connect patients with the resources they need, such as food banking services, transportation services, and more. “A pharmacy might have helped a patient with finding these resources in the past, [and] community health workers are able to expand and expedite this service,” said Fish.

Richard Logan Jr, PharmD, Logan & Seiler, Inc L&S Pharmacy, Medical Arts Pharmacy, Charleston, Missouri, echoed Fish’s recognition of the pharmacist’s role in patient’s health care: “This relationship has been for years the cornerstone of clinical pharmacy services. From addressing access to medications for reasons clinical or financial to acting as a triage and referral site into the health care system, no one spends more eyeball-to-eyeball time with the patient than their pharmacist,” he said.

Logan noted that the best health care system in the world is of no use to a patient who cannot access it. If an individual has an appointment with a physician but has no way to get to the office, that appointment is pointless. “People who have poor access to food are worrying about their next meal, not their [high-density lipoprotein] levels,” said Logan. SDOH in various forms can create a significant barrier to health care. “[The Centers for Medicare & Medicaid Services] has recognized this and legitimized it with a whole series of ICD-10 [

International Classification of Diseases, Tenth Revision

] codes addressing SDOH as a barrier to care," said Logan.

A patient with a chronic disease usually has 35 or more visits to a pharmacy in a year, making the pharmacy the logical “go-to place” to delve into how SDOH are affecting a patient’s care, according to Logan. Often the pharmacy is the canary in a coal mine for patient access to health care. “We see patient struggles first, either through conversations in the pharmacy or when we deliver to their home and step into their lives. In our practice, and others of which I’m aware, we employ trained community health workers to interact with patients, interview patients, refer patients to services, and assist them in any way possible to address their SDOH [and] access to care in a caring, compassionate, effective way,” said Logan. Logan said by focusing on SDOH, his group has had great success, in both positive patient outcomes and increased professional awareness among local health care colleagues.

Linn Gould, MPH, executive director of Just Health Action in Seattle, Washington, said the term SDOH has existed for more than 20 years. Yet many pharmacists have never even heard of it. “From 2001 to 2003, the jargon started being adopted more widely. So it is fascinating that there are so many people who have never heard of it,” said Gould.

Medical and pharmacy schools appear to be failing in addressing SDOH. One recent article suggested that major structural and cultural transformations in medical education are warranted to address social and economic issues. The authors wrote that educators need to discuss not only poverty but also oppression, racism, sexism, and homophobia. One local pharmacist in Seattle told 

® that he had never heard much about SDOH. He said he is surprised by how little attention SDOH receive and that most pharmacists have a total lack of awareness of SDOH. Yet most pharmacists would probably adopt a model if they had the knowledge and were given the opportunity, he added. Unfortunately, the current operational model for retail pharmacies is now extremely transactional and, for the most part, does not allow pharmacists to take into account SDOH.

Currently, the COVID-19 pandemic is requiring that pharmacies address SDOH in many areas. Mass unemployment, for instance, has led to myriad new needs. “Pharmacies delivering medications are calling their patients to see whether they need anything else, such as groceries, before going to the home,” said Fish. She said during the current period of social distancing, calling patients once a week to check on their general well-being and mental health may be appropriate. “In addition to employing community health workers, we’ve seen pharmacies partner with local farmers’ markets to provide fresh produce for patients coming to the pharmacy. Further, insurers are recognizing the impact SDOH have on health outcomes and are expressing a desire to work with pharmacies to address these concerns,” said Fish.

Logan said pharmacists are rising to meet the challenge of remote patient care via enhanced deliveries, curbside services, expanded personal patient outreach, and an increase in those patient touch points even as patients shelter in place. Many older patients in particular are now unable to make physician visits, putting them at risk of uncontrolled chronic comorbidities. “Our pharmacies are checking in regularly with our patients with chronic conditions to make sure they are not ignoring other conditions for the sake of COVID-19,” Logan told 

Gould works in Seattle’s Duwamish Valley, a community with environmental justice concerns as a result of significant air pollution problems. “It has one of the highest childhood asthma hospitalization rates in the city of Seattle, and now we have evidence that the higher air pollution [is], the higher the COVID-19 death rate [is]. We have also learned that there is a link between asthma and COVID-19 rates," said Gould.

The physical distancing measures required to slow the spread of COVID-19 are substantially more difficult for those with adverse social determinants. According to Denise Fu, PharmD, clinical programs manager in Patient Care Services at Johns Hopkins Home Care Group Pharmacy Services in Baltimore, Maryland, although many pharmacists can identify SDOH issues, they need more education regarding available resources to help them address the barriers. “For example, pharmacists may be able to assist the patient with access to prescription medication but would need to refer the patient to other resources for employment, food insecurity, or housing instability,” she said.

Fu also said that improving information technology can help by filling in the gaps with SDOH data. One published study suggested that a lack of policy standards around SDOH data may be hindering adoption. However, commercial vendors are interested in collaboratively discussing policy solutions such as standards and guidelines. The investigators evaluated the development of electronic health record (EHR) software products that allow health care providers to identify and address patients’ SDOH. They conducted interviews with 6 EHR vendors with large market shares in both ambulatory and inpatient settings. The study results showed that SDOH appear to be an area for growth and that vendors offer a wide range of SDOH-related products with various levels of sophistication.

“If health care providers are able to collect and document SDOH risk factors, technology can help by seeing how many and to what extent of the 5 SDOH domains a particular patient is experiencing. If a patient is unable to keep the water on in their house or food on the table for their family, they are most likely not going to be able to afford and take their medicines,” said Fu.

A century ago, helping individuals with SDOH made a significant impact against tuberculosis, another highly infectious disease. At that time, better housing, a reduction in overcrowding, and improved nutrition saved countless lives. Now pharmacy is stepping up to formally address SDOH to help lower both morbidity and mortality during the current pandemic and beyond.

Enhanced pharmacy services such as home delivery, curbside services, and expanded personal patient outreach create opportunities to address social determinants of health during the pandemic.

Drug Topics July 2020

Go to Bat for Patients in Need

UMass Memorial Provides Model for Curbside Medication Delivery

Selpercatinib for NSCLC and Thyroid Cancer With RET Mutations or Fusions

Microbiome Research Calls for Due Diligence in Pharmacy

COVID-19 Testing Is Not an Automatic Choice for Pharmacists

Psychedelic Medicines for Pain Go Mainstream

Pharmacies Must Prepare for a COVID-19 Vaccine

Pharmacists Are Key Players in Asthma Management

Social Determinants of Health: Tackle Disparities From the Pharmacy

NYC-Based Study Improves A1c Levels in Poverty Areas With High Diabetes Prevalence

Addressing Diabetes Management Disparities in Minority Children

COVID-19 and Telemedicine: A Conversation