More than a year into the COVID-19 pandemic, the mental health burden resulting from the public health crisis is becoming more and more apparent.

Social isolation amid widespread lockdowns, coupled with fear and anxiety over becoming infected by the SARS- CoV-2 virus, have undoubtedly affected the mental well-being of many individuals. In fact, the results of a recent study published in Psychiatry Research showed increased levels of clinical depression symptoms and a reduction in overall well-being among young adults during the lockdown. May is Mental Health Awareness Month, and our 

 dives into how pharmacists can address the mental health burden in their patients and communities. From specialized training and medication management to simply checking in on patients’ mental welfare when they visit the pharmacy, opportunities exist for pharmacists across health care settings. Read our story on page 10 to learn more.


It is also important for pharmacists to take care of their own mental health during these times. Tune in to our Medical World News® broadcast to catch our new “Wellbeing Checkup” segment for tips and tricks from peers and experts on how to practice self-care and prevent burnout. Visit 

Additionally, as more Americans become eligible for COVID-19 vaccinations, pharmacists undoubtedly will be asked questions regarding the vaccines’ safety profiles. Pharmacists should arm themselves with the knowledge to properly educate vaccine-hesitant patients. Turn to page 24 for an 

overview of the current safety data for each available vaccine

 and what is known about the adverse effects.

You’ll also find in this issue great insights into 

integrating pharmacists into the stroke care team

. Check back to drugtopics.com for the latest pharmacy news, including expert interviews, podcasts, and conference coverage.

Chairman and Founder of MJH Life Sciences

Articles

From the chairman

May Is Mental Health Awareness Month

One day, my wife Denise and I went to our local bank with a plastic card and put it in the machine. We had the option of withdrawing either $25 or $50 out of our checking account. The money dropped down in an envelope with the cash inside. This was amazing technology for 1981. I then went to work and pulled out the Smith Corona typewriter and started typing prescription labels.

Yesterday, I went to our warehouse club and pulled up to the gas pumps. I took out my phone and waved it at the QR code on the screen. I began pumping my gas without ever getting my wallet out of my pocket. I checked my email and saw I had spent $28.54 on pump #4 at 7:46 am. I went to the pharmacy, fired up the computer, and began my working day.

A new patient needed a shingles vaccine. She handed me her 2 prescription cards. We had to enter all the insurance data by hand, making sure we typed in the right bank identification, processor control, ID, and group numbers. After we submitted the claim, it was denied and we needed to use the Medicare Part D card. Next, we entered the alphanumeric information carefully to make sure all the letters and digits were correct. I got out my cheat sheet to make sure I added 4 additional fields, including administration fee, because this was for a vaccine. Then we went to another website to print out her prescreening form, and logged in the site of administration, lot number, and expiration date of the vaccine.

Two outstanding pharmacists who are working to make massive changes in our profession are Stephanie McGrath, PharmD, and my daughter Gretchen Garofoli, PharmD, BCACP. Both are working tirelessly to have pharmacists get paid for their clinical expertise through CPESN-USA. Their focus is on e-care plans, which enable pharmacists to show what interventions they have made that will produce optimal outcomes for our patients.

The biggest challenge with e-care plans is that the technology is clunky at best. Like anything else in health care, it takes more time to document your actions than to carry them out. I’m familiar with 3 of the major e-care plans and I’m not impressed with any of them. The one I use to bill for services to a provider requires 5 different systematized nomenclature of medicine clinical terms (SNOMED CT) codes to be documented. Whether you are documenting hypertension, chronic obstructive pulmonary disease, or asthma, you should not have to search through layers and layers for the appropriate 5 SNOMED codes.

The very best pharmacy software I was ever exposed to was in the late 1990s. It was built by a couple of pharmacists. To this day, I have yet to see a pharmacy filing system that was more pharmacist friendly than that one. I would love to see more pharmacists on the ground floor of software development. If only our pharmacy software could be as intuitive as the iPhones we all carry with us. When’s the last time you read the user manual for your smartphone?

When I stand in front of my pharmacy computer for 10 hours at a time, I often wonder why this technology seems so far behind the other technology I use daily. If we want to move this profession toward more patient-centric care, we must have the tools to do that. All I ask is that my pharmacy computer have the same technology as my gas pump.

Innovation is everywhere, but cumbersome pharmacy technology remains an issue.  

Technology Advances Are Needed to Advance the Profession 

Medications used to treat stroke are complex and their preparations are complicated. Pharmacists’ knowledge and familiarity with these brain-saving medications is crucial in the typically narrow time windows to effectively treat stroke patients, according to Deborah Sadowski, RPh, BSPharm, MHA, director of pharmacy services at Deborah Heart and Lung Center in Browns Mills, New Jersey.

“The pharmacist is uniquely positioned to assess the safety and appropriateness of these medications for each patient as well as dose and prepare them in a safe and expedient manner,” Sadowski said.

As a result, including pharmacists in stroke care teams can greatly improve patient outcomes. They can be incorporated into a stroke patient care team in a variety of practice settings, including inpatient units, outpatient clinics, and community pharmacies, in addition to emergency departments.

At Mount Sinai Hospital in New York, New York, clinical pharmacist Nicole Davis, PharmD, BCCCP, an assistant professor in the Department of Pharmacy Practice at Touro College of Pharmacy, also in New York, said the pharmacy team is alerted when a stroke patient arrives in the emergency department. When this occurs, a pharmacist will bring a thrombolytic directly to the bedside to assess eligibility as well as to compound the medication. The patient is then transferred to the neurology intensive care unit (ICU) or to a step-down unit or floor bed depending upon their condition, where they are followed by an ICU-trained pharmacist or inpatient pharmacist.

Kristina Stein, PharmD, a neurology clinical pharmacist at the University of Alabama at Birmingham Hospital, is part of a multidisciplinary team that responds to “code strokes.” She receives an alert when a patient has a neurologic change or event that could be concerning for a stroke. “Pharmacists can identify candidates for thrombolytic therapy and reduce time to thrombolytic therapy,” she said. Furthermore, they can facilitate adjunctive therapy, such as blood pressure control or reversing anticoagulation therapy in the case of hemorrhagic strokes.

Pharmacists can also participate in medication reconciliation, secondary stroke prevention, risk reduction, patient counseling and education, and transitions of care initiatives. Stein attends transition-of-care rounds, where she meets with an interdisciplinary group to review each patient with stroke. She also counsels patients who start oral anticoagulants during their hospitalization or who will start one after discharge, works with providers to choose the best agent for patients, and helps monitor heparin, enoxaparin, and warfarin.

Stein would advise smaller organizations to train some inpatient pharmacists in stroke care. First gauge staff interest, then have that group develop a continuing education presentation or other training session. Choose someone who is interested in this effort to take ownership and be responsible for developing house-wide education. The 2019 update to the 

Guidelines for the Early Management of Patients With Acute Ischemic Stroke

 is a great place to start when developing education.

If an institution is looking for other ways to incorporate pharmacists into stroke care, opportunities exist with developing or reviewing stroke electronic order sets; completing competencies in stroke identification, management, and thrombolytic therapy administration; participating in stroke simulation education experiences; and serving on stroke committees, Stein added.

When looking to make a change, such as adding a pharmacist to a stroke care team, it’s helpful to have a physician promote it. After a pharmacist has joined the team, Alyssa Bernard, PharmD, a patient care pharmacist in the stroke unit and neurosensory ICU at Jefferson Hospital for Neuroscience in Philadelphia, Pennsylvania, recommends a few first steps. To begin with, she said, it’s important to review team- and unit-specific policies and procedures, as well as team- and unit-specific disease states and guidelines.

Bernard’s stroke unit and intermediate neurosensory step-down units are the hospital’s only non-ICU units in which IV push administration of labetalol and hydralazine is permitted. “Having some baseline knowledge about disease states that a pharmacist will focus on and the workings of a new unit will allow a pharmacist to make more targeted and useful recommendations to their team,” she said.

Bernard also advises establishing the best point of contact for recommendations and other messages, as well as obtaining other team members’ communication preferences. Her usual go-to individual is a junior resident, but the entire team should be informed of interventions that involve radically changing a patient’s therapy.

Pharmacists can facilitate appropriate medication use by familiarizing themselves with the latest acute ischemic stroke guidelines from the American Heart Association and American Stroke Association, including secondary prevention strategies (ie, antiplatelets, statin therapy, blood pressure management, glucose control, and vasospasm prevention after subarachnoid hemorrhage). This will enable them to intervene throughout a patient’s hospital stay and encourage optimal pharmacotherapy, according to Doug Humber, PharmD, a health sciences clinical professor and clinical pharmacist specialist at Skaggs School of Pharmacy and Pharmaceutical Sciences Department of Pharmacy at the University of California, San Diego.

Humber also noted that pharmacists can be involved in developing computerized prescriber order sets for alteplase to ensure that appropriate decision pathways are followed and that medication orders are entered and viewed in a timely manner. Moreover, hospitals can incorporate pharmacists into the development of an acute stroke care pathway. This would include all aspects of the alteplase process, such as indications and contraindications for alteplase, dosing and administering alteplase, and monitoring patients after giving alteplase, explained Humber.

Further, Bernard noted there are many ways in which a pharmacist can assist in proper medication usage in an inpatient setting, but one that is often overlooked is route of administration. Many patients with stroke experience difficulty swallowing as one of their major presenting symptoms. These patients require nutritional support and medication administration via tubes. “It is vital, therefore, that a pharmacist know which medications can be crushed and which interact with tube feedings,” she said. This can also extend to which medications can be given rectally or converted to IV formulations if a patient does not yet have other access to their gastrointestinal system.

Pharmacists also need to be aware of the different outcome measures for preventing future strokes. Ensuring that patients have good outpatient poststroke discharge plans is important to make sure they are monitored for high blood pressure, high cholesterol, diabetes management, smoking cessation, and other health maintenance concerns, according to Sarah Clark, PharmD, BCPS, a senior pharmacy manager for neurology, psychiatry, and emergency medicine, at Mayo Clinic in Rochester, Minnesota. Outpatient pharmacists can play a role in the ongoing medication management of these patients.

By working collaboratively with providers, pharmacists can build mutual trust and confidence with them, making providers more open to accepting recommendations from pharmacists on medication use. This partnership will benefit patients and provide them with optimum care through team collaboration, Sadowski said.

Karen Appold is a medical writer in Lehigh Valley, Pennsylvania.

Pharmacist inclusion in stroke interventions improves patient outcomes. 

Integrating Pharmacists Into Stroke Care Teams

On February 26, 2021, melphalan flufenamide (Pepaxto; Oncopeptides AB) in combination with dexamethasone was granted accelerated approval by the FDA for adult patients with relapsed or refractory multiple myeloma.

 Relapsed or refractory multiple myeloma is defined in patients who have received at least 4 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody. Melphalan flufenamide, a peptide-drug conjugate, targets aminopeptidases and selectively releases alkylating agents into tumor cells.

 Melphalan flufenamide is taken up by myeloma cells because of its lipophilicity. It is rapidly hydrolyzed by peptidases, and cross-linking of DNA is involved in the antitumor activity. Melphalan flufenamide shows synergistic cytotoxicity with dexamethasone in both melphalan-resistant and nonresistant multiple myeloma cell lines.

Accelerated approval of melphalan flufenamide was based on results of the multicenter, single-arm, phase 2 HORIZON trial (NCT02963493).

 To be eligible for the trial, patients were required to have relapsed or refractory multiple myeloma. They had to have received 2 or more prior lines of therapy and been refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 pomalidomide and/or a CD38-directed antibody. The primary end point was overall response rate (ORR) and the secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, clinical benefit rate, best response, time to response, time to progression, and time to next treatment.

 The ORR was 29% in the all-treated population (95% CI, 22%-37%), with 26% in the triple-class-refractory population (95% CI, 18%-35%). In the all-treated population, median DOR was 5.5 months (95% CI, 3.9-7.6 months), median PFS was 4.2 months (95% CI, 3.4-4.9 months), and median OS was 11.6 months (95% CI, 9.3-15.4 months) at a median follow-up of 14 months.

The most common adverse effects were fatigue (55%), nausea (32%), diarrhea (27%), pyrexia (24%), and respiratory tract infection (24%). The most common grade 3 or 4 laboratory abnormalities were decreases in leukocytes (88%), platelets (80%), lymphocytes (95%), neutrophils (82%), and hemoglobin (50%).

 Melphalan flufenamide carries warnings for thrombocytopenia, neutropenia, anemia, infections, secondary malignancies, and embryo-fetal toxicity. Additionally, this medication should not be interchanged with regular melphalan hydrochloride, such as when prescribed in high doses for conditioning regimens for hematopoietic stem cell transplantation, as higher-than-recommended doses of melphalan flufenamide may be associated with mortality.

Complete blood counts with differential should occur at baseline, during treatment, and as clinically indicated to monitor for thrombocytopenia, neutropenia, and anemia. Melphalan flufenamide should be withheld if the patient’s platelet count is less than 50 × 109/L or neutrophil count is less than 1 × 109/L. Pharmacists should advise patients to take this medication as prescribed, and patients should be monitored for signs and symptoms of infection while taking this medication. Patients should also be monitored long term for development of secondary malignancies. If applicable, patients should use contraception while on melphalan flufenamide because of the potential embryo-fetal toxicity. For females, contraception should be continued for 6 months after the last dose, and for males, 3 months after the last dose. Although it is unknown if melphalan flufenamide passes into breast milk, patients should be advised to not breastfeed during treatment and for 1 week after the last dose of melphalan flufenamide.

The recommended dosage of melphalan flufenamide is 40 mg intravenously over 30 minutes on day 1 of each 28-day treatment cycle in combination with dexamethasone. A serotonin (5-HT3) receptor antagonist, such as ondansetron, or other antiemetics may be taken to prevent nausea and vomiting.

 If needed because of adverse effects, the first dose reduction would be to 30 mg of melphalan flufenamide and the second dose reduction would be to 20 mg. If the patient cannot tolerate 20 mg, melphalan flufenamide should be permanently discontinued.

Kendall Szulimowski is a 2021 PharmD candidate at the University of Connecticut School of Pharmacy in Storrs.

Samantha Troy is a 2021 PharmD candidate at the University of Connecticut School of Pharmacy in Storrs.

Lisa M. Holle, PharmD, BCOP, FHOPA, FISOPP, is an associate clinical professor at the University of Connecticut School of Pharmacy in Storrs.

FDA grants accelerated approval to melphalan flufenamide for relapsed or refractory multiple myeloma. FDA. Updated March 1, 2021. Accessed March 18, 2021. 

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-melphalan-flufenamide-relapsed-or-refractory-multiple-myeloma

Richardson PG, Oriol A, Larocca A, et al. Melflufen and dexamethasone in heavily pretreated relapsed and refractory multiple myeloma. 

 2021;39(7):757-767. doi:10.1200/JCO.20.0225

Pepaxto. Prescribing information. Accessed March 18, 2021. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214383s000lbl.pdf

Melphalan flufenamide: drug information. Accessed March 18, 2021. http://

www.uptodate.com/contents/melphalan-flufenamide-drug-information

Melphalan flufenamide (Pepaxto; Oncopeptides AB) in combination with dexamethasone was granted accelerated approval on February 26, 2021, by the FDA for adult patients with relapsed or refractory multiple myeloma. 

Melphalan Flufenamide for Relapsed or Refractory Multiple Myeloma

Back in December 2020, the FDA issued an emergency use authorization for Pfizer-BioNTech’s COVID-19 vaccine, followed by authorization for the Moderna and Janssen (Johnson & Johnson) vaccines. Many Americans have yet to be vac- cinated, with the most common reasons for refusing being fear of potential adverse effects (AEs) and concerns about the rapid vaccine development process.

Pharmacists must be familiar with the safety profiles of the vaccines to assure the public of their safety.

COVID-19 Vaccines Available in the United States

Three vaccines are currently available on the US market. The Pfizer and Moderna vaccines are both messenger RNA (mRNA) vaccines, whereas the Janssen is a viral-vector vaccine.

 All 3 result in the production of SARS-CoV-2 spike proteins, which trigger the development of antibodies. The development of immunity and memory cells typically takes a few weeks and, when complete, these protect the body against COVID-19 infections.

 Although the vaccines stimulate an immune response, they do not cause a full COVID-19 infection.

Before a vaccine receives FDA approval, it undergoes a series of trials during which its efficacy and safety profiles are established. Trials begin in animal models and continue with 3 phases of clinical trials. A vaccine gains FDA approval only if the efficacy and safety data prove that its benefits outweigh the risks. Once a vaccine has been approved and launched, postmarketing surveillance begins. Such surveillance allows for the collection of safety data in a larger and more diverse population.

Postmarketing safety information for COVID-19 vaccines has been gathered in several ways. For all vaccines, the FDA’s Center for Biologics Evaluation and Research monitors vaccine safety through passive and active surveillance.

 Passive surveillance consists of adverse event reports received from the public and health care professionals, which are entered into the Vaccine Adverse Event Reporting System. Active surveillance involves proactively obtaining and analyzing information from large health care data systems to verify safety signals identified through passive surveillance or to detect additional safety signals. If a possible link between a vaccine and an AE is identified, public health officials assess the benefits and risks and determine whether the vaccine can continue to be administered and whether administration guidelines require adjustment.

Reported Adverse Effects Associated With COVID-19 Vaccines

The AEs reported with the COVID-19 vaccines are generally mild and resolve within a few days.

 These effects tend to be more intense after the second dose of the mRNA vaccines and are more likely to occur in younger individuals. Ongoing surveillance has identified additional AEs, but it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure (see 

 This point can be illustrated by the reporting in mid-April 2021 of a few cases of thrombocytopenia with cerebral venous sinus thrombosis in individuals who had received the Janssen COVID-19 vaccine. Although these cases appear to be very rare, as of the time of this writing, the FDA and CDC have recommended a pause in the use of this vaccine until this matter is thoroughly investigated.

The more commonly reported AEs associated with the use of COVID-19 vaccines are usually related to the vaccine’s pharmacology and not considered immune-mediated or allergic reactions.

 Despite that, news reports concerning severe postmarketing reactions including anaphylaxis instilled fear among the public.

Anaphylaxis is a severe acute-onset immunologic reaction, generally immunoglobulin E (IgE) mediated, which typically occurs in response to preformed IgE antibodies.

 Acute-onset immunologically mediated reactions commonly manifest as urticaria, swelling, gastrointestinal upset, respiratory distress, or cardiovascular collapse associated with severe cases of anaphylaxis. The onset of acute allergic reactions generally occurs within 30 minutes of exposure, although a reaction may also develop hours to days later, in which case it usually presents as a cutaneous reaction. Generally, the mRNA, DNA, or other antigen components in vaccines are not the culprits for allergic reactions. Allergic reactions are usually attributed to other product components such as stabilizing agents and adjuvants, and, rarely, to latex in the vial’s rubber stopper. The Pfizer and Moderna COVID-19 vaccines contain mRNA, lipids, polyethylene glycol (PEG) 2000, electrolytes, sucrose, and a saline diluent. Although the etiology of anaphylaxis to the COVID-19 vaccines is not known, PEG and related polysorbates have been associated with cases of anaphylaxis to other agents. Individuals who exhibit signs of allergic reaction after COVID-19 vaccination are advised to avoid new PEG exposure and to undergo further evaluation with a board-certified allergist or immunologist.

Although cases of anaphylaxis were not reported in clinical trials with the mRNA vaccines, 21 incidents of possible anaphylaxis were subsequently reported with the Pfizer vaccine (11.1 cases per million doses), with 70% occurring within 15 minutes of administration.

 Ten cases of possible anaphylaxis were reported after vaccination with the Moderna vaccine (2.5 cases per million doses) and 1 case of anaphylaxis was reported with the Janssen vaccine.

 The less extensive use of the Janssen vaccine to date prohibits a comparative assessment of the overall safety of this vaccine relative to the mRNA vaccines.

The CDC recommends that the COVID-19 vaccines not be administered to individuals who have a history of severe or immediate allergic reaction to any vaccine component (eg, PEG in the case of the mRNA vaccines, polysorbate in the case of the Janssen vaccine).

 Patients who experienced a severe or immediate allergic reaction to a COVID-19 vaccine should not receive subsequent doses.

The CDC recommends a postvaccination observation period of 30 minutes for those at high risk for anaphylactic reactions and 15 minutes for all other individuals.

When providing counseling, it is important to emphasize the vaccine’s efficacy. Individuals receiving the mRNA vaccines also should be counseled on the importance of completing the vaccination series with the same product. They should be counseled on the expected postvaccination symptoms: Of those receiving the mRNA vaccines, local symptoms are experienced by 80% to 89%, and systemic symptoms by 55% to 83%; of those receiving the viral-vector vaccine, local symptoms are experienced by 50%, and systemic symptoms by 55%. Reassure recipients that systemic postvaccination symptoms are generally mild to moderate in severity, occur within the first 3 days of vaccination, and resolve within 3 days of onset. Advise recipients that antipyretic or analgesic medications can be taken for postvaccination local or systemic symptoms.

The available COVID-19 vaccines are effective in reducing the spread of the disease. Serious reactions are rare, and the public should be educated on the overall safety of these vaccines.

1. WHO coronavirus (COVID-19) dashboard. World Health Organization. Updated April 6, 2021. Accessed April 6, 2021. 

2. Nguyen KH, Srivastav A, Razzaghi H. COVID-19 vaccination intent, perceptions, and reasons for not vaccinating among groups prioritized for early vaccination–United States, September and December 2020. 

. 2021;70(6):217-222. doi:10.15585/mmwr.mm7006e3

3. Understanding how COVID-19 vaccines work. CDC. Updated March 9, 2021. Accessed April 1, 2021. 

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/how-they-work.html

4. COVID-19 vaccine safety surveillance. Food & Drug Administration. Updated February 9, 2021. Accessed April 1, 2021. 

https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/covid-19-vaccine-safety-surveillance

5. Ensuring the safety of vaccines in the United States. CDC. Updated January 2018. Accessed April 1, 2021

https://www.cdc.gov/vaccines/hcp/conversations/downloads/vacsafe-ensuring-color-office.pdf

6. Possible side effects after getting a COVID-19 vaccine. CDC. Updated March 16, 2021. Accessed April 2, 2021. 

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/expect/after.html

7. Pfizer-BioNTech COVID-19 Vaccine- bnt162b2 injection, suspension. DailyMed. Updated February 26, 2021. Accessed April 1, 2021. 

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=908ecbe7-2f1b-42dd-94bf-f917ec3c5af8

8. Moderna COVID-19 Vaccine- cx-024414 injection, suspension. DailyMed. Updated March 29, 2021. Accessed April 1, 2021. 

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0651c7a-2fe2-459d-a766-0d59e919f058

9. Janssen COVID-19 Vaccine- ad26.cov2.s injection, suspension. DailyMed. Updated April 2, 2021. Accessed April 6, 2021. 

https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14a822ff-f353-49f9-a7f2-21424b201e3b

10. Recommendation to pause use of Johnson & Johnson’s Janssen COVID-19 vaccine. Centers for Disease Control and Prevention website. Accessed April 15, 2021. 

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/JJUpdate.html

11. Kuder MM, Lang DM, Patadia DD. Anaphylaxis to vaccinations: a review of the literature and evaluation of the COVID-19 mRNA vaccinations. 

. Published online March 1, 2021. doi:10.3949/ccjm.88a.ccc075

12. Rolla G, Brussino L, Badiu I. Maintaining safety with SARS-CoV-2 vaccines. 

. 2021;384(10):e37. doi:10.1056/NEJMc2100766

13. Information about COVID-19 vaccines for people with allergies. CDC. Updated March 25, 2021. Accessed April 5, 2021. 

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/specific-groups/allergies.html

14. Interim clinical considerations for use of COVID-19 vaccines currently authorized in the United States. CDC. Last reviewed March 5, 2021. Accessed April 5, 2021. 

https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html

Ease patients’ concerns by being well versed in the safety profiles of each vaccine.

COVID-19 Vaccines: A Focus on Safety

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint pain, stiffness, swelling, and decreased joint movement.

 According to the American College of Rheumatology (ACR), RA affects over 1.3 million individuals in the United States and approximately 75% are women.

 Unfortunately, there is no cure for the condition but early treatment can reduce joint pain and swelling and improve patients’ ability to perform daily activities. As drug information experts, pharmacists are well equipped to help patients select the most appropriate RA treatment option and educate them about potential drug and disease state interactions as well as lifestyle modifications to improve symptoms (see 

Pharmacologic treatment options for RA include conventional disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. Therapies are available orally, as injections, or as intravenous infusions

The ACR recommends using the treat-to-target approach, which involves setting a therapeutic goal and working with patients to achieve the best health outcomes.

 Conventional DMARDs can take several weeks for patients to experience the full benefits, but they improve active RA symptoms, slow the disease course, and improve radiographic outcomes.

Examples of conventional DMARDs include methotrexate (eg, Rheumatrex, Trexall), sulfasalazine (Azulfidine), leflunomide (Arava), and hydroxychloroquine (Plaquenil).

The ACR recommends methotrexate as the first-line DMARD for RA because most patients continue to take the therapy after 5 years based on its efficacy and tolerability.

 Pharmacists should advise patients to take methotrexate once weekly and not daily to prevent toxicity; many fatal errors have been reported to the Institute for Safe Medication Practices regarding this high-alert medication.

As methotrexate can cause hepatotoxicity, patients should limit alcohol- containing beverages to no more than 1 to 2 per week.

 Folic acid supplementation can help reduce the incidence of hepatotoxicity and of gastrointestinal (GI) adverse effects (AEs) associated with the drug.

Patients should avoid taking the antibiotic trimethoprim because it can increase methotrexate levels and cause nephrotoxicity and myelosuppression (low blood counts).

 If trimethoprim is necessary in the event there is no alternative antibiotic, the methotrexate should be held that week. Caution should be exercised if NSAIDs are used with methotrexate because of an increased risk of methotrexate toxicity; patients should be closely monitored.

 In addition, the herbal supplement echinacea also can cause hepatotoxicity and its use should be avoided with methotrexate.

Concomitant use of sulfasalazine and NSAIDs can increase the risk of GI bleeding. Patients taking leflunomide should limit alcohol consumption because it can cause liver damage.

 Higher doses of hydroxychloroquine for  COVID-19 treatment has been associated with QTc prolongation.

 However, evidence suggests that lower doses of the drug for RA treatment should not itself increase the risk of QTc prolongation or the fatal arrhythmia torsades de pointes.

 Pharmacists should review patients’ medication profiles for possible drugs that could cause QTc prolongation in individuals taking hydroxychloroquine, especially those with heart conditions.

Medications that can cause QTc prolongation include

antipsychotics (eg, haloperidol, ziprasidone, risperidone);

antiarrhythmics (eg, amiodarone, quinidine);

antibiotics (eg, azithromycin, fluoroquinolones); 

Tumor necrosis factor (TNF) inhibitors were the first biological DMARDs to be approved for the treatment of RA.

infliximab (Remicade; Janssen Biotech, Inc);

certolizumab pegol (Cimzia; UCB, Inc); and

golimumab (Simponi; Janssen Biotech, Inc).

Adalimumab-fkjp (Hulio; Mylan Pharmaceuticals Inc) is a biosimilar to Humira that was approved in 2020 to potentially reduce cost and improve patient access.

 Because reactivation of hepatitis B can occur with TNF treatment, it is important to screen patients prior to their starting therapy.

 An increased risk of infection exists with TNF inhibitors, and ongoing studies are evaluating the temporary hold of any biologic DMARD in patients with an active infection and antibiotic use.

Abatacept (Orencia; Bristol-Myers Squibb Company) is the first medication of the T-cell costimulation modulator class.

 Its concomitant use with TNF inhibitors is not recommended because of an increased risk of serious infections and no added efficacy.

 Rituximab (Rituxan; Genentech, Inc) is a B-cell therapy, and its biosimilar rituximab-arrx (Riabni; Amgen, Inc) was approved in 2020.

 As hepatitis B reactivation can occur in patients taking rituximab, individuals should be screened before receiving treatment.

Interleukin-6 (IL-6) receptor blockers include tocilizumab (Actemra; Genentech, Inc) and sarilumab (Kevzara; Regeneron and Sanofi Genzyme).

 Patients taking medications including warfarin or theophylline should have their blood levels monitored closely, with possible dose adjustments when starting or discontinuing tocilizumab or sarilumab.

The Janus kinase (JAK) inhibitors tofacitinib (Xeljanz; Pfizer), baricitinib (Olumiant; Eli Lilly and Company), and upadacitinib (Rinvoq; AbbVie Inc) are the only oral biologic DMARDs for RA.

 The FDA recently issued an updated drug safety communication regarding preliminary safety trial results for tofacitinib; compared with TNF inhibitors, both doses of the drug showed an increased risk of serious heart-related problems and cancer for patients with RA.

 The agency previously added a boxed warning, in 2019, when evidence showed an increased risk of blood clots and death with the higher 10-mg twice daily dose.

Baricitinib and upadacitinib also include boxed warnings about the risk of blood clots.

 Pharmacists can play an important role in counseling patients about these risks, especially individuals who have a history of cardiovascular conditions and cancer. The administration of tofacitinib or upadacitinib with strong cytochrome P450 3A4 (CYP3A4) inducers (eg, rifampin) should be avoided, as the JAK inhibitor efficacy can be decreased.

Additionally, the tofacitinib dose should be decreased for patients who are also taking strong CYP3A4 inhibitors (eg, ketoconazole) or a moderate CYP3A4 inhibitor with a strong CYP2C19 inhibitor (eg, fluconazole).

Further, a baricitinib dose should be reduced when the drug is taken concomitantly with a strong organic anion transporter 3 inhibitor (eg, probenecid).

Adjunctive treatments for RA include NSAIDs and corticosteroids, which can reduce inflammation and control pain.

Many NSAIDs are available OTC and include aspirin, ibuprofen, and naproxen; co-administration with a proton pump inhibitor can prevent the GI bleeding associated with NSAIDs.

Counseling patients about avoiding multiple products that contain NSAIDs by reading the OTC drug facts label is critical to prevent serious AEs. Additionally, as NSAIDs can increase the risk of cardiovascular events and impair renal function,

 their long-term use should be avoided, especially in patients with heart disease or renal dysfunction. Corticosteroids (eg prednisone, methylprednisolone) should be used short-term for treatment and tapered before discontinuing.

 They can increase blood glucose levels, therefore patients with diabetes should be closely monitored. Individuals can also develop osteoporosis.

 Further, patients with a history of mental illness may be at an increased risk of developing neuropsychiatric AEs (eg, aggression, insomnia, depression, psychosis) with corticosteroid therapy, but these symptoms can also occur in those without such history.

Rheumatoid arthritis. American College of Rheumatology. Updated March 2019. Accessed March 14, 2021. https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis 

Singh JA, Saag KG, Bridges Jr SL, et al; American College of Rheumatology. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. 

Rheumatoid arthritis treatment. Johns Hopkins Arthritis Center. Accessed March 20, 2021. 

https://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/

Rheumatoid arthritis. Mayo Clinic. March 1, 2019. Accessed March 20, 2021. 

https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648

Severe harm and death associated with errors and drug interactions involving low-dose methotrexate. Institute for Safe Medication Practices. October 8, 2015. Accessed March 20, 2021. https://www.ismp.org/resources/severe-harm-and-death-associated-errors-and-drug-interactions-involving-low-dose doi:10.1097/RHU.0000000000000810

Chua D. Chronic use of echinacea should be discouraged. Am Fam Physician. 2003;68(4):617.

Pflugbeil S, Böckl K, Pongratz R, Leitner M, Graninger W, Ortner A. Drug interactions in the treatment of rheumatoid arthritis and psoriatic arthritis. 

. 2020;40(4):511-521. doi:10.1007/s00296-020-04526-3

Pareek A, Sharma TS, Mehta RT. Hydroxychloroquine and QT prolongation: reassuring data in approved indications. 

. 2020;4(2):rkaa044. doi:10.1093/rap/rkaa044

Farzam K, Tivakaran VS. QT prolonging drugs. StatPearl. Updated November 27, 2020. Accessed March 20, 2021. 

https://www.ncbi.nlm.nih.gov/books/NBK534864/

New drug therapy approvals 2020. FDA. Updated January 8, 2021. Accessed March 20, 2021. 

https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2020

Orencia. Prescribing information. Bristol-Myers Squibb Company; 2020. Accessed March 20, 2021. 

https://packageinserts.bms.com/pi/pi_orencia.pdf

Actemra. Prescribing information. Genentech; 2021. Accessed March 20, 2021. 

https://www.gene.com/download/pdf/actemra_prescribing.pdf

Xeljanz, Xeljanz XR (tofacitinib): drug safety communication – initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine. FDA. February 4, 2021. Accessed March 20, 2021. 

https://www.fda.gov/safety/medical-product-safety-information/xeljanz-xeljanz-xr-tofacitinib-drug-safety-communication-initial-safety-trial-results-find-increased

Xeljanz. Prescribing information. Pfizer; 2020. Accessed March 20, 2021. 

http://labeling.pfizer.com/ShowLabeling.aspx?id=959#section-7

Rinvoq. Prescribing information. AbbVie Inc; 2020. Accessed March 20, 2021. 

https://www.rxabbvie.com/pdf/rinvoq_pi.pdf

Olumiant. Prescribing information. Eli Lilly and Company; 2020. Accessed March 20, 2021. 

https://uspl.lilly.com/olumiant/olumiant.html#s10

Yasir M, Goyal A, Bansal P, Sonthalia S. Corticosteroid adverse effects. StatPearls. Updated March 3, 2021. Accessed March 20, 2021. https://pubmed.ncbi.nlm.nih.gov/30285357/

Rheumatoid arthritis. American College of Rheumatology. Updated March 2019. Accessed March 21, 2021. 

https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis

Pharmacists can play an important role as part of an interdisciplinary team in treating patients with rheumatoid arthritis.

Drug Topics May 2021

May Is Mental Health Awareness Month

Technology Advances Are Needed to Advance the Profession

Integrating Pharmacists Into Stroke Care Teams

Melphalan Flufenamide for Relapsed or Refractory Multiple Myeloma

COVID-19 Vaccines: A Focus on Safety

Rheumatoid Arthritis Treatment

Digital Health Tools in Diabetes

Emerging Roles in Mental Health Care for Pharmacists