Ohio society of
health-system pharmacy

Author: Payton Winghart, PharmD.

With the frequency of seasonal influenza outbreaks, it is easy to forget that the flu can often be associated with severe morbidity and mortality, especially in certain populations, like pediatrics.¹ Children, in particular, those that are less than 5 years of age or those with underlying medical conditions such as asthma, sickle cell disease, epilepsy, or metabolic disorders are at high risk for severe influenza complications. ¹In pharmacy, we understand that primary prevention is the most effective way of combating the flu. A primary role of a pharmacist is to promote influenza vaccinations and educate parents and caregivers on the benefits of receiving the vaccine to those who are eligible (i.e. children 6 months old and older).¹ However, vaccination rates are not as high as one would like. Thus,secondary treatment measures are often utilized. One of the newest agents used to combat the flu is baloxavir (Xofluza).²

Baloxavir was FDA approved on October 24, 2018 for the treatment of acute, uncomplicated influenza for patients ages 12 years old and older.³ Baloxavir works by inhibiting the endonuclease within the polymerase acidic protein sub-unit of the viral polymerase. ³ In targeting a particular site on the virus than other antivirals currently on the market, baloxavir has the added advantage of aiming to inhibit a different part of the viral replication process. Therefore, it can be used in oseltamivir-resistant strains of influenza. It should be administered within 48 hours of symptom onset and is given as a single 40 mg dose if the patient is between 40 and 80 kg or 80 mg dose if the patient is greater than 80 kg.⁴ The cost of the dose of this medication is approximately $150.³ Some of the common adverse effects associated with baloxavir are diarrhea, nose and throat irritation, headache, and upset stomach, similar to oseltamivir and the other neuraminidase inhibitors.⁴ The Institute for Safe Medication Practices has issued an alert regarding life-threatening hypersensitivity reactions associated with baloxavir after a single dose. As for administration,it should not be taken concomitantly with calcium or calcium containing products.⁴ Baloxavir is the first and only FDA-approved treatment specifically indicated for those at high risk of flu complications.⁵

The CAPSTONE-2 Trial was one of the trials that was conducted to evaluate the efficacy of a single, oral dose of baloxavir compared with placebo.⁶ The main outcome measure was time to improvement of influenza symptoms from day 1 up to day 14. This was a randomized, parallel, double blind, placebo-controlled trial with a total of 2,184 participants. Results showed that baloxavir was well-tolerated and associated with faster recovery in high risk influenza patients compared to placebo, ultimately leading to FDA approval.⁶ Another trial known as the MINISTONE-2 trial evaluated the safety and efficacy of baloxavir in children ages 1-12 compared to the safety and efficacy of oseltamivir in this population. The primary endpoint of the study was the proportion of patients with adverse events at day 29. The study results demonstrated that baloxavir successfully reduced the length of viral shedding by one day when compared to oseltamivir. Baloxavir also had a favorable tolerability profile in terms of adverse effects, and was similar to those of oseltamivir.⁷

There are certain advantages and disadvantages to using baloxavir in clinical practice. As far as benefits are concerned, the one-time dose allows for ease of administration and encourages adherence.

³ It also provides coverage for patients who may be infected with oseltamivir-resistant influenza strains.³ There is also evidence that it may reduce time to symptom alleviation by one day in comparison to oseltamivir.⁶ In terms of detriments of baloxavir therapy, the cost of the one-time therapy is higher than that of a full course of oseltamivir.⁶ Baloxavir has also been shown to be less effective against influenza B strains, which is particularly an issue this season, as most of the outbreaks have been caused by influenza B.⁷ The use of baloxavir has also not been studied in as many populations as oseltamivir, so safety in the very young and very old is still to be determined.⁷ In conclusion, despite the limitations associated with baloxavir therapy, influenza infection remains a healthcare burden in our society, and the development of new medications such as baloxavir are our next best step secondary to promoting vaccination.

References:

1. People at High Risk for Flu Complications. Centers for Disease Control and Prevention. 2018; https://www.cdc.gov/flu/highrisk/index.htm

2. Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018;379(10):913-923.

3. Mushtaq A. Baloxavir: game-changer or much ado about nothing? Lancet Respir Med. 2018;6(12):903-904.

4. Ng KE. Xofluza (Baloxavir Marboxil) for the Treatment Of Acute Uncomplicated Influenza. P T. 2019;44(1):9-11.

5. Takashita E, Morita H, Ogawa R, et al. Susceptibility of Influenza Viruses to the Novel Cap-Dependent Endonuclease Inhibitor Baloxavir Marboxil. Front Microbiol. 2018;9:3026.

6. Ison M, Portsmouth S, Uehara T, et al. Phase 3 Trial of Baloxavir Marboxil in High-Risk Influenza Patients (CAPSTONE-2 Study. Open Forum Infectious Diseases. 2018;5:S764-S765.

7. Koshimichi H, Tsuda Y, Ishibashi T, Wajima T. Population Pharmacokinetic and Exposure-Response Analyses of Baloxavir Marboxil in Adults and Adolescents Including Patients With Influenza. J Pharm Sci. 2019;108(5):1896-1904.

 Author: Katie McKinney, PharmD, MS, BCPS, FACHE, FASHP.     

  

“The first time I ever flew in a plane, I was skydiving.”

“I coach a high school dance team.”

“I am an officer in the Ancient Accepted Scottish Rite.”

“I have gone waterfall rappelling!”

“Last month I competed in my first chess tournament.”

OSHP has amazing members.

Each of the above statements came from an active member in OSHP!

How do you celebrate what makes others’ unique?

How might you recognize the gifts and contributions of your colleagues at your practice sites, local affiliated chapters and in our state organization?

Now’s the time!

Nominations for OSHP’s eleven awards are open through January 15, 2020.

Visit https://www.ohioshp.org/Awards to view the award criteria and submit nominations.

Click into “About” for each award.

The Nomination Form can be found within the individual award description.

As we consider the beginning of a new year, and a new decade, be reminded that OSHP has partnered with the National Academy of Medicine Action Collaborative on Clinician Well-Being and Resilience. “In positive psychology research, gratitude is strongly and consistently associated with greater happiness. Gratitude helps people feel more positive emotions, relish good experiences, improve their health, deal with adversity, and build strong relationships.”¹

Please take a moment to cultivate gratitude for a colleague by nominating her or him for one of OSHP’s Awards. Perhaps this may allow you to accomplish one of your 2020 goals early in the year, in the recognition and appreciation of others or appreciating others as a way to strengthen your individual resilience and improve your well-being.

You might also consider involving someone new in your professional activities as a way to recognize his or her contributions to patient care and your department. Extend the invitation to a newly hired technician to join you at an upcoming event with your local-affiliated chapter. You will enjoy the opportunity to learn more about your colleague, make introductions to others and contribute to her or his professional development and advancement. Embrace opportunities in 2020 for your growth as well as your role in the growth of others.

Thank you to the members of OSHP for your voluntary work in 2019 and living into our mission to optimize patient health by advocating for the advancement of pharmacy practice to promote comprehensive, quality care across the health-care continuum.

Please enjoy a safe, happy and healthy 2020!

Katie McKinney, PharmD, MS, BCPS, FACHE, FASHP

President, OSHP, 2019-2020

1.      https://www.health.harvard.edu/newsletter_article/in-praise-of-gratitude

Author: Brittany Bates, OSHP President-Elect

As the holiday season is upon us, I thought I would share a personal story of gratitude.

In my fourth year as a pharmacist, I received a  call that changed the trajectory of my life and my career. My healthy, forty-nine-year old mother was being rushed to a large medical center with suspected bacterial meningitis. That first day was a mix of blurred chaos and vivid images that will forever be etched in my mind. During the nine days my mother spent in the hospital, I experienced fear and uncertainty. I also experienced joy and amazement at each stage of her improvement. Looking back, I feel an immense amount of gratitude for what this experience taught me.

First, I am thankful for my education and my clinical experiences during residency. This training allowed me to understand what was happening to my mother and interpret medical terminology for my family. I am also thankful for the medical professionals who took extra time with me, answered my questions, and even accepted recommendations from “the patient’s daughter who is a pharmacist.” Being on the other side of the healthcare team provided me with insights into the scary and frustrating role of being a patient or advocating for a family member. I attempt to keep this in mind each time I interact with patients or their families.

Next, I am thankful for my pharmacy and physician colleagues. In the true spirit of teamwork, they covered my service and allowed me to take off the time I needed. Further, they were a resource to me when I had complicated questions about my mother’s condition. At this point in my career I was rounding on an internal medicine service, but I found myself drawn to infectious diseases. The firsthand experience with my mother’s diagnosis strengthened my passion for infectious diseases and shaped the direction of my career in the following years. Today I teach CNS infections to students at Ohio Northern University, and my students are likely to hear about my mother’s case!

Finally, I am most grateful that my mother made a full recovery. An underlying medical problem was identified during her hospitalization that will require lifelong treatment, but her condition is manageable. We are fortunate. My whole experience with my mother’s illness helped me to appreciate that I am part of one of the greatest professions. The work we do, and our collaboration with other health care professionals, benefits so many—including, at times, our own families.

I hope that in this holiday season all of us can remember special moments of gratitude as we embrace the serious challenges we face each day. I also want to express my own gratitude for your support of OSHP and for the opportunity I have to lead this organization.

Happy Holidays!

Brittany Bates, OSHP President-Elect

Author: Chad Harvey, PharmD, BCPS

The Greater Cincinnati Society of Health-System Pharmacists (GCSHP) has had a busy year so far and there are no signs of that letting up. This is by design of course! The chapter has focused a lot of energy on drumming up participation from pharmacists while also expanding programming to be more inclusive of technicians, residents, and pharmacy students. While overall participation improvements have been modest, they have still been noticeable.

The biggest event of the year for the chapter is our annual “GCSHP CE Day” which successfully completed its 3^rd year in September. This event provides 4 hours of ACPE-accredited CE (including 1 hour of medication safety) and provides CE for pharmacy technicians. Registration is free for members and students (small charge for non-members) and all attendees are provided a catered meal. CE presentations are provided by clinical pharmacists, pharmacy administration, and pharmacy technicians, among others, which allows participants to learn from a variety of leaders in the field of pharmacy. New to the event is the involvement of pharmacy students through collaboration with the University of Cincinnati James L. Winkle College of Pharmacy’s CoCA programming. This year’s event had about 30 attendees, which unfortunately was a steep decline from previous years. Many factors for this decline have been identified and will be considered in the future as plans to continue growing the event have already begun.

In each November and December, the chapter will have sponsored drug dinners for members. The November dinner was an extra event to allow participating GCSHP members to learn from a renowned speaker. The December dinner will be our annual “holiday dinner” to aid in increasing membership, as well as collect toy donations for a family in need. The latter has historically been well attended and we expect a great turnout again this year.

In the spring we will host two more events. The first event is our annual Ohio Law CE. This event has a large turnout each year and provides pharmacists and pharmacy technicians with 1 hour of ACPE-accredited law CE. This event has a catered dinner and a presentation, which is provided by an Ohio Board of Pharmacy representative. The second spring event is our annual Best Practices and Research Symposium, which allows pharmacy students, residents, and practicing pharmacists, an opportunity to present their research. This interactive symposium uses electronic posters and small groups to provide a unique presentation setting and creates the chance to view many presentations in a short time frame.

The year will wrap-up in late spring/early summer with officer elections and transitions, along with our annual GCSHP social event, and finally the yearly planning event. So far, this has been a successful year for GCSHP and we look to continue growing our chapter through this year and into the future.

Thank you,

Chad Harvey, PharmD, BCPS.  President - Greater Cincinnati Society of Health-System Pharmacists

What’s the mechanism of resistance (gene, and effect) seen in Escherichia coli (E. coli) that induces resistance to piperacillin-tazobactam but retains susceptibility to cephalosporins?

Benjamin Newell, PharmD, PGY1 Resident; Nathan Wirick, PharmD, BCPS, BCIDP; Sandra Axtell, PharmD, BCPS. Cleveland Clinic Hillcrest Hospital

There are various resistance mechanisms that have been described forE. coli. However, in the case of piperacillin-tazobactam resistance and cephalosporin susceptibility it involves an amino acid substation in the bla_TEM-1 and bla_SHV-1gene markers.¹These gene variations are capable of hydrolyzing penicillins and first generation cephalosporins, without effecting oxyimino cephalosporins. Ceftazidime, cefuroxime,ceftriaxone, and cefepime are all oxyimino cephalosporins.^1,2

Investigators explored E. coli isolates with these gene characteristics and of the 32 isolates, 28 (88%) harbored bla_TEM-1 and bla_SHV-1 and none contained an extended-spectrum beta lactamase (ESBL)-AmpC beta-lactamase gene which would elicit greater cephalosporin resistance.² Common risk factors associated with TEM-1 and SHV-1 isolates are recenthospitalization, hematologic malignancy, and gastrointestinal tract infection. The ability to recognize these high-risk patients can potentially aid in de-escalation of carbapenems and utilization of cephalosporins instead to assist in reserving carbapenems for ESBL-AmpC producing enterobacteriaceae.² Testing for these variations would be ideal but without commercial laboratory tests for these genes, providers will need to utilize susceptibilities to identify possible mutated isolates.

A case report describing this particular resistance mechanism involved a patient who presented with sepsis and was initiated on piperacillin-tazobactam, however did not exhibit clinical improvement after four days of therapy. Once susceptibility data was available, the patient was transitioned to ceftriaxone, andthere was significant clinical improvement.³Investigators examined a similar scenario that de-escalation of therapy to ceftriaxone is safe and effective once the blood stream isolate is identified as E. coli in the absence of ESBL.⁴

In conclusion, the incidence of TEM-1 or SHV-1 genes is low, only 3% ratereportedat one health-system over 2 years.³ Initiating a third or fourth generation cephalosporin may be beneficial over piperacillin-tazobactam, if these isolates are more frequent unless anaerobic or enteroocccal coverage is necessary. There may also be consideration of converting patients to cefepime or ceftriaxone if the patient is slow to respond to piperacillin-tazobactam, since it will take approximately two days to have susceptibilities back from the culture draw and there is no commercial product to detect these genes on a susceptibility report. This way patients are treated appropriately and de-escalation can occur at a timely rate.

References

Shaikh S, Fatima J, Shakil S, Rizvi, S, Kamal MA. Antibiotic resistance and extended spectrum beta-lactamases: Types epidemiology and treatment. Saudi J Biol Sci. 2015 Jan;22(1):90-101.

Baker TM, Rogers W, Chavada KD, Westblade LF, Jenkins SG, Nicolau DP. Epidemiology of Bloodstream Infections Caused by Escherichia coli and Klebsiella pneumonia that are piperacillin-tazobactam-nonsusceptible but ceftriaxone-susceptible. Open forum Infect Dis. 2018 Nov 19;5(12):300-7.

Carlisle L, Justo JA, Al-Hasan MN. Bloodstream infection due to piperacillin/tazobactam non-susceptible, cephalosporin-susceptible Escherichia coli: A missed opportunity for de-escalation of therapy. Antibiotics 2018;(7)4:104.

Bookstaver PB, Nimmich EB, Smith TJ, Justo JA, Krohn J, Hammer KL, Troficanto C. Cumulative effect of an antimicrobial stewardship and rapid diagnostic testing bundle on early streamlining of antimicrobial therapy in gram negative bloodstream infections. Antimicrob Agents Chemother.2017 Aug 24;61(9):189-17.

Author: Morgan Krause, PharmD, BSPS

Preparing for residency can be an overwhelming process! An important component of residency preparation is attendance at showcases. Whether you are attending the residency showcase at Ohio Society of Health-System Pharmacists (OSHP) or the residency showcase at American Society of Health-System Pharmacists (ASHP)’s Midyear Meeting, it is important to do your research about the programs you are interested in and arrive prepared. After reflecting on my residency preparation, I have some of my tips regarding preparation, attendance and interactions at the residency showcase.

Be honest with yourself.

Take the time to self-reflect prior to attending the showcase. Why do you want to participate in post-graduate training? What are your goals related to residency training? What skills and experiences would you like to enhance throughout your training? What areas of pharmacy are you NOT interested in? What type of pharmacist do you want to be when you grow up?

If you ponder residency-related goals early, your journey will be much smoother. By establishing your values and goals upfront, you will feel more confident as you navigate the available programs. Understanding your goals, values, and important aspects that you are looking for in a program is an important before even stepping into a residency showcase.

Be honest with the programs.

Residents and the residency program directors are at the showcase to answer your questions and to get to know you better. If you are not interested in their program, politely move along. No feelings will be hurt, and no bridges will be burned. Also, do not pretend to be interested in a program. Pretending to be interested in pediatric intensive care does not bode well to the program you just expressed your ambulatory care interest to; your interests may not be in clear alignment with what the program has to offer.

On the contrary, it is okay to have some uncertainty related to what you want to do with your career. Do not be afraid to explore programs outside of your comfort zone. This may include programs in an unfamiliar location, or with unique learning experiences. You may discover more about your own interests and find a mentor in the least expected way.

Treat the showcase as an interview

Dress for success! If you own a suit or a nice blazer, wear it. Suitable colors include black, navy blue, or grey. If you decide to wear a dress or skirt, wear the appropriate length. In general, keep the dress or skirt at least one inch above the knee. If you are uncertain if your clothing is appropriate, do not wear it. It is important to showcase your professionalism while you interact with the residents and directors. Do not allow your clothing to serve as a distraction!

“What questions do you have?” is a common saying you will experience throughout the residency process. The showcase is no exception. Identify what questions you want to ask each program prior to the showcase.You will appear more professional if you are able to have a conversation with the resident or residency director. If you are fidgeting through your papers or struggling to think of a question, you may appear unprepared or uninterested in the program.

Come prepared!

ASHP has an online residency directory – take advantage of it! Additionally, the ASHP directory will have a link to the program’s website if one is available. Read through the descriptions of the programs that will be in attendance at the showcase. Find the programs that have your specialty of interest. What else would you like to know about a certain learning experience within the program? How could you incorporate that learning experience into a research project? Write those questions down and bring them with you.

In addition to the ASHP online residency directory, explore the website of residency programs as well. If the information is visibly available on both of these resources, avoid formulating questions around this material. Take the time to reflect on your own interests and values and formulate unique questions to ask of the programs.

Also, bring your business cards and CVs. Stay hydrated. The day will fly by, and all of the programs will begin to blend together. Bring a notebook to quickly jot down notes after talking with residency programs. Go somewhere private after each interaction to collect your thoughts. Remember to grab the business card of each resident or residency director you talked with! Write down what you discussed on the back of the card. You have a lot of thank-you e-mails or hand-written letters to construct after the showcase, and you want to guarantee you have the correct person. In your follow up, be sure to reference something specific you discussed with your new connection. This demonstrates that the conversation was meaningful. Remember, this is the beginning of a career-long professional relationship with the person.

The residency showcase is a long day, but it is very rewarding. While you are able to interact with the residency programs, you are also able to interact with your friends and classmates that you may not have seen since rotations started. Stay positive, enjoy the support of your peers, and absorb the positive energy around you! You are one step closer to your dreams. Do not forget how far you have come, and how far you will go.

Good luck!

Morgan Krause, PharmD, BSPS

Author: Katie McKinney, OSHP President

In each of our departments and facets of practice, we recognize the key roles Pharmacy Technicians play on our teams. During Pharmacy Month, I’d like to extend a heartfelt Thank You to those who chose Pharmacy Technician as their career and recognize a few of those that have shaped my own professional journey.

Thank you to Jim Myers Jr., who introduced me to hospital pharmacy practice as my first trainer. The lessons he imparted for patient safety while sterile compounding resound today. Thank you for teaching best practice when I was first learning preparation and process.

Thank you to Tracy Adkins. Tracy and I worked together during my residency training, where she supported our repackaging service. She taught me foundational aspects and critical thinking associated with inventory management and pharmacy automation. Tracy and I have continued to work together as both our scopes have expanded; it was kismet when our paths crossed again and is such a pleasure to maintain our relationship.

Thank you to the technician leadership within my current practice. With a department mix of approximately 50% technicians and 50% pharmacists, the expansion of practice of technicians within our department and representation on our leadership team has been an area of focus. Thank you to Sue Janson for being one of several technician members of our pharmacy leadership team. Sue’s perspective regarding the evolution of pharmacy practice over her career and experience throughout our department offers meaningful perspective to our team.

Thank you to Crista Parsons, who lead the first Technician Division of OSHP, and Timmi Anne Boesken, the current Technician Division Director. Your leadership and contributions to this organization are invaluable. Thank you for the education and advocacy for the profession for technicians within our state through OSHP. Of note, OSHP is the ONLY professional pharmacy organization in Ohio actively engaging technician members! Please contact Timmi Anne if you or your colleagues have interest in participation and contribution to OSHP’s Technician Division.

As we continue to navigate the regulatory changes regarding technician registration with the Ohio Board of Pharmacy and in supporting our technician team members in meeting the training requirements, please remember the resources OSHP offers. OSHP has partnered with the publisher of Pharmacy Technician’s Letter (Therapeutic Research Center). Don’t forget to mention the Ohio Society of Health-System Pharmacists if you leverage the services offered by Pharmacy Technician’s Letter in aligning training modules for your employer-based training program.

Additionally, OSHP support pharmacy technician development through recognition. OSHP annually recognizes one individual as Pharmacy Technician of the Year and our Annual Meeting (May 7 and 8, 2020). Nominations for all of OSHP’s awards will open in November. Support technician contributions, as well as those of many others by nominating your colleagues for an OSHP Award.

The Legal Affairs Division, lead by Garrett Eggers, has initiated conversations regarding tech-check-tech. Registration requirements from the Board of Pharmacy have clearly delineated opportunities for technicians based on registration/certification. Research in states with technician product verification show a lower rate of product selection errors. Please contact Garrett and the Legal Affairs Division if you have thoughts and contributions for the work of this team within our state.

Every pharmacist would be a different practitioner, a practitioner who would be limited in foundational knowledge or recognition of opportunities for improvement in the medication use system, if it weren’t for the insight and collaboration with previous and current technician colleagues. Please extend your Thank Yous to those you have and have had the privilege in collaborating in our professions.

Happy Pharmacy Month!

Happy Pharmacy Technician Day, Tuesday, October 15th!

-Katie McKinney, OSHP President

Author: Aaron Barber, PharmD Candidate, Northeast Ohio Medical University

Esketamine(SPRAVATO™) is approved for treatment-resistant major depressive disorder (MDD) in combination with an oral antidepressant in adults. Treatment-resistant depression entails two failed antidepressant trials of adequate doses and durations. Esketamine is a schedule III controlled substance and requires a Risk Evaluation and Mitigation Strategies (REMS) program (SPRAVATO™ REMS). This represents the first breakthrough for MDD since the introduction of fluoxetine in 1987, and it offers an alternative for the many patients whose depressive symptoms are uncontrolled with current regimens.

Esketamine is the S-enantiomer of racemic ketamine, and it is a non-selective, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. The mechanism by which it exhibits antidepressant effects are unknown. Bioavailability of intranasal administration is 48%, and the time to peak plasma concentration is20-40 minutes. Esketamine is metabolized to noresketamine, its major active metabolite, primarily by cytochrome P450 (CYP) 2B6 and CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Noresketamine is then metabolized by different CYP dependent pathways. Following nasal administration, less than 1% of the dose is excreted unchanged in the urine.

Esketamine is contraindicated in patients who may experience deleterious effects secondary to increased blood pressure or intracranial pressure. Contraindications include aneurysmal vascular disease, arteriovenous malformation, or intracerebral hemorrhage. Avoid esketamine in patients with hypersensitivity reactions to either esketamine or ketamine. Warnings include sedation, dissociation, abuse, and suicidal thoughts and behaviors. In clinical trials, up to 61% of patients experienced sedation, whereas up to 75% experienced dissociative or perceptual changes (e.g.,distortion of time, space, and illusions, derealization, depersonalization).

Administration of esketamine is associated with an increase in blood pressure.Patients experience an average increase of 7-9 mmHg systolic and 4-6 mmHg diastolic at 40 minutes post administration. This increase dropped at the 1.5 hour mark to 2-5 mmHg systolic and 1-3 mmHg diastolic.Concurrent use of esketamineand monoamine oxidase inhibitorsor psychostimulants may increase blood pressure and requires close monitoring.

Several phase III clinical trials evaluated esketamine. Short-term, fixed and flexible-dosed trials were conducted in adults with treatment-resistant depression. Patients received either esketamineor intranasal placebo; all patients received antidepressant therapy. Esketamine significantly improved scores from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS). Despite positive results in adult trials, a 4-week trial in patients 65 years and older found no significant difference between esketamine and intranasal placebo on the MADRS. Longer-term trials investigated relapse prevention and safety. Time to relapse was significantly longer for esketamine than placebo. Cognitive impairment and interstitial cystitis have been reported with ketamine misuse and abuse. Neither adverse effect was observed over the course of 12months with esketamine; however, higher rates of dysuria, micturition urgency, and nocturia occurred.

Esketamine is available in 28 mg unit dose devices (2 sprays [1 spray in each nostril] = 28 mg). Dosing ranges from 56-84 mg; therefore, multiple devices are needed for each dose. The dosing schedule begins with 56 mg for the first dose and either 56 mg or 84 mg for all subsequent doses.

Prior to the first intranasal spray only,instruct the patient to blow their nose. Do not prime the device before use. Instruct the patient to tilt their head back at a 45° angle and insert the device in the first nostril until the nose rest touches the skin between nostrils. Close the opposite nostril and press the plunger while inhaling through the nose. After the spray, sniff gently. Repeat these steps with second nostril, and ensure that the patient does not blow their nose. Wait 5 minutes before administering each subsequent device needed to achieve the desired dose. After administration of the full dose, the patient must be observed by a health care provider for at least 2 hours to monitor for adverse effects such as sedation, dissociation, and hypertension. Additionally, patients should be advised to avoid drinking any liquids for 30 minutes prior to administration and to avoid any food intake for 2 hours before administration due to the risk of nausea and vomiting.

Up to one-third of adults with MDD experience persistent symptoms of sadness, sleep disturbances, low energy, or thoughts of suicide or death. Esketamine represents the first new antidepressant mechanism of action in over 30 years. It is difficult to predict if widespread adoption of this therapy will occur secondary to its REMS requirements, strict post-administration monitoring parameters, and need for frequent office visits. This could, however, open the door to exciting opportunities, such as pharmacist-run esketamine clinics. No matter what the future holds, it is comforting to know that there is now a new tool for patients to battle depression.

References:

Ionescu DF, Rosenbaum JF, Alpert JE. Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues Clin Neurosci. 2015;17(2):111–26.

Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sánchez E, Gutiérrez-Rojas L, Meana JJ. Antidepressant efficacy and tolerability of ketamine and esketamine: a critical review. CNS Drugs. 2018;32(5):411-20.

Spravato [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; March 2019.