Dravet syndrome is a rare and chronic form of epilepsy characterized by severe and unrelenting seizures. This debilitating disease typically manifests within the first year of life with frequent and prolonged seizures often triggered by hyperthermia, developmental delays, and other health problems.

Initial therapy of Dravet syndrome has been limited to the use of valproate in combination with agents such as clobazam and stiripentol, with limited e cacy data in the United States.

 On June 25, 2020, fenfluramine (Fintepla), a Schedule IV amphetamine derivative that exhibits agonist activity at the 5-HT2 receptor, was approved for the treatment of seizures associated with Dravet syndrome in patients 2 years and older.

 Although the mechanism by which it exerts its therapeutic effect is unknown, patients treated with fenfluramine have consistently shown significantly greater reductions in the frequency of convulsive seizures than those receiving placebo in clinical trials.

Two randomized, double-blind placebocontrolled clinical trials were conducted in 202 patients with Dravet syndrome between the ages of 2 and 18 years. Study 1 (N = 117) compared 3 treatment groups; 0.7 mg/kg/day of fenfluramine, 0.2 mg/kg/day of fenfluramine, and placebo, respectively, in patients on 1 to 4 antiepileptic drugs, excluding stiripentol, who were inadequately controlled. Study 2 (N = 85) compared 0.4 mg/kg/day of fenfluramine with placebo in patients inadequately controlled on 2 to 4 antiepileptic drugs including stiripentol and either clobazam, valproate, or both. 

Both studies only included patients with a baseline of 6 or more convulsive seizures over 6 weeks, and observed a primary efficacy end point of a change from this baseline, per 28 days, during the 14- or 15-week treatment periods.

 In both studies, the reduction in frequency of convulsive seizures was significantly greater for all dose groups of fenfluramine, compared with placebo. This reduction was seen within 3 to 4 weeks of starting fenfluramine, and the eff ect was seen throughout the duration of both studies. The majority of patients using all doses of fenfluramine experienced a 50% or greater reduction in monthly convulsive seizures.

Fenfluramine has a boxed warning for valvular heart disease and pulmonary arterial hypertension. Fenfluramine is only available under a risk evaluation and mitigation strategy and requires an echocardiogram assessment prior to initiation of therapy, frequently throughout, and after therapy.

Furthermore, 37% and 19% of patients in clinical trials reported decreased appetite and decreased weight, respectively.

Fenfluramine is associated with sedation, suicidal ideation, hypertension, and glaucoma.

 This medication is contraindicated in patients with concomitant use, or use within 14 days of, monoamine oxidase inhibitors due to the increase in risk of serotonin syndrome. Fenfluramine should be gradually titrated to discontinuation to minimize the risk of a rebound in seizure frequency and status epilepticus.

Fenfluramine is administered as an oral solution with or without food and is dispensed as a 2.2 mg/mL (360 mL) vial with 2 oral syringes. Initial dosing for both pediatric and adult patients begins at 0.1 mg/kg/dose twice daily and can be titrated on a weekly basis up to 0.2 mg/kg/dose, and then 0.35 mg/kg/dose twice daily, based on response and tolerability. The maximum recommended dose for adult and pediatric patients is 26 mg/day and 13 mg/day, respectively. The labeling does not provide dose adjustments in renal impairment, and use is not recommended in hepatic impairment. Of note, these dosing recommendations are for adults without concomitant stiripentol therapy and for pediatric patients 2 to 18 years old on at least 1 other antiepileptic drug.

1. FDA approves new therapy for Dravet syndrome. News release. FDA; June 25, 2020. Accessed July 28, 2020. 

fda.gov/news-events/press-announcements/fda-approves-new-therapy-dravet-syndrome

2. Tanabe T, Awaya Y, Matsuishi T, et al. Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome)—a nationwide questionnaire survey in Japan. 

3. Aras LM, Isla J, Mingorance-Le Meur A. The European patient with Dravet syndrome: results from a parent-reported survey on antiepileptic drug use in the European population with Dravet syndrome. 

4. Fintepla. Package Insert. Zogenix, Inc; 2020. Accessed July 28, 2020. 

zogenix.com/pi/Fintepla-prescribing-information.pdf

5. Zogenix, Inc. Clinical Efficacy. Accessed July 19, 2020. 

finteplahcp.com/efficacy-clinical-trials/

6. Lexicomp: Lexi-drugs online. Fenfluramine. Updated July 21, 2020. Accessed July 21, 2020. online.lexi.com. Subscription required to view.

7. Fintepla (fenfluramine) oral solution, C-IV. Medication Guide. Zogenix, Inc; June 2020. Accessed July 28, 2020. 

zogenix.com/mg/Fintepla-medication-guide.pdf

Articles

On June 25, 2020, fenfluramine (Fintepla) was approved for the treatment of seizures associated with Dravet syndrome in patients 2 years and older.

Fenfluramine for the Treatment of Seizures Associated With Dravet Syndrome 

ince I’ve been teaching a class of 55 physician assistants for the past 15 years, I’ve come to know some of them very well. One of my former students and I were discussing the coronavirus disease 2019 (COVID-19) mayhem. He said, “It has taught me the difference between essential versus expendable personnel.” 

to say that since the lockdown began in this country, essential personnel have been going to work. Whether you are a kid stocking shelves at the grocery store, a police officer patrolling the streets, a physician seeing patients, or a pharmacist filling prescriptions, we are all described as being essential. Sounds like a big compliment. However, my physician assistant friend suggested that “expendable” is a more appropriate term.

My friend went on to add that the truly “essential” personnel are walled off safely in their homes, sitting on their couches with their laptops, working remotely. They must be important—say, more important than 

those of us at work—because they are afforded much more protection than those of us stocking shelves, seeing patients, patrolling streets, or filling prescriptions, he said.

I was amazed to find out that even the folks who run the pharmacy benefi t managers (PBMs) are working from home. It is too dangerous for them to come to our stores to do an audit, so they fax us a “bench audit” to fill out. They can continue to underpay us, for example, by $60 for a sight-saving medication, as I discussed in my June essay, from the comfort of their living room couch.

Yes, the managed care organizations are also working from home, away from this deadly virus. From the safety of their homes, they continue to underpay us $0.79 for a lisinopril prescription. So, we pharmacies lose $60 providing a sight-saving drug, get paid less than a buck for a month’s worth of blood pressure medications, and lose over a grand on a bench audit. What do we get for our efforts? 

talking with told me her boyfriend was making his bonus $600 a week for unemployment. That is $15 an hour for a 40-hour week. My “essential” pharmacy technicians are salivating at that fi gure. The government decided to give hazard pay of $3 an hour to those who worked during the shutdown, except for pharmacy technicians. I immediately contacted our state senator, Judy Ward, who quickly sent a letter to Pennsylvania’s governor.

“We find it hard to believe that the program considers food retail facilities (grocery and convenience stores) an eligible industry but not pharmacies and drug stores,” wrote senators Lisa Boscola, D-Bethlehem, and Ward, R-Hollidaysburg.“ The employees of pharmacies/drug stores were just as much on the front line as employees in grocery stores during the COVID-19 pandemic and faced an equally high risk given that these businesses remained open during the emergency order when other businesses were closed.”

My pharmacy technicians who worked diligently through this crisis, never missing a day of work, waiting on sick people, and providing lifesaving medications, were not considered “essential.” Pharmacy technicians work alongside pharmacists to meet unprecedented demands during these times. They are not expendable.

1. Thompson C. Pennsylvania’s new hazard pay program will mean green for some; but leaves others green with envy. 

 Published July 23, 2020. Accessed August 10, 2020. 

https://www.pennlive.com/business/2020/07/pennsylvanias-new-hazard-pay-program-will-mean-green-for-some-but-leaves-others-green-with-envy.html

Pharmacy technicians work alongside pharmacists to meet unprecedented demands during these times. They are not expendable.

Pharmacy Employees: Essential Workers Amid Pandemic but Often Overlooked

s the pandemic dominates headlines, the United States continues to face another major public health crisis—the opioid epidemic.

One bright spot is at Boston Medical Center, where the city’s safety net hospital’s pharmacy team has reduced inpatient opioid use among surgical patients by 41% since 2017 and cut discharge opioid prescribing for surgery patients by 25%. The initiative involved pharmacists across the hospital’s ambulatory, inpatient, 

Kevin Horbowicz, PharmD, BCPS, associate director of inpatient clinical pharmacy services, described witnessing the opioid overdose epidemic as his driving force. “It was very central to us at Boston Medical Center… where it’s having a big impact on our patients, many of whom struggle with opioid use disorder and other disorders,” he said.

Success depended on coordinating with the hospital’s information technology team and more than 20 surgical specialties. Today, surgeons can order sets in the electronic health record that prompt them to prescribe agents such as acetaminophen to manage patients’ pain.

included procedures such as abdominal surgeries, which tend to involve large incisions and “a lot of pain,” said David McAneny, MD, the medical center’s chief surgical officer. He was so impressed by how well using agents such as angiotensin-converting enzyme inhibitors and acetaminophen managed postsurgical pain that he supported including all surgeries in the program.

In line with this effort, the hospital was implementing the enhanced recovery after surgery (ERAS) protocols, McAneny said. This multimodal, multidisciplinary approach to the care of surgical patients includes surgeons, anesthesiologists, and surgical care staff. ERAS protocols generally include minimally invasive approaches rather than large surgical incisions, and early mobilization.

Before this initiative, even a patient with mild pain would typically be discharged with 60 to 90 oxycodone pills, Horbowicz said. That’s dangerous for an individual who might become dependent or whose medication is accessible to other household members, he explained.

Pharmacist participation during rounds with the surgical team is key, McAneny said. The pharmacist can provide insight on topics such as appropriate medications, when to 

stop antibiotics, and when to switch from an intravenous to an oral route. McAneny, who mostly performs endocrine surgery, said he hasn’t prescribed opioids for postsurgical recovery in 10 years.

He also emphasized the importance of patient education. For example, McAneny tells patients who have had thyroid surgery that neither oxycodone nor acetaminophen will take away the resulting sore throat, which should subside by the end of the day.

Developing a consensus among more than 20 surgery subspecialties proved the most difficult part of implementing the program, according to Horbowicz. The fields of orthopedics, plastic surgery, and trauma have very different needs, he said. 

Another challenge involved scheduling a meeting with the chair of neurosurgery to discuss the program, he added. Still, he highlighted Boston Medical Center’s “collaborative, multidisciplinary culture,” with physicians, nurses, and pharmacists working well together. “That was part of the secret sauce,” Horbowicz said. 

As a result of Horbowicz’ leadership, Boston Medical Center’s Opioid Utilization Improvement Team won the Pharmacy Health-System Award from the Massachusetts Society of Health-System Pharmacists.

Pharmacists, nurses, and physicians work together to combat the overuse of powerful pain relievers.

Boston Medical Center Reduces Opioid Use in Surgical Patients 

Outcomes-based programs, also sometimes referred to as value-based programs, focus on quality of care, rather than quantity of patient visits, to encourage providers to deliver interventions that 

How Pharmacists Benefit Value-Based Programs

” highlights the role of pharmacists in some of these payment programs. 

HealthPartners (HP), a regional health plan based in Minnesota, embodies this “pay for value” philosophy through its Partners in Excellence (PIE) program. Pharmacists are eligible to participate in the medication therapy management (MTM) program by providing comprehensive medication management (CMM), as defined by the CMM patient care process, encounters, and value-based compensation through clinical performance and engagement performance metrics.

The HealthPartners’ PIE program is a performance and recognition program for physicians, medical groups, and pharmacies that achieve top marks in patient-centered metrics 

including health, experience, and affordability. The health plan evolved and expanded its MTM program after internal analyses demonstrated a significant return on investment when high-risk patients receive CMM services. Pharmacy providers are eligible for performance-based payments associated with achievements in blood pressure control, diabetes control (A1C), and a tobacco-free lifestyle. Pharmacy entities meeting performance benchmarks for clinical metrics are then eligible for a second-tier performance payment based on plan member engagement in CMM services. 

as an integral part of building a strong network of CMM providers for patients; however, these pharmacists often experience competing priorities and unique barriers that limit participation.

The Slice of PIE initiative is a collaborative effort between 

the Alliance for Integrated Medication Management

 designed to improve and increase delivery of CMM within the HP CMM provider network. Twelve Minnesota community pharmacy organizations, representing over 100 pharmacies, are engaged in the initiative. Implementation supports that help expand patient access include lists from HP identifying patients in most need of CMM interventions, a community of learning that connects participants across the initiative, frequent meetings with implementation coaches, monthly learning events (webinars), and additional strategies designed to help support expansion of patient access.

Slice of PIE will investigate research questions defined under 3 separate study aims. First, the initiative will evaluate the eectiveness of the learning collaborative as an implementation strategy to drive the adoption and sustainability of CMM delivery. The second aim will be to rigorously evaluate the implementation inputs and patient outcomes of initiating the PIE program in community pharmacies. Third, the research team will determine the clinical effectiveness and sustainability of the interventions delivered by Slice of PIE participants.

This initiative has the opportunity to change the trajectory of outcomes-based care nationally, thereby allowing patients across the country access to enhanced care and better health outcomes. 

 initiative, including more details about the implementation strategies and the outcomes-based model, tune into the blog series regularly updated on the 

Sign up to the communications list to receive email updates on the project, blog posts and presentations.

 For more information or if you have questions about 

, please contact Lindsay Sorge, Slice of PIE Project Coordinator, at 

Initiative promotes adoption of value-based care models in community pharmacy settings. 

A Partnership to Optimize Medication Use and Patient Outcomes

Biosimilars, which offer the potential for more treatment options and less expensive alternatives, are having a good year in 2020 and may have a significant impact on the prescription product market in 2021. With the approval of more biosimilar medications, experts hope that greater competition may occur and help lower overall costs. “As intellectual property protections for biological products continue to expire in the US

, we can expect many more applications for potential biosimilar and interchangeable products, and increased uptake of approved products too,” said Sarah Yim, MD, the director of the Office of Therapeutic Biologics and Biosimilars at the FDA’s Center for Drug Evaluation and Research, in Bethesda, Maryland.

 Some of the key issues affecting biosimilar uptake involve reimbursement factors and insurance coverage, according to Yim. However, she said, business and intellectual property concerns also have contributed to the delayed launch of some FDA-approved biosimilars. In 2009, the Biologics Price Competition and Innovation Act created an abbreviated regulatory pathway for biological products demonstrating to be biosimilar or interchangeable with an FDA-approved drug. Since then, the FDA has approved biosimilar medications to treat a host of conditions, including cancer, colitis, Crohn disease, rheumatoid arthritis, and psoriasis.

Biologics are medicines that generally come from living organisms, which include animals and microorganisms (yeast and bacteria). A biosimilar is defined by the FDA as a biologic that has no clinically meaningful differences from another biologic that is already FDA approved. Biosimilars are made with the same types of natural sources as the original medication and are delivered the same way. They have the same strength and dosage and the same potential adverse effects.

The FDA has outlined 4 key strategies in its Biosimilars Action Plan (BAP) to accelerate biosimilar competition. “We continue to work on the key elements of the BAP, and we have ongoing activities that fit within all of the elements,” Yim told 

Improve the development and approval process for biosimilar and interchangeable products.

Maximize scientific and regulatory clarity for the developers of biosimilar products.

Improve the understanding of biosimilars among patients, clinicians, and payers.

Support market competition by reducing gaming of FDA requirements and other attempts to unfairly delay competition.

Right now, there are 28 FDA-approved biosimilar products, and 17 are on the market. “We have seen a jump in the past year of launched products. In addition, the biosimilars that are on the market have typically launched with initial list prices 15% to 35% lower than the list prices of the reference products,” Yim said.

Over the next 6 to 18 months, the landscape will be evolving for biosimilar and interchangeable insulin products and other transition biological products. Under new regulations, insulin and other biological products such as human growth hormone (somatropin), pancrelipase, chorionic gonadotropin, follitropin alfa, and menotropins are regulated by the FDA in biologics license applications. This means that manufacturers can submit marketing applications for proposed biosimilar and interchangeable products that reference transitioned biological products. “If approved, these products will help bring competition to those markets, and patients may have more affordable access to the medications they need,” Yim said. “I am hopeful that we will see the FDA’s first interchangeable biosimilar product during the time period [6 to 18 months].”

Once an interchangeable product is approved and available on the market, Yim said it can then be substituted for the reference product without the intervention of the prescriber. It is hoped that this will lead to increased access and lower costs for patients. There are more than 80 biosimilars in the development pipeline. Five biosimilars have been approved in the last year, with adalimumab-fkjp (Hulio) and pegfilgrastim-apgf (Nyvepria) most recently approved (

Sandoz Inc has 8 approved biosimilars worldwide and 4 in the United States. Sheila Frame, the vice president of marketing, market access, and patient services at Sandoz in Princeton, New Jersey, said reimbursement policies do not support the use of biosimilars, and despite progress in certain therapeutic areas, some hesitancy remains among many clinicians to switch to a biosimilar. “To realize the full promise of biosimilars in the US, we need to support policies that increase their adoption and help create a more balanced and competitive marketplace,” Frame told 

She said that within Medicare Part D, Sandoz supports reducing administrative burdens for patients and providers by removing redundant prior authorization for a biosimilar when one has been granted for the reference biologic. Widespread adoption of biosimilars in clinical practice has faced headwinds, in part because of targeted misinformation campaigns, Frame said.

A recent article examining the impact of biosimilar misinformation and disparagement campaigns suggested these campaigns can harm opportunities to increase patient access.

 “We are encouraged by action from the FDA and the FTC [Federal Trade Commission] to combat pervasive misinformation, but it is the responsibility of all stakeholders to challenge biosimilar disparagement and misinformation when encountered. Clear and unbiased scientific messaging is crucial to helping patients and clinicians better understand the value of biosimilars,” Frame said.

She said the cost savings from biosimilar medicines could be enormous, saving the US health care system billions of dollars over the coming years.

Andrew Powaleny, director of public affairs at the Pharmaceutical Research and Manufacturers of America in Washington, DC, said the rich pipeline of potential biosimilar products in development and market experience suggest there still is significant potential for cost savings in the marketplace.

A recent analysis of the market dynamics of 4 biologics and their biosimilars demonstrated that the net prices of all the originator biologics decreased following the entry of biosimilars. In the Medicaid program, discounts increased by between 20.1 and 35.2 percentage points.

 “As the market experience with biosimilars increases, we expect product usage to play an expanded role in options for patients and further decrease prescription drug spending. Experts have argued that the coming wave of biosimilars will penetrate the market even more quickly than those already available for patients,” Powaleny said.

COVID-19 Pandemic and Prescription Drug Costs

Currently, the coronavirus disease 2019 (COVID-19) pandemic is crippling the economy. Frame said everyone is looking toward rebuilding, so any and all cost savings are on the table. “Supporting and advancing policies that increase access and use of lower-cost biosimilars can help,” she said. 

At the University of California, San Francisco (UCSF), Health, leadership has endorsed the adoption of biosimilars for clinical care, according to Candy Tsourounis, PharmD, a professor in the department of clinical pharmacy at the UCSF School of Pharmacy. As a member of the department’s Medication Outcomes Center, Tsourounis is involved in providing evidence-based reviews of recently approved prescription medications and performing medication utilization analyses for UCSF Health. She said the endorsement of biosimilars aligns with the national adoption of biosimilars across health systems to ensure safe and cost-effective therapies are available to advance health. Now, during the COVID-19 pandemic this may be more important than ever.

“We anticipate significant cost savings while maintaining high-quality care and ensuring similar clinical outcomes. Over the next 6 to 18 months, we hope to show similar clinical outcomes but with significant reductions in drug spending, not only within UCSF Health, but also more broadly for UC Health,” which oversees and provides strategic direction across all 6 health systems, including UCSF Health, 

Brian Komoto, PharmD, past president of the California Pharmacists Association in Visalia, California, said biosimilars will could help improve patient access and reduce copays for many more individuals in the coming year. He noted that educating clinicians is vital. “Hopefully, physicians are receptive and the use of biosimilars can increase,” Komoto told 

®. “This should also allow pharmacies that are not able to get contract pricing, the ability to work with manufacturers of biosimilar products.”

Francis B. Palumbo, PhD, JD, a professor and executive director at the University of Maryland School of Pharmacy’s Center on Drugs and Public Policy in Baltimore, is a member of the biosimilars working group for the American Pharmacists Association, and he agrees that at this time clinician acceptance is vital. The trend appears positive, and it seems that biosimilars are having a significant impact in terms of patient access and lowering overall costs. “Biosimilars are now being approved at an increasing pace and have most likely reached some level of critical mass where they can exert real influence on the market,” Palumbo told 

FDA. Biosimilar product information. Updated July 7, 2020. Accessed August 7, 2020. 

fda.gov/drugs/biosimilars/biosimilar-product-information

Cohen, HP, McCabe, D. The importance of countering biosimilar disparagement and misinformation. 

 2020;34(4):407-414. doi:10.1007/s40259-020-00433-y 

San-Juan-Rodriguez A, Gellad WF, Good CB, Hernandez I. Trends in list prices, net prices, and discounts for originator biologics facing biosimilar competition. 

. 2019;2(12):e1917379. doi:10.1001/jamanetworkopen.2019.17379

How will biosimilars continue to affect the prescription product market in 2021?

Biosimilars May Lead to Improved Competition and Lower Costs

Pharmacists can play an important role in educating patients about autoimmune drugs to prevent medication errors.

Autoimmune diseases affect more than 24 million individuals in the United States, and the most common conditions are type 1 diabetes, multiple sclerosis (MS), lupus, inflammatory bowel disease (IBD), and rheumatoid arthritis (RA).

At least 80 known autoimmune diseases exist, and a plethora of therapies can be used to manage symptoms.

 Pharmacists can play a vital part of patient care by educating individuals about their autoimmune therapies to prevent drug-related problems at home. Evidence demonstrates that pharmacists can also decrease medication errors after hospital discharge through transition of care interventions and reduce emergency department visits.

Autoimmune Drug Medication Errors and Counseling Pearls

According to the National Coordinating Council for Medication Error Reporting and Prevention, “a medication error is any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer.”

 Methotrexate (Rheumatrex) is prescribed for RA and psoriasis, and it is critical to ensure proper dosing and patient education for this medication to prevent adverse events.

Dosing of methotrexate for RA or psoriasis is once weekly as low-dose therapy, but is generally administered daily when used for cancer treatment.

Harmful or fatal errors with low-dose oral methotrexate have been reported to the Institute for Safe Medication Practices (ISMP), with the most common involving accidental daily dosing intended for weekly administration.

 Therefore, ISMP considers methotrexate a high-alert medication in both the hospital and community settings.

Patients should receive both verbal and printed instructions emphasizing the importance of once per week dosing for methotrexate prior to hospital discharge. ISMP’s ConsumerMedSafety.org website includes a free educational handout.

 Pharmacies can also dispense methotrexate as a weekly dose pack to prevent administration errors.

Patients should pick a day of the week that they will be taking methotrexate, and the pharmacy can include this with the instructions.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to reduce pain associated with RA or lupus.

 Educating patients to read the OTC product’s Drug Facts label is extremely important to ensure they are not taking multiple NSAID products, which can lead to an increased risk of gastrointestinal bleeding.

 Corticosteroids are generally used for RA, IBD (short term), and lupus. Patients should avoid abruptly stopping therapy if they have been taking these medications for 3 or more weeks as they need to be tapered slowly to prevent disease flare-ups and adrenal insufficiency.

Levothyroxine (Synthroid) is commonly used to treat hypothyroidism, which can be caused by the autoimmune condition Hashimoto disease. Patients should be counseled to take levothyroxine on an empty stomach 30 to 60 minutes before breakfast for optimal absorption.

 Also, certain medications including calcium, antacids, and iron can bind to levothyroxine and potentially reduce the efficacy, so they should be separated by at least 4 hours.

Growing evidence suggests that hydroxychloroquine is not effective for the coronavirus disease 2019 (COVID-19) and could be harmful.10 However, hydroxychloroquine is FDA approved for the treatment of lupus and RA and has demonstrated efficacy for these conditions. The American Heart Association along with other organizations have emphasized the importance of identifying potential drug interactions that could cause cardiovascular adverse events (eg QTc prolongation, fatal arrhythmias) in patients with COVID-19, especially with the combination of hydroxychloroquine and azithromycin.

 These risks also apply to those using hydroxychloroquine for the FDA-approved indications, and pharmacists should educate patients about these cardiac effects.

Insulins used for type 1 diabetes are considered high-alert medications, and it’s important that patients know their dose to prevent administration errors. The U-500 insulin is concentrated and contains 5 times more insulin per ml than standard insulin.

 Patients should also be cautioned about severe worsening of MS after stopping the medication fingolimod (Gilenya). It is important for patients to consult their pharmacist and physician prior to discontinuing the therapy.

Autoimmune diseases. National Institutes of Health. Updated May 6, 2020. Accessed July 26, 2020. 

niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm

De Oliveira GS, Castro-Alves LJ, Kendall MC, McCarthy R. Effectiveness of pharmacist intervention to reduce medication errors and health-care resources utilization after transitions of care: a meta-analysis of randomized controlled trials. 

. Published online June 30, 2017. doi: 10.1097/PTS.0000000000000283 

About medication errors. National Coordinating Council for Medication Error Reporting and Prevention. Accessed July 30, 2020. 

Grissinger M. Severe harm and death associated with errors and drug interactions involving low-dose methotrexate. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871236/

2020-2021 ISMP targeted medication safety best practices for hospitals. ISMP. Accessed July 30, 2020. 

ismp.org/sites/default/files/attachments/2020-02/2020-2021%20TMSBP-%20FINAL_1.pdf

High-alert medications-methotrexate. ConsumerMedSafety.org. Accessed July 30, 2020. 

consumermedsafety.org/tools-and-resources/medication-safety-tools-and-resources/high-alert-medications/methotrexate-rheumatrex-trexal

Rheumatoid Arthritis Treatment. Johns Hopkins Arthritis Center. Accessed July 31, 2020. 

hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/

Chang-Miller A. Prednisone withdrawal: why taper down slowly? June 19, 2020. Accessed July 31, 2020. 

mayoclinic.org/prednisone-withdrawal/expert-answers/faq-20057923

Levothyroxine (oral route). Mayo Clinic. Updated February 1, 2020. Accessed August 1, 2020. 

mayoclinic.org/drugs/levothyroxine-oral/drg-20072133?p=1

Roden DM, Harrington RA, Poppas A, Russo AM. Considerations for drug interactions on QTc in exploratory COVID-19 treatment. 

. 2020;141(24):e906-e907. doi: 10.1161/CIRCULATIONAHA.120.047521 

Humulin R U-500. ConsumerMedSafety.org. Accessed August 1, 2020. 

ismp.org/sites/default/files/attachments/2018-11/u-500-insulinfinal.pdf

FDA warns about severe worsening of multiple sclerosis after stopping the medicine Gilenya (fingolimod). FDA. November 20, 2018. Accessed August 1, 2020. 

fda.gov/drugs/drug-safety-and-availability/fda-warns-about-severe-worsening-multiple-sclerosis-after-stopping-medicine-gilenya-fingolimod

Prevent Medication Errors in Autoimmune Disease

The generic pipeline continues to provide significant value to payers and patients as key products in top therapeutic classes lose patent protection.

Matt Gibbs, PharmD, president of commercial markets for Capital Rx, Inc, said although the second generic wave peaked in 2018, many impactful generics entered the market over the past 12 months—most notably, the launch of multiple generics for pregabalin (Lyrica; Pfizer) in July 2019.

“Because there wasn’t a single generic with a 180-day exclusivity period, it resulted in an immediate significant price drop for payers and patients,” he said. “Fourth quarter 2019 also saw the first generic for popular contraceptive NuvaRing enter the market, providing patients who prefer a nonsystemic contraceptive a generic option. This will also benefit payers providing $0 contraceptive coverage to their members under the Affordable Care Act, as brand NuvaRing is a key driver of plan spend in the contraceptive category.”

Early 2020 saw the return of generics to the market for albuterol rescue inhalers ProAir HFA and Ventolin HFA. Generic albuterol inhalers utilizing chlorofluorocarbon propellants existed in the market by the late ’90s, but the requirement to change to alternate propellants shifted these products back to brands.

“The availability of generics in the class will benefit both patients and plans in mitigating spend in the asthma category,” Gibbs said.

He feels the biggest notable generic coming in 2020 is the availability of generic emtricitabine/tenofovir (Tru

vada; Gilead) for use in HIV preexposure prophylaxis (PrEP).

“As plans begin to implement $0 ACA coverage for PrEP, the availability of generic Truvada will significantly decrease overall cost to plans as we see awareness of and access to PrEP improve across the US,” Gibbs said. “This improved awareness and focus on access to PrEP is one step in the global and US goals of getting to zero new HIV transmissions by 2030.”

Ryan Schmidt, associate director of formulary services for Madison, Wisconsin–based Navitus Health Solutions, says that overall, the generic market this past year has been relatively slow.

“There haven’t been many blockbuster generic releases, and the ones that hit the news are generally ‘authorized generics,’ where the manufacturer of the generic product either has an agreement with the brand manufacturer, or in some instances is the brand manufacturer,” he said. “The other thing that limits impact of these releases is a lot of them have come from classes with multiple alternative generic options already, meaning the amount of use in the brand space has been limited.”

Ross Goetz, PharmD, director of business development and national pharmacy compliance administrator for Healthwarehouse.com, noted that digital companies with direct-to-consumer models have increased access to generic medications at an affordable price, making generic drugs more desirable to the consumers opting to manage their own cost portfolio.

Still, when referring to abbreviated new drug application (ANDA) approvals,or first-time approvals of generic drugs, he calls 2020 “a weak year,” citing a few HIV therapies pending generic launch, and the generic for varenicline (Chantix; Pfizer), which has been delayed since the initial date. At press time, the FDA has so far approved 35 first-time generics.

 In 2019, the FDA approved 107 first generic drugs out of a total of 1014 approved or tentatively approved ANDAs, according to the 2019 Office of Generic Drugs annual report.

Shashank Upadhye, JD, a pharmaceutical patent attorney with Chicago, Illinois-based Upadhye Cwik LLP, who has practiced in generic drug law for more than 20 years, said it’s been a tough year for companies that are in just traditional, simple solid oral dosage forms.

An exception, he noted, is Mylan, which obtained recent approval for its biosimilar for insulin glargine— called Semglee, which is a biosimilar to Sanofi’s Lantus insulin.

“Mylan had won some patent litigation and thus had removed the patent obstacle. But it finally won FDA approval for its pen and vial product,” he said. “Mylan [and its production partner Biocon] had some troubles getting approval. It is a complex product, and thus it was not a question of simply copying the Lantus product. Now patients have new options, with hopefully better pricing, now that the FDA has approved more insulins.”

The most notable generic products, Schmidt shared, have not had the major financial impact one would typically expect over the last year.

“Generic insulin products offer significant price decreases for those 

patients without insurance, reducing prices to where they were back in 2012,” he explained. “However, rebates offered on the original brand products still make the brand medications less expensive to plans in most situations, meaning we haven’t seen these have impact on overall spend.”

Similarly, a number of generic inhalers have come to market for common products such as Advair, Symbicort, Proair, and Ventolin. Although the increased competition has had some impact on overall spending, major savings opportunities haven’t risen yet, as the complexity of these devices have prevented a scenario where multiple low-cost generic products are available.

Experts agree that there is an unmet need for more less expensive, generic versions of complex medications in the market.

“Significant savings to payers and the federal government from approving more generic versions of complex medication could be realized,” Bob Lobo, PharmD, director of clinical programs at Vanderbilt University Medical Center, Nashville, Tennessee, told 

 He cited a recent study on the economic burden associated with extended-release (ER) versus immediate-release (IR) formulation among Medicare and Medicaid beneficiaries, in which the findings showed a potential annual cost savings of $2.6 billion by switching certain ER drugs to comparable generic IR formulations.

 The study looked at only 20 ER oral medications, but it suggests that the annual savings from greater access to generic medications are quite significant.

According to Schmidt, the drug with one of the largest effects on spending in the past 12 months has been pregabalin, the generic equivalent to Lyrica.

“There were multiple manufacturers ready to go at launch, meaning costs for the generics were significantly lower than the brand at launch,” he said. “This is important as it helps drive down patient cost, regardless of copay or coinsurance, helping to facili

tate conversion to the generic product, saving both the patient and the plan money right away.”

Conversely, ramelteon, Rozerem’s equivalent, was first released at a similar time, but due to lack of competition in the market, has retained a higher cost relative to other generic medications in the class.

“Pregabalin has dropped in price by over 95% compared with brand Lyrica, [which also took an approximately 5% price increase on January 1, 2020,] and is covered nearly universally,” Schmidt said. “Ramelteon, on the other hand, still costs close to $100 per month.”

Goetz agreed that pregabalin has been the most significant generic over the past year.

“When you look into medications for nerve pain, there is not a great depth of options. Outside of narcotic pain medications, gabapentin stood as the most cost-effective option,” he said. “Although gabapentin comes tied with challenges like a notable [adverse effect] profile, it is often the drug of choice on insurance formularies. For those who rely on their insurance coverage to afford medications, paying for brand name Lyrica was simply not an option. Now available as generic pregabalin, patients can more comfortably elect to switch away from gabapentin without a major cost burden, if any.”

Due to the coronavirus disease 2019 (COVID-19), the FDA has stopped conducting foreign inspections. Given that more than 80% of the generic drugs sold in the United States are made outside the country, the lack of inspections has resulted in delayed or aborted new generic drug launches.

Upadhye said COVID-19 has caused several problems, including decreased profitability for existing generic companies’ products; increased price pressures by the buyers who them- selves are facing business pressures; pressures on existing patent litigation to either do very little to advance the case or to settle the case quickly on whatever terms being offered; and the FDA’s refusal to conduct foreign 

inspections, resulting in delayed or aborted new generic drug product launches or delays in relaunches.

It’s not a surprise that the pandemic is affecting the generic drug market, as when the disease was spreading rapidly in March, there was a major rush to refill medications, leading to a large increase in claims and even shortages. This was immediately followed by a drop-off in overall claims volume, which is now returning closer to normal.

“One major shift is from 30-day claims to more patients getting 90-day supplies via delivery or mail order,” Schmidt said.“The interesting component of this is that maintenance medications seem to have rebounded well, whereas acute medications aren’t rebounding quite as quickly. This isn’t as surprising, as many elective clinical visits are being delayed, and general improved health precautions are likely leading to less non-COVID infections.”

From a new product perspective, the FDA is still in full swing, and the industry has continued to see new approvals of both brand and generic products. The impact of these new releases may be seen a couple of years down the road as some clinical trials have gone on hold or been delayed due to COVID-19.

Goetz believes the market is shifting heavily toward convenience and safety over price alone.

“Utilization of telehealth services reached an all-time high in April 2020, while ambulatory prescriber practices were down roughly 60% in office visits,” he said. “Now that patients are more aware of the options available, it can be expected that they will consider the financial and personal impact of each option as they weigh their plans for their future. As we have seen with many areas of modern commerce, the power is no longer with the large chains with storefronts in every area; it falls with the companies who can provide a service at a fair price, with a larger focus on convenience than ever before.”

1. FDA. First generic drug approvals. Updated July 14, 2020. Accessed August 12, 2020. 

https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals

2. FDA. 2019 Office of Generic Drugs annual report. February 2020. Accessed August 12, 2020. 

https://www.fda.gov/media/135329/download

3. Schieszer J. Barriers coming down for complex generic drug products. 

®. April 14, 2020. Accessed August 12, 2020. 

https://www.drugtopics.com/view/barriers-coming-down-complex-generic-drug-products 

4. Sumarsono A, Sumarsono N, Das SR, et al. ​Economic burden associated with extended-release vs immediate-release drug formulations among Medicare Part D and Medicaid beneficiaries. 

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