- New Biologic Drug Approved for Psoriasis: Ilumya® (tildrakizumab-asmn)
- Add-on Asthma Drug Nucala® (mepolizumab) Receives Expanded Indication
- Study Suggests Gabapentin + Opioid Combination Increases the Risk of Opioid-Related Death
- Advisory Committee to the FDA Votes in Support for Approval of Cannabidiol Treatment
- Lofexidine for Opioid Withdrawal Receives Favorable FDA Committee Review
- Inadequacies in Safe Storage and Disposal Information for Opioids
- National Prescription Drug Take Back Day: Saturday, April 28th
- Drug Discontinuation: Bydureon® (exenatide extended-release) Single Dose Tray
Specialty Drug Approval
New Biologic Drug Approved for Psoriasis: Ilumya® (tildrakizumab-asmn)
In March 2018, the U.S. Food and Drug Administration (FDA) approved Ilumya® (tildrakizumab-asmn) for the treatment of adults with moderate to severe plaque psoriasis. It is indicated specifically for patients who are candidates for systemic therapy or phototherapy and is given as a subcutaneous injection. Ilumya acts by binding to interleukin-23 (IL-23), thereby preventing the interleukin from interacting with its receptor. Inhibition of this interaction prevents the release of inflammatory mediators. Tildrakizumab is expected to compete with the other IL-23 antagonists indicated for plaque psoriasis: Tremfya® (guselkumab) and Stelara® (ustekinumab).
Approval was based on results from two randomized, double-blind, placebo-controlled Phase III clinical studies evaluating more than 900 adults with moderate to severe plaque psoriasis. Patients who received tildrakizumab demonstrated significant improvement in skin clearance at week 12 compared to patients who received placebo. Treatment effect persisted through week 64 in the patients who continued to receive tildrakizumab.
Tildrakizumab carries warnings and precautions for hypersensitivity reactions and infections. Prior to starting therapy, patients should be evaluated for tuberculosis (TB), and patients with latent TB should have TB therapy initiated before receiving Ilumya. Patients with active TB should not receive Ilumya. The administration of live vaccines should also be avoided in patients receiving treatment with tildrakizumab. The most common side effects experienced with therapy include upper respiratory infections, injection site reactions, and diarrhea.
Ilumya is supplied as a 100 mg/mL solution in a single-dose prefilled syringe and is dosed as 100 mg at week 0, week 4, and then every 12 weeks. It is expected to become commercially available this summer. Upon launch, NPS is planning to review Ilumya for placement on the national formularies. For additional details on the product, view the manufacturer’s press release.
Add-on Asthma Drug Nucala® (mepolizumab) Receives Expanded Indication
The injectable asthma therapy Nucala® (mepolizumab) recently received FDA approval for the treatment of patients with the rare, chronic disease eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome. Approval marks the first FDA-approved treatment for patients with this inflammatory condition. Patients with EGPA exhibit increased levels of white blood cells known as eosinophils, inflammation of blood vessels, and asthma.
The efficacy and safety of mepolizumab for the new use was based on findings from the 52-week, Phase III MIRRA study which evaluated more than 130 patients with relapsing and/or refractory EGPA. Mepolizumab was compared to placebo as add-on therapy to corticosteroids, with or without immunosuppressants. Patients who received mepolizumab demonstrated a statistically significant improvement in the time in remission and more patients in the mepolizumab group than the placebo group achieved remission at weeks 36 and 48. In addition, more mepolizumab-treated patients exhibited remission within 24 weeks of starting therapy and continued to be in remission for the duration of the 52-week study. The most common side effects, occurring at an incidence of 5% or greater, in patients who received mepolizumab include: headache, injection site reaction, back pain, and fatigue. The product also carries warning/precautions for hypersensitivity reactions and infections.
Nucala was first approved by the FDA in 2015 as add-on maintenance treatment for patients 12 years and older with severe asthma with an eosinophilic phenotype. When used as add-on asthma therapy, it is dosed as 100 mg subcutaneously once every 4 weeks. For the new indication of EGPA, it is dosed as three separate 100-mg injections (300 mg total) subcutaneously once every 4 weeks. The average wholesale price (AWP) for four weeks of therapy for EGPA is $10,327.20.
The manufacturer of Nucala, GlaxoSmithKline, has also submitted a supplemental application for using Nucala for the treatment of chronic obstructive pulmonary disease (COPD). It is also being evaluated for severe hypereosinophilic syndrome and nasal polyposis. For additional details on Nucala’s new indication, view the FDA’s news release or manufacturer’s press release.
Study Suggests Gabapentin + Opioid Combination Increases the Risk of Opioid-Related Death
A new database study led by Tara Gomes, PhD of the Ontario Drug Policy Research Network (ODPRN) demonstrated an association between patients using the combination of prescription opioids concurrently with gabapentin and a nearly a 50% increased risk of opioid-related death compared to using only opioids alone. Administrative database cases of death due to an opioid-related cause were matched with controls in a 4:1 ratio. A total of 1,256 cases were matched with 4,619 controls based on age, sex, year of index date, history of chronic kidney disease, as well as disease risk index.
It was evaluated whether the cases and controls had concurrently received gabapentin within 120 days of the index date. Gabapentin is an oral medication FDA-approved to treat post-shingles nerve pain in adults as well as partial onset seizures in adults and pediatric patients 3 years and older with epilepsy. It has been used off-label for several other indications such as alcohol dependence, nerve pain, and restless leg syndrome. It was found 12.3% of opioid users who experienced an opioid-related death had been prescribed gabapentin compared with 6.8% of the controls.
The increased risk of an opioid-related death with concurrent gabapentin use remained after adjustments were made for opioid dose, other medications, alcohol use, and chronic illnesses, such as diabetes or chronic lung disease. An additional analyses found that exposure to gabapentin in daily doses of 900 mg or higher was associated with almost a 60% risk increase for opioid-related death compared to when opioids were used alone. Researchers did not find a significant increase in the risk of opioid-related death for users of low doses of gabapentin (<900 mg per day) + opioids compared with those who used opioids alone.
Although case-control studies such as this one are not designed to determine cause and effect, the findings suggest an association between concurrent gabapentin use with opioids and opioid-related deaths. It is not clear why the use of gabapentin and opioids could potentially increase the risk of opioid-related death but slowing of the gastrointestinal tract motility allowing for enhanced absorption of the gabapentin has been proposed as a potential reason. Dr. Gomes encourages awareness of the potential risks of using gabapentin and opioids together and recommends carefully monitoring patients who require the combination.
Advisory Committee to the FDA Votes in Support for Approval of Cannabidiol Treatment
In April 2018, an advisory committee to the FDA voted 13 to 0 in favor of approval of Epidiolex® (cannabidiol oral solution) for the adjunctive treatment of seizures associated with Lennox Gastaut Syndrome (LGS) and Dravet Syndrome in patients 2 years of age and older. LGS and Dravet Syndrome develop in childhood and are associated with multiple seizures per day. In clinical studies, cannabidiol significantly reduced the number of seizures these patients experienced and was generally well tolerated.
If approved, Epidiolex would be the first pharmaceutical product of plant-based cannabidiol (CBD). This specific cannabinoid, CBD, does not exhibit the euphoria associated with marijuana and the active ingredient would likely be considered a new type of anti-epileptic drug. If granted FDA approval, Epidiolex would be the first FDA-approved therapy for Dravet Syndrome. Although the potential for abuse of the product is thought to be minimal, residual tetrahydrocannabinol (THC) may result in the drug being scheduled by the Drug Enforcement Administration (DEA) as a controlled medicinal substance (Schedule II – V).
The FDA is expected to make a decision regarding approval by June 27th. However, some experts speculate approval may occur prior to the expected decision date due to the positive clinical trial data and advisory committee recommendation. If approved, it is expected to become commercially available in latter half of 2018. Epidiolex is also being studied for use in other rare seizure disorders including infantile spasms and tuberous sclerosis complex. For additional details, view the manufacturer’s press release.
Lofexidine for Opioid Withdrawal Receives Favorable FDA Committee Review
Lucemyra® (lofexidine) is an oral alpha 2-adrenergic receptor agonist currently being reviewed by the U.S. Food and Drug Administration (FDA). On March 27, 2018, the FDA Psychopharmacologic Drugs Advisory Committee voted 11 to 1 in favor of approval of lofexidine for the mitigation of opioid withdrawal symptoms. Lofexidine acts to prevent the release of norepinephrine that results in the acute and painful symptoms of opioid withdrawal. Opioid withdrawal symptoms usually include unease, nausea, vomiting, muscle aches, runny nose or watery eyes, diarrhea, fever, and insomnia.
The New Drug Application (NDA) for lofexidine includes data from two randomized, double-blind, placebo-controlled clinical trials as well as supportive studies. These studies have demonstrated a reduction in the severity of opioid withdrawal symptoms with lofexidine compared to placebo. Additionally, more patients who received lofexidine were able to complete opioid discontinuation than those who received placebo.
Other medications with similar FDA-approved indications include: methadone (detoxification and maintenance of opioid addiction), buprenorphine (induction of opioid dependence treatment), and buprenorphine/naloxone (short-acting opioid withdrawal). If approved, Lucemyra would be the first non-opioid, FDA-approved treatment for opioid withdrawal. The alpha 2-adrenergic agonist clonidine is used off-label to manage opioid withdrawal symptoms but is not FDA approved for this use. The FDA is expected to make a decision regarding the approval of lofexidine in the second quarter of 2018. For additional details, view the manufacturer’s press release.
Inadequacies in Safe Storage and Disposal Information for Opioids
A research letter published in the Annals of Internal Medicine highlighted inconsistencies of opioid prescribing information regarding safe storage and proper disposal. The study analyzed information on the storage and disposal from package inserts for six commonly prescribed and misused opioid pain medications. Researchers found instructions on safely disposing of these medications were frequently not consistent or not present on the medication’s prescribing information or package insert.
Of the 98 package inserts that were randomly selected for review, there was one set of instruction on how to safely store the medication but three different sets of instruction on safe disposal. The instructions on safe storage recommended patients keep medications in a secure location to prevent theft and was found in 35 of the package inserts of which approximately 66% were for oxycodone or morphine. The instructions on safe disposal recommended patients discard of medications (31 messages), flush medications down the toilet (34 messages), or that health care professionals should provide instructions on safe disposal (28 messages). A majority of package inserts with directions on safe disposal were for oxycodone or morphine medications. There were no tramadol package inserts and only one hydrocodone package insert, out of 33 evaluated, which contained instructions on disposal and storage.
Although the product’s package insert may not provide adequate information regarding proper disposal of these products, the Drug Enforcement Administration (DEA) and U.S. Food and Drug Administration (FDA) have a number of resources and tools available to assist patients and healthcare providers. Please view the next article directly below for further details.
National Prescription Drug Take Back Day: Saturday, April 28th
The 15th National Prescription Drug Take Back Day is scheduled for this Saturday, April 28th from 10 AM until 2 PM. Coordinated by the Drug Enforcement Administration (DEA), this biannual event provides patients with a safe and convenient disposal method for unused medications while also providing education to the public regarding the potential for drug abuse.
Unused and expired pharmaceutical agents present a risk to public safety and if not disposed of properly can be found and used inappropriately by others or contaminate the environment. Events such as the National Prescription Drug Take Back Day provide an opportunity to safely dispose of old or unused medications. However, if a collection site or take back event cannot be identified, medications may be disposed of by: 1) removing the product from the bottle, 2) mixing with an unappealing substance (such as kitty litter or coffee grounds), 3) sealing in a bag, and 4) disposing in the trash.
In previous years, the DEA has sponsored two Drug Take Back events per year. The 2017 events resulted in collection of a total of 1,812,691 pounds of unused medications. This Saturday will mark the first Drug Take Back Day for 2018. Collection sites can be found by visiting DEATakeBack.com. This website also provides information on what to do with unused medications, year-round drug disposal sites, and information regarding treatment of substance use disorders.
The FDA also recently revised their Disposal of Unused Medications webpage. Common medication disposal questions and answers as well as options for disposing of unused or expired medications are also provided. For additional details on the past and upcoming National Prescription Drug Take Back Day events, visit the DEA’s website.
Drug Shortages and Discontinuations
Drug Discontinuation: Bydureon® (exenatide extended-release) Single Dose Tray
In April 2018, the U.S. FDA announced the Bydureon® (exenatide extended-release [ER]) Single Dose Tray will be discontinued from commercialization in the U.S. by September 30, 2018. The two other formulations of exenatide ER, the Bydureon® Dual Chamber Pen and the Bydureon BCise autoinjector, will continue to be commercially available. Both the pen and autoinjector contain 2 mg of exenatide ER and carry an average wholesale price (AWP) of $198.05 per pen or autoinjector.
Bydureon is a glucagon-like peptide-1 (GLP-1) receptor agonist FDA-approved as add-on to diet and exercise to improve blood glucose control in adults with type 2 diabetes mellitus. It is given as a 2 mg subcutaneous injection once a week without regard to meals. For the most up-to-date information on drug shortages and product discontinuations, visit the ASHP Current Shortages Database or the FDA Drug Shortages Database.
- FDA approves Ilumya for plaque psoriasis. National Psoriasis Foundation. https://www.psoriasis.org/advance/fda-approves-ilumya-plaque-psoriasis. Updated March 22, 2018. Accessed April 20, 2018.
- Ilumya [package insert]. Merck & Co, Inc; Whitehouse Station, NJ: March 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761067s000lbl.pdf. Accessed April 20, 2018.
- Sun Pharma. Sun Pharma announces U.S. FDA approval of Ilumya (tildrakizumab-asmn) for the treatment of moderate-to-severe plaque psoriasis. Cision PR Newswire. https://www.prnewswire.com/news-releases/sun-pharma-announces-us-fda-approval-of-ilumya-tildrakizumab-asmn-for-the-treatment-of-moderate-to-severe-plaque-psoriasis-300617454.html. Updated March 21, 2018. Accessed April 20, 2018.
- Brooks M. FDA clears tildrakizumab (Ilumya) for plaque psoriasis. Medscape: FDA Approvals. https://www.medscape.com/viewarticle/894314. Updated March 21, 2018. Accessed April 20, 2018.
- New Psoriasis Biologic Ilumya Receives FDA Approval. P&T Community. https://www.ptcommunity.com/news/20180323/new-psoriasis-biologic-ilumya-receives-fda-approval. Updated March 22, 2018. Accessed April 20, 2018.
- Nucala [package insert]. GlaxoSmithKline, LLC: Philadelphia, PA; December 2017. https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Nucala/pdf/NUCALA-PI-PIL.PDF. Accessed April 23, 2018.
- FDA approves first drug for Eosinophilic Granulomatosis with Polyangiitis, a rare disease formerly known as the Churg-Strauss Syndrome. FDA News Release. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm588594.htm. Updated December 12, 2017. Accessed April 23, 2018.
- Yasgur BS. Gabapentin and Opioids a Potentially Deadly Combination. PainMedicineNews.com. https://www.painmedicinenews.com/Clinical-Pain-Medicine/Article/03-18/Gabapentin-and-Opioids-a-Potentially-Deadly-Combination/47053. Published March 19, 2018. Accessed April 19, 2018.
- GW Pharmaceuticals (GWPH): Epidiolex will be approved much before the PDUFA date, bets Cantor. SmarterAnalyst. https://www.smarteranalyst.com/research-analysts/gw-pharmaceuticals-gwph-epidiolex-will-approved-much-pdufa-date-bets-cantor/. Published April 19, 2018. Accessed April 23, 2018.
- Unanimous positive result of FDA Advisory Committee meeting for first plant-based pharmaceutical cannabidiol treatment for seizures in patients with two rare, severe forms of epilepsy. GW Pharmaceuticals. http://ir.gwpharm.com/news-releases/news-release-details/gw-pharmaceuticals-and-us-subsidiary-greenwich-biosciences-1. Published April 19, 2018. Accessed April 23, 2018.
- GW wins panel backing for Epidiolex, looks to FDA decision. BioPharmaDive. https://www.biopharmadive.com/news/gw-wins-panel-backing-for-epidiolex-looks-to-fda-decision/521854/. Updated April 20, 2018. Accessed April 23, 2018.
- Hee Han D. Lofexidine gets FDA committee nod for opioid withdrawal. EMPR.com. https://www.empr.com/news/lucemyra-lofexidine-fda-committee-opioid-withdrawal-symptoms/article/754280/. Updated March 28, 2018. Accessed April 17, 2018.
- FDA Advisory Committee votes in favor of Lucemyra (lofexidine) for the mitigation of opioid withdrawal symptoms. PRNewswire.com. https://www.prnewswire.com/news-releases/fda-advisory-committee-votes-in-favor-of-lucemyra-lofexidine-for-the-mitigation-of-opioid-withdrawal-symptoms-300620526.html. Published March 27, 2018. Accessed April 17, 2018.
- United States Food and Drug Administration Center for Drug Evaluation and Research. FDA Briefing Document: Meeting of Psychopharmacologic Drugs Advisory Committee. FDA.gov. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM602417.pdf. Published March 27, 2018. Accessed April 17, 2018.
- Dolophine [package insert]. Columbus, OH: Roxane Laboratories, Inc; April 2015.
- Subutex [package insert]. Richmond, VA: Indivior Inc; December 2016.
- Suboxone [package insert]. North Chesterfield, VA: Aquestive Therapeutics; February 2018.
- Opioid Packaging Often Lacks Info on Safe Storage, Disposal. EMPR.com https://www.empr.com/news/opioid-packaging-safe-disposal-storage-absent-missing/article/759111/. Published April 17, 2018. Accessed April 20, 2018.
- Diversion Control Division. National Prescription Drug Take Back Day. U.S. Department of Justice. Drug Enforcement Administration. Available at: https://www.deadiversion.usdoj.gov/drug_disposal/takeback/. Accessed April 20, 2018.
- Take Back Day. US Drug Enforcement Administration. https://takebackday.dea.gov/. Accessed April 20, 2018.
- DEA National RX Take Back. https://takebackday.dea.gov/sites/default/files/pictures/DEA_TakeBack2018_Pamphlet_3.5×8.5_English.pdf. Accessed April 20, 2018.
- Exenatide (Bydureon) extended release for injectable suspension. FDA Drug Shortages. https://www.accessdata.fda.gov/scripts/drugshortages/dsp_ActiveIngredientDetails.cfm. Updated April 3, 2018. Accessed April 23, 2018.
- Bydureon BCise [package insert]. AstraZeneca Pharmaceuticals: Wilmington, DE; December 2017. https://www.azpicentral.com/bydureon_bcise/bydureon_bcise_pi.pdf#page=1. Accessed April 23, 2018.
- Bydureon [package insert]. AstraZeneca Pharmaceuticals: Wilmington, DE; April 2018. https://www.azpicentral.com/bydureon/pi_bydureon.pdf#page=1. Accessed April 23, 2018.