- Firvanq® (vancomycin HCl) Approved for Infectious Diarrhea
- Lynparza® (olaparib) Receives Approval for Use in Certain Breast Cancer Patients
- FDA Proposes New Packaging for Over-the-Counter Anti-Diarrheal
- Ocaliva® (obeticholic acid) Receives Boxed Warning
- New Generic Version of Multiple Sclerosis Drug Copaxone® 40 mg/mL Available
- Intranasal Flu Vaccine Recommended by CDC Advisory Committee for Upcoming Flu Season
- Tanzeum® (albiglutide) Expected to be Unavailable by May 2018
New Drug Approvals
Firvanq® (vancomycin HCl) Approved for Infectious Diarrhea
Firvanq® (vancomycin hydrochloride) oral solution received U.S. Food and Drug Administration (FDA) approval in January 2018 for the treatment of Clostridium difficile-associated diarrhea and enterocolitis caused by Staphylococcus aureus (including methicillin-resistant strains). Firvanq is the first and only FDA-approved vancomycin oral liquid indicated for C. difficile-associated diarrhea. Each Firvanq kit contains 1 bottle of vancomycin hydrochloride USP powder and 1 bottle of pre-measured grape-flavored diluent for reconstitution by a healthcare provider. Following reconstitution, the concentration of vancomycin is 25 mg/mL or 50 mg/mL supplied in 150 mL, 210 mL, or 300 mL final volumes.
Firvanq is indicated for oral use only as vancomycin is required to be given orally in order to effectively treat C. difficile-associated diarrhea and S. aureus enterocolitis. There is the potential for drug absorption into the blood stream in certain patients, including those with renal insufficiency and/or colitis or in patients receiving specific antibiotics. Firvanq carries warnings/precautions regarding the potential for kidney toxicity and hearing loss (which may be temporary or permanent). The most common side effects, occurring in 10% or more of patients, were nausea, stomach pain, and low potassium levels.
Doses of Firvanq should not be omitted as doing so can result in decreased effectiveness and increase the potential for developing drug-resistant bacteria. Reconstituted Firvanq should be stored in the refrigerator and shaken well before each use. Dosing of Firvanq is dependent on the indication for use and requires administration 3 to 4 times daily for 7 to 10 days. Following reconstitution, Firvanq should be discarded after 14 days or if the solution becomes hazy or develops particles. This new formulation will replace CutisPharma’s FIRST-Vancomycin Unit-of-Use® Compounding Kit. Firvanq is expected to become commercially available on April 2, 2018.
Lynparza® (olaparib) Receives Approval for Use in Certain Breast Cancer Patients
In January 2018, Lynparza® (olaparib) received FDA-approval for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer that have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients who have hormone receptor positive (HR+) breast cancer should have received prior endocrine therapy or be considered inappropriate for endocrine therapy. An FDA-approved diagnostic test from Myriad Genetics is used to determine patients who are candidates for Lynparza.
Metastatic breast cancer (MBC) affects more than 150,000 American women and occurs when cancer spreads from the initial breast tissue. The BRCA1 and BRCA2 genes are responsible for repairing DNA damage. Mutations in the BRCA genes can result in impairment of DNA repair and lead to the development of cancerous cells. The approval of olaparib for MBC marks the first and only poly (ADP-ribose) polymerase (PARP) inhibitor approved for this indication.
Approval of olaparib for MBC was based on results from the Phase III OlympiAD trial. This randomized, open-label study compared olaparib to the physician’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine). Patients who received olaparib exhibited significantly longer progression-free survival (PFS) compared to those who received chemotherapy (median of 7.0 months vs. 4.2 months). In addition, the risk for disease progression or death was reduced by 42% in patients receiving olaparib compared to chemotherapy. Common adverse reactions, occurring in 20% or more of patients receiving olaparib, included: nausea, anemia, fatigue, vomiting, respiratory tract infections, low white blood cell counts, diarrhea, and headache. Less patients in the olaparib group discontinued treatment than patients receiving chemotherapy (5% vs. 8%, respectively).
Lynparza is available as an oral tablet in the strengths of 150 mg and 100 mg and is doses as 300 mg orally twice daily with therapy continued until disease progression or unacceptable toxicity. The average wholesale price (AWP) for one day of therapy at a dose of 300 mg twice daily is $555.46.
FDA Safety Update
FDA Proposes New Packaging for Over-the-Counter Anti-Diarrheal
The U.S. Food and Drug Administration (FDA) announced in January 2018, the anti-diarrhea drug loperamide would be receiving new packaging to encourage safe use by limiting the number of doses per package. Loperamide is available over-the-counter (OTC) and is used for the management of diarrhea, including Travelers’ Diarrhea. By binding to opioid receptors in the gastrointestinal tract, it slows intestinal movement resulting in a reduction in the number of bowel movements. The product is commercially available as brand-name Imodium A-D® and as a generic product.
In 2016, the FDA released a Drug Safety Communication concerning serious events arising from using more than the maximum recommended dose of loperamide. When used OTC, the maximum dose of loperamide is 8 mg per day; prescription loperamide has a maximum dose of 16 mg per day. The majority of reported adverse events with loperamide have involved individuals who intentionally misused and abused the product to self-treat opioid withdrawal symptoms or to achieve feelings of euphoria. If taken at doses higher than recommended, heart rhythm abnormalities and/or death can occur. As a result of the reported adverse events, the potential for serious heart problems was added as a warning on the product labels for prescription loperamide and to the Drug Facts label of OTC products.
An update released on January 30, 2018 discussed continued reports of serious heart problems and deaths due to use of higher than recommended doses of the product. In response, the FDA is collaborating with drug manufacturers to package OTC loperamide in blister packs or single-dose packages in order to restrict the total number of doses available in a package. The FDA has requested OTC manufacturers institute changes to the packaging of loperamide to limit the amount supplied per package. Packages are recommended to contain only the amount of loperamide needed for treating short-term diarrhea. In order to address the public health issue, the FDA has requested manufacturers initiate changes in a prompt manner.
The FDA is also reminding patients and consumers to use loperamide as directed by their healthcare prescriber or according to the OTC Drug Facts label due to the potential for serious consequences if taken in doses greater than recommended. Patients with diarrhea lasting more than two days, despite OTC loperamide use, should stop taking the product and contact their healthcare provider. Patients should also be counseled on drug interactions that may increase the potential for cardiac issues. Immediate medical attention is needed if a patient taking loperamide experiences fainting, a rapid or irregular heartbeat, or becomes unresponsive. Healthcare professionals should be aware that higher than recommended doses of loperamide may lead to adverse cardiac events; cases of abuse may include the use of other drugs to increase loperamide absorption or inhibits its metabolism.
For additional details on the new packaging for loperamide, please view the FDA’s Safety Alert. To view the FDA Commissioner’s Statement on loperamide packaging and other efforts to address the opioid epidemic, please visit the FDA website.
Ocaliva® (obeticholic acid) Receives Boxed Warning
In September 2017, the FDA released a Drug Safety Communication regarding Ocaliva® (obeticholic acid) and the risk for severe liver damage due to incorrect dosing. Ocaliva was approved in May 2016 for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who do not respond adequately to UDCA or as monotherapy in adults who cannot tolerate UDCA. A typical starting dose is 5 mg by mouth daily; patients with moderate to severe liver impairment should be initiated on a decreased dose of 5 mg once a week with a maximum dose of 10 mg given twice weekly. Through the FDA Adverse Reporting System (FAERS), it was found that patients with moderate to severe liver impairment were incorrectly receiving 5 mg daily which resulted in cases of serious liver injury, worsening PBC, and/or death.
The FDA issued an update on February 1, 2018 with the addition of a Boxed Warning to Ocaliva labels as well as a Medication Guide for patients. Boxed Warnings are added to labels to call attention to serious or life-threatening risks associated with a medication and are considered to be the FDA’s most prominent warning. With the approval of Ocaliva, the FDA mandated the manufacturer to continue evaluating the product in patients with advanced PBC. The trials are ongoing and results are anticipated in 2023. The FDA plans to continue monitoring Ocaliva and will provide updates as appropriate.
Healthcare providers are recommended to follow the Ocaliva dosing information provided in the product label; this includes calculating a Child-Pugh score in PBC patients with liver cirrhosis in order to correctly determine the appropriate dose. Patients who receive doses higher than the recommended regimens may be at an increased risk for worsening of liver disease, liver failure, and potentially death. Patients should be regularly monitored for drug response, tolerability, and disease progression. Dose reduction or drug discontinuation should be considered in cases of worsening liver conditions.
The FDA advises patients to be aware that their healthcare provider should provide routine checks to determine liver function while on Ocaliva. Symptoms such as new or worsening severe skin itching should be reported to their provider. Patients and healthcare professionals should report any adverse events or side effects to FDA’s MedWatch Safety Information and Adverse Event Reporting Program at www.fda.gov/MedWatch/report.
New Generic Version of Multiple Sclerosis Drug Copaxone® 40 mg/mL Available
In February 2018, Novartis’ Sandoz division announced the approval and launch of a generic version of multiple sclerosis drug Copaxone® (glatiramer acetate injection) in the strength of 40 mg/mL. Sandoz’s generic product, Glatopa® (glatiramer acetate injection) 40 mg/mL, is a fully substitutable, generic version of Copaxone 40 mg/mL. The 20 mg/mL strength of Glatopa became commercially available in 2015, and now with the approval and launch of the 40 mg/mL strength, Sandoz’s generic products provide the full range of dosing strengths for the treatment of patients with relapsing forms of multiple sclerosis.
Glatopa 40 mg/mL is given three times a week and was developed in collaboration with Momenta Pharmaceuticals, Inc. Glatopa is contraindicated in patients who are allergic to glatiramer acetate or mannitol. Approximately 2% of patients on Glatopa 40 mg/mL experienced varying symptoms, that included at least two of the following: flushing, chest pain or palpitations, a rapid heart rate, anxiety, shortness of breath, throat constriction, and hives. In comparison, none of the patients receiving placebo reported these symptoms. These side effects usually emerged a few months after starting treatment but may appear earlier. Most of these side effects do not require treatment and are self-limiting, however some patients have required emergency care.
Intranasal Flu Vaccine Recommended by CDC Advisory Committee for Upcoming Flu Season
In February 2018, the Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) voted in support of the FluMist Quadrivalent® (influenza vaccine live, intranasal) for prevention of influenza in the United States during the upcoming 2018 to 2019 flu season. The FluMist Quadrivalent is a live attenuated influenza vaccine (LAIV) supplied as a nasal spray. Previously, the ACIP recommended against use of the LAIV for the 2016-2017 and 2017-2018 flu seasons due to concerns regarding the vaccine’s effectiveness during the 2013-2014 and 2015-2016 flu seasons.
The renewed recommendation by the advisory committee is based on data from a study conducted in children two to less than 4 years of age. It was demonstrated the 2017-2018 H1N1 strain elicited significantly improved responses compared to the 2015-2016 H1N1 strain. The antibody responses observed with the 2017-2018 strain were similar to that exhibited with a prior highly effective LAIV strain.
The manufacturer of FluMist expects the nasal spray flu vaccine to be available in the United States for the upcoming 2018 to 2019 flu season, if the strain receives approval from the U.S. Food and Drug Administration. FluMist is indicated for use in patients 2 through 49 years of age. The ACIP’s recommendation requires review and approval by the CDC director to be considered official CDC policy. NPS plans to provide ongoing communication regarding the finalized CDC recommendations for the 2018-2019 flu season and the availability of FluMist Quadrivalent.
For additional details on the ACIP’s recommendation, please view the manufacturer’s press release.
Drug Shortages and Discontinuations
Tanzeum® (albiglutide) Expected to be Unavailable by May 2018
GlaxoSmithKline announced in July 2017 plans to discontinue the type 2 diabetes medication, Tanzeum® (albiglutide for injection) citing availability of other treatment options as the basis on which the decision was made. The manufacturer has stated discontinuation of the product was not related to safety issues. At the time of the announcement, existing supplies were expected to be depleted by July 2018. A recent update has moved the anticipated discontinuation date to May 2018.
Tanzeum was approved in 2014 to improve blood glucose control in adults with type 2 diabetes when used in addition to diet and exercise. Other medications from this class of medications, the glucagon-like peptide-1 (GLP-1) receptor agonists, remain commercially available. Patients should not discontinue Tanzeum without first consulting their healthcare prescriber and determining an alternative treatment option. Healthcare professionals are instructed to transition patients from Tanzeum to an acceptable alternative prior to the discontinuation date.
- CutisPharma. CutisPharma announces FDA approval of FIRVANQ. CutisPharma.com. http://cutispharma.com/cutispharma-announces-fda-approval-firvanq/. Published January 29, 2018. Accessed February 22, 2018.
- Firvanq [package insert]. Wilmington, MA: CutisPharma; January 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208910s000lbl.pdf. Accessed February 22, 2018.
- AstraZeneca. Lynparza approved by US FDA in germline BRCA-mutated metastatic breast cancer. AstraZeneca Website. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2018/lynparza-approved-by-us-fda-in-germline-brca-mutated-metastatic-breast-cancer-12012018.html. Published January 12, 2018. Accessed January 24, 2018.
- Lynparza [package insert]. Wilmington, DE: AstraZeneca; January 2018. https://www.azpicentral.com/lynparza_tb/pi_lynparza_tb.pdf#page=1. Accessed January 24, 2018.
- U.S. Food and Drug Administration. Imodium (loperamide) for over-the-counter use: Drug Safety Communication – FDA limits packaging to encourage safe use. FDA.gov. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm594403.htm. Published January 30, 2018. Accessed February 20, 2018.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. FDA.gov. https://www.fda.gov/Drugs/DrugSafety/ucm504617.htm. Published June 7, 2016. Accessed February 20, 2018.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA limits packaging for anti-diarrhea medicine Loperamide (Imodium) to encourage safe use. https://www.fda.gov/Drugs/DrugSafety/ucm594232.htm. Published January 30, 2018. Accessed February 20, 2018.
- U.S. Food and Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on new steps to help prevent new addiction, curb abuse and overdose related to opioid products. FDA.gov. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm594443.htm. Published January 30, 2018. Accessed February 20, 2018.
- U.S. Food and Drug Administration. Safety Announcement: FDA warns about serious liver injury with Ocaliva (obeticholic acid) for rare chronic liver disease. FDA.gov. https://www.fda.gov/Drugs/DrugSafety/ucm576656.htm. Updated September 26, 2017. Accessed October 9, 2017.
- U.S. Food and Drug Administration. Safety Alerts for Human Medical Products: Ocaliva (obeticholic acid): Drug Safety Communication – Boxed warning added to highlight correct dosing. FDA.gov. https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm594901.htm. Published February 1, 2018. Accessed February 22, 2018.
- U.S Food and Drug Administration. FDA Consumer Health Information: A guide to drug safety terms at FDA. FDA.gov. https://www.fda.gov/downloads/forconsumers/consumerupdates/ucm107976.pdf. Published November 2012. Accessed February 22, 2018.
- Ocaliva [package insert]. New York, NY: Intercept Pharmaceuticals; February 2018. https://ocalivahcp.com/_assets/_pdfs/ocaliva-us-package-insert-for-commercial-use.pdf. Accessed February 27, 2018.
- Novartis. Sandoz announces US FDA approval and launch of Glatopa 40 mg/mL three times-a-week generic option for relapsing forms of multiple sclerosis. Novartis.com. https://www.novartis.com/news/media-releases/sandoz-announces-us-fda-approval-and-launch-glatopar-40-mgml-three-times-week-generic-option-relapsing-forms-multiple-sclerosis. Published February 13, 2018. Accessed February 23, 2018.
- AstraZeneca announces renewed recommendation and availability of FluMist quadrivalent vaccine in the U.S. BusinessWire. https://www.businesswire.com/news/home/20180221006221/en/AstraZeneca-Announces-Renewed-Recommendation-Availability-FLUMIST-QUADRIVALENT. Updated February 21, 2018. Accessed February 22, 2018.
- Ernst D. ACIP votes in favor of intranasal flu vaccine FluMist Quadrivalent. EMPR.com. https://www.empr.com/news/flumist-quadrivalent-nasal-flu-vaccine-acip-recommendation/article/745900/. Updated February 22, 2018. Accessed February 22, 2018.
- ACIP backs nasal flu vaccine for first since 2016. P&T Community. https://www.ptcommunity.com/news/20180222/acip-backs-nasal-flu-vaccine-first-time-2016. Accessed February 22, 2018.
- ACIP reinstates FluMist for 2018-2019 flu season. MedPage Today. https://www.medpagetoday.com/meetingcoverage/acip/71298. Updated February 21, 2018. Accessed February 28, 2018.
- GSK. Tanzeum (albiglutide) Discontinuation – Q&A. Tanzeum.com. https://www.tanzeum.com/pdfs/consumer-faq.pdf. Accessed February 27, 2018.
- Han DH. Update Regarding Tanzeum Injection Availability. EMPR.com. https://www.empr.com/news/tanzeum-albiglutide-discontinued-diabetes-treatment/article/739712/. Published January 26, 2018. Accessed February 27, 2018.
- Ernst D. Type 2 diabetes injectable therapy will soon be unavailable. EMPR.com. https://www.empr.com/news/tanzeum-diabetes-glp-1-receptor-agonist-discontinued-glaxosmithkline/article/682925/. Published August 18, 2017. Accessed February 27, 2018.