The arrival of FDA-approved Zohydro ER© (Zogenix, Inc.) in October 2013 continues to shake up medical, political, and special interest communities alike.
This new opioid analgesic has distinguishing features that both support and call to question its use. Regardless of the debate, Zohydro ER© is available and is being prescribed to patients. Our charge, as pharmacists and future pharmacists, is not only to familiarize ourselves with Zohydro ER©, but also to ensure patient access to appropriate pain management and to optimize therapy and treatment outcomes.
Zohydro ER© (extended-release hydrocodone bitartrate capsules) is the first and only FDA-approved single-component, extended-release hydrocodone formulation available. According to the FDA news release and Lexicomp (Lexi-Drugs), Zohydro ER© is indicated for the management of severe, chronic pain that necessitates “daily, around-the-clock, long-term treatment” – NOT on an “as needed” basis – and in situations where “alternative treatment options are inadequate.”
Zohydro ER© capsules are supplied in strengths of 10, 15, 20, 30, 40, and 50 mg, with starting dosing being 10 mg every 12 hours in those patients who are prescribed Zohydro ER© as initial monotherapy or for patients who are not already tolerant to opioids. Dose titration is permissible every 3-7 days by 10 mg increases every 12 hours; titration should be tailored to the individual patient to achieve tolerable pain levels and minimize side effects.
What makes Zohydro ER© a viable treatment option? Patients who have previously achieved tolerable pain levels with combination hydrocodone products (e.g. hydrocodone-acetaminophen) but no longer see relief may benefit from the extended-release formulation. Another population to consider patients with hepatic dysfunction, as this formulation does not contain the potentially hepatotoxic acetaminophen component. A final thought is that pain is a highly-individualized medical condition. Zohydro ER© gives prescribers another option to treat opioid-tolerant patients or patients experiencing intolerable effects from other pain medications.
Many national pharmacy organizations have reservations about the approval of Zohydro ER© due to discrepancy with past FDA precedent, as well as timing of the approval. Advisement from the FDA’s own Anesthetic and Analgesic Drug Products Advisory Committee in December 2012 was overwhelmingly in opposition to Zohydro ER© approval (11-2, 1 abstaining), and within days before the approval of Zohydro ER©, the FDA also announced it would be recommending the DEA move all hydrocodone products – single-ingredient formulations as well as those containing acetaminophen, ibuprofen, etc. –from Schedule III to Schedule II. Pharmacist representatives from several national organizations (American Association of Colleges of Pharmacy, American College of Clinical Pharmacy, Academy of Managed Care Pharmacy, American Pharmacists Association, the American Society of Consultant Pharmacists, National Community Pharmacists Association, National Association of Chain Drug Stores, and the National Alliance of State Pharmacy Associations) submitted a letter to the DEA, urging against rescheduling these C-III products. The pharmacy organization collective describes impact of “rescheduling” as greatly decreasing patient access to treatment, as well as increasing health care expenditures, especially during a shortage of primary care physicians (each refill would require a doctor’s visit for approval); it would also add burden to pharmacies as more time, space, and personnel will be needed to inventory the new Schedule II products.
Separate from these issues, but also an important consideration, is the fear of potential abuse and misuse of the new product. In the past, Oxycontin© (Purdue Pharma) had its approval revoked upon patent expiration to stop generic companies from producing the more opioid analgesics without abuse-preventing features, such as being impervious to crushing to causing irritation when taken by an unintended route of administration (e.g. intranasal). At present, Zohydro ER© is not designed or formulated with any mechanisms to discourage abuse. Without these features, legislation is popping up all over the country to “Ban Zohydro ER©” or even make it a Schedule I controlled substance. The Center for Lawful Access and Abuse Deterrence issued a petition to the FDA regarding this matter. To this concern, the FDA answered that Zohydro ER© complies with new safety labeling that warns of the risk of addiction and abuse, has a REMS program for further monitoring, and will be required to have post-marketing studies regarding safety, abuse/addiction potential, and efficacy beyond 12 weeks of use. The FDA noted that such “abuse-deterrent” mechanisms are only expected to decrease abuse, and that there is not enough data to fully support this assertion. Furthermore, oral administration, a common form of opiate abuse, is not prevented by the aforementioned “abuse-deterrent” mechanisms.
How Zohydro ER© will Impact Your Practice and Patients
- The potential for change is vast in the area of prescription opioid-analgesics, and it is the responsibility of the pharmacist to contribute a fiscally-conscious, patient-centered approach to chronic pain management.
- Patient education is of utmost importance with the arrival of name-brand only Schedule II Zohydro ER©. Pharmacists must provide appropriate patient counseling, not only in terms of what to expect from the medication in terms of benefits and side effects, but also in terms of available inventory and cost.
Dosing and Administration Considerations. Patients titrated up from immediate-release hydrocodone-combination products will need to be made aware of the change to twice-daily dosing. Expectations must be set that this is NOT a medication to be taken “as needed” and doing so will fall short of achieving the quick pain relief desired. And, while a proposed benefit of Zohydro ER© is safety in liver impairment due to the absence of acetaminophen from the formulation, Zohydro ER© itself is not recommended in severe hepatic impairment due to it being metabolized primarily by CYP3A4 and to a minor extent, CYP2D6 and should not be taken concomitantly with alcohol. Also noted in the literature is that when taken with a high-fat content meal, time to peak concentration is delayed by ~25%, which can also hinder a patient from reaching a tolerable pain level in a timely fashion. Lastly (but certainly not least), providers should always screen patients for abuse, addiction, and diversion potential before prescribing a Schedule II controlled substance.
Cost, Refill, and Inventory Considerations. It is likely that Zohydro ER© will require multiple trials of generic opioid-analgesics or prior authorization before insurance approval, and therefore, patient expectation must be set accordingly. Cost could prove an issue, as the drug is name-brand only and patients may be accustomed to paying for generics. It must also be discussed with the patient that although Zohydro ER© contains hydrocodone as its active ingredient, no refills can be provided on Zohydro ER© prescriptions like its C-III hydrocodone-combination product counterparts. Patients will need to make appointments with their prescribing physicians for each subsequent refill, which can escalate health care costs. With potential gaps in the refill process, pharmacists should be cognizant of how many patients are actively filling Zohydro ER© to ensure it is available to meet the need.
Mindful of each of these considerations – Zohydro ER©’s role in opioid-analgesic prescribing, the controversy surrounding its approval, and its many impacts on pharmacy practice – the pharmacist must advocate for patient access to care while carefully investigating, discerning, and reporting prescription abuse and misuse. Doing so will maintain the integrity of the prescribing and dispensing process, minimize unnecessary health care expenditures, and allow the pharmacist to continue to provide a high level of patient-centered care.
UMKC School of Pharmacy
Pharm.D. Candidate 2015
MPA Rotation Student, June 2014