The Food and Drug Administration’s own advisory committee met in December 2012 to discuss a new formulation of hydrocodone. Hydrocodone is an opiate ingredient found in many prescription pain medications such as Vicodin, Norco, Lorcet, Xodol, Zydone, Hydrogesic, Hycet, and many others. This new formulation has been named Zohydro™ by its maker Zogenix Inc. The FDA’s own experts on pain management voted by a wide margin to reject Zohydro™ in an 11-2 vote with one abstention. The FDA usually goes along with the recommendation of the advisory panel. On October 25, 2013, the FDA ultimately approved Zohydro™. Zogenix Inc. planned to get it on the shelves about 4 months following its approval. Zogenix recently reported that manufacturing is complete and the product is ready for shipment to wholesalers.
This newly approved formulation is very different than the other hydrocodone containing medications on the market. All of the other formulations have been combined with other analgesics such as acetaminophen or aspirin. In addition, they are all immediate release products which are usually dosed on an every four to six hour basis as needed. Zohydro™ is an extended release product which has hydrocodone as its only active ingredient. These two factors may very well spell disaster for those who take this product in an unlabeled manner.
Opiate pain medications currently account for the vast majority (about 75%) of prescription drug overdoses in this country. The deaths associated with these overdoses have more than tripled in the past decade alone. Most of these deaths are associated with hydrocodone, methadone, or oxycodone products such as Oxycontin and Percocet. Most people involved in the various aspect of this issue would certainly declare it to be an epidemic. Prescription overdoses not only involve the loss of human life. Losses are incurred as health care expenditures rise, productivity decreases, and increased costs to the courts, law enforcement and other emergency medical personnel.
Zohydro™ is currently classified as a Schedule II medication as categorized by the Drug Enforcement Agency since it only contains a single active ingredient. Other hydrocodone products such as Lorcet and Vicodin are currently categorized as a less restrictive Schedule III medication.
Schedule II medications require the physical copy of the prescription to be delivered to the pharmacy with very few exceptions. They are also not refillable without a new prescription being written by the practitioner. The pharmacies are required to keep a very strict count and record keeping of inventory movement.
Prescriptions for Schedule III medications may be written or called into a pharmacy for dispensing. Refills are allowed for up to 6 fills if approved by the practitioner and expire within 6 months from the date the prescription was written. The pharmacy inventory is more loosely controlled and does not require for the accounting of each tablet or capsule.
The FDA, one day before the approval of Zohydro™, sent over a formal recommendation to the US Department of Health and Human Services to reclassify all hydrocodone combination products to Schedule II. They cited their growing concern in the abuse of the hydrocodone combination products. Interesting enough, just one day after that announcement, they approved Zohydro™ despite the advisory committee’s recommendation and their own abuse concern of the hydromorphone combination products.
Much of the surge of prescription drug abuse can be attributed to the launch of Oxycontin in 1996. Oxycontin is an extended release formulation of oxycodone. In 2000, reports starting coming in from the eastern part of the United States that Oxycontin tablets were being crushed allowing the product to be ingested, injected and inhaled. Crushing of these extended release products allowed for the immediate release of the active ingredient (oxycodone) which was meant to be absorbed over a 12 hours period. In response to the abuse, the FDA decided to strengthen the product labeling to include additional warnings despite the fact that most prescription drug abusers are not even the ones that were prescribed the medication. In 2008, the FDA began to discuss the reformulation of Oxycontin which was eventually completed in 2010. This was a decade after alarm bells were initially sounded regarding the abuse.
The new formulation of Oxycontin made it much more difficult to crush as it turned into a jelly type substance. Youtube videos quickly popped up on ways to defeat this new formulation. The methods ranged from using sledgehammers, microwaves and dissolving the tablets in acid. Street prices of reformulated Oxycontin dropped but users quickly moved to another product called Opana ER. Opana is another opiate containing analgesic which contains oxymorphine. Recently, Opana has also been reformulated to be crush resistant. Of interest is that the FDA recently denied approval of the generic versions of Oxycontin despite the expiration of its patient. They felt that not having the crush resistant formulation was just too risky for approval.
Now, Zohydro™ is about to hit the pharmacy shelves. It utilizes a proprietary drug absorption system. This system is not crush resistant and no claims are being made to that effect. Crushing of this product allows for immediate availability of hydrocodone either intravenously, intranasally or orally. Zohydro™ comes in 6 different strength up to 50 mg. Just one of these 50 mg capsules would be the equivalent of taking 10 Vicodin tablets.
History is about to repeat itself. Availability of an extended release non crush resistant product with a single opiate ingredient is coming to market. It will make the news, it will kill, it will addict, it will increase crime and there will be an increase in pharmacy robberies. Unfortunately, it will also be another reason for changes by legitimate prescribers and pharmacies due to the misdirection of enforcement. It is hard enough for patients to get pain medications filled for legitimate purposes but now it will only get worse.
Pressure is currently being mounted on the FDA regarding the approval decision of Zohydro™. The Attorney Generals in 29 states have submitted a letter to the FDA regarding their concerns. Many other groups have ramped up their efforts as well to protest the decision.
A quick search today shows that at least one wholesaler currently has this product in their warehouse. This is a sign that the commercial release of Zohydro™ is imminent. Retail pricing appears to be between $6-$9 per capsule depending on the strength. Compare this to the $25 cost for 100 tablets of the generic version of Vicodin.
In an interesting side note….. Zogenix bought the rights to market Zohydro™ from Elan Pharmaceuticals. Another company, Alkermes, about a year later purchased the unit from Elan that makes Vivitrol and held the agreement with Zogenix. Vivitrol is a monthly intramuscular injection given for the treatment of alcoholism and opiate addiction. Cost of this monthly injection is in excess of $1000 per dose.
“Those that fail to learn from history, are doomed to repeat it.”
Winston S. Churchill
Steven L. Hirschfield earned this PharmD from the University of Florida College of Pharmacy. Previous he has worked extensively in the arena of drugs of abuse from working with law enforcement, rehabilitation/intervention programs, and in the criminal justice system . In addition, he has worked in many aspects of pharmacy including retail, hospital, and currently in the area of home infusion/specialty pharmacy. Email: firstname.lastname@example.org / email@example.com