There’s a new monster-sized painkiller on the market, with full approval from the FDA. It makes Vicodin and Lortab, arguably the most common addictive painkillers, seem low-risk by comparison.
Zohydro ER is a new opioid painkiller from the pharmaceutical company Zogenix, available by prescription starting in March. The FDA approved the drug despite its own advisory board voting 11-2 against approval, and numerous pleas from the drug enforcement and drug treatment communities (see Citizen.org PDF in “Resources”).
Attorneys general from 28 states also petitioned the FDA against approval of Zohydro, saying there was no need for another high-strength hydrocodone pill, and predicting big problems with abuse.
Zohydro is the first FDA-approved hydrocodone “single-entity” pill, meaning it is almost entirely hydrocodone. Most painkillers contain a much lower concentration. According to complaints, Zohydro’s lowest dosage (10mg) contains twice as much hydrocodone as found in a Vicodin pill. The highest single dose of Zohydro contains as much hydrocodone as 5 to 10 tablets of Vicodin or Lortab. Zohydro mixed with alcohol can be fatal.
After the reschedule of hydrodocone products to Schedule II classification on the FDA Controlled Subtances Act list, Zohydro is a Schedule II controlled substance. The big complaint about abuse potential is related to the time-release nature of the Zohydro formulation. Zohydro ER is “extended release”, which means a single pill contains multiple doses of hydrodocone.
The “time release” technology is intended to prevent the hydrocodone from being accessed in a single dose. Yet Zohydro ER pills are crushable. Drug abusers crush such pills to bypass the time-release technology. When the time-release coating is removed, one pill can deliver a fatal dose of hydrocodone. The drug enforcement and substance abuse treatment communities gained detailed experience with this problem when the Oxycontin market took off, and users bypassed the same time release technology. Oxycontin is now crush-proof, and no longer the “king” of pain killer addiction.
Zogenix claims to be working on non-crushable technology for Zohydro, with a 2 year or so timeline for availability.
There is a large black market for opioid painkillers. The FDA reported that Zohydro pills were being stolen even during the trial phase, suggesting the demand is in place for diversion of prescription pills to the black market.
According to Zogenix, Zohydro is intended for “the management of pain severe enough to require daily, around-the-clock, long-term treatment and for which alternative treatment options are inadequate.” Effects of Zohydro resemble those of Oxycontin (oxycodone) and heroin. See the differences between oxycodone and hydrocodone.
- Citizen.org Plea to the FDA to not approve Zohydro (PDF)
- Letter from States Attorneys General (PDF)
- ref: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm372287.htm
- ref: http://www.npr.org/2014/02/26/282836473/critics-question-fdas-approval-of-zohydro
- ref: http://www.cnn.com/2014/02/26/health/zohydro-approval/
- ref: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=cf68f7fe-30a9-4f1a-a3a4-6352dc436bbe
Discussion notes from the FDA Panel Discussion on Zohydro Approval (PDF):
A review of the recent scientific literature of the relative abuse potential of hydrocodone in humans reveals that hydrocodone as a single entity [Schedule II] or in combination products [Schedule III] produces typical mu-opioid agonist activity similar to morphine, oxycodone and hydromorphone [all Schedule II] in a dose-related manner (Zacny 2003, Zacny et al, 2005, Zacny and Gutierrez, 2008 and 2009, Walsh et al. 2008, Stoops et al. 2010). These effects include subjective opioid effects such as “drug liking” and “high.” Depending on the study population and product administered, unpleasant effects such as dizziness and increased rating of nausea also occur.
All studies were crossover, placebo controlled designs, and enrolled non-opioid- dependent subjects. Some of the methodological variables differentiated these studies. These variables included the subject population studied, the various formulations of hydrocodone administered and routes of administration. One of these studies evaluated the abuse potential of hydrocodone single entity when used intravenously (Stoops et al. 2010), while the others used oral administration. The number of subjects included in these studies varied from nine to twenty. Some of the studies included subjects with prior history of recreational drug use, whereas others enrolled subjects with a prior history of opioid abuse or prescription opioid abuse. In all the studies, the reinforcing effects of several doses of either compounded single entity hydrocodone products, or hydrocodone combined with either acetaminophen or homatropine, were compared to the effects mediated by other prescription opioids. The single entity products, as well as the high strength hydrocodone combination products studied are not currently approved marketed products in the United States.
These studies showed that hydrocodone, as single entity and in combination with other drugs, produces subjective abuse-related effects at doses of hydrocodone bitartrate equal to or greater than 15 mg when taken orally. When administered intravenously, a dose of 10 mg of hydrocodone hydrochloride was associated with significantly higher levels of “drug liking” compared to placebo (Stoops et al. 2010). Although the preferred FDA Background Material – NDA 202880 Zohydro ER (hydrocodone) for the management of moderate to severe chronic pain Page 35 route of abuse of marketed hydrocodone combination products is oral followed by lower levels of intranasal abuse, the intranasal and intravenous routes of administration might become more relevant routes of administration for the single entity product. (Butler et al. 2011)
It is relevant to mention that human abuse potential studies measure the relative abuse potential of a drug when compared to another drug of abuse, and contribute to the assessment of the likelihood of abuse of a drug when introduced on the market. However, these studies do not measure several variables that might impact the abuse of a product when introduced to the market. These abuse potential studies do not measure intrinsic properties of a formulation or other factors that might impact the levels of abuse of a particular formulation, such as availability of other opioid products, information available on the abuse of the novel product, street prices, and fads among other factors.
As a hydrocodone single-entity, extended-release product, it is expected that Zohydro ER (if approved and marketed) will be associated with higher levels of abuse than the hydrocodone combination products. These expected higher levels of abuse are based on what has been observed for oxycodone products. Like hydrocodone, oxycodone is also marketed as a combination product, but there are also single-entity, extended release (ER) products available. As a result, the available data on drug abuse of oxycodone combination and single-entity ER products can provide indirect evidence for the abuse patterns we might see with Zohydro ER.
The 2008 national estimates of abuse-related Emergency Department (ED) visits were obtained from the Drug Abuse Warning Network (DAWN). To adjust for drug utilization, the Total Number of Tablets Dispensed was obtained from IMS Health and used as the denominator to compute abuse ratios11. The abuse ratio for hydrocodone combination products was 14 ED visits per million tablets dispensed. The abuse ratio for oxycodone combination products was 24 ED visits per million tablets dispensed, compared to 85 ED visits per million tablets dispensed for oxycodone single-entity ER products. This difference is substantial and it is likely that similar patterns will be observed between hydrocodone combination products and Zohydro ER.