Oxymorphone HCl Extended-Release Tablets (Opana® ER) CII
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a new formulation of oxymorphone extended-release tablets that is designed to be crush-resistant in order to reduce the potential for diversion and abuse. It is marketed by Endo under the same name, dosage strength, color, packaging along with similar tablet size as the previous formulation of oxymorphone. Both the previous and new form are marketed as Opana ER.
Oxymorphone extended-release tablets are indicated for the relief of moderate-to-severe pain in patients who require around-the-clock pain management for an extended period of time.1
The initial recommended dose is 5 mg every 12 hours taken on an empty stomach at least 1 hour prior to or 2 hours after eating.1
Oxymorphone ER tablets are available as 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, and 40 mg.
Oxymorphone is embedded in a hard polymer matrix that is designed to be crush-resistant, potentially reducing the risk for misuse or abuse.
There are no disadvantages with the new formulation compared to the old one.
The new formulation of oxymorphone (Oxy-CR) is designed to be crush-resistant while still able to release the drug appropriately for therapeutic response. Oxy-CR has been shown to be bioequivalent to the oxymorphone extended-release tablets (Opana ER) in three open-label, randomized, single-dose, replicate, crossover studies.2 In study 1, patients were randomized to 5 mg of Oxy-CR or Opana ER in a crossover, four period, replicate design (each subject received each dose twice) under fasting conditions. Study 2 studied the 40-mg dose under fasting conditions and study 3 the 40-mg dose after a high-fat meal. To reduce the potential for opioid-related adverse events, subjects taking the 40-mg dose received three single doses of naltrexone 50 mg in each study period (4 × 3 = 12 tablets). Bioequivalence was based on the FDA criteria of 90% confidence interval of the ratio of least square geometric mean area under the curve (extent of absorption) and maximum plasma concentration (rate of absorption) between 0.80 and 1.25. Adverse events were monitored from 1 day before treatment to 15 days after the last dose. Oxy-CR is bioequivalent to Opana ER for both the 5 mg and 40 mg dose under both fasting and fed conditions. The frequencies of adverse events were similar between formulations.
Prescription painkiller use is at a record high for Americans and prescription opioid abuse is responsible for more deaths than crack cocaine in the 1980s.3 Misuse and abuse of extended-release opioids is particularly dangerous because of the high and potentially fatal dose in these formulations. One of the most common methods used by abusers is to chew or crush extended-release formulations.4 OxyContin was reformulated in 2010 to prevent the grinding of the tablets for insufflation for injection. Oxycodone appears to be a favorite among opioid abusers.5 The newly approved crush-resistant Opana ER would potentially reduce this method of abuse for oxymorphone.
1. Opana® ER Prescribing Information. Newark, DE: Endo Pharmaceuticals; December 2011.
2. Benedek IH, et al. Bioequivalence of oxymorphone extended release and crush-resistant oxymorphone extended release. Drug Des Devel Ther 2011;5:455-63.
4. Passik SD, et al. Psychiatric and pain characteristics of prescription drug abusers entering drug rehabilitation. J Pain Palliat Care Pharmacother 2006;20:5-13.
5. Rosenblum A, et al. Prescription opioid abuse among enrollees into methadone maintenance treatment. Drug Alcohol Depend 2007;90:64-71.