Hydromorphone Extended Release for Chronic Pain

Fort Lauderdale—In clinical practice, patients with moderate-to-severe chronic pain received doses of hydromorphone extended release that were nearly 50% lower than the doses given to patients who were prescribed oxymorphone extended release or oxycodone controlled release, according to prescription data. However, the authors noted, clinical trials have found that hydromorphone extended release is safe and effective at doses from 8 mg to >96 mg.

Results were presented during a poster session at the AAPM meeting. The poster was titled Clinical Utility of Once-Daily Hydromorphone Extended Release (OROS Hydromorphone ER) Compared to Other Strong Extended-Release Opioids.

In August 2012, the FDA approved a 32-mg dose of hydromorphone extended release, an oral, once-daily therapy for patients with moderate-to-severe pain. The drug was previously approved in 8-mg, 12-mg, and 16-mg tablets. Oxymorphone extended release and oxycodone controlled release are also FDA approved.

For this analysis, the authors obtained information from IMS Health’s IMS LRx Xponent database that includes 65% of retail prescriptions in the United States. They included data on 21,172 patients taking hydromorphone extended release for a total of 66,774 prescriptions, 178,827 patients taking oxymorphone extended release for a total of 988,200 prescriptions, and 1,125,030 patients taking oxycodone controlled release for a total of 6,509,335 prescriptions to treat chronic pain between April 2010 and November 2011. They tracked the date of prescription transactions, the prescribing physicians, the products received, the therapy days, and the payment method. More than 75% of patients were between 21 and 60 years of age, approximately 53% were male, and there were no significant differences in age and sex of patients in the treatment groups.

The authors also pooled data from 13 trials on 2335 patients with chronic cancer or noncancer pain who received at least 1 dose of hydromorphone extended release. The studies ranged from <3 weeks to 52 weeks and included 2 double-blind, placebo-controlled studies, 4 active-controlled studies, and 7 uncontrolled studies. Each study used a 5:1 morphine:hydromorphone extended-release dose equivalency ratio when converting from previous opioid therapy. Of the patients, 78% were between 18 and 64 years of age and 56% were female.

According to the IMS Health data, the mean daily doses prescribed were 21.4 mg for hydromorphone extended release, 63.7 mg for oxymorphone extended release, and
102.5 mg for oxycodone controlled release. That equates to a mean morphine equivalent dose of 107 mg, 191 mg, and 205 mg, respectively. In addition, 78% of the prescriptions for hydromorphone extended release were for morphine equivalent doses of ≤120 mg compared with 47% of oxycodone controlled release prescriptions. Further, 40% of patients receiving hydromorphone extended release and 22% of patients taking oxymorphone extended release began treatment with at least a 50% reduction in equianalgesic dose compared with their prior opioid therapy.

The pooled clinical trial data found that the mean stable daily dose of hydromorphone extended release was 36.7 mg for a morphine equivalent dose of 183.5 mg, while the mean stable daily dose in studies without dose capitation was 57.4 mg for a morphine equivalent dose of 287 mg. The most common adverse events included constipation, nausea, vomiting, somnolence, and headache.

The authors cited a few study limitations, including that hydromorphone extended release has not been available for as long as oxymorphone extended release and oxycodone controlled release. They also noted that the IMS Health data provided only limited information during the time period and that physicians and patients may have had different access to the medications.

This poster was supported by Mallinckrodt Pharmaceuticals.