FDA Approves Extended-Release Hydromorphone for Chronic Pain
By Yael Waknine
Medscape Medical News
March 3, 2010 — The US Food and Drug Administration (FDA) has approved hydromorphone HCl extended-release tablets (Exalgo, CombinatoRx, Inc) for the management of moderate to severe pain in opioid-tolerant patients requiring continuous, around-the-clock opioid analgesia for an extended period.
The once-daily formulation uses a proprietary osmotic delivery system (Oros Push-Pull) to provide a steady release of hydromorphone, thereby avoiding the peaks and troughs associated with immediate-release products.
FDA approval was based on data from a 12-week phase 3 clinical trial in which 268 opioid-tolerant patients with chronic moderate-to-severe low back pain were randomly assigned to receive extended-release hydromorphone or placebo.
Results showed that extended-release hydromorphone (mean dose, 37.8 mg/day; range, 12 - 64 mg/day) was significantly more effective than placebo for reducing mean pain intensity from baseline, as measured using an 11-point Likert numerical rating scale obtained from patient diaries (P < .0001).
Adverse events most commonly reported in the study were consistent with the safety profile for opioids and most commonly (>10%) included constipation, nausea, vomiting, somnolence, headache, and dizziness.
Because hydromorphone is subject to abuse and misuse, the extended-release product was approved with a risk evaluation and mitigation strategy that includes a restricted distribution program requiring registration of prescribers, pharmacies, and patients. The program emphasizes the need for clinician and pharmacist education and patient counseling regarding the attendant risks of hydromorphone therapy.
The recommended dose of extended-release hydromorphone is 8 to 64 mg daily; because of the risk for a potentially fatal dose, tablets should be swallowed whole and not broken, chewed, dissolved, crushed, or injected.
Extended-release hydromorphone should be reserved for use in opioid-tolerant patients with chronic pain, defined as those requiring 60 mg oral morphine daily (or an equianalgesic dose of another opioid) for a week or longer. Use in non-opioid-tolerant patients or for acute, postoperative, or intermittent pain may cause potentially fatal respiratory depression.
Coadministration of other central nervous system depressants with hydromorphone has an additive effect on the risk for respiratory depression, hypotension, profound sedation, and coma. When hydromorphone is administered in conjunction with other opioids, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, skeletal muscle relaxants, alcohol, or other central nervous system depressants, significant dose reduction of one or both agents is advised.
Extended-release hydromorphone should not be used within 14 days of monoamine oxidase inhibitor therapy or in patients with significantly impaired pulmonary function, paralytic ileus, narrowed/obstructive gastrointestinal tract, or known hypersensitivity to sulfite-containing medications.
