/publications/issue/2005/2005-09/2005-09-9844

RxPRODUCT NEWS: PROFILE: DepoDur (morphine sulfate extended-release liposome injection)

Author: Claudio Faria, PharmD; Carolyn Soo, PharmD; and Diem Chi Tran

Although several techniques are available to control postoperative pain, these options can be costly and inconvenient and often result in low patient satisfaction.1,2 In 2004, the FDA approved DepoDur, an extended-release liposomal formulation of morphine sulfate. Marketed by Endo Pharmacuticals Inc and developed by SkyePharma, DepoDur is administered epidurally at the lumbar level and is indicated for the treatment of pain following major surgery, including hip replacement, lower abdominal, and elective cesarean section surgery.3

Pharmacology

DepoDur is an opiate agonist, specifically at the receptor.4 At high doses, it may interact with other opiate receptors.4 Resembling opioids like enkephalins and endorphins, Depo- Dur produces analgesia in the central nervous system.5

Clinical Trials

A randomized, double-blind, placebo- controlled, parallel-group, doseranging study compared single epidural doses of DepoDur (15, 20, and 25 mg) versus placebo in patients undergoing hip arthroplasty. The 194 patients who underwent surgery were able to self-administer intravenous fentanyl for breakthrough pain. Results demonstrated that all DepoDur doses significantly delayed the time to the first dose of fentanyl and reduced fentanyl administration versus placebo (P < .0001). Postoperative pain control (48 hours postdose) had also improved in all DepoDur groups versus placebo (P < .0005).5

Another similarly designed study involved approximately 500 patients undergoing lower abdominal surgery. The trial compared 6 different treatments for postoperative pain for up to 48 hours, such as single epidural doses of DepoDur 10, 15, 20, and 25 mg, single- dose DepoDur 5 mg, and standard epidural morphine sulfate 5 mg. A dose-response relationship between the DepoDur doses and postsurgical PCA fentanyl use for breakthrough pain was also established 48 hours after the procedure. Results revealed that patients using 10, 20, and 25 mg DepoDur used significantly less fentanyl versus DepoDur 5 mg (P = .0446, P = .0221, and P = .0001, respectively). Moreover, the DepoDur 10-, 15-, 20-, and 25-mg groups obtained significantly lower pain intensity scores and greater pain relief.1

Safety

DepoDur is an effective option for those who may have impaired hepatic or renal function. This is attributed to less morphine metabolite accumulation because of single-dose administration.4 DepoDur is contraindicated in patients with known morphine hypersensitivity, respiratory depression, acute or severe bronchial asthma, upper airway obstruction, paralytic ileus, head injury, or increased intracranial pressure. Common adverse events include hypotension, urinary retention, nausea, vomiting, constipation, pruritus, pyrexia, anemia, headache, and dizziness. Respiratory depression is a severe side effect and can occur at high doses.6 DepoDur should not be substituted for other morphine products, since its liposomal formulation allows for extended release for up to 48 hours.4

Outlook

DepoDur is available in 10-mg/mL, 15/1.5-mg/mL, and 20/2-mg/mL preservative- free, single-use, amber vials and must be refrigerated. DepoDur is a Schedule II controlled substance, so addiction and diversion could present problems, but these concerns should not deter proper postoperative pain management.4 DepoDur appears to be an effective option for the treatment of pain in postsurgical patients.

Drs. Faria and Soo are both senior research pharmacists with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Dr. Faria also is a senior human research specialist at Partners HealthCare System. Diem Chi Tran is a sixth-year PharmD candidate from the Massachusetts College of Pharmacy currently on clinical clerkship in the Investigational Drug Service at Brigham and Women's Hospital.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.