/publications/issue/2004/2004-11/2004-11-4710

RxPRODUCT NEWS PROFILE: Palladone (hydromorphone extended-release capsules)

Author: Claudio Faria, PharmD, RPh, and Carolyn Soo, PharmD, RPh

Palladone, manufactured by Purdue Pharma LP, has been approved in the United States for the management of persistent moderate-to-severe pain in patients requiring continuous around-the-clock opioid pain relief for an extended period of time. The drug is appropriate for patients requiring high doses of potent opioid analgesics for pain relief, such as patients with arthritis.1 According to an FDA Talk Paper, "Palladone offers a therapeutic choice for opioid-tolerant patients who otherwise might be candidates for other opioids and who do not achieve satisfactory therapeutic results with other products."2

Pharmacology

Hydromorphone, the active ingredient in Palladone, is a semisynthetic congener of morphine. It is a pure opioid agonist with a primary therapeutic action of analgesia. It binds to opiate receptors in the central nervous system (CNS), causing the inhibition of ascending pain pathways. The result is a diminished awareness of and reaction to pain.3

Clinical Trials

In a double-blind, randomized, placebo-controlled trial, Palladone was studied in patients experiencing pain for at least a month due to musculoskeletal disorders. The patients included were maintained on one or more opioid analgesics, most likely in addition to nonopioid analgesics. After it was determined that patients needed approximately 12 mg of immediate-release hydromorphone around the clock to improve analgesia, 210 patients with chronic moderate-to-severe pain were randomized to receive either Palladone 12 mg once daily or placebo.

The results showed better analgesic control for a longer period of time in the Palladone group, compared with the placebo group (P >.0001). These results demonstrated that, in this studied patient population, Palladone capsules were superior in managing pain control, when compared with placebo.1

Safety

FDA officials recommend the use of Palladone only in patients who already are taking opioid analgesics and require at least 12 mg of oral hydromorphone or equivalent medication.1,2 Purdue Pharma LP issued a boxed warning for the product, stating that Palladone is recommended in patients requiring all-day therapy who have difficulty controlling pain with immediate-release opioid formulations.1

Common adverse reactions to Palladone include headache, asthenia, constipation, nausea, and vomiting. Serious adverse events with Palladone are similar to those produced by other products containing hydromorphone and other opioid analgesics. Examples of such events include respiratory depression, apnea, and respiratory arrest. Therefore, this product should be used only in those who are opioid-tolerant. Less common serious events include circulatory depression, hypotension, and shock or cardiac arrest.1,2

Palladone is not recommended for patients who require opioid analgesia for a short period of time. It also should not be used on an as-needed basis. Patients concurrently taking other opioid analgesics, phenothiazines, tricyclic antidepressants, or other CNS depressants may experience additional CNS effects. Palladone doses in these cases should be adjusted accordingly and side effects more intensely monitored. The use of histamine2 receptor blockers or proton pump inhibitors does not affect Palladone steady-state pharmacokinetics.1

Outlook

Palladone is a Schedule II controlled substance. It is available as 12-, 16-, 24-, and 32-mg extended-release capsules.1 Although Palladone should not be prescribed as the first agent used to control pain, it offers an additional option for patients not achieving appropriate therapeutic results with other opioids.1,2

Drs. Faria and Soo are both senior research pharmacists for 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.

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@mwc.com.