The Food and Drug Administration (FDA) announced today the approval of Palladone (hydromorphone hydrochloride) capsules 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.

Palladone is an extended-release formulation that comes in 12, 16, 24, and 32 milligram (mg.) capsules. This drug should only be used in patients who are already receiving opioid therapy and who require a total daily dose of at least 12 mg. of oral hydromorphone or its equivalent. Palladone offers a therapeutic choice for opioid-tolerant patients who might otherwise be candidates for other opioids and who do not achieve satisfactory therapeutic results with these other products.

The active ingredient in Palladone, hydromorphone, is currently a Scheduled II controlled substance, which is the highest level of control for drugs with a recognized medical use. Based on the risks associated with the drug, including the potential for abuse of Palladone, FDA has worked with the sponsor to develop a comprehensive risk management program (RMP).

The RMP was designed with three potential risk situations identified. These are the risks posed by improper dosing, indication, or patient selection; the risk posed by accidental pediatric exposure to the drug; and the risk posed by abuse or diversion of Palladone Capsules.

As a controlled substance in Schedule II of the Controlled Substances Act (CSA), Palladone also comes under the jurisdiction of the Drug Enforcement Administration (DEA), which administers the CSA. Schedule II drugs are subject to manufacturing quotas set by DEA with input on medical need from FDA, distribution tracking, import and export controls, registration of prescribers and dispensers, and written prescriptions without refills.

In addition to the protection afforded patients through the status of Palladone as a controlled substance, the RMP includes provisions for clear and appropriate labeling, and appropriate education of healthcare professionals, patients, and caregivers. In addition, the sponsor has committed to offer appropriate training to sales representatives. To guard against the inappropriate use of the drug, the RMP also establishes a multifaceted program for monitoring and surveillance of abuse. If abuse, misuse, and diversion occur the program includes an array of interventions.

As part of the RMP, a Medication Guide (FDA-approved patient information which is required to be dispensed with each prescription) has been written for patients prescribed Palladone. FDA requires a Medication Guide only when one or more of the following circumstances exists: (1) the drug is one for which patient labeling could help prevent serious adverse effects; (2) the drug is one that has serious risks of which patients should be made aware because information concerning the risks could affect patients' decision to use, or continue to use the drug; and (3) the drug is important to health and patient adherence to directions for use is crucial to the drug's effectiveness. In addition, the physician labeling for Palladone contains a "black box" warning.

FDA is also part of a larger initiative to reduce diversion and abuse of prescription drugs. On March 1, 2004, the Office of National Drug Control Policy was joined by the Surgeon General, the DEA Administrator, and the FDA Commissioner to announce the National Drug Control Strategy . The strategy emphasized new collaborative efforts at the federal, state, and local levels to prevent and reduce diversion and abuse of prescription drugs. This strategy focused on three core tactics: (1) Business Outreach and Consumer Protection, (2) Investigation and Enforcement, and (3) Protecting Safe and Effective Use of Medications. During the approval process for Palladone, FDA incorporated many of the elements of this strategy as exhibited by inclusion of the "black box" warnings on the labeling, the Medication Guide, and the implementation of a RMP.

In addition to the potential for abuse and addiction, respiratory depression is the chief potential risk associated with Palladone, if not properly dosed. Respiratory depression is manifested by a reduced urge to breathe and a decreased rate of respiration, often referred to as "shallow" breathing, and can result in severe effects or fatalities. The risk of respiratory depression is greater in patients not used to taking opiates, and in elderly or debilitated patients.

Palladone must be swallowed whole because chewing, dissolving, or crushing the contents of the capsules leads to the rapid absorption of a potentially fatal dose.

Other common side effects include nausea, vomiting, dry mouth, dizziness, urinary retention, and constipation.

Palladone is manufactured and distributed by Purdue Pharma L.P., located in Stamford, Conn.