Hydromorphone

The approval of an extended-release formulation of the potent opioid agonist hydromorphone was accompanied by a risk management plan aimed at reducing abuse and minimizing diversion of the drug, a notorious problem with the controlled-release opioid agonist oxycodone.

The Food and Drug Administration approved extended-release hydromorphone for "the management of persistent moderate to severe pain in patients requiring continuous around-the-clock analgesia with a high potency opioid for an extended period of time," generally lasting "weeks to months or longer."

The new agent, marketed as Palladone, is expected to become available sometime during the first half of 2005; but for the first 18 months on the market, it will only be marketed to a limited number of health professionals experienced in prescribing opioid analgesics, according to Purdue Pharma, the Stamford, Conn.-based company that also manufactures oxycodone under the trade name OxyContin.

Purdue worked with the FDA to develop a Risk Management Program (RMP) that is intended to facilitate proper patient selection, reduce abuse, minimize diversion, and avoid pediatric exposure and other improper uses of the opioid, according to a Purdue Pharma statement that announced the approval.

Elements of the plan include extensively educating prescribers, caregivers, and patients.

In addition, a program will be established to monitor utilization, with interventions in place if abuse, misuse, and diversion of the drug are identified.

A medication guide containing FDA-approved information for patients will also be required to be dispensed with each prescription. Guides generally are required by the FDA when, for example, patient labeling could help prevent serious adverse effects.

Extended-release hydromorphone, a schedule II controlled substance, is administered once every 24 hours and is intended only for patients who have taken opioids and show tolerance for them and who require a minimum total daily opiate dose equal to 12 mg of oral hydromorphone, according to the black box warning in the drug's label.

The black box also includes precautions about its high potential for abuse and the risk of fatal respiratory depression in non-opioid tolerant patients.

The drug formulation is in capsules, which contain controlled-release pellets, should be swallowed whole, and should not be chewed, broken, dissolved, or crushed, which can increase absorption and possibly cause a fatal overdose, according to warnings in the label.

"The real advantage of this [approval] will be the convenience of taking this medication once a day," said B. Eliot Cole, M.D., a consultant to the pain management service of Kaiser Permanente, Honolulu, and executive director of the American Society of Pain Educators, Montclair, N.J.

A dilemma with standard hydromorphone is that it is dosed every 4 hours, so a patient who needs around-the-clock pain relief would need 5-6 doses a day, while extended-release hydromorphone could be taken once a day to "maintain the same degree of comfort," he said in a telephone interview.

The availability of extended-release hydromorphone will be helpful as an alternative to oral, controlled-release morphine, which is administered once every 24 hours. "For some individuals, morphine becomes a very toxic medicine," especially in those with poor kidney function and in women, he added.

Large amounts of oral morphine can also lead to a confusional state, delirium, and even increase the pain, he noted.

Hydromorphone is more potent than morphine, so a smaller dose is required to achieve the same degree of pain relief, according to Dr. Cole, who has not conducted any clinical trials for Purdue Pharma, but is on the company's paid speakers' bureau.

BY ELIZABETH MECHCATIE

Senior Writer

COPYRIGHT 2004 International Medical News Group
COPYRIGHT 2004 Gale Group