Warning letters raise patient safety concerns for Fentora

October 22, 2007

In response to a number of deaths and serious adverse events reported by patients taking Fentora, warning letters were sent to health care professionals. According to Cephalon, Inc., the deaths primarily occurred as a result of improper patient selection, improper dosing, and/or improper product substitution.

In response to a number of deaths and serious adverse events reported by patients taking fentanyl buccal tablets (Fentora, Cephalon), warning letters were sent on Sept. 10 to physicians and healthcare professionals by the manufacturer. According to the company, the deaths occurred primarily as a result of improper patient selection, improper dosing, and/or improper product substitution.

Fentora, which is a Schedule II controlled buccal formulation of fentanyl, is indicated only for the management of breakthrough pain in patients with cancer who are already receiving and are tolerant to opioid therapy for their underlying persistent cancer pain. Cephalon previously introduced Actiq, which is better known as the "fentanyl lollipop," as the first medication approved for the treatment of breakthrough pain in opioid-tolerant cancer patients. However, both Fentora and Actiq have often been prescribed for "off-label" uses in patients who don't have cancer.

Although Cephalon denies marketing the drugs outside of their indication, its sales and marketing practices are currently under investigation by the Connecticut Attorney General's office as well as by the House Committee on Oversight & Government Reform. Cephalon has been under scrutiny since 2004, when it received subpoenas from the U.S. Attorney's office in Philadelphia related to marketing tactics for Actiq.

The Food & Drug Administration issued a Public Health Advisory on Sept. 26 to alert patients, caregivers, and healthcare professionals to the potential for serious adverse events with improper use of Fentora. The agency has also asked Cephalon to update the Fentora label and Medication Guide for patients. In the letter recently sent to healthcare professionals by Cephalon, the firm urged prescribers to use Fentora only for labeled indications, and it stressed that it is not an appropriate agent for patients with acute pain, postoperative pain, headache/migraine, or sports injuries, nor is it appropriate for use in opioid-nontolerant patients.

The letter defined opioid-tolerant patients as those taking at least 60 mg of oral morphine, 30 mg of oral oxycodone, or 8 mg of oral hydromorphone daily; patients taking at least 25 mcg of transdermal fentanyl per hour; or patients taking an equianalgesic dose of another opioid for at least one week. Dosing instructions were included in the letter, which specified that patients should not take more than two Fentora tablets per episode of unrelieved breakthrough pain, with a period of at least four hours between treatments.

Cephalon noted that Fentora is not a generic equivalent to Actiq and that it should not be substituted for Actiq or for any fentanyl-containing product on a microgram-per-microgram basis.

Pharmacists' role

It is hoped that the letter from Cephalon will prevent further misuse of Fentora and remind prescribers of the serious hazards associated with such potent opioids. "Unfortunately, until FDA warnings are circulated, prescribers often take the degree of risk associated with medications too lightly," said Michael Serra, Pharm.D., BCPS, clinical pharmacy coordinator at Morristown (N.J.) Memorial Hospital. "The unfortunate deaths associated with Fentora should serve as testimony that prescribers must completely understand a medication's mechanism of action and its safety profile before prescribing it to their patients."

Serra believes R.Ph.s can play a key role in educating patients. "Pharmacists must appreciate the fact that we can prevent severe patient harm, including death, by spending the time to properly counsel patients," he said.

Cephalon continues to work with the FDA to encourage appropriate patient selection, dosing, and administration through its Fentora Risk Minimization Action Plan (RiskMAP).

THE AUTHOR is a writer and hospital pharmacist based in New Jersey.