FDA Issues Public Health Advisory for Fentora

Yael Waknine

September 26, 2007 — The US Food and Drug Administration has issued a public health advisory today to alert healthcare professionals and consumers regarding reports of life-threatening and sometimes fatal events in patients receiving fentanyl buccal tablets (Fentora, Cephalon, Inc).
These events were associated with improper patient selection (eg, opioid-intolerant patients or patients who did not have cancer), improper dosing (incorrect dose or dose too high), and/or improper product substitution for nonequianalgesic fentanyl-containing products.
Physicians and other healthcare professionals are strongly advised to follow product labeling when prescribing fentanyl buccal tablets to minimize the risk for respiratory depression.
Fentanyl buccal tablets are indicated only for the management of breakthrough pain in opioid-tolerant cancer patients. Patients considered physiologically opioid tolerant are those who have been taking at least 60 mg of oral morphine per day, 25 µg of transdermal fentanyl per hour, 30 mg of oral oxycodone daily, 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid for 1 week or longer.
Opioid-intolerant patients and those with acute pain, postoperative pain, headache/migraine, or sports injuries should not receive this medication.
Patients must be under a physician's care and be closely supervised during treatment. In addition, physicians should make careful dose adjustments for breakthrough pain, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program.
Because the buccal tablet formulation results in higher blood levels of fentanyl, conversion from fentanyl citrate transmucosal lozenges (Actiq, Cephalon) must include a dose reduction. Treatment with 200- or 400-µg lozenges is equivalent to a 100-µg fentanyl buccal tablet, a 600- or 800-µg lozenge is equivalent to a 200-µg buccal tablet, and treatment with a 1200- or 1600-µg lozenge is equivalent to a 400-µg buccal tablet.
For opioid-tolerant patients receiving any other around-the-clock opioids for breakthrough cancer pain, the initial dose for fentanyl buccal tablets is 100 µg. During titration and after dose selection, no more than 2 fentanyl buccal tablets should be taken per episode of breakthrough pain and 4 hours must elapse prior to treating the next episode.
Healthcare professionals and patients/caregivers should be aware of symptoms associated with fentanyl overdose that require immediate medical attention, such as trouble breathing or shallow breathing; tiredness; extreme sleepiness or sedation; inability to think, talk, or walk normally; and feeling faint, dizzy, or confused.

Improper Use of Fentora Linked to Patient Deaths

Yael Waknine
Medscape Medical News 2007. © 2007 Medscape
September 14, 2007 — Serious adverse events, including death, have resulted from improper use of fentanyl buccal tablets (Fentora, Cephalon, Inc), the US Food and Drug Administration warned healthcare professionals yesterday.
The deaths were caused by improper patient selection (eg, opioid-intolerant patients), improper dosing, and/or improper product substitution for other drugs, according to an alert sent from MedWatch, the FDA's safety information and adverse event reporting program.
In a letter to healthcare professionals, the company emphasized the importance of adhering to certain prescribing guidelines to reduce the risk for respiratory depression.
Fentanyl buccal tablets are indicated only for the management of breakthrough pain in opioid-tolerant cancer patients. Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, 25 µg transdermal fentanyl/hour, 30 mg oral oxycodone daily, 8 mg oral hydromorphone daily, or an equianalgesic dose of another opioid for a week or longer.
Opioid-intolerant patients and those with acute pain, postoperative pain, headache/migraine, or sports injuries should not receive this medication.
Because the buccal tablet formulation is distinct and not a generic version of fentanyl citrate transmucosal lozenges (Actiq, Cephalon), it should not be substituted for this or other fentanyl-containing products.
Dosing instructions should be carefully followed: no more than 2 fentanyl buccal tablets should be taken per episode of breakthrough pain, and 4 hours must elapse before treating the next episode.
For patients switching from fentanyl citrate therapy, a conversion table must be followed to select the initial dose: Those currently taking 200- or 400-µg lozenges should receive a 100-µg fentanyl buccal tablet, patients receiving a 600- or 800-µg lozenge should receive a 200-µg buccal tablet, and those taking 1200- or 1600-µg lozenges should receive a 400-µg buccal tablet.

Deaths Linked to Drug for Breakthrough Cancer Pain Prompt Warning

ROCKVILLE, Md., Sept. 13 -- Adverse events including deaths have been linked to Fentora, a drug for breakthrough pain in cancer patients who are opioid tolerant, according to the FDA.
Cephalon, maker of the fentanyl buccal tablets marketed as Fentora, has issued letters warning physicians of the risks and outlining a strict set of recommendations for the drug's use.
According to the FDA the deaths occurred as "a result of improper patient selection (e.g. use in opioid non-tolerant patients), improper dosing, and/or improper product selection."
The drug is indicated only for the management of breakthrough pain in patients with cancer in persistent pain who are already receiving and who are tolerant to opioid therapy.
In the letters, Jeffrey M. Dayno, M.D., vice-president of medical services at Cephalon, issued these warnings:
Do not use Fentora in opioid non-tolerant patients:
Use Fentora only for labeled indications.
Do not prescribe the drug for patients with acute pain, postoperative pain, headache/migraine, or sports injuries.
Be aware that Fentora is not a generic version of Actiq, therefore do not substitute Fentora for Actiq or other fentanyl-containing produces.
Dr. Dayno also advised physicians to carefully follow these dosing directions:
For unrelieved breakthrough pain, patients should not take more than two Fentora tablets per episode.
Patients must wait at lease four hours before treating another breakthrough pain episode with Fentora.