Serious Adverse Events, Deaths; Abuse and Risk of Overdose; Do Not Substitute; Risk Evaluation and Mitigation Strategy (REMS)

Serious Adverse Events

• Reports of serious adverse events, including deaths in patients treated with Fentanyl buccal tablets have been reported.
• Deaths occurred as a result of improper patient selection (e.g., use in opioid non-tolerant patients) and/or improper dosing.
• The substitution of Fentanyl buccal tablet formulation for any other fentanyl product may result in fatal overdose.

Schedule II Controlled Substance: Abuse Potential and Risk of Overdose

• Fentanyl buccal tablets contain an opioid agonist and a Schedule II controlled substance with an abuse liability potential similar to other opioid analgesics.
• Fentanyl buccal tablets can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing fentanyl buccal tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
• Schedule II opioid substances which include morphine, oxycodone, hydromorphone, oxymorphone, and methadone have the highest potential for abuse and risk of fatal overdose due to respiratory depression.

Indications, Dosing

• Fentanyl buccal tablets is indicated only for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to around the clock opioid therapy for their underlying persistent cancer pain.
• Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine/day, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.
• Special care must be used when dosing this drug in buccal form. If the breakthrough pain eposide is not relieved after 30 minutes, patients may take ONLY one additional dose using the same strength and must wait at least 4 hours before taking another dose. (See DOSAGE AND ADMINISTRATION)

Contraindications

• Because life-threatening respiratory depression could occur at any dose in opioid non-tolerant patients, fentanyl buccal tablets are contraindicated in the management of acute or postoperative pain, including headache/migraine. Deaths have occurred in opioid non-tolerant patients.
• This product is not for use in opioid non-tolerant patients including those with only as needed (prn) prior exposure.

Patient Counseling: Risk of Fatal Pediatric Poisoning

• Patients and their caregivers must be instructed that fentanyl buccal tablets contains a medicine in an amount which can be fatal to a child. Patients and their caregivers must be instructed to keep all tablets out of the reach of children (See Information for Patients and Caregivers for disposal instructions).

Converting Patients Between Fentanyl Products

• When prescribing, do not convert patients on a mcg per mcg basis from Actiq (transmucosal) to fentanyl buccal tablet.
• Carefully consult the Initial Dosing Recommendations table.(See DOSAGE AND ADMINISTRATION)

Do Not Substitute

• When dispensing, do not substitute a fentanyl buccal tablet prescription for other products.
• Substantial differences exist in the pharmacokinetic profile of buccal tablet formulation compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl. As a result of these differences, the substitution of Fentanyl products may results in fatal overdose.

Skilled Healthcare Professionals

• Fentanyl buccal tablets are intended for use only in the care of opioid tolerant cancer patients and only by healthcare professional who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain.

Cytochrome P450 3A4 Inhibitors: Risk of Concurrent Use

• The concomitant use of this drug with strong and moderate cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially datal respiratory depression.

Addiction, Abuse, and Misuse

• Benzodiazepines or other CNS Depressants exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing these medications, and monitor all patients regularly for the development of these behaviors and conditions.
• Patients at increased risk may be prescribed opioids, but use in such patients necessitates intensive counseling about the risks and proper use along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose.

Lactation (Fentanyl Citrate Preservative Free Injection)

• Fentanyl is present in breast milk. One published lactation study reports a relative infant dose of fentanyl of 0.38%. However, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production. 

Life-Threatening Respiratory Depression

• Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to:

• complete a REMS-compliant education program,
• counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
• emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
• consider other tools to improve patient, household, and community safety.