Fentora (fentanyl citrate)

WARNING

RISK OF RESPIRATORY DEPRESSION, MEDICATION ERRORS, ABUSE POTENTIAL

RESPIRATORY DEPRESSION

Fatal respiratory depression has occurred in patients treated with Fentora, including following use in opioid non-tolerant patients and improper dosing. The substitution of Fentora for any other fentanyl product may result in fatal overdose.

Due to the risk of respiratory depression, Fentora is contraindicated in the management of acute or postoperative pain including headache/migraine and in opioid non-tolerant patients.

Fentora must be kept out of reach of children.

The concomitant use of Fentora with CYP3A4 inhibitors may result in an increase in fentanyl plasma concentrations, and may cause potentially fatal respiratory depression.

MEDICATION ERRORS

Substantial differences exist in the pharmacokinetic profile of Fentora compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl that could result in fatal overdose.

• When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products to Fentora.
• When dispensing, do not substitute a Fentora prescription for other fentanyl products.

ABUSE POTENTIAL

Fentora contains fentanyl, an opioid agonist and a Schedule II controlled substance, with an abuse liability similar to other opioid analgesics. Fentora can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Fentora in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion.

Because of the risk for misuse, abuse, addiction, and overdose, Fentora is available only through a restricted program required by the Food and Drug Administration, called a Risk Evaluation and Mitigation Strategy (REMS). Under the Transmucosal Immediate Release Fentanyl (TIRF) REMS Access program, outpatients, healthcare professionals who prescribe to outpatients, pharmacies, and distributors must enroll in the program. Further information is available at www.TIRFREMSAccess.com or by calling 1-866-822-1483.

The possible side effects of Fentora are:

• constipation,
• nausea,
• sleepiness,
• vomiting,
• tiredness,
• headache,
• dizziness,
• abdominal pain,
• low red blood cell count, and
• swelling of the arms, hands, legs and feet.

Call your healthcare provider if you have any of these symptoms and they are severe:

• Decreased blood pressure. This can make you feel dizzy or lightheaded if you get up too fast from sitting or lying down.
• Pain, irritation, or sores at the application site (on your gum, on the inside of your cheek, or under your tongue). Tell your healthcare provider if this is a problem for you.

Get emergency medical help if you have:

• trouble breathing,
• shortness of breath,
• fast heartbeat,
• chest pain,
• swelling of your face, tongue, or throat,
• extreme drowsiness,
• light-headedness when changing positions,
• feeling faint,
• agitation,
• high body temperature,
• trouble walking,
• stiff muscles, or
• mental changes such as confusion.

These symptoms can be a sign that you have taken too much Fentora or the dose is too high for you. These symptoms may lead to serious problems or death if not treated right away. If you have any of these symptoms, do not take any more Fentora until you have talked to your healthcare provider.

These are not all the possible side effects of Fentora. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov

Important Dosage And Administration Instructions

• Healthcare professionals who prescribe Fentora for outpatients must enroll in the TIRF REMS and comply with the requirements of the REMS to ensure safe use of Fentora.
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
• It is important to minimize the number of strengths available to patients at any time to prevent confusion and possible overdose.
• Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse.
• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Fentora and adjust the dosage accordingly.
• Instruct patients and caregivers to take steps to store Fentora securely and to properly dispose of unused Fentora as soon as no longer needed.
• Fentora is not bioequivalent with other fentanyl products. Do not convert patients on a mcg per mcg basis from other fentanyl products. There are no conversion directions available for patients on any other fentanyl products other than ACTIQ (Note: This includes oral, transdermal, or parenteral formulations of fentanyl.)
• Fentora is NOT a generic version of any other transmucosal fentanyl product.

Patient Access To Naloxone For The Emergency Treatment Of Opioid Overdose

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with Fentora.

Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program).

Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient.

Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.

Table 4 includes clinically significant drug interactions with Fentora.

Table 4: Clinically Significant Drug Interactions with Fentora

Drug Abuse And Dependence

Controlled Substance

Fentora contains fentanyl, a Schedule II controlled substance.

Abuse

• Fentora contains fentanyl, a substance with high potential for abuse similar to other opioids including hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Fentora can be abused and is subject to misuse, addiction, and criminal diversion.
• All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
• Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.
• Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes physical withdrawal.
• “Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
• Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
• Fentora, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
• Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific To The Abuse Of Fentora

• Fentora is for oral transmucosal use only. Abuse of Fentora poses a risk of overdose and death. This risk is increased with concurrent abuse of Fentora with alcohol and other central nervous system depressants.

Dependence

• Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
• Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug.
• Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene) mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
• Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs.

• Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome.
• Available data with Fentora in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.
• Fentanyl is present in breast milk. One published lactation study reports a relative infant dose of fentanyl of 0.024%. However, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production.
• Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Fentora.