Indicated for the management of breakthrough pain in cancer patients 18 years of age and older who are already receiving and who are tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain.

FENTORA is not for use in opioid non-tolerant patients and is not for use in the management of acute or postoperative pain, including headache/migraine, or dental pain.

As a part of the TIRF REMS, FENTORA may be dispensed by outpatient pharmacies only to outpatients enrolled in the program. Inpatient administration of FENTORA, patient and prescriber enrollment are not required.

Patients should never take more than two doses of Fentora to treat an episode of breakthrough pain and must wait a minimum of four hours after the second dose before treating another episode of breakthrough pain.

If the patient experiences greater than four breakthrough pain episodes per day, the dose of the around the-clock opioid used for persistent pain should be reevaluated.

The initial dose of fentanyl buccal tablets is always 100 mcg with the only exception being patients already using ACTIQ.

Patients considered opioid tolerant are those who are taking, for one week or longer, around-the-clock medicine consisting of at least 60 mg of oral morphine per day, at least 25 mcg per hour of transdermal fentanyl, at least 30 mg of oral oxycodone per day, at least 8 mg of oral hydromorphone per day, at least 25 mg oral oxymorphone per day, at least 60 mg of oral hydrocodone per day, or an equianalgesic dose of another opioid daily for a week or longer. Patients must remain on around-the-clock opioids while taking FENTORA.

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.

FENTORA is not a generic version of other transmucosal immediate release fentanyl (TIRF) formulations. When dispensing, do not substitute a FENTORA prescription for any other TIRF formulation under any circumstances. Other TIRF formulations and FENTORA are not equivalent.

Substantial differences exist in the pharmacokinetic profile of FENTORA compared to other fentanyl products including other TIRF formulations that result in clinically important differences in the rate and extent of absorption of fentanyl. As a result of these differences, the substitution of FENTORA or any other fentanyl product may result in a fatal overdose.

FENTORA 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 FENTORA, and monitor all patients regularly for the development of these behaviors or conditions.

Because of the risk for misuse, abuse, addiction, and overdose, FENTORA is available only through a restricted program called the TIRF REMS Access program. Under the TIRF REMS Access program, outpatients, healthcare professionals who prescribe for outpatient use, pharmacies, and distributors must enroll in the program. For inpatient administration (e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use) of FENTORA, patient and prescriber enrollment is not required.

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.

Accidental ingestion of even one dose of FENTORA, especially by children, can result in a fatal overdose of fentanyl.

For patients no longer requiring opioid therapy, consider discontinuing FENTORA along with a gradual downward tapering (titration) of other opioids to minimize possible withdrawal effects. In patients who continue to take their chronic opioid therapy for persistent pain but no longer require treatment for breakthrough pain, FENTORA therapy can usually be discontinued immediately.

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of FENTORA, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of FENTORA.

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.

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.

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. 

Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

FENTORA may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients.

In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), FENTORA may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with FENTORA.

Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of FENTORA in patients with impaired consciousness or coma.

The fentanyl in FENTORA may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

The fentanyl in FENTORA may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures.

FENTORA may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Intravenous fentanyl may produce bradycardia. Therefore, use FENTORA with caution in patients with bradyarrhythmias.

FENTORA is contraindicated for:

• Opioid non-tolerant patients: Life-threatening respiratory depression and death could occur at any dose in opioid non-tolerant patients
• Significant respiratory depression
• Acute or postoperative pain including headache/migraine and dental pain, or acute pain in the emergency department
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Known hypersensitivity (e.g. anaphylaxis) to fentanyl or components of FENTORA (e.g., anaphylaxis)

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of FENTORA and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.

Fentanyl may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

The concomitant use of FENTORA with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in fentanyl plasma concentration. Monitor patients receiving FENTORA and any CYP3A4 inhibitor or inducer.

The concomitant use of FENTORA and CYP3A4 inhibitors (e.g, macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), grapefruit juice) can increase the plasma concentration of fentanyl, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of FENTORA is achieved.

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the fentanyl plasma concentration will decrease resulting in decreased opioid efficacy or a withdrawal syndrome in patients  who had developed physical dependence to fentanyl.

The concomitant use of FENTORA and CYP3A4 inducers (e.g, rifampin, carbamazepine, phenytoin) can decrease the plasma concentration of fentanyl resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to fentanyl.

After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

FENTORA is not recommended for use in patients who have received MAO inhibitors within 14 days, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of FENTORA with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including MAO inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). This may occur within the recommended dosage range.

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.

The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

Prolonged use of FENTORA during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Fentanyl is present in breast milk. 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.

GoToSource

• Use in patients who only need an opioid on an intermittent, as needed basis. GoToSource

• Management of acute or postoperative pain, headaches, migraines, non-cancer-related pain and sports injuries. GoToSource

• Use in patients under the age of 18. GoToSource

Serotonin syndrome (life-threatening drug reaction). GoToSource

Decreased sex hormone levels (low libido, impotence, erectile dysfunction, lack of menstruation or infertility). GoToSource

Seizures. GoToSource

Abuse and diversion. GoToSource

Respiratory depression. GoToSource

Bradycardia (slow heart rate). GoToSource

Peripheral vasodilation (widening of blood vessels), hypotension (low blood pressure) and slowing of intestine motility. GoToSource

Sedation, confusion, euphoria, physical and psychological dependence and death. GoToSource

Constipation. GoToSource

Lawsuits filed for death.