Indicated for the management of breakthrough pain in cancer patients 16 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.

Oral transmucosal fentanyl citrate contains fentanyl, a Schedule II controlled substance.

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 of transdermal fentanyl per hour, 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.

Patients must remain on around-the-clock opioids when taking ACTIQ.

Not for use in opioid non-tolerant patients.

Not for use in the management of acute or postoperative pain, including headache/migraine or dental pain.

The use of ACTIQ in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

As a part of the TIRF REMS Access program, oral transmucosal fentanyl citrate may be dispensed only to outpatients enrolled in the program. For inpatient administration of oral transmucosal fentanyl citrate (e.g., hospitals, hospices, and long-term care facilities that prescribe for inpatient use), patient and prescriber enrollment is not required.

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 ACTIQ, 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 ACTIQ.

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

Accidental ingestion of oral transmucosal fentanyl citrate, especially by children, can result in a fatal overdose of fentanyl. Keep out of reach of children. Ensure proper storage and disposal.

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 ACTIQ.

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 concomitant use of oral transmucosal fentanyl citrate 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 oral transmucosal fentanyl citrate and any CYP3A4 inhibitor or inducer.

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 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.

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

When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products to oral transmucosal fentanyl citrate.

Other TIRF formulations and ACTIQ are not equivalent. DO NOT substitute an ACTIQ prescription for any other TIRF formulation under any circumstances. Do not convert patients on a mcg per mcg basis from any other fentanyl product to ACTIQ.

Prolonged use of oral transmucosal fentanyl citrate 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.

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse.

The initial dose of ACTIQ to treat episodes of breakthrough cancer pain is always 200 mcg.

Patients should be prescribed an initial titration supply of six 200 mcg ACTIQ units, thus limiting the number of units in the home during titration. Patients should use up all units before increasing to a higher dose to prevent confusion and possible overdose.

In cases where the breakthrough pain episode is not relieved after 15 minutes after completion of the ACTIQ unit (30 minutes after the start of the unit), patients may take ONLY ONE additional dose using the same strength for that episode. Thus patients should take a maximum of two doses of ACTIQ for any episode of breakthrough pain.

Patients MUST wait at least 4 hours before treating another episode of breakthrough pain with ACTIQ.

Limit consumption to four or fewer units per day once successful dose is found. 

When opioid therapy is no longer required, consider discontinuing oral transmucosal fentanyl citrate along with a gradual downward of other opioids to minimize possible withdrawal effects.

Oral transmucosal fentanyl citrate is contraindicated:

• Opioid non-tolerant patients
• Significant respiratory depression
• Management of acute or postoperative pain including headache/migraines and dental pain
• Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus

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.

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.

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

Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of oral transmucosal fentanyl citrate 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), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), 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.

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

Oral transmucosal fentanyl citrate may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics).

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), oral transmucosal fentanyl citrate 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 oral transmucosal fentanyl citrate.

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

The fentanyl in oral transmucosal fentanyl citrate 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 oral transmucosal fentanyl citrate 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.

Oral transmucosal fentanyl citrate 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 oral transmucosal fentanyl citrate with caution in patients with bradyarrhythmias.

The concomitant use of oral transmucosal fentanyl citrate 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.

MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma). The use of oral transmucosal fentanyl citrate is not recommended for patients taking MAOIs (e.g., phenelzine, tranylcypromine, linezolid) or within 14 days of stopping such treatment.

Avoid concomitant use with mixed agonist/antagonist and partial agonist opioid analgesics (e.g., butorphanol, nalbuphine, pentazocine, buprenorphrine).

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

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.

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.

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 oral transmucosal fentanyl citrate.

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• Use in patients under 16 years of age. GoToSource

• Noncancer pain including acute or postoperative pain, headache, migraine or dental pain. GoToSource

Urinary retention and death. GoToSource

Abuse and misuse. GoToSource

Neonatal abstinence syndrome (withdrawal syndrome in newborns after exposed opioids during pregnancy). GoToSource

Hyperalgesia (increased sensitivity to pain), tolerance and withdrawal. GoToSource

Sphincter of oddi dysfunction (gastrointestinal disorder). GoToSource

Serotonin syndrome (potentially life-threatening drug reaction), decreased sex hormone levels (reduced interest in sex, impotence, or infertility), adrenal insufficiency (adrenal glands do not make enough of hormone cortisol) and addiction. GoToSource

Nausea, somnolence (sleepiness), dizziness, asthenia (lack of energy and strength), constipation, confusion, abdominal pain, dyspepsia (indigestion), mouth ulceration, dry mouth, vasodilatation, hallucinations, vertigo (sense of spinning dizziness), dyspnea (shortness of breath), pruritus (severe itching), sweating, respiratory depression, circulatory depression, hypotension (low blood pressure) and shock. GoToSource

Lawsuits filed for respiratory failure and death.