• Management of breakthrough pain in patients with cancer who are already receiving opioids and are tolerant to around-the-clock opioids for persistent cancer pain (60 mg/day of oral morphine or equivalent).

Contraindicated in:

• Known intolerance or hypersensitivity
• Acute/postoperative pain, including headache/migraine, dental pain, or emergency room use
• Opioid-naive (nontolerant) patients
• Concurrent use of MAO inhibitors
• OB: Labor and delivery
• Lactation: Lactation.

Use Cautiously in:

• Chronic obstructive pulmonary disease or pre-existing medical conditions predisposing to hypoventilation
• Concurrent use of CNS active drugs
• History of substance abuse
• Severe renal/hepatic impairment (use lowest effective starting dose)
• Bradyarrhythmias
• OB: Use during pregnancy only if the potential maternal benefit justifies the potential fetal risk
• Pedi: Safety and effectiveness not established in children
• Geri: Older adults may be more sensitive to effects and may have an ↑ risk of adverse reactions; titrate dosage carefully.

Exercise Extreme Caution in:

• Patients susceptible to intracranial effects of CO₂ retention, including those with ↑ intracranial pressure, head injuries, or impaired consciousness.

CV: hypotension.

Endo: adrenal insufficiency.

GI: constipation, nausea, vomiting, abdominal pain, anorexia, dry mouth.

Neuro: dizziness, drowsiness, headache, confusion, depression, fatigue, hallucinations, headache, insomnia, weakness.

Resp: dyspnea, RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA).
Misc: (INCLUDING ANAPHYLAXIS)HYPERSENSITIVITY REACTIONS , physical dependence, psychological dependence.

Drug-Drug:

• Should not be used within 14 days of MAO inhibitors because of possible severe and unpredictable reactions.
• CYP3A4 inhibitors, including ritonavir, ketoconazole, itraconazole, fluconazole, clarithromycin, erythromycin, nefazodone, diltiazem, verapamil, nelfinavir, and fosamprenavir, ↑ levels and risk of opioid toxicity; careful monitoring during initiation, dose changes, or discontinuation of the inhibitor is recommended.
• CYP3A4 inducers, including barbiturates, carbamazepine, efavirenz, corticosteroids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, or rifampin, may ↓ levels and analgesia; if inducers are discontinued or dosage ↓, patients should be monitored for signs of opioid toxicity and necessary dose adjustments should be made.
• Use with benzodiazepines or other CNS depressants including other opioids, non-benzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
• Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5–HT₃ receptor antagonists, linezolid, methylene blue, and triptans ↑ risk of serotonin syndrome.

Drug-Natural Products:

• St. John's wort is an inducer of CYP3A4; concurrent use may ↓ levels and analgesia; if inducers are discontinued or dosage decreased, patients should be monitored for signs of opioid toxicity and necessary dosage adjustments made.

Drug-Food:

• Grapefuit juice is a moderate inhibitor of CYP3A4 enzyme system; concurrent use may ↑ levels and the risk of CNS and respiratory depression. Careful monitoring and dose adjustment may be necessary.

(Generic available)

• Buccal tablets: 100 mcg; 200 mcg; 400 mcg; 600 mcg; 800 mcg;
• Oral transmucosal lozenge on a stick (berry flavor-sugar free): 200 mcg; 400 mcg; 600 mcg; 800 mcg; 1200 mcg; 1600 mcg;

• Buccal (Adults): Tablets: 100 mcg, then titrate to dose that provides adequate analgesia without undue side effects.
• Oral transmucosal (Adults): One 200-mcg unit dissolved in mouth (see Implementation section) over 15 min; additional unit may be used 15 min after first unit is completed. If more than 1 unit is required per episode (as evaluated over several episodes), dose may be ↑ as required to control pain. Optimal usage/titration should result in using no more than 4 units/day.

Fentanyl (Buccal Tablet): Fentora

Fentanyl (Oral Transmucosal Lozenge): Actiq

• Binds to opioid receptors in the CNS, altering the response to and perception of pain.

• Decrease in severity of breakthrough pain.

Therapeutic Classification: opioid analgesics

Pharmacologic Classification: opioid agonists

Absorption: Buccal tablet: 65% absorbed from buccal mucosa; 50% is absorbed transmucosally, remainder is swallowed and is absorbed slowly from the GI tract. Buccal absorption is enhanced by an effervescent reaction in the dose form; Transmucosal lozenge: Initial rapid absorption (25%) from buccal mucosa is followed by more prolonged absorption (25%) from GI tract (combined bioavailability 50%).

Distribution: Readily crosses the placenta and enters breast milk.

Metabolism/Excretion: Mostly metabolized in the liver and intestinal mucosa via the CYP3A4 isoenzyme; inactive metabolites are excreted in urine; <7% excreted unchanged in urine.

Half-life: Buccal tablet: 2.6–11.7 hr (↑ with dose); Transmucosal lozenge: 7 hr.

Schedule II (C-II)

(↓ pain)

• Instruct patient to take fentanyl transmucosal as directed. Instruct patient in correct technique for use and disposal. Do not take more often than prescribed, keep out of reach of children, protect it from being stolen, and do not share with others, even if they have the same symptoms. Open only when ready to administer. Advise patient to review Medication Guide before and with each Rx refill in case of changes. Advise patient to notify health care professional if breakthrough pain is not alleviated, worsens, if >4 units/day are required to control pain, or if excessive opioid effects occur.
• REMS: Explain TIRF REMS program to patient and caregiver. Patients must sign the Patient-Prescriber Agreement Form to confirm they understand the risks, appropriate use, and storage of fentanyl transmucosal.
• Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Inform patients and caregivers about various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (by prescription, directly from a pharmacist, or as part of a community-based program).
• Advise patient to avoid grapefruit juice during therapy.
• Advise patient that transmucosal fentanyl is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children and in a location not accessible by others.
• Caution patient to make position changes slowly to minimize orthostatic hypotension.
• Medication causes dizziness and drowsiness. Advise patient to call for assistance during ambulation and transfer, and to avoid driving or other activities requiring alertness until response to medication is known.
• Instruct patient to avoid concurrent use of alcohol or other CNS depressants, such as sleep aids.
• Advise patient to notify health care professional if sores on gums or inside cheek become a problem.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Instruct females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal symptoms (irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight); usually occur the first days after birth. Monitor infants exposed to fentanyl through breast milk for excess sedation and respiratory depression. Chronic use may reduce fertility in females and males.
• Actiq: Inform patient that this drug may contain sugar and may cause dry mouth. Advise patient to maintain good oral hygiene regular dental exams.

FEN-ta-nil