Fentanyl Transmucosal

Fentanyl Transmucosal is a prescription medication used to relieve breakthrough cancer pain

• Fentanyl Transmucosal is available under the following different brand names: Actiq, Fentora, Abstral, Onsolis, Subsys

Common side effects of Fentanyl Transmucosal include:

• Slowed breathing,
• Slow heart rate,
• Muscle stiffness,
• Dizziness,
• Vision problems,
• Nausea,
• Vomiting,
• Itching,
• Sweating,
• Confusion,
• Anxiety, and
• Pounding in the neck or ears

Serious side effects of Fentanyl Transmucosal include:

• Hives,
• Difficulty breathing,
• Swelling of the face, lips, tongue, or throat,
• Slow breathing or breathing that stops,
• Weak or shallow breathing,
• Fast or slow heart rate,
• Stiff muscles,
• Severe weakness,
• Lightheadedness,
• Fainting,
• Agitation,
• Hallucinations,
• Fever,
• Sweating,
• Shivering,
• Fast heart rate,
• Muscle stiffness,
• Twitching,
• Loss of coordination,
• Nausea,
• Vomiting, and
• Diarrheal

Rare side effects of Fentanyl Transmucosal include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Troche/lozenge (Actiq): Schedule II

• 200 mcg
• 400 mcg
• 600 mcg
• 800 mcg
• 1200 mcg
• 1600 mcg

Tablet, sublingual (Abstral): Schedule II

• 100 mcg
• 200 mcg
• 300 mcg
• 400 mcg
• 600 mcg
• 800 mcg

Buccal tablet (Fentora): Schedule II

• 100 mcg
• 200 mcg
• 400 mcg
• 600 mcg
• 800 mcg

Soluble film (Onsolis): Schedule II

• 200 mcg
• 400 mcg
• 600 mcg
• 800 mcg
• 1200 mcg

Sublingual spray (Subsys): Schedule II

• 100 mcg/spray
• 200 mcg/spray
• 400 mcg/spray
• 600 mcg/spray
• 800 mcg/spray

Breakthrough Cancer Pain

Adult dosage

• Abstral
  • Initial dose: 100 mcg SL
  • Individually titrate to a tolerable dose that provides adequate analgesia for breakthrough pain
  • Not to exceed 2 doses/breakthrough pain episode
  • Wait at least 2 hours before treating another episode of breakthrough pain
  • Limit consumption to 4 or fewer breakthrough pain episodes/24 hours
  • Administer on the floor of the mouth directly under the tongue and allow to completely dissolve
• Actiq
  • 200 mcg dissolve in the mouth over 15 min period, as needed; wait 15 min before taking the next dose
  • Titrate up to 1600 mcg: limit consumption to below 4 units/day
  • Gradual downward titration for discontinuation
• Fentora
  • Initial 100 mcg, may reduce once after 30 min (place tab between upper cheek and gum till dissolves, any remnant after 30 min may be drunk with water); must wait at least 4 hours before treating another episode of breakthrough pain
• Onsolis
  • Initial dose: 200-mcg film placed buccally with breakthrough pain episode
  • If pain relief is not achieved, titrate using multiples of the 200-mcg film (.e, increase the dose by 200 mcg in each subsequent episode until adequate pain relief); not to exceed 4 of the 200-mcg films per breakthrough pain episode; do not place films on top of one another, but may place on both sides of the mouth
  • Once pain relief is achieved: Treat subsequent breakthrough pain using the determined dose within the range of 200-800 mcg
  • If pain relief is not achieved with 800 mcg
  • Treat the next episode using 1 film containing 1200 mcg; not to exceed 1200 mcg per pain episode
  • Separate each dose by at least 2 h, use only once per breakthrough pain episode (do not reduce), and limit to 4 or fewer doses daily; if experiencing above 4 breakthrough pain episodes per day, consider increasing the dose of around-the-clock opioid medication for persistent pain
  • Rescue pain medication may be used as directed after 30 min following Onsolis if adequate pain relief is not achieved
• Subsys
  • Initial dose is always 100 mcg SL
  • Individually titrate after the initial dose to provide adequate analgesia and minimize side effects
  • When prescribing, do not switch patients on an mcg per mcg basis from any other oral Transmucosal fentanyl product (not equivalent on mcg per mcg with other fentanyl products)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Fentanyl Transmucosal has severe interactions with the following drugs
  • alvimopan
  • isocarboxazid
  • phenelzine
  • rasagiline
  • safinamide
  • selegiline
  • selegiline transdermal
  • tranylcypromine
• Fentanyl Transmucosal has serious interactions with at least 141 other drugs.
• Fentanyl Transmucosal has moderate interactions with at least 92 other drugs.
• Fentanyl Transmucosal has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to drug or components of the formulation
• 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 the absence of resuscitative equipment
• Opioid non-tolerant patients
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Within 2 weeks of MAO inhibitors
• Significant respiratory depression

Effects of drug abuse

• Addiction

Short-Term Effects

• See “What Are Side Effects Associated with Using Fentanyl Transmucosal?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Fentanyl Transmucosal?”

Cautions

• Acute pancreatitis, Addison's disease, BPH, cardiac arrhythmias, CNS depression, drug abuse/dependence, emotional lability, gallbladder disease, GI disorder, pseudomembranous colitis, GI surgery, head injury, hypothyroidism/untreated myxedema, intracranial HTN, brain tumor, toxic psychosis, urethral stricture, urinary tract surgery, seizures, acute alcoholism, delirium tremens, shock, cor pulmonale, chronic pulmonary disease, emphysema, hypercapnia, kyphoscoliosis, severe obesity, renal/hepatic impairment, elderly/debilitated 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 opioid dosage using best practices for opioid taper
• Fentora is not a generic version of other transmucosal immediate-release fentanyl (TIRF) formulations; there are no safe conversion directions available for patients on any other fentanyl products except ACTIQ (Note: This includes oral, transdermal, or parenteral formulations of fentanyl); therefore, for opioid-tolerant patients, the initial dose of FENTORA should always be 100 mcg. Individually titrate each patient’s dose to provide adequate analgesia while minimizing side effects
• To dispose of, flush the drug matrix down the toilet
• Addiction can occur at recommended dosages and if the drug is misused or abused
• Assess each patient’s risk for opioid addiction, abuse, or misuse before prescribing opioids and monitor; risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (.g., major depression); potential for these risks should not prevent the proper management of pain in any given patient; patients at increased risk may be prescribed opioids, but use in such patients necessitates intensive counseling about risks and proper use of opioid sulfate along with intensive monitoring for signs of addiction, abuse, and misuse; prescribe the drug in smallest appropriate quantity and advise patient on proper disposal of unused drug
• Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occurs within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected
• Therapy 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); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock
• In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitoring such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure the clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma
• Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; 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
• Therapy may increase the frequency of seizures in patients with seizure disorders and other clinical settings associated with seizures; monitor patients for worsened seizure control during therapy
• Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms; when discontinuing therapy in a physically dependent patient, gradually taper dosage; do not abruptly discontinue therapy in these patients
• Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of the drug and know how they will react to the medication
• While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, the risk is greatest during initiation of therapy or following dosage increase; monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases; accidental ingestion of even one dose, especially by children, can result in respiratory depression and death due to overdose of opioid
• Concomitant use with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of fentanyl and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of fentanyl injection is achieved; similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in fentanyl-injection treated patients may increase fentanyl plasma concentrations and prolong opioid adverse reactions; when using fentanyl Injection with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in fentanyl-Injection treated patients, monitor patients closely at frequent intervals and consider dosage reduction of fentanyl injection until stable drug effects are achieved
• Concomitant use of fentanyl injection with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease fentanyl plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed a physical dependence on fentanyl; when using fentanyl injection with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur
• Deaths have occurred in nursing infants exposed to high levels of opioids in breast milk because mothers were ultra-rapid metabolizers of opioid
• Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if concomitant use with a benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
• Use in patients with acute or severe bronchial asthma in an unmonitored setting or absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of the decreased respiratory drive including apnea, even at recommended dosages
• 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; monitor closely
• Monoamine oxidase inhibitors (MAOIs) may potentiate the effects of opioids, opioid active metabolite, including respiratory depression, coma, and confusion; therapy should not be administered within 14 days of initiating or stopping MAOIs
• Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency
• Use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and concomitant disease or other drug therapy; because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function
• Opioid pharmacokinetics may be altered in patients with renal failure; clearance may be decreased, and metabolites may accumulate much higher plasma levels in patients with renal failure as compared to patients with normal renal function; start with a lower than normal dosage or with longer dosing intervals and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension
• Actiq: prescribe 6 units of each new dose during the titration period
• Use caution in patients with mucositis (above Grade I)
• Do not break the tab in your mouth or swallow
• After Onsolis buccal placement, do not drink for at least 5 min, and do not eat until the film dissolves (15-30 min)
• 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 Risk Evaluation and Mitigation Strategy (REMS) for these products
• Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
• Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
• Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
• To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint
• Patient access to naloxone for emergency treatment of opioid overdose
• Discuss the availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing a treatment with opioids
• Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
• Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help 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 (.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 an 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

Pregnancy and Lactation

• Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly; opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; opioid sulfate is not recommended for use in pregnant women during or immediately before labor when other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions which temporarily reduce strength, duration, and frequency of uterine contractions
• Fertility
  • Because of androgen deficiency, chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether the effects on fertility are reversible
• Lactation
  • Opioid is secreted into human milk; in women with normal opioid metabolism (normal CYP2D6 activity), the amount of opioid secreted into human milk is low and dose-dependent; some women are ultra-rapid metabolizers of opioid; these women achieve higher-than-expected serum levels of opioid's active metabolite, opioid, leading to higher-than-expected levels of opioid in breast milk and potentially dangerously high serum opioid levels in their breastfed infants that can potentially lead to serious adverse reactions, including death, in nursing infants
  • Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from therapy or underlying maternal condition