Duragesic

Action

Binds to specific opioid receptors in CNS, inhibiting pain pathways, altering pain perception, and increasing pain threshold

Availability

Buccal soluble film: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1,200 mcg

Buccal tablets: 100 mcg, 200 mcg, 400 mcg, 600 mcg, 800 mcg

Injection: 0.05 mg/ml

Nasal spray: 100 mcg, 400 mcg in 5-ml bottle

Sublingual spray: 100 mcg, 200 mcg, 400 mcg, 600 mcg, 800 mcg

Tablets (buccal): 100 mcg, 200 mcg, 300 mcg, 400 mcg, 600 mcg, 800 mcg

Tablets (sublingual): 100 mcg, 200 mcg, 300 mcg, 400 mcg, 600 mcg, 800 mcg

Transdermal system: 12 mcg/hour, 25 mcg/hour, 50 mcg/hour, 75 mcg/hour, 100 mcg/hour

Transmucosal lozenges: 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1,200 mcg, 1,600 mcg

Indications and dosages

➣ Breakthrough pain in opioid-tolerant patients with cancer

Adults: One 200-mcg lozenge (Actiq) dissolved in mouth over 15 minutes; additional unit may be given 15 minutes later. If patient needs more than 1 unit per episode (evaluated over several episodes), dosage may be increased; for optimal use or titration, don't exceed 4 units daily. For patient not being converted from Actiq, give 100 mcg (Fentora). For patient being converted from Actiq, follow dosing recommendations below for Fentora.

If breakthrough pain doesn't ease after 30 minutes, give another dose once, using same strength previously given. Administer maximum of two doses for any breakthrough episode. Wait at least 4 hours before giving Fentora for another breakthrough episode.

For patients receiving sublingual tablets (Abstral), initially 100 mcg. Individually titrate to a tolerable dose that provides adequate analgesia. Give no more than two doses per breakthrough pain episode. Wait at least 2 hours before treating another episode of breakthrough pain with Abstral. Limit consumption to treat four or fewer breakthrough pain episodes per day once a successful dose is found.

For patients receiving buccal soluble film (Onsolis), 200 mcg as initial starting dose; titrate using 200-mcg increments (up to a maximum of four 200-mcg films or a single 1,200-mcg film) to provide adequate analgesia without undue adverse effects. Maximum is one dose per episode, no more than four doses per day; separate by at least 2 hours.

For patients receiving sublingual spray (Subsys), initially 100 mcg. Individually titrate to a tolerable dose that provides adequate analgesia using a single dose per breakthrough pain episode. For each breakthrough pain episode treated, if pain isn't relieved after 30 minutes, patients may take only one additional dose of the same strength for that episode; patients should take a maximum of two doses of Subsys for any breakthrough pain episode. Patients must wait at least 4 hours before treating another episode of breakthrough pain. If necessary, increase dose to next highest strength (200 mcg). Subsequent titration steps are 400 mcg, 600 mcg, 800 mcg, 1,200 mcg, and 1,600 mcg. For maintenance, once dosage has been titrated to a level that provides adequate pain relief and tolerable adverse effects, patients should generally use only one dose of the appropriate strength per breakthrough pain episode.

For patients receiving nasal spray, initially 100 mcg (a single spray into one nostril or a single spray into each nostril). Individually titrate to an effective dose, from 100 mcg to 200 mcg to 400 mcg, up to a maximum of 800 mcg, that provides adequate analgesia with tolerable adverse effects. Maximum dose is a single spray into one nostril or single spray into each nostril per episode; no more than four doses per 24 hours. Wait at least 2 hours before treating another episode of breakthrough pain with Lazanda. During any episode, if adequate pain relief isn't achieved within 30 minutes, patients may use a rescue drug as directed by prescriber.

Patients must require and use around-the-clock opioids when taking Abstral, Actiq, Fentora, Lazanda, Onsolis, or Subsys.

➣ Management of chronic pain in patients requiring opioid analgesics

Adults: Initially, 25 mcg/hour (transdermal system); no more than 25 mcg/hour in patients who haven't been receiving opioids. To calculate dosage for patients already receiving opioids, assess 24-hour requirement for current opioid. Using equianalgesic table in prescribing information, convert to equivalent amount of morphine per 24 hours; then convert morphine dosage to appropriate dosage of transdermal fentanyl. During initial application, keep short-acting opioids on hand to treat breakthrough pain; morphine 10 mg I.M. or 60 mg P.O. q 4 hours (60 mg/24 hours I.M. or 360 mg/24 hours P.O.) is roughly equivalent to transdermal fentanyl 100 mcg/hour. For most patients, transdermal patch lasts 72 hours, but some require new patch q 48 hours.

➣ Short-term analgesia during anesthesia and immediate preoperative and postoperative periods

Adults: Individualized; 0.05 to 0.1 mg (Sublimaze) I.M. 30 to 60 minutes before surgery and as adjunct to general anesthesia; total dosage is 0.002 mg/kg. Maintenance dosage during surgery is 0.025 to 0.1 mg I.V. or I.M. Postoperatively, 0.05 to 0.1 mg I.M. to control pain, tachypnea, or emergence delirium; repeat in 1 to 2 hours if needed.

Children ages 2 to 12: Individualized; 2 to 3 mcg/kg (Sublimaze) I.V. depending on vital signs, or 5 to 15 mcg/kg (Fentanyl Oralet) transmucosally

➣ General anesthesia (with oxygen only)

Adults: Individualized; 0.05 to 0.1 mg/kg (Sublimaze) I.V. for high-dose therapy. Up to 0.12 mg/kg may be necessary.

➣ Adjunct to regional anesthesia

Adults: Individualized; 0.05 to 0.1 mg (Sublimaze) I.M. or slow I.V. over 1 to 2 minutes

Dosage adjustment

• Elderly patients

Contraindications

• Hypersensitivity to drug or transdermal adhesive (with fentanyl transdermal)

• Opioid-nontolerant patient

• Intermittent pain (on as-needed basis)

• Management of acute or mild pain

• Management of postoperative pain (except for injection form)

• Acute or severe bronchial asthma (Duragesic), significant respiratory depression, especially in unmonitored settings without resuscitation equipment

• Known or suspected paralytic ileus

Precautions

Use cautiously in:

• diabetes mellitus, severe or chronic pulmonary or hepatic disease, cardiovascular disease, CNS tumors, adrenal insufficiency, hypothyroidism, renal impairment, head injury or increased intracranial pressure (use with extreme caution)

• concurrent use of CNS depressants

• alcoholism or drug abuse

• MAO inhibitor use within 14 days (not recommended)

• elderly patients

• pregnant patients

• labor and delivery

• breastfeeding patients (not recommended)

• children younger than age 2 (Duragesic, Sublimaze), younger than age 16 (Actiq), or younger than age 18 (Abstral, Fentora, Lazanda, Onsolis, Subsys) (safety not established).

Administration

• Before applying transdermal patch, clip hair at site; don't use razor. Wash area with clean water only; dry well.

• Apply transdermal patch to nonirritated, nonirradiated flat surface. Press firmly in place for 30 seconds.

• In elderly patients, don't initiate fentanyl patch at dosages above 25 mcg/hour unless patient is already receiving more than 135 mg/day of oral morphine or equivalent.

• Don't open buccal tablet blister pack until ready to administer; don't push tablet through blister backing.

• Open buccal soluble film and spray packages immediately before use.

• Be aware that in some patients, dosages of both Fentora and maintenance (around-the-clock) opioid analgesic may need to be adjusted to provide ongoing relief of breakthrough pain. Generally, Fentora dosage should be increased if patient needs more than one dose per breakthrough pain episode for several consecutive episodes.

• Inject I.V. dose slowly over 3 to 5 minutes.

See Keep opioid antagonist (naloxone) and emergency equipment available when giving drug I.V.

• Administer sublingual tablets on floor of mouth directly under tongue and allow to completely dissolve.

• Prime nasal spray device before use as directed by manufacturer.

• For patients no longer requiring opioid therapy, consider discontinuing sublingual tablets or nasal spray along with gradual downward titration of other opioids to minimize possible withdrawal effects. For patients who continue to take long-term opioid therapy for persistent pain but no longer require treatment for breakthrough pain, sublingual tablets or nasal spray can usually be discontinued immediately.

• Be aware that drug isn't recommended for control of mild or intermittent pain.

• Be aware that fentanyl products are generally not interchangeable or substitutable on a mcg-per-mcg basis with other fentanyl products.

Adverse reactions

CNS: headache, dizziness, vertigo, floating feeling, lethargy, confusion, light-headedness, nervousness, hallucinations, delirium, insomnia, anxiety, fear, mood changes, tremor, sedation, coma, seizures

CV: palpitations, hypotension, hypertension, tachycardia, bradycardia, arrhythmias, circulatory depression, cardiac arrest, shock

EENT: blurred vision, diplopia, pharyngolaryngeal pain, laryngospasm

GI: nausea, vomiting, constipation, biliary tract spasm, dry mouth, anorexia

GU: urinary retention or hesitancy, ureteral or vesical sphincter spasm, decreased libido, erectile dysfunction

Musculoskeletal: skeletal and thoracic muscle rigidity

Respiratory: epistaxis, cough, nasal discomfort, rhinorrhea, nasal congestion, postnasal drip (Lazanda), dyspnea, slow and shallow respirations, suppressed cough reflex, apnea, bronchospasm

Skin: local skin irritation (with transdermal system), rash, urticaria, pruritus, diaphoresis, flushing, erythema, cold sensitivity

Other: oral mucosal reactions (at application site with buccal tablets), physical or psychological drug dependence, drug tolerance, pain or phlebitis at injection site, hypersensitivity, anaphylaxis (with oral transmucosal forms)

Interactions

Drug-drug. Barbiturate anesthetics: decreased effects of both drugs

Buprenorphine, dezocine, nalbuphine: decreased analgesic effect

CNS depressants (antidepressants, general anesthetics, other opioid analgesics, sedating antihistamines, sedative-hypnotics, skeletal muscle relaxants), CYP4503A4 inhibitors: profound sedation, hypoventilation, and hypotension

CYP4503A4 inducers (such as phenytoin, rifabutin, rifapentin): possible decrease in fentanyl blood level

CYP4503A4 inhibitors (such as amiodarone, amprenavir, aprepitant, clarithromycin, diltiazem, erythromycin, fluconazole, fosamprenavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin, verapamil): increased fentanyl blood level with increased adverse reactions, leading to greater risk of toxicity (including fatal respiratory depression)

MAO inhibitors: severe, unpredictable reactions

Opioid antagonists, partial-antagonist opioid analgesics: withdrawal in physically dependent patients

Drug-diagnostic tests. Amylase, lipase: increased levels

Granulocytes, hemoglobin, neutrophils, platelets, white blood cells: decreased levels

Drug-food. Grapefruit, grapefruit juice: increased fentanyl blood level, increased risk of toxicity

Drug-herbs. Chamomile, hops, kava, skullcap, valerian: increased CNS depression

Drug-behaviors. Alcohol use: profound sedation, hypoventilation, and hypotension

Patient monitoring

See Assess for muscle rigidity in patients receiving high doses; discuss need for neuromuscular blockers with prescriber. Patient receiving blocker will need ventilator.

• Monitor respiratory and cardiovascular function and urine output.

• With transdermal system, monitor patient's pain level often to determine if patch is effective for 72 hours or needs to be replaced after 48 hours. Know that drug level rises gradually for first 24 hours after patch is applied; supplemental analgesics may be needed then.

• If patient develops fever, assess for signs and symptoms of opioid toxicity, as more drug is absorbed at higher body temperatures.

• If adverse reactions to transdermal system occur, monitor patient for at least 12 hours after patch removal.

• Carefully monitor hematologic studies and hepatic enzyme levels.

Patient teaching

See Caution patient to keep transmucosal (lozenge) form out of children's reach even though it is supplied in individually sealed, child-resistant pouch. One lozenge can be fatal to a child.

• Instruct patient to place lozenge between cheek and gum and suck on it for 15 minutes without chewing or swallowing.

• Teach patient proper technique for applying and disposing of transdermal patch.

• Tell patient that transdermal form is absorbed more rapidly if skin is warm from fever or hot environment. Instruct patient to avoid electric blankets, heating pads, heat lamps, hot tubs, and heated water beds and to promptly report fever or a move to a hot climate.

• Instruct patient not to open buccal tablet blister pack until ready to use. Teach patient to peel back blister backing to expose buccal tablet and not to push tablet through blister.

• Caution patient not to break, suck, chew, or swallow buccal tablet.

• Instruct patient to place buccal tablet between upper check and gum near rear molar until it dissolves, and to swallow remnants with a glass of water after 30 minutes.

• Instruct patient to use alternate sides of mouth when taking subsequent doses of buccal tablets.

• Instruct patient to open buccal soluble film or spray packages immediately before use.

• Instruct patient to rinse mouth with water to wet area for placement of buccal soluble film. Tell patient to place entire buccal soluble film near tip of a dry finger with pink side facing up and to place pink side of film against inside of cheek; then to press and hold film in place for 5 seconds, after which film should stay in place on its own. Tell patient that liquids may be consumed after 5 minutes. Instruct patient that film will dissolve in 15 to 30 minutes and not to chew, swallow, or manipulate film with tongue or fingers or eat food until film has dissolved. Advise patient or caregiver to properly dispose of Onsolis film because drug can be fatal to children.

• Tell patient to place sublingual tablets on floor of mouth directly under tongue immediately after removal from blister unit. Tell patient not to chew, suck, or swallow tablets and allow tablets to completely dissolve in the sublingual cavity. Instruct patient not to eat or drink anything until tablets have completely dissolved. Advise patient who has a dry mouth that water may be used to moisten buccal mucosa before taking tablets.

• Instruct patient to carefully spray contents of sublingual spray unit into mouth underneath tongue. Tell patient or caregiver to dispose of used unit-dose systems immediately after use. Also tell patient to dispose of any unneeded unit-dose systems remaining from a prescription as soon as they are no longer needed. Consumed units represent a special risk because they are no longer protected by the child-resistant blister package, yet may contain enough drug to be fatal to children.

• Instruct patient on proper use of nasal spray and to press down firmly on finger grips until a "click" is heard and number in counting window advances by one. Tell patient that the fine mist spray isn't always felt on nasal mucosal membrane and to rely on the audible click and advancement of dose counter to confirm that a spray has been administered. Advise patient or caregiver that nasal spray contains an amount of drug that could be fatal to children, to individuals for whom it isn't prescribed, and to those who aren't opioid-tolerant.

• Tell patient to avoid grapefruit and grapefruit juice while taking drug.

• Advise patient not to breastfeed while taking drug.

• Caution patient to avoid driving and other hazardous activities until drug's effects on concentration and alertness are known.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.