fentanyl transmucosal

fentanyl transmucosal Warning - High-alert drug!

Actiq, Fentanyl Oralet

Pharmacologic class: Opioid agonist

Therapeutic class: Opioid analgesic, anesthesia adjunct

Controlled substance schedule II

Pregnancy risk category C

FDA Boxed Warning

• Actiq is indicated only for managing breakthrough pain in cancer patients already receiving and tolerant to opioids. Opioid-tolerant patients are those taking at least 60 mg morphine daily, 25 mcg transdermal fentanyl hourly, 30 mg oxycodone daily, 8 mg oral hydromorphone daily, or equianalgesic dose of another opioid for 1 week or longer.
• Actiq is contraindicated for managing acute or postoperative pain, because life-threatening hypoventilation can arise at any dosage in patients not taking chronic opioids. Don't administer to opioid-nontolerant patients.
• Inform patients and caregivers that Actiq can be fatal to a child. Instruct them to keep all units out of children's reach and to discard opened units properly.
• Duragesic is for use only in opioid-tolerant patients. It contains high concentration of potent Schedule II opioid agonist, with highest potential for abuse and risk of fatal overdose. Drug can be abused and is subject to criminal diversion. High fentanyl content in patches may be a particular target for abuse and diversion.
• Duragesic is indicated for managing persistent moderate to severe chronic pain that can't be managed by other means. Use only in patients already receiving opioids who have demonstrated opioid tolerance and need total daily dose at least equivalent to Duragesic 25 mcg/hour.
• Duragesic is contraindicated in opioid-nontolerant patients; management of postoperative, acute, mild, or intermittent pain; and in patients who need short-term opioid analgesia.
• Fentanyl levels peak between 24 and 72 hours of treatment; serious or life-threatening hypoventilation may arise during initial Duragesic application period.
• Concomitant use of Duragesic with potent CYP450 3A4 inhibitors may raise fentanyl blood level, possibly increasing or prolonging adverse effects and causing potentially fatal respiratory depression. Closely monitor patients receiving this combination for an extended time; adjust dosage if needed.
• Duragesic safety hasn't been established in children younger than age 2. Administer only to opioid-tolerant children age 2 or older.
• Overestimating Duragesic dosage when converting patients from another opioid can lead to fatal overdose with first dose. Patients who've had serious adverse events (including overdose) must be monitored and treated for at least 24 hours.
• Stay alert for Duragesic abuse. Patients at increased risk are those with personal or family history of substance abuse or mental illness. Routinely monitor all patients receiving opioids for signs of misuse, abuse, and addiction.
• Use of damaged or cut Duragesic patch can lead to rapid release of contents and absorption of potentially fatal dose.

Action

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

Availability

Injection: 0.05 mg/ml

Transdermal system: 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 dissolved in mouth over 15 minutes; an additional unit may be given 15 minutes later. If patient requires more than 1 unit per episode (as evaluated over several episodes), dosage may be increased; for optimal use or titration, don't exceed 4 units/day.

➣ 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 have not been receiving opioids. To calculate dosage for patients already receiving opioids, assess 24-hour requirement for current opioid. Using recommended equianalgesic table, convert to an equivalent amount of morphine/24 hours. Then use recommended fentanyl conversion table to convert to fentanyl transdermal. During dosage titration, keep additional short-acting opioids at 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. Transdermal patch lasts 72 hours in most patients, but some patients require new patch q 48 hours. Titrate upward by 25 mcg/hour q 72 hours.

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

Adults: 0.05 to 0.1 mg 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: 2 to 3 mcg/kg I.V., depending on vital signs; or 5 to 15 mcg/kg transmucosally

➣ General anesthesia (with oxygen only)

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

➣ Adjunct to regional anesthesia

Adults: 0.05 to 0.1 mg I.M. or slow I.V. over 1 to 2 minutes

Dosage adjustment

• Elderly patients

Contraindications

• Hypersensitivity to drug or transdermal adhesive
• Alcohol intolerance
• Acute bronchial asthma
• Pregnancy (transdermal system)
• Breastfeeding
• Children younger than age 18 who weigh less than 50 kg (110 lb)

Precautions

Use cautiously in:
• diabetes mellitus, severe or chronic pulmonary or hepatic disease, cardiovascular disease, CNS tumors, adrenal insufficiency, hypothyroidism, renal impairment
• alcoholism or drug abuse
• elderly patients
• pregnant patients
• children younger than age 2 (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.
• Inject I.V. dose slowly over 3 to 5 minutes.
☞ Have narcotic antagonist (naloxone) and emergency equipment available when giving drug I.V.
• Be aware that drug isn't recommended to control mild or intermittent pain.

Route	Onset	Peak	Duration
I.V.	1-2 min	3-5 min	0.5-1 hr
I.M.	7-8 min	20-30 min	1-2 hr
Transdermal	6 hr	12-24 hr	72 hr
Transmucosal	Rapid	15-30 min	Several hr

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, 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, oliguria

Musculoskeletal: skeletal and thoracic muscle rigidity

Respiratory: 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: physical or psychological drug dependence, drug tolerance, pain or phlebitis at injection site

Interactions

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

Buprenorphine, dezocine, nalbuphine: decreased analgesic effect

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

Erythromycin, ketoconazole, some protease inhibitors: decreased metabolism and increased effects of fentanyl, possibly leading to profound sedation, hypoventilation, and hypotension

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 juice: decreased drug metabolism, 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

☞ Assess for muscle rigidity in patients receiving high doses; discuss need for neuromuscular blockers with prescriber. Patient will need ventilator if blocker is given.
• Monitor respiratory and cardiovascular function and urinary output.
• In patient using transdermal system, monitor pain level often to determine whether 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 during this period.
• If patient develops fever, assess for signs and symptoms of opioid toxicity, because more drug is absorbed at higher body temperatures.
• If patient has adverse reactions to transdermal system, monitor him for at least 12 hours after patch removal.
• Carefully monitor hematologic studies and hepatic enzyme levels.

Patient teaching

☞ Caution patient to keep transmucosal (lozenge) form out of children's reach even though it's 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.
• Tell patient that transdermal form is absorbed more rapidly if skin becomes warm by fever or hot environment. Instruct him 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.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.