Trade Names:Actiq- Lozenge on a stick 200 mcg- Lozenge on a stick 400 mcg- Lozenge on a stick 600 mcg- Lozenge on a stick 800 mcg- Lozenge on a stick 1,200 mcg- Lozenge on a stick 1,600 mcg
Trade Names:Fentora- Tablets, buccal 100 mcg- Tablets, buccal 200 mcg- Tablets, buccal 400 mcg- Tablets, buccal 600 mcg- Tablets, buccal 800 mcg
Trade Names:Onsolis- Soluble film, buccal 200 mcg- Soluble film, buccal 400 mcg- Soluble film, buccal 600 mcg- Soluble film, buccal 800 mcg- Soluble film, buccal 1,200 mcg
Trade Names:Sublimaze- Injection 50 mcg (as base)/mL
A potent, short-acting, rapid-onset opiate agonist that relieves pain by stimulating opiate receptors in CNS; also causes respiratory depression and peripheral vasodilation; inhibits intestinal peristalsis and sphincter of Oddi spasm; stimulates chemoreceptors that cause vomiting; increases bladder tone.
Absolute bioavailability is 50% total between transmucosal and GI absorption. C max is 0.39 to 2.51 ng/mL; T max is 20 to 480 min.Fentora
Absolute bioavailability is 65%. C max is 1.02 ng/mL; T max is 46.8 min.Onsolis
Absolute bioavailablity is 71%. C max is 1.67 ng/mL; T max is 1 h.
Highly lipophilic. It is 80% to 85% protein bound.Actiq , Onsolis , Sublimaze
Vd at steady state is 4 L/kg.Fentora
Vd at steady state is 25.4 L/kg.
Metabolized in the liver and intestinal mucosa to the inactive metabolite norfentanyl by CYP3A4.
Total plasma Cl is 0.5 L/h/kg; half-life is about 7 h (14 h for Onsolis ). Less than 7% is excreted unchanged in the urine and about 1% is excreted unchanged in feces. Inactive metabolites are primarily excreted in the urine.
7 to 8 min.
1 to 2 h. Therapeutic concentration for analgesia at 1 to 2 ng/mL, for surgical anesthesia and profound respiratory depression at 10 to 20 ng/mL.
Alters kinetics because of alterations in Cl and plasma proteins. Individualize dose and use caution.Hepatic Function Impairment
Alters kinetics because of alterations in Cl and plasma proteins. Individualize dose and use caution.
Short-term analgesia before, during, and after anesthesia; supplement to general or regional anesthesia; for administration with neuroleptic during anesthesia; anesthesia with oxygen for high-risk patients ( Sublimaze ). Management of breakthrough cancer pain in patients with malignancies who are already receiving and are tolerant to opioid therapy for their underlying cancer pain ( Actiq , Fentora , Onsolis ).
Known intolerance or hypersensitivity to any component of the product or other opioid agonists.Actiq , Fentora , Onsolis
Management of acute or postoperative pain; non–opioid-tolerant patients.
IM 0.05 to 0.1 mg, 30 to 60 min before surgery. Elderly patients may need reduced dose.Postoperative (Recovery Room) ( Sublimaze )
IM / IV 0.05 to 0.1 mg for pain control, tachypnea, or emergent delirium. May repeat in 1 to 2 h.Adjunct to Regional Anesthesia ( Sublimaze )
IM / IV 0.05 to 0.1 mg; dose administered over 1 to 2 min as needed.Adjunct to General Anesthesia ( Sublimaze )Total dosage
Low depth: 0.002 mg/kg. Moderate depth: 0.002 to 0.02 mg/kg. High depth: 0.02 to 0.05 mg/kg.Maintenance dose
Given when vital signs indicate surgical stress/lightening of anesthesia.Low depth
Usually not needed.Moderate depth
0.025 to 0.1 mg IM / IV .High depth
0.025 mg to 50% of induction dose.General Anesthesia ( Sublimaze )
IV 0.05 to 0.1 mg/kg with oxygen and muscle relaxant. Max IV, 0.15 mg/kg.Children 2 to 12 yr of age
For induction and maintenance, reduce IV dose as low as 2 to 3 mcg/kg.Breakthrough Cancer Pain ( Actiq , Fentora , Onsolis )Adults
PO Titrate to dose that provides adequate analgesia and minimal adverse reactions.Actiq
The initial dose should be 200 mcg. Start titration with an initial supply of six 200 mcg units. Patients should use all units before increasing to a higher dose. Until an appropriate dose is reached, patients may find it necessary to use an additional Actiq unit during a single episode.Redosing
May start 15 min after the previous unit has been completed (30 min after the start of the previous unit). No more than 2 units should be taken for each individual breakthrough cancer pain episode while patients are in the titration phase and consuming units that may be subtherapeutic.Dose increase
If treatment of several consecutive breakthrough cancer pain episodes requires more than 1 Actiq per episode, consider an increase in dose to the next higher available strength. Evaluate each new dose of Actiq in a titration period over several episodes of breakthrough cancer pain, generally 1 to 2 days, to determine whether it provides adequate pain relief with acceptable adverse reactions.Daily limit
Once a successful dose has been established, limit consumption to 4 units/day or less. If consumption increases above 4 units/day, reevaluate the dose. Generally, the Actiq dose should be increased when patients require more than 1 dosage unit per breakthrough pain episode for several consecutive episodes. When discontinuing, a gradual downward titration is recommended.Fentora
Initial dose should be 100 mcg. For patients switching from oral transmucosal fentanyl ( Actiq ) to Fentora , the starting Fentora dose is as follows:
If current Actiq dose is 200 or 400 mcg, initial Fentora dose should be 100 mcg.
If current Actiq dose is 600 or 800 mcg, Fentora dose should be 200 mcg.
If current Actiq dose is 1,200 or 1,600 mcg, initial Fentora dose should be 400 mcg.Redosing
Dose may be repeated once during a single episode of breakthrough pain if pain is not adequately relieved by 1 dose. Redosing may occur 30 min after the start of Fentora administration; the same dosage should be used.Dose increase
From the initial dose, dosage strength may be changed until the patient reaches a dose that provides adequate analgesia with tolerable adverse reactions using a single Fentora tablet. Initiate titration using multiples of the Fentora 100 mcg tablet. Patients needing to titrate above 100 mcg can use two 100 mcg tablets (1 on each side of the mouth in buccal cavity). If this dose is not successful, the patient may place two 100 mcg tablets on each side of the mouth in the buccal cavity. Titrate above 400 mcg by 200 mcg increments. Once a successful dose has been established, if more than 4 breakthrough pain episodes/day occur, reevaluate the dose of the maintenance (around-the-clock) opioid used for persistent pain.Dosage adjustment
Dosage adjustment of both Fentora and the maintenance (around-the-clock) opioid analgesic may be required. Generally, the Fentora dose should be increased when patients require more than 1 dose per breakthrough pain episode for several consecutive episodes.Onsolis
Initial dose should be a single Onsolis 200 mcg buccal film for all patients.Dose increase
From the initial dose, dosage strength may be changed until the patient reaches a dose that provides adequate analgesia with tolerable adverse reactions. Initiate titration using multiples of the Onsolis 200 mcg buccal film (for doses of 400, 600, or 800 mcg). Increase the dose by 200 mcg in each subsequent episode. Do not use more than 4 of the Onsolis 200 mcg buccal films simultaneously. When multiple 200 mcg buccal films are used they should not be placed on top of each other. They can be placed on both sides of the mouth. If adequate pain relief is not achieved after Onsolis 800 mcg (4 Onsolis 200 mcg buccal films) and the patient has tolerated the 800 mcg dose, treat the next episode using 1 Onsolis 1,200 mcg buccal film. Doses above 1,200 mcg should not be used. Once a successful dose is found, each episode is treated with a single film. Single doses should be separated by at least 2 h. Onsolis buccal films should only be used once per breakthrough pain episode.Dosage adjustment
Increase the dose as previously described if at any time the prescribed dose no longer adequately manages the breakthrough pain episode for several consecutive episodes. Onsolis buccal films should be limited to 4 or fewer uses per day. Consider increasing the around-the-clock pain medicine if patient experiences more than 4 breakthrough pain episodes daily.
Store at 59° to 86°F. Protect from freezing and moisture. Do not use if package has been opened.Sublimaze
Store at room temperature (59° to 77°F) and protect from light.
Profound bradycardia, sinus arrest, and hypotension may occur.Anesthesia (conduction, peridural, spinal)
When used with fentanyl, management of respiration may be complicated.Diazepam
May produce CV depression when given with high doses of fentanyl.Droperidol
May cause hypotension and decrease pulmonary arterial pressure.MAOIs
Fentanyl not recommended for use in patients who have received MAOIs within 14 days.Neuroleptics
Risk of hypertension may be increased. In addition, ECG monitoring is indicated.Nitrous oxide
Nitrous oxide may cause CV depression with high-dose fentanyl.CYP3A4 inducers (eg, barbiturates, carbamazepine, efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, rifampin, St. Johns' wort)
Decreased fentanyl plasma concentrations may occur with coadministration.CYP3A4 inhibitors (eg, aprepritant, cimetidine, clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole, nefazodone, protease inhibitors [eg, ritonavir], telithromycin, verapamil), other CNS depressants (eg, alcohol, barbiturates, benzodiazepines, general anesthetics, other opioids, phenothiazines, sedating antihistamines, sedatives/hypnotics, skeletal muscle relaxants, tranquilizers)
Increased depressant effects; hypoventilation, hypotension, profound sedation, and life-threatening respiratory depression may occur.
Increased amylase and lipase may occur up to 24 h after dose.
Hypotension (5%); bradycardia, chest wall rigidity, deep thrombophlebitis, deep vein thrombosis, hot flush, hypertension, migraine, pallor, palpitation, tachycardia, vascular disorder (at least 1%).
Asthenia (38%); headache (20%); dizziness, fatigue (16%); anxiety, somnolence (15%); confusional state (14%); confusion (13%); depression (11%); insomnia (8%); abnormal gait (5%); dry mouth, myoclonus, nervousness, stupor, vasodilation, vertigo (4%); abnormal thinking, convulsion, tremor (2%); abnormal dreams (1%); agitation, amnesia, balance disorder, disorientation, dysgeusia, euphoria, hallucination, hypesthesia, hypokinesia, lethargy, malaise, mental status changes, migraine, neuropathy, paresthesia, peripheral neuropathy, pyrexia, sedation, speech disorder (at least 1%); incoordination; light-headedness.
Rash (8%); sweating (4%); pruritus (2%); alopecia, cold sweat, hyperhidrosis, skin ulcer (at least 1%); urticaria.
Abnormal vision (3%); blurred vision, conjunctivitis, diplopia, ear disorder, nasopharyngitis, pharyngitis, pharyngolaryngeal pain, rhinitis, taste perversion, tinnitus (at least 1%).
Nausea (45%); vomiting (31%); constipation (20%); diarrhea (12%); abdominal pain (9%); dry mouth (7%); intestinal obstruction (4%); abdominal distention, anorexia, dry mouth, dyspepsia, dysphagia, enlarged abdomen, eructation, flatulence, gastroesophageal reflux disease, GI hemorrhage, gingival pain, gingivitis, glossitis, glossodynia, mouth ulceration, oral moniliasis, periodontal abscess, rectal disorder, rectal hemorrhage, stomach discomfort, stomatitis, tooth abscess, upper abdominal pain (at least 1%); dental decay, gum line erosion, tooth loss (postmarketing).
Urinary retention (2%); breast neoplasm, breast pain, dysuria, hematuria, hydronephrosis, impaired urination, kidney failure, scrotal edema, urinary hesitancy, urinary incontinence, urinary urgency, UTI, vaginal hemorrhage, vaginitis (at least 1%).
Anemia (13%); neutropenia (6%); decreased hematocrit, decreased hemoglobin, decreased platelet count, ecchymosis, leukopenia, lymphadenopathy, lymphedema, pancytopenia, thrombocytopenia (at least 1%).
Jaundice (at least 1%)
Application-site irritation and pain (at least 1%).
Dehydration (13%); anorexia (9%); decreased appetite (8%); weight loss (7%); hypokalemia (6%); hypercalcemia, hypoalbuminemia, hypomagnesemia, hyponatremia, increased blood glucose (at least 1%).
Arthralgia (6%); back pain (5%); bone pain, chest wall pain, joint disorder, leg cramps, muscle spasm, myalgia, neck pain, pain in extremity, pathological fractures, pelvic pain, shoulder pain (at least 1%); skeletal muscle rigidity.
Dyspnea (22%); cough (7%); pneumonia (6%); asthma, bronchitis, decreased breathing sounds, epistaxis, exertional dyspnea, hemoptysis, increased cough, increased sputum, pericardial effusion, sinusitis, upper respiratory tract infection, wheezing (at least 1%); apnea; depression of cough reflex; laryngospasm; rebound respiratory depression postoperatively; respiratory depression.
Peripheral edema (12%); accidental injury (9%); cancer pain (5%); hypertonia (3%); ascites, cachexia, cellulitis, chest pain, chills, contusion, edema, fever, flu syndrome, fungal infection, infection, influenza, injury (eg, fall, fracture, spinal compression), mucosal inflammation, pain, sepsis, viral infection (at least 1%); anaphylaxis; psychological and physical dependence with long-term use; tolerance.
Fentanyl has an abuse liability similar to other opioid analgesics. Actiq , Fentora , and Onsolis must not be used in nonopioid-tolerant patients. Actiq , Fentora , and Onsolis are indicated for breakthrough pain in cancer patients and should only be used by oncologists and pain specialists knowledgeable of the use of opioids to treat cancer pain. Actiq , Fentora , and Onsolis contain a quantity of fentanyl that can be fatal to a child.
Assess pain type and intensity prior to administration; assess efficacy of pain relief shortly after administration. Assess respiratory rate, heart rate, and BP frequently.
Category C . The use of fentanyl is not recommended in labor and delivery.
Excreted in breast milk.
Safety and efficacy not established in children younger than 16 yr of age ( Actiq ). Safety and efficacy not established in children younger than 18 yr of age ( Fentora , Onsolis ). Safety and efficacy not established in children younger than 2 yr of age ( Sublimaze ).
May be more sensitive to the effects of fentanyl; use with caution.
Duration of action may be prolonged; may need to reduce dose.
Duration of action may be prolonged; may need to reduce dose.
Use with caution in elderly patients and patients with acute abdominal conditions, acute alcoholism, bradycardia, circulatory shock, COPD, decreased respiratory reserve, depleted blood volume, head injury or increased intracranial pressure, hypoxia, myxedema, supraventricular tachycardia, or ulcerative colitis.
Because products are not bioequivalent, when converting patients from other oral fentanyl products, do not substitute on a mcg per mcg basis.
Fentanyl has abuse potential.
Clinically important hypoventilation may occur; monitor patients for symptoms of respiratory depression.
May persist longer than the analgesic effect.
May cause skeletal muscle rigidity, particularly of the truncal muscles.
Cardiopulmonary arrest, circulatory collapse, CNS depression, death, hypoventilation, miosis, respiratory depression, seizures.
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