Medication Guide App

Fentanyl

Pronunciation

Pronunciation: FEN-ta-nil
Class: Opioid analgesic

Trade Names

Abstral
- Tablet, sublingual 100 mcg
- Tablet, sublingual 200 mcg
- Tablet, sublingual 300 mcg
- Tablet, sublingual 400 mcg
- Tablet, sublingual 600 mcg
- Tablet, sublingual 800 mcg

Actiq
- Lozenge, transmucosal 200 mcg
- Lozenge, transmucosal 400 mcg
- Lozenge, transmucosal 600 mcg
- Lozenge, transmucosal 800 mcg
- Lozenge, transmucosal 1,200 mcg
- Lozenge, transmucosal 1,600 mcg

Fentanyl Citrate
- Injection, solution 50 mcg/mL

Fentora
- Tablets, buccal 100 mcg
- Tablets, buccal 200 mcg
- Tablets, buccal 400 mcg
- Tablets, buccal 600 mcg
- Tablets, buccal 800 mcg

Lazanda
- Spray, intranasal 100 mcg
- Spray, intranasal 400 mcg

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

Subsys
- Spray, sublingual 100 mcg
- Spray, sublingual 200 mcg
- Spray, sublingual 400 mcg
- Spray, sublingual 600 mcg
- Spray, sublingual 800 mcg

Pharmacology

A potent, short-acting, rapid-onset opioid agonist that relieves pain by stimulating opioid 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.

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Pharmacokinetics

Absorption

Abstral

Absolute bioavailability is 54%. C max is 0.187 to 1.42 ng/mL; T max is 30 to 60 min.

Actiq

Absolute bioavailability is 50% total between transmucosal and GI absorption. C max is 0.39 to 2.51 ng/mL; median T max is 20 to 40 min.

Fentora

Absolute bioavailability is 65%. C max is 1.02 ng/mL; T max is 46.8 min.

Lazanda

C max is between 351.5 and 2,844 pg/mL. T max ranges from 15 to 21 min after a single dose.

Onsolis

Absolute bioavailability is 71%. C max is 1.67 ng/mL; T max is 1 h.

Subsys

Absolute bioavailability is 76%. C max is 0.813 ng/mL; T max is 1.5 h.

Distribution

Highly lipophilic. It is 80% to 85% protein bound.

Abstral , Actiq , Lazanda , Onsolis , Subsys , injection

Vd at steady state is 4 L/kg.

Fentora

Vd at steady state is 25.4 L/kg.

Metabolism

Metabolized in the liver and intestinal mucosa to the inactive metabolite norfentanyl by CYP3A4.

Elimination

Total plasma Cl is 0.5 L/h/kg; half-life is approximately 7 h for Actiq , 5 to 13.5 h for Abstral , 2.6 to 11.7 h for Fentora , 15 to 25 h for Lazanda , 14 h for Onsolis , and 5 to 12 h for Subsys . Less than 7% is excreted unchanged in the urine and approximately 1% is excreted unchanged in feces. Inactive metabolites are primarily excreted in the urine.

IV

Approximately 75% is released in the urine, mostly as metabolites, with less than 10% representing the unchanged drug; approximately 9% is released in the feces, primarily as metabolites. Terminal elimination half-life is 219 min.

Onset

Immediately (IV); 7 to 8 min (IM).

Duration

30 to 60 min (IV); 1 to 2 h (IM).

Special Populations

Renal Function Impairment

Alters kinetics because of alterations in Cl and plasma proteins. Insufficient information exists to make recommendations regarding the use of fentanyl intranasal in patients with renal impairment. Individualize dose and use caution.

Hepatic Function Impairment

Alters kinetics because of alterations in Cl and plasma proteins. Insufficient information exists to make recommendations regarding the use of fentanyl intranasal in patients with hepatic impairment. Individualize dose and use caution.

Gender

Systemic exposure was higher in women after administration of Fentora ; this difference was largely attributed to differences in weight.

Race

Systemic exposure was higher in Japanese subjects after administration of Fentora ; this difference was largely attributed to differences in weight.

Seasonal allergic rhinitis

No clinically relevant differences in rate or extent of exposure of fentanyl intranasal were observed in patients with known seasonal allergic rhinitis.

Indications and Usage

Buccal/Intranasal/Sublingual/Transmucosal

Management of breakthrough cancer pain in patients with malignancies who are already receiving and are tolerant of opioid therapy for their underlying cancer pain.

Injection

For analgesic action of short duration during the anesthetic periods, premedication, induction and maintenance, and in the immediate postoperative period; for use as a narcotic supplement in general or regional anesthesia; for administration with a neuroleptic (such as droperidol injection), as an anesthetic premedication for the induction of anesthesia, and as an adjunct in the maintenance of general and regional anesthesia; for use as an anesthetic agent with oxygen in selected high-risk patients.

Contraindications

Hypersensitivity to any component of the product.

Buccal/Intranasal/Sublingual/Transmucosal

Acute or postoperative pain, including headache/migraine, dental pain, and use in the emergency room; opioid-nontolerant patients.

Dosage and Administration

Premedication
Adults

IM 50 to 100 mcg 30 to 60 min before surgery.

Postoperative
Adults

IM 50 to 100 mcg. May repeat in 1 to 2 h as needed.

Adjunct to regional anesthesia
Adults

IM/IV 50 to 100 mcg IM or IV over 1 to 2 min as needed.

Adjunct to general anesthesia
Adults Initial dosage

IM/IV 2 to 20 mcg/kg. Respiratory depression necessitates artificial ventilation and careful observation of postoperative ventilation. 20 to 50 mcg/kg may be used for open heart surgery and certain more complicated neurosurgical and orthopedic procedures; postoperative ventilation and observation are required with this dose.

Maintenance dosage

IM/IV 2 to 50 mcg/kg. Additional doses are needed infrequently in minor procedures. Use 25 to 100 mcg IV or IM when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. 25 mcg to one-half the initial loading dose may be used for open heart surgery and certain more complicated neurosurgical and orthopedic procedures.

Children 2 to 12 y of age

IV For induction and maintenance, reduce dose to as low as 2 to 3 mcg/kg.

General anesthesia
Adults

IV 50 to 100 mcg/kg with oxygen and a muscle relaxant. Up to 150 mcg/kg may be necessary.

Breakthrough cancer pain
Adults

PO Titrate to dose that provides adequate analgesia and minimal adverse reactions. Reevaluate the dose of the around-the-clock opioid used for persistent pain in patients experiencing greater than 4 breakthrough pain episodes per day.

Abstral

Sublingual Start all patients with a single 100 mcg tablet. If adequate analgesia is obtained within 30 min of administration of the 100 mcg tablet, continue to treat subsequent episodes of breakthrough pain with this dose.

Redosing

If adequate analgesia is not obtained by 30 min after a dose, the patient may repeat the same dose of Abstral . No more than 2 doses may be used to treat an episode of breakthrough pain.

Dosage titration

If adequate analgesia was not obtained with the first 100 mcg dose, continue dose escalation in a stepwise manner over consecutive breakthrough episodes until adequate analgesia with tolerable adverse effects is achieved. Increase the dose by 100 mcg multiples up to 400 mcg as needed. If adequate analgesia is not obtained with a 400 mcg dose, the next titration step is 600 mcg. If adequate analgesia is not obtained with a 600 mcg dose, the next titration step is 800 mcg. During titration, patients can be instructed to use multiples of 100 mcg tablets and/or 200 mcg tablets for any single dose. Instruct patients not to use more than 4 tablets at one time.

Maintenance dosage

Once an appropriate dose for pain management has been established, instruct patients to use only 1 sublingual tablet of the appropriate strength per dose. Maintain patients on this dose. Limit use of Abstral to treat 4 or fewer episodes of breakthrough pain per day.

Dosage adjustment

If the response (analgesia or adverse reactions) to the titrated fentanyl sublingual tablet dose markedly changes, an adjustment of dose may be necessary to ensure that an appropriate dose is maintained. If the long-acting opioid or dose of long-acting opioid is changed, reevaluate and retitrate the dose as necessary to ensure the patient is on an appropriate dose.

Discontinuation of therapy

For patients no longer requiring opioid therapy, consider discontinuing with a gradual downward titration of other opioids to minimize possible withdrawal effects. In patients who continue to take their long-term opioid therapy for persistent pain but no longer require treatment for breakthrough pain, Abstral can be discontinued immediately.

Actiq

Transmucosal 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.

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. No more than 6 units of each strength should be prescribed initially. Patients must wait at least 4 h before treating another episode with Actiq .

Maintenance dosage

Once a successful dose is found, generally only 1 unit should be used per episode. Limit consumption to 4 units per day or less.

Dosage adjustment

Increase the dose if the prescribed dose no longer adequately manages the breakthrough pain episode for several consecutive episodes.

Discontinuation

A gradual downward titration is recommended.

Fentora

Buccal Initial dose should be 100 mcg. For patients switching from 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

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. No more than 4 tablets should be used simultaneously. Patients should wait 4 h before treating another episode with Fentora .

Maintenance dosage

Once a successful dose is found, each episode is treated with a single tablet.

Dosage adjustment

Generally, the Fentora dose should be increased when patients require more than 1 dose per breakthrough pain episode for several consecutive episodes.

Lazanda

Intranasal One 100 mcg spray (1 spray in 1 nostril) as initial treatment. If adequate analgesia is obtained within 30 min of administration of the 100 mcg single spray, treat subsequent episodes of breakthrough pain with this dose.

Dosage titration

If adequate analgesia is not achieved with the first 100 mcg dose, escalate dose in a stepwise manner over consecutive episodes of breakthrough pain until adequate analgesia with tolerable adverse effects is achieved. Patients must wait at least 2 h before treating another episode of breakthrough cancer pain. Increase the dose up to 200 mcg (one 100 mcg spray in each nostril). If adequate analgesia is not obtained with a 200 mcg dose, the next titration step is 400 mcg (one 400 mcg spray). If adequate analgesia is not obtained with a 400 mcg dose, the next titration step is 800 mcg (one 400 mcg spray in each nostril). Max is 4 doses/day (up to 3,200 mcg/day).

Maintenance dosage

Once an appropriate dose has been established, instruct patients to use that dose for each subsequent breakthrough cancer pain episode. Limit fentanyl intranasal use to 4 or fewer doses per day. Patients must wait at least 2 h before treating another episode of breakthrough cancer pain.

Dosage adjustment

If the response (analgesia or adverse reactions) to the titrated fentanyl intranasal dose markedly changes, an adjustment of dose may be necessary to ensure that an appropriate dose is maintained. If the long-acting opioid or dose of long-acting opioid is changed, reevaluate and retitrate the fentanyl intranasal dose as necessary to ensure the patient is on an appropriate dose. Limit the use of fentanyl to treat 4 or fewer episodes of breakthrough pain per day

Discontinuation of therapy

For patients no longer requiring opioid therapy, consider discontinuing Lazanda along with a gradual downward titration of other opioids to minimize possible withdrawal effects. In patients who continue to take their long-term opioid therapy for persistent pain but no longer require treatment for breakthrough pain, fentanyl therapy can usually be discontinued immediately.

Onsolis

Buccal Initial dose should be a single Onsolis 200 mcg buccal film for all patients.

Dose increase

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. If adequate pain relief is not achieved after Onsolis 800 mcg (four Onsolis 200 mcg buccal films) and the patient has tolerated the 800 mcg dose, treat the next episode using one Onsolis 1,200 mcg buccal film. Doses above 1,200 mcg should not be used. Single doses should be separated by at least 2 h. Onsolis buccal films should only be used once per breakthrough pain episode.

Maintenance dosage

Once a successful dose is found, each episode is treated with a single film. Onsolis buccal films should be limited to 4 or fewer uses per day.

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.

Subsys

Sublingual Start all patients with 100 mcg.

Redosing

If adequate analgesia is not obtained by 30 min after a dose, the patient may repeat the same dose of Subsys . No more than 2 doses may be used to treat an episode of breakthrough pain.

Dosage titration

If there is a need to titrate to a 200 mcg dose, prescribe 200 mcg spray units. Subsequent titration steps are 400, 600, 800, 1,200, and 1,600 mcg. Patients must wait at least 4 h before treating another episode of breakthrough cancer pain.

Maintenance dosage

Once an appropriate dose for pain management has been established, patients should generally use only 1 unit of the appropriate strength per dose. Maintain patients on this dose. Limit use of Subsys to treat 4 or fewer episodes of breakthrough pain per day.

Dosage adjustment

Dosage adjustment may be required to continue to provide adequate relief of breakthrough pain. Only increase the dose when a single administration of the current dose fails to adequately treat the breakthrough pain episode for several consecutive episodes. If signs of excessive opioid effects appear following the administration of a single dose, subsequent doses should be decreased.

General Advice

  • Because of the differences in pharmacokinetic properties and individual variability, do not switch patients on a mcg-per-mcg basis from one fentanyl product to another.
  • Injection
  • Administer IV dose slowly over 1 to 2 min.
  • Elderly and debilitated patients and those who have received other depressant drugs may need a reduced dose.
  • Buccal/Sublingual/Transmucosal
  • The package/blister pack should not be opened until ready to administer. Films, lozenges, and tablets should not be stored for future use once removed from the packaging.
  • Abstral sublingual tablets should not be chewed, sucked, or swallowed. The tablet should be placed on the floor of the mouth, directly under the tongue. Tablets should be allowed to completely dissolve in the sublingual cavity. Patients should not eat or drink anything until the tablet is completely dissolved. In patients who have a dry mouth, water may be used to moisten the buccal mucosa before taking the sublingual tablets.
  • The Actiq lozenge should be sucked, not chewed. The lozenge should be placed between the cheek and lower gum, occasionally moving it from one side to the other using the handle. The lozenge should be consumed over a 15-min period.
  • Fentora tablets should not be sucked, chewed, or swallowed. The tablet should be placed between the cheek and the gum and left there until disintegrated (approximately 14 to 25 min). If remnants remain after 30 min, they may be swallowed with a glass of water.
  • Onsolis buccal films should not be cut or torn prior to use, or chewed and swallowed. Onsolis buccal films should be placed on the inside of the cheek (pink side against cheek) and held in place for 5 sec. Liquids can be consumed after 5 min, and the film should dissolve within 15 to 30 min. The film should not be manipulated with the tongue or finger, and eating food should be avoided until the film is dissolved.
  • When multiple Onsolis films are used, they should not be placed on top of each other, and they may be placed on both sides of the mouth.
  • Carefully spray the contents of 1 unit of Subsys into the mouth under the tongue.
  • Intranasal
  • Prime the device before use by spraying into the pouch (4 sprays total). Device will remain primed for up to 5 days after priming or use.
  • Insert the nozzle of the intranasal bottle a short distance (approximately ½ inch or 1 cm) into the nose and point toward the bridge of the nose, tilting the bottle slightly.
  • Press down firmly on the finger grips until a click is heard and the number in the counting window advances by 1.
  • Any remaining liquid in bottles must be sprayed into the pouch provided until the number “8” appears in the counting window. Then push down on the finger grips 4 additional times to expel any residual medicine from the bottle into the pouch. Place pouch in the child-resistant container for safe disposal in trash.
  • Hands must be washed with soap and water immediately after handling the pouch.

Storage/Stability

Store buccal and sublingual tablets, buccal films, sublingual spray, and lozenges between 59° and 86°F. Protect from freezing and moisture. Do not use if package has been opened. Store injection between 68° and 77°F and protect from light. Store intranasal spray up to 77°F. Do not freeze; protect from light. Return the bottle to the child-resistant container after each use.

Drug Interactions

Amiodarone

Profound bradycardia, sinus arrest, and hypotension may occur. Use with caution and closely monitor hemodynamic function. Close cardiac and pulmonary monitoring during and after anesthesia is warranted. Inotropic and vasopressor agents may be needed to maintain cardiac output and hemoperfusion

Anesthesia (conduction, peridural, spinal)

When used with fentanyl, management of respiration may be complicated. Use with caution and closely monitor the clinical response.

Barbiturate anesthetics (eg, thiopental)

May have additive effects. Reduce dosage of one or both agents.

Buprenorphine

The analgesic effects of fentanyl may be decreased. Opioid withdrawal symptoms in opioid-dependent patients may occur if buprenorphine therapy is not initiated properly. Coadminister with caution.

Cimetidine

The actions of opioid analgesics may be enhanced, resulting in toxicity. If excessive CNS or respiratory depression occurs, discontinue both drugs. Administer a narcotic antagonist, if needed.

CNS depressants (eg, alcohol, benzodiazepines [eg, diazepam], general anesthetics, hypnotics, other opioids, phenothiazines, sedating antihistamines, sedatives, skeletal muscle relaxants, tranquilizers)

Concomitant use may produce increased depressant effects (eg, hypotension, profound sedation, respiratory depression). Close monitoring is warranted. Alcohol should be avoided.

Crizotinib

Fentanyl plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Avoid coadministration.

CYP3A4 inducers (eg, barbiturates, carbamazepine, efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, troglitazone)

Decreased fentanyl plasma concentrations may occur with coadministration. When CYP3A4 therapy is stopped, patients may experience a sudden increase in fentanyl concentrations. Monitor the clinical response when CYP3A4 inducer therapy is started or stopped. Adjust the fentanyl dose as needed.

CYP3A4 inhibitors (eg, aprepitant, clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole, nefazodone, protease inhibitors [eg, fosamprenavir, nelfinavir, ritonavir], telithromycin, verapamil, voriconazole)

Increased depressant effects; hypoventilation, hypotension, profound sedation, and life-threatening respiratory depression may occur. Monitor for signs of opioid toxicity. Increase the fentanyl dose conservatively.

Diazepam

May produce CV depression when given with high doses of fentanyl. Closely monitor the clinical response. Lower fentanyl doses may be needed.

Droperidol

May cause hypotension and decrease pulmonary arterial pressure. If either of these occur, the possibility of hypovolemia should also be considered and managed with appropriate parenteral fluid therapy.

Grapefruit juice

Fentanyl Cl may be decreased, which could increase or prolong adverse reactions, including serious respiratory depression. Closely monitor the patient for an extended period of time. Adjust the fentanyl dose as needed.

MAOIs (eg, phenelzine)

Fentanyl is not recommended for use in patients who have received MAOIs within 14 days.

Naltrexone

The analgesic effects of fentanyl may be decreased or attenuated. Opioid withdrawal symptoms in opioid-dependent patients may occur. Close clinical monitoring for signs of opioid withdrawal or reduced opioid efficacy is warranted. Opioid-dependent patients should be detoxified before treatment with naltrexone.

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.

Serotonin reuptake inhibitors (eg, fluoxetine)

Toxic effects of serotonin reuptake inhibitors and fentanyl may be additive, increasing the risk of serotonin syndrome. Close clinical monitoring for signs of serotonin syndrome is warranted.

Sibutramine

The risk of serotonin syndrome may be increased. Avoid coadministration.

Sodium oxybate

Concurrent use of sodium oxybate with fentanyl may result in an increase in sleep duration and CNS depression because of additive pharmacologic effects. Coadministration is contraindicated.

Vasoconstrictive nasal decongestants (eg, oxymetazoline)

Fentanyl intranasal C max may be reduced and T max may be delayed, leading to a decrease in efficacy. In addition, dose titration while patients are experiencing an acute episode of rhinitis could lead to incorrect dosing of fentanyl, especially in patients using a vasoconstrictive decongestant. Avoid concurrent use.

Adverse Reactions

Cardiovascular

Hypotension (5%); bradycardia, cardiorespiratory arrest, deep thrombophlebitis, deep vein thrombosis, hot flush, hypertension, pallor, palpitation, pulmonary embolism, tachycardia, vascular disorder (at least 1%).

CNS

Asthenia (38%); dizziness (32%); fatigue, headache, somnolence (20%); confusional state (16%); anxiety (15%); dysgeusia (14%); confusion (13%); depression, insomnia (11%); abnormal gait (5%); myoclonus, nervousness, stupor, vasodilation, vertigo (4%); hypertonia (3%); abnormal thinking, convulsion, hallucinations, tremor (2%); affect lability, agitation, amnesia, balance disorder, disorientation, disturbance in attention, dysphoria, euphoria, fall, hypesthesia, hypokinesia, irritability, lethargy, malaise, mental status changes, migraine, neuropathy, pain, paranoia, paresthesia, parosmia, peripheral neuropathy, restlessness, sedation, sleep disorder, speech disorder, tremor (at least 1%); abnormal dreams (1%).

Dermatologic

Rash (8%); pruritus (5%); sweating (4%); alopecia, cold sweat, night sweats, skin lesions, skin ulcer (at least 1%).

EENT

Abnormal vision (3%); blurred vision, conjunctivitis, diplopia, ear disorder, nasopharyngitis, oropharyngeal pain, pharyngitis, pharyngolaryngeal pain, rhinitis, taste perversion, throat tightness, tinnitus (at least 1%).

Intranasal

Dry eye, epistaxis, eye swelling, nasal congestion, nasal discomfort, postnasal drip, ptosis, rhinorrhea, strabismus, swelling (at least 1%).

GI

Nausea (45%); vomiting (31%); constipation (26%); diarrhea (16%); abdominal pain (15%); anorexia (11%); stomatitis (8%); dry mouth (7%); intestinal obstruction (4%); abdominal distention, aphthous stomatitis, ascites, dry mouth, dyspepsia, dysphagia, enlarged abdomen, eructation, flatulence, gastritis, gastroenteritis, gastroesophageal reflux disease, GI hemorrhage, gingival pain, gingival ulceration, gingivitis, glossitis, glossodynia, hematemesis, impaired gastric emptying, lip ulceration, mouth ulceration, oral moniliasis, periodontal abscess, proctalgia, rectal disorder, rectal hemorrhage, stomach discomfort, tongue disorder, tooth abscess, upper abdominal pain (at least 1%); dental decay, gum line erosion, tooth loss (postmarketing).

Genitourinary

Urinary retention (2%); breast neoplasm, breast pain, dysuria, erectile dysfunction, hematuria, hydronephrosis, impaired urination, kidney failure, scrotal edema, urinary incontinence, urinary urgency, UTI, vaginal hemorrhage, vaginitis (at least 1%).

Hematologic-Lymphatic

Anemia (32%); neutropenia (7%); decreased Hct, decreased Hgb, decreased platelet count, ecchymosis, leukopenia, lymphadenopathy, lymphedema, pancytopenia, thrombocytopenia (at least 1%).

Hepatic

Increased AST, jaundice (at least 1%).

Local

Application-site reactions, including bleeding, paresthesia, and ulceration (10%); application-site irritation and pain (at least 1%).

Metabolic-Nutritional

Hypokalemia (15%); dehydration, weight decreased (13%); decreased appetite (8%); hypercalcemia, hyperglycemia, hypoalbuminemia, hypocalcemia, hypomagnesemia, hyponatremia, increased blood alkaline phosphatase, increased blood glucose, increased blood lactate (at least 1%).

Musculoskeletal

Back pain (11%); arthralgia (8%); bone disorder, bone pain, chest wall pain, joint disorder, joint swelling, leg cramps, muscle spasm, muscular weakness, myalgia, neck pain, pain in extremity, pathological fractures, pelvic pain, shoulder pain (at least 1%); skeletal muscle rigidity.

Respiratory

Dyspnea (22%); pneumonia (16%); cough (9%); asthma, bronchitis, decreased breathing sounds, epistaxis, exertional dyspnea, exertional hypoxia, hemoptysis, increased bronchial secretion, increased sputum, pleural effusion, sinusitis, upper respiratory tract infection, wheezing (at least 1%); apnea, laryngospasm, rebound respiratory depression postoperatively, respiratory depression.

Miscellaneous

Peripheral edema (32%); cancer pain (16%); accidental overdose (14%); pyrexia (7%); cachexia, cellulitis, chest pain, chills, contusion, edema, fever, flu syndrome, fungal infection, hypersensitivity, infection, influenza, mucosal inflammation, oral herpes, sepsis, spinal compression fracture, viral infection, withdrawal syndrome (at least 1%).

Precautions

Warnings

Fentanyl has an abuse liability similar to other opioid analgesics. Abstral , Actiq , Fentora , Lazanda , Onsolis , and Subsys must not be used in opioid-nontolerant patients. Fatal respiratory depression has occurred in patients treated with these products. Abstral , Actiq , Fentora , Lazanda , Onsolis , and Subsys 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. Abstral , Actiq , Fentora , Lazanda , Onsolis , and Subsys contain a quantity of fentanyl that can be fatal to a child, in individuals for whom it is not prescribed, and in those who are not opioid tolerant.

Do not convert patients on a mcg-per-mcg basis from one oral transmucosal fentanyl product to another. When dispensing, do not substitute Abstral , Actiq , Fentora , Lazanda , Onsolis , and Subsys for any other fentanyl product. Substantial differences exist in the pharmacokinetic profile of these products, which result in clinically important differences in the extent of fentanyl absorption.

Abstral , Actiq , Fentora , Lazanda , Onsolis , and Subsys are available only through a restricted program, called the Transmucosal Immediate-Release Fentanyl Risk Evaluation and Mitigation Strategy. Under the program, outpatients, health care providers who prescribe to outpatients, pharmacies, and distributors must enroll in the program to prescribe, receive, dispense, and distribute Abstral , Actiq , Fentora , Lazanda , Onsolis , and Subsys .


Monitor

Assess pain type and intensity prior to administration; assess efficacy of pain relief shortly after administration. Assess respiratory rate, heart rate, and BP frequently. Closely monitor for respiratory depression and CNS effects in elderly patients and patients with renal and/or hepatic impairment. Monitor for signs of misuse, abuse, or addiction.


Pregnancy

Category C . The use of fentanyl is not recommended in labor and delivery.

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established in pediatric patients younger than 16 y ( Actiq ). Safety and efficacy not established in pediatric patients younger than 18 y ( Abstral , Fentora , Lazanda , Onsolis , Subsys ). Safety and efficacy not established in children younger than 2 y (injection).

Elderly

May be more sensitive to the effects of fentanyl; use with caution.

Hypersensitivity

Anaphylaxis and hypersensitivity have been reported.

Renal Function

Duration of action may be prolonged; may need to reduce dose.

Hepatic Function

Duration of action may be prolonged; may need to reduce dose.

Special Risk Patients

Use with caution in patients with bradyarrhythmias, bradycardia, COPD, decreased respiratory reserve, head injury, or increased intracranial pressure.

Hazardous Tasks

May impair mental and/or physical ability required to perform potentially dangerous tasks (eg, driving a car, operating machinery). Warn patients taking fentanyl of these dangers and counsel them accordingly.

Drug dependence

Fentanyl has abuse potential.

Respiratory depression

Clinically important hypoventilation may occur; monitor patients for symptoms of respiratory depression. Respiratory depression may persist longer than the analgesic effect.

Skeletal muscle rigidity

May cause skeletal muscle rigidity, particularly of the muscles of respiration.

Overdosage

Symptoms

Cardiopulmonary arrest, circulatory collapse, CNS depression, death, hypoventilation, miosis, respiratory depression, seizures.

Patient Information

  • Advise patients receiving Abstral , Actiq , Fentora , Lazanda , Onsolis , or Subsys to read the Medication Guide before using the product for the first time and with each refill.
  • Instruct patient to avoid use of other CNS depressants or alcohol and to avoid driving after administration.
  • Advise patients that drug may impair mental and physical ability required to perform potentially dangerous tasks (eg, driving, operating machinery).
  • Instruct patient about adverse reactions and how to identify signs and symptoms that should be reported.
  • Explain that light-headedness and dizziness are frequently experienced and that transfer assistance should be used as needed.
  • Explain potential for tolerance with continued use.
  • Inform patients that they should not take Abstral , Actiq , Fentora , Lazanda , Onsolis , or Subsys for acute pain, postoperative pain, pain from injuries, headache, migraine, or any other short-term pain.
  • Advise patients that if they are not taking an opioid medication on a scheduled basis, they should not take Abstral , Actiq , Fentora , Lazanda , Onsolis , or Subsys .
  • Advise patients to inform their health care provider if breakthrough pain is not alleviated or worsens.
  • Instruct patients taking Abstral , Actiq , Fentora , Lazanda , Onsolis , or Subsys that medication is only available through restricted distribution programs and that they must be enrolled in the program to receive the drug.
  • Instruct patients to keep fentanyl out of the reach of children. Advise patients that these products contain an amount of fentanyl that could be fatal to a child, individuals for whom it is not prescribed, and those who are not opioid tolerant.
  • Advise patients to take medication exactly as prescribed, with special regard to dosage, dose titration, and administration route. Advise patients not to switch from one fentanyl product to another without discussing it with their health care provider.
  • Abstral
  • Inform patients that Abstral sublingual tablets should not be chewed, sucked, or swallowed. Instruct patients to place the tablet on the floor of the mouth, directly under the tongue. Allow the tablet to completely dissolve in the sublingual cavity. Instruct patients not to eat or drink anything until the tablet is completely dissolved; patients who have a dry mouth may use water to moisten the buccal mucosa before taking the sublingual tablets.
  • Advise patients to dispose of unused Abstral tablets by removing them from the blister cards and flushing them down the toilet. Inform patients that blister cards and cartons should not be disposed of down the toilet.
  • Actiq
  • Inform patients that Actiq contains approximately 2 g of sugar per unit and that dry mouth associated with fentanyl use may increase the risk of dental decay.
  • Advise diabetic patients that Actiq contains 2 g of sugar per unit.
  • Inform patients that Actiq lozenge should be sucked, not chewed. The lozenge should be placed between the cheek and lower gum, occasionally moving it from one side to the other using the handle. The lozenge should be consumed over a 15-min period.
  • Instruct patients that if a breakthrough pain episode is not relieved 15 min after finishing the lozenge, they may take 1 additional lozenge of the same strength for that episode. Advise patients that they must wait at least 4 h before treating another episode of breakthrough pain with Actiq .
  • Advise patients to properly dispose of partially used lozenges as soon as possible. Instruct them to place the handle under hot running water until all of the lozenge has dissolved. Handles without any drug left may be disposed of in a trash container that is out of the reach of children.
  • Instruct patients to dispose of unused lozenges by removing them from the packaging and using wire-cutting pliers to cut the lozenge off of the handle. Advise patients to do this over the toilet bowl so that the unused lozenge falls into the toilet. This should be repeated for additional unused lozenges. Flush the toilet twice after 5 lozenges have been cut and deposited in the toilet. Packaging and handles should be disposed of in a trash container out of the reach of children and not in the toilet.
  • Fentora
  • Advise patients that Fentora tablets should not be sucked, chewed, or swallowed. The tablet should be placed between the cheek and the gum and left there until disintegrated (approximately 14 to 25 min). If remnants remain after 30 min, they may be swallowed with a glass of water.
  • Instruct patients that if a breakthrough pain episode is not relieved after 30 min, they may take 1 additional dose of the same strength for that episode. Advise patients that they must wait at least 4 h before treating another episode of breakthrough pain with Fentora .
  • Lazanda
  • Patients must be instructed to keep Lazanda in its child-resistant container at all times. Once the bottle is empty, seal the pouch and place into the child-resistant storage container and discard in trash.
  • Instruct patient that to dispose of Lazanda properly, the remaining liquid in all bottles must be sprayed into the pouch provided in the pack for safe disposal as soon as possible. This includes any unwanted therapeutic sprays remaining in the bottle. After the counter has advanced to “8,” the patient should continue to push down on the finger grips a total of 4 times in order to expel any residual medicine from the bottle. After the 8 therapeutic sprays have been emitted, the patient will not hear a click and the counter will not advance beyond “8”; further sprays emitted will not be full sprays and should always be trapped in the pouch.
  • Advise patients that the fine mist spray is not always felt on the nasal mucosal membrane and to rely on the audible click and the advancement of the dose counter to confirm a spray has been administered.
  • Instruct patient to wash hands with soap and water immediately after handling the pouch.
  • Tell patients that they must wait at least 2 h before treating another episode of breakthrough pain with Lazanda .
  • Instruct patients to dispose of the Lazanda bottle and start a new one if it has been 5 days or more since the bottle was last used and/or it has been 14 days or more since the bottle was primed.
  • Onsolis
  • Inform patients that Onsolis films should not be cut or torn prior to use, or chewed and swallowed. Films should be placed on the inside of the cheek (pink side against cheek) and held in place for 5 sec. Liquids can be consumed after 5 min, and the film should dissolve within 15 to 30 min. The film should not be manipulated with the tongue or finger, and eating food should be avoided until the film is dissolved.
  • Advise patients that when multiple Onsolis films are used, they should not be placed on top of each other. They may be placed on both sides of the mouth.
  • Instruct patients to dispose of unused Onsolis films by removing them from the foil package and dropping them in the toilet. Repeat for each unused film and flush the toilet after all unused films have been put in the toilet. Advise patients not to flush the foil packages or cartons down the toilet.
  • Subsys
  • Inform patients not to open the blister package until immediately prior to use. Advise patient to carefully spray the contents of the unit into the mouth under the tongue.
  • Advise patients to dispose of unused Subsys units by removing them from the blister package and spraying the contents into the provided disposal bottle. The process should be repeated for each unused unit; after all units are disposed, close the disposal bottle and shake. Instruct patient to then place the disposal bottle into the provided bag; seal the bag and discard into a trash container out of the reach of children.

Copyright © 2009 Wolters Kluwer Health.

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