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Drugs reference index «Fentanyl Citrate»

Fentanyl Citrate

Pronunciation: (FEN-ta-nil SIT-rate)Class: Opioid analgesic

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

Pharmacology

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.

Pharmacokinetics

Absorption

Actiq

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.

Distribution

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.

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 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.

Onset

7 to 8 min.

Duration

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.

Special Populations

Renal Function Impairment

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.

Indications and Usage

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 ).

Contraindications

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.

Dosage and Administration

Premedication ( Sublimaze )Adults

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.

General Advice

  • Use Sublimaze immediately after dilution.
  • Administer Sublimaze IV dose slowly over 1 to 2 min.
  • The Actiq unit should be sucked, not chewed.
  • The Actiq unit should be placed between the cheek and lower gum, occasionally moving the drug matrix from 1 side to the other, using the handle.
  • The Actiq unit should be consumed over a 15-min period.
  • Do not open the Fentora blister pack or Onsolis buccal film package until ready to administer.
  • Do not store the Fentora tablet once it has been removed from the blister package.
  • Fentora tablets should not be sucked, chewed, or swallowed.
  • Fentora tablets should be left between the cheek and gum until disintegrated, which usually takes 14 to 25 min. If remnants remain after 30 min, they may be swallowed with a glass of water.
  • Onsolis buccal films are only available through a restricted distribution program, the FOCUS program. Health care providers, pharmacies, and patients must be registered with this program to prescribe, dispense, and receive Onsolis .
  • 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 seconds. 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.

Storage/Stability

Actiq , Fentora , Onsolis

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.

Drug Interactions

Amiodarone

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.

Laboratory Test Interactions

Increased amylase and lipase may occur up to 24 h after dose.

Adverse Reactions

Cardiovascular

Hypotension (5%); bradycardia, chest wall rigidity, deep thrombophlebitis, deep vein thrombosis, hot flush, hypertension, migraine, pallor, palpitation, tachycardia, vascular disorder (at least 1%).

CNS

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.

Dermatologic

Rash (8%); sweating (4%); pruritus (2%); alopecia, cold sweat, hyperhidrosis, skin ulcer (at least 1%); urticaria.

EENT

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

GI

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).

Genitourinary

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%).

Hematologic-Lymphatic

Anemia (13%); neutropenia (6%); decreased hematocrit, decreased hemoglobin, decreased platelet count, ecchymosis, leukopenia, lymphadenopathy, lymphedema, pancytopenia, thrombocytopenia (at least 1%).

Hepatic

Jaundice (at least 1%)

Local

Application-site irritation and pain (at least 1%).

Metabolic-Nutritional

Dehydration (13%); anorexia (9%); decreased appetite (8%); weight loss (7%); hypokalemia (6%); hypercalcemia, hypoalbuminemia, hypomagnesemia, hyponatremia, increased blood glucose (at least 1%).

Musculoskeletal

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.

Respiratory

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.

Miscellaneous

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.

Precautions

Warnings

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.

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.

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 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 ).

Elderly

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

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 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.

Bioavailability

Because products are not bioequivalent, when converting patients from other oral fentanyl products, do not substitute on a mcg per mcg basis.

Drug dependence

Fentanyl has abuse potential.

Hypoventilation

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 truncal muscles.

Overdosage

Symptoms

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

Patient Information

  • Instruct patient to avoid use of other CNS depressants or alcohol and to avoid driving after administration.
  • Advise patient 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.
  • Advise patient to inform health care provider if breakthrough pain is not alleviated or worsens.
  • Actiq , Fentora , Onsolis
  • Advise patient to read the Medication Guide before using product the first time and with each refill. The Medication Guide contains detailed instructions for storage, administration, disposal, and management of overdose.
  • Inform patient that Actiq , Fentora , and Onsolis contain an amount of medicine that can be fatal to a child.
  • Inform patient 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.
  • Instruct patient on proper method of disposal of used Actiq units and no longer needed, unopened Actiq units.
  • Instruct patient to place the Actiq unit between the cheek and lower gum. The unit should not be sucked or chewed and should be consumed over a 15-min period.
  • Instruct patient not to open the Fentora blister until ready to administer.
  • Instruct patient that once the Fentora tablet is removed from the blister unit, the entire tablet should be placed in the buccal cavity. The tablet should not be split, crushed, or chewed.
  • Instruct patient not to swallow Fentora tablets whole; tablets should be left between the cheek and gum until disintegrated, which usually takes 14 to 25 min. If remnants remain after 30 min, they may be swallowed with a glass of water.
  • Advise patients that Onsolis buccal films are only available through a restricted distribution program, the FOCUS program. Patients must be registered with this program to receive Onsolis .
  • Instruct patients not to open Onsolis buccal film packages until ready to administer. Buccal films should not be cut or torn prior to use, or chewed and swallowed.
  • Instruct patient that 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.

Copyright © 2009 Wolters Kluwer Health.

  • Fentanyl MedFacts Consumer Leaflet (Wolters Kluwer)
  • Actiq Consumer Overview
  • Actiq Prescribing Information (FDA)
  • Actiq Lozenge MedFacts Consumer Leaflet (Wolters Kluwer)
  • Actiq Advanced Consumer (Micromedex) - Includes Dosage Information
  • Duragesic Consumer Overview
  • Duragesic Prescribing Information (FDA)
  • Duragesic Advanced Consumer (Micromedex) - Includes Dosage Information
  • Duragesic Detailed Consumer Information (PDR)
  • Duragesic Patch MedFacts Consumer Leaflet (Wolters Kluwer)
  • Fentora Prescribing Information (FDA)
  • Fentora Detailed Consumer Information (PDR)
  • Fentora MedFacts Consumer Leaflet (Wolters Kluwer)
  • Fentora Consumer Overview
  • Ionsys Prescribing Information (FDA)
  • Ionsys Detailed Consumer Information (PDR)
  • Ionsys Consumer Overview
  • Onsolis Prescribing Information (FDA)
  • Onsolis Consumer Overview
  • Onsolis Soluble Film MedFacts Consumer Leaflet (Wolters Kluwer)
  • Sublimaze Prescribing Information (FDA)

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