Professional Information

Fentanyl Citrate

Pronouncation: (FEN-ta-nil SYE-trate)
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:
Sublimaze
- Injection 0.05 mg (as base)/mL

Pharmacology

Feedback for Fentanyl Citrate

As a treatment for...	Avg User Ratings [?]
Breakthrough Pain	0 comments Rate it!	10
Pain	31 comments Rate it!	8.9
Sedation	Be the first to rate it 0 comments

Showing 3 of 6 conditions - Show All...

Compare with other drugs.

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

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.

Distribution

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

Actiq , 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 active metabolite norfentanyl by CYP-450 3A4.

Elimination

Total plasma Cl is 0.5 L/h/kg; t _½ is about 7 h. 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 ).

Contraindications

Known intolerance or hypersensitivity to any component of the product or other opioid agonists.

Actiq , Fentora

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 60ߙmin 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 IV/IM. 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 )
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 up 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 or less units/day. 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.

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 until ready to administer.
Do not store 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.

Storage/Stability

Actiq , Fentora

Store at 59° to 86°F. Protect from freezing and moisture. Do not use if blister 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.

Potent CYP3A4 inhibitors (eg, clarithromycin, diltiazem, erythromycin, ketoconazole, itraconazole, nefazodone, protease inhibitors [eg, ritonavir]), 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

Hepatic

Actiq

Jaundice (at least 1%).

Fentora

Jaundice (at least 1%).

Local

Accidental injury (9%); hypertonia (3%); ascites, cachexia, cellulitis, chills, fever, flu syndrome, fungal infection, infection, pain, sepsis, viral infection (at least 1%).

Fentora

Peripheral edema (12%); cancer pain (5%); cellulitis, chest pain, chills, edema, influenza, injury (eg, fall, fracture, spinal compression), mucosal inflammation, pain (at least 1%).

Sublimaze

Anaphylaxis; psychological and physical dependence with chronic use; tolerance.

Precautions

Warnings

Fentanyl has an abuse liability similar to other opioid analgesics. Actiq and Fentora must not be used in non–opioid-tolerant patients. Actiq and Fentora 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 and Fentora 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.

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 ). Safety and efficacy not established in children younger than 2 yr of age ( Sublimaze ).

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, 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

Fentanyl may cause skeletal muscle rigidity, particularly of the truncal muscles.

Overdosage

Symptoms

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

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.

Actiq , Fentora
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 and Fentora contain an amount of medicine that can be fatal to a child.
Inform patient that Actiq contains approximately 2 g of sugar/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/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 patient to inform health care provider if breakthrough pain is not alleviated or worsens.