fentanyl citrate
Sublimaze

fentanyl transdermal system
Duragesic-25, Duragesic-50, Duragesic-75, Duragesic-100

fentanyl transmucosal
Actiq, Fentanyl Oralet

Available forms
Available by prescription only
Injection: 50 mcg/ml
Transdermal system: Patches designed to release 25 mcg, 50 mcg, 75 mcg, or 100 mcg of fentanyl/ hour.
Transmucosal: 100 mcg, 200 mcg, 300 mcg, 400 mcg (Oralet); 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1,200 mcg, 1,600 mcg (Actiq)

Indications and dosages
 Preoperatively. Adults: 50 to 100 mcg I.M. 30 to 60 minutes before surgery.
Children and adults who weigh less than 15 kg (33 lb): 5 mcg/kg as lozenge (Oralet only) P.O. for patient to suck until dissolved, 20 to 40 minutes before surgery.
 Adjunct to general anesthetic.
Low-dose regimen for minor procedures. Adults: 2 mcg/kg I.V.
Moderate-dose regimen for major procedures Adults: Initial dose is 2 to 20 mcg/kg I.V. May give additional doses of 25 to 100 mcg I.V. or I.M., p.r.n.
High-dose regimen for complicated procedures Adults: Initial dose is 20 to 50 mcg/kg I.V. May give additional doses of 25 mcg to one-half the initial dose, p.r.n.
 Adjunct to anesthesia. Lozenge. Adults and children older than age 2: 5 mcg/kg lozenge (Oralet only) P.O.
 Adjunct to regional anesthesia. Adults: 50 to 100 mcg I.M. or slow I.V. over 1 to 2 minutes.
 Induction and maintenance of anesthesia. Children ages 2 to 12: Reduced dose as low as 1.7 to 3.3 mcg/kg.
 Postoperative analgesic. Adults: 50 to 100 mcg I.M. q 1 to 2 hours, p.r.n.
 Management of chronic pain in patients who can’t be managed by lesser means. Adults: Apply one transdermal patch to a portion of the upper torso on an area of skin that isn’t irritated and hasn’t been irradiated. Start with the 25-mcg/hour system; adjust dosage as needed and tolerated. Each system may be worn for 72 hours.
 Management of breakthrough cancer pain. Actiq. Adults: Initial dose is 200 mcg. Give second dose 15 minutes after the previous dose (unit) has been completed. Don’t give more than 2 units for each breakthrough pain episode while the patient is in the adjustment phase. Evaluate each new dose used in the adjustment period over 1 to 2 days. Once an effective dose is established, limit patient to 4 units/day or less. Discontinue Actiq via gradual downward adjustment.
≡ Dosage adjustment. Lower doses are usually indicated for elderly patients who may be more sensitive to the therapeutic and adverse effects of drug.

Pharmacodynamics
Analgesic action: Fentanyl binds to the opiate receptors as an agonist to alter the patient’s perception of painful stimuli, thus providing analgesia for moderate to severe pain. Its CNS and respiratory depressant effects are similar to those of morphine. Drug has little hypnotic activity and rarely causes histamine release.

Pharmacokinetics
Absorption: Varies with form administered.
Distribution: Redistribution has been suggested as the main cause of the brief analgesic effect of fentanyl.
Metabolism: Metabolized in the liver.
Excretion: Excreted in urine as metabolites and unchanged drug. Elimination half-life is about 7 hours after parenteral use, 5 to 15 hours after transmucosal use, and 18 hours after transdermal use.

Contraindications and precautions
Contraindicated in patients intolerant of drug. Use cautiously in elderly or debilitated patients and in those with head injuries, increased CSF pressure, COPD, decreased respiratory reserve, compromised respirations, arrhythmias, or hepatic, renal, or cardiac disease.

Interactions
Drug-drug. Cimetidine, protease inhibitors: May increase respiratory and CNS depression. Reduce fentanyl dosage as needed.
CNS depressants (antihistamines, barbiturates, benzodiazepines, general anesthetics, muscle relaxants, narcotic analgesics, phenothiazines, sedative-hypnotics, tricyclic antidepressants): Causes potentiated respiratory and CNS depression, sedation, and hypotensive effects of drug. Use together cautiously.
Diazepam, general anesthetics: May cause severe CV depression. Avoid use together.
Droperidol: Causes hypotension and decreased pulmonary artery pressure. Use together cautiously.
Drugs extensively metabolized in the liver (digitoxin, phenytoin, rifampin): Causes drug accumulation and enhanced effects. Use together cautiously.
MAO inhibitors: Increases CNS effects. Don’t give fentanyl to patient who has taken an MAO inhibitor within 14 days.
Narcotic antagonists: May cause acute withdrawal syndrome. Use cautiously.
Spinal anesthesia, some peridural anesthetics: Fentanyl can alter respiration by blocking intercostal nerves. Avoid use together.
Drug-lifestyle. Alcohol use: May cause additive effects. Discourage alcohol use.

Adverse reactions
CNS: sedation, somnolence, clouded sensorium, euphoria, dizziness, headache, confusion, asthenia, nervousness, hallucinations, anxiety, depression.
CV: hypotension, hypertension, arrhythmias, chest pain.
GI: nausea, vomiting, constipation, ileus, abdominal pain, dry mouth, anorexia, diarrhea, dyspepsia.
GU: urine retention.
Respiratory: respiratory depression, hypoventilation, dyspnea, apnea.
Skin: reaction at application site (erythema, papules, edema), pruritus, diaphoresis.
Other: physical dependence.

Effects on lab test results
• May increase plasma amylase and lipase levels.

Overdose and treatment
The most common signs and symptoms are extensions of drug action. They include CNS depression, respiratory depression, and miosis. Other acute toxic effects include hypotension, bradycardia, hypothermia, shock, apnea, cardiopulmonary arrest, circulatory collapse, pulmonary edema, and seizures.
 To treat acute overdose, first establish adequate respiratory exchange via a patent airway and ventilation as needed; administer a narcotic antagonist (naloxone) to reverse respiratory depression. (Because the duration of action of fentanyl is longer than that of naloxone, repeated dosing may be needed.) Naloxone shouldn’t be given unless the patient has clinically significant respiratory or CV depression. Monitor vital signs closely.
 Provide symptomatic and supportive treatment. Monitor laboratory values, vital signs, and neurologic status closely.

Special considerations
• Fentanyl may cause bradycardia. Pretreatment with an anticholinergic (such as atropine or glycopyrrolate) may minimize this effect.
• High doses can produce muscle rigidity. This effect can be reversed by naloxone.
• Many anesthesiologists use epidural and intrathecal fentanyl as a potent adjunct to epidural anesthesia.
Transmucosal form
• The fentanyl Oralet is used as an adjunct to anesthesia; Actiq is used for breakthrough cancer pain.
 ALERT Amount of drug in lozenges can be fatal to a child.
Transdermal form
 ALERT Transdermal fentanyl isn’t recommended for postoperative pain.
• Dosage adjustments in patients using the transdermal system should be made gradually. Reaching steady state levels of a new dose may take up to 6 days; delay dose adjustment until after at least two applications.
• Most patients experience good control of pain for 3 days while wearing the transdermal system, although a few may need a new application after 48 hours. Because serum fentanyl level increases for the first 24 hours after application, analgesic effect can’t be evaluated for the first day.
• When reducing opiate therapy or switching to a different analgesic, withdraw the transdermal system gradually. Because the serum level of fentanyl decreases very gradually after removal, give half of the equianalgesic dose of the new analgesic 12 to 18 hours after removal.
• Observe patient for delayed onset of respiratory depression.
• Monitor patient for at least 12 hours for adverse reactions to transdermal system. Serum fentanyl levels decrease very gradually and may take as long as 17 hours to decline by 50%.
Pregnant patients
• Drug is contraindicated during pregnancy unless benefits outweigh risks to fetus.
Breast-feeding patients
• Drug appears in breast milk; don’t administer to breast-feeding women.
Pediatric patients
• Safe use in children younger than age 2 hasn’t been established for parenteral or transmucosal (buccal) use.
• Safe use in children younger than age 12 hasn’t been established for transdermal system.
• Don’t use transdermal system in children younger than age 18 who weigh less than 50 kg (110 lb).
• Don’t use buccal form in any child who weighs less than 15 kg (33 lb).
Geriatric patients
• Use cautiously in elderly patients.

Patient education
• Teach proper application of transdermal patch.
• Tell patient to apply a replacement patch to a new site if another patch is needed after 72 hours.
• Warn patient to keep lozenges out of reach of children.
• Advise patient on proper disposal of lozenges.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use