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Pronunciation |
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(FEN
ta
nil) |
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U.S. Brand
Names |
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Actiq® Oral Transmucosal;
Duragesic® Transdermal; Fentanyl Oralet®; Sublimaze®
Injection |
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Generic
Available |
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No |
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Synonyms |
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Fentanyl Citrate |
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Pharmacological Index |
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Analgesic, Narcotic; General Anesthetic |
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Use |
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Dental: Adjunct in preoperative intravenous conscious sedation in patients
undergoing dental surgery
Medical: Sedation, relief of pain, preoperative medication, adjunct to
general or regional anesthesia, management of chronic pain (transdermal product)
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Restrictions |
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C-II |
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Pregnancy Risk
Factor |
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B/D (if used for prolonged periods or in high doses at
term) |
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Contraindications |
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Hypersensitivity to fentanyl or any component; increased intracranial
pressure; severe respiratory depression; severe liver or renal insufficiency
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Warnings/Precautions |
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Fentanyl shares the toxic potentials of opiate agonists, and precautions of
opiate agonist therapy should be observed; use with caution in patients with
bradycardia; rapid I.V. infusion may result in skeletal muscle and chest wall
rigidity impaired
ventilation
respiratory distress
apnea,
bronchoconstriction, laryngospasm; inject slowly over 3-5 minutes;
nondepolarizing skeletal muscle relaxant may be required. Tolerance of drug
dependence may result from extended use.
Topical patches: Serum fentanyl concentrations may increase approximately
one-third for patients with a body temperature of 40°C
secondary to a temperature-dependent increase in fentanyl release from the
system and increased skin permeability. Patients who experience adverse
reactions should be monitored for at least 12 hours after removal of the patch.
The elderly may be particularly susceptible to the CNS depressant and
constipating effects of narcotics |
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Adverse
Reactions |
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>10%:
Cardiovascular: Hypotension, bradycardia
Central nervous system: CNS depression, drowsiness, sedation
Gastrointestinal: Nausea, vomiting, constipation
Respiratory: Respiratory depression
1% to 10%:
Cardiovascular: Cardiac arrhythmias, orthostatic hypotension
Central nervous system: Confusion
Gastrointestinal: Biliary tract spasm
Ocular: Miosis
<1%: Circulatory depression, convulsions, dysesthesia, paradoxical CNS
excitation or delirium; cold, clammy skin; dizziness, erythema, pruritus, rash,
urticaria, itching, ADH release, urinary tract spasm, bronchospasm,
laryngospasm, physical and psychological dependence with prolonged use
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Overdosage/Toxicology |
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Symptoms of overdose include CNS depression, respiratory depression, miosis
Treatment of an overdose includes support of the patient's airway,
establishment of an I.V. line, and administration of naloxone 2 mg I.V. (0.01
mg/kg for children) with repeat administration as necessary up to a total of 10
mg |
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Drug
Interactions |
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CYP3A3/4 enzyme substrate |
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Stability |
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Protect from light; incompatible when mixed in the same syringe with
pentobarbital |
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Mechanism of
Action |
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Binds with stereospecific receptors at many sites within the CNS, increases
pain threshold, alters pain reception, inhibits ascending pain
pathways |
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Pharmacodynamics/Kinetics |
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Respiratory depressant effect may last longer than analgesic effect
I.V.: Onset of analgesia: Almost immediate; Duration: 0.5-1 hour
Transmucosal:
Onset of effect: 5-15 minutes with a maximum reduction in
activity/apprehension
Peak analgesia: Within 20-30 minutes
Duration: Related to blood level of the drug
Absorption: Transmucosal: Rapid, ~25% from the buccal mucosa; 75% swallowed
with saliva and slowly absorbed from gastrointestinal tract
Distribution: Highly lipophilic, redistributes into muscle and fat
Metabolism: In the liver
Bioavailability: Transmucosal: ~50% (range: 36% to 71%)
Half-life: 2-4 hours
Transmucosal: 6.6 hours (range: 5-15 hours)
Elimination: In urine primarily as metabolites and 10% as unchanged drug
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Usual Dosage |
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Doses should be titrated to appropriate effects; wide range of doses,
dependent upon desired degree of analgesia/anesthesia
Sedation for minor procedures/analgesia:
I.M., I.V.: 1-2 mcg/kg/dose; may repeat at 30- to 60-minute intervals.
Note: Children 18-36 months of age may require 2-3 mcg/kg/dose
Transmucosal (dosage strength is based on patient weight): 5 mcg/kg if child
is not fearful; fearful children and some younger children may require doses of
5-15 mcg/kg (which also carries an increased risk of hypoventilation); drug
effect begins within 10 minutes, with sedation beginning shortly thereafter
Continuous sedation/analgesia: Initial I.V. bolus: 1-2 mcg/kg then 1
mcg/kg/hour; titrate upward; usual: 1-3 mcg/kg/hour
Pain control: Transdermal: Not recommended
Children >12 years and Adults:
Sedation for minor procedures/analgesia:
I.M., I.V.: 0.5-1 mcg/kg/dose; higher doses are used for major procedures
Transmucosal: 5 mcg/kg, suck on lozenge vigorously approximately 20-40
minutes before the start of procedure, drug effect begins within 10 minutes,
with sedation beginning shortly thereafter.
Dosage recommendations for transmucosal fentanyl
(Oralet®) based on patient age/weight:
Children <2 years of age OR <10 kg: CONTRAINDICATED
10 kg: 5-10 mcg/kg/dose (100 mcg): 10-15 mcg/kg/dose (100 mcg)
15 kg: 5-10 mcg/kg/dose (100 mcg): 10-15 mcg/kg/dose (200 mcg)
20 kg: 5-10 mcg/kg/dose (100 or 200 mcg): 10-15 mcg/kg/dose (200 or 300 mcg)
25 kg: 5-10 mcg/kg/dose (200 mcg): 10-15 mcg/kg/dose (300 mcg)
30 kg: 5-10 mcg/kg/dose (300 mcg): 10-15 mcg/kg/dose (300 or 400 mcg)
35 kg: 5-10 mcg/kg/dose (300 mcg): 10-15 mcg/kg/dose (400 mcg)
greater than or equal to 40 kg; 5-10 mcg/dose (400 mcg): 10-15 mcg/dose (400
mcg)
Adult dose: 400 mcg
Preoperative sedation, adjunct to regional anesthesia, postoperative pain:
I.M., I.V.: 50-100 mcg/dose
Adjunct to general anesthesia: I.M., I.V.: 2-50 mcg/kg
General anesthesia without additional anesthetic agents: I.V. 50-100 mcg/kg
with O2 and skeletal muscle relaxant
Pain control: Transdermal: Initial: 25 mcg/hour system; if currently
receiving opiates, convert to fentanyl equivalent and administer equianalgesic
dosage titrated to minimize the adverse effects and provide analgesia. To
convert patients from oral or parenteral opioids to
Duragesic®, the previous 24-hour analgesic requirement
should be calculated. This analgesic requirement should be converted to the
equianalgesic oral morphine dose.
Equianalgesic doses of opioid agonists*:
Codeine: 130 mg I.M.; 200 mg oral
Hydromorphone: 1.5 mg I.M.; 7.5 mg oral
Levorphanol: 2 mg I.M.; 4 mg oral
Meperidine: 75 mg I.M.
Methadone: 10 mg I.M.; 20 mg oral
Morphine: 10 mg I.M.; 60 mg oral
Oxycodone: 15 mg I.M.; 30 mg oral
Oxymorphone: 1 mg I.M.; 10 mg rectal
*From N Engl J Med, 1985, 313:84-95.
Corresponding doses of oral/intramuscular morphine and
Duragesic™*:
45-134 mg morphine oral/24 hours = 8-22 mg morphine I.M./24 hours = 25
mcg/hour Duragesic™
135-224 mg morphine oral/24 hours = 28-37 mg morphine I.M./24 hours = 50
mcg/hour Duragesic™
225-314 mg morphine oral/24 hours = 38-52 mg morphine I.M./24 hours = 75
mcg/hour Duragesic™
315-404 mg morphine oral/24 hours = 53-67 mg morphine I.M./24 hours = 100
mcg/hour Duragesic™
405-494 mg morphine oral/24 hours = 68-82 mg morphine I.M./24 hours = 125
mcg/hour Duragesic™
495-584 mg morphine oral/24 hours = 83-97 mg morphine I.M./24 hours = 150
mcg/hour Duragesic™
585-674 mg morphine oral/24 hours = 98-112 mg morphine I.M./24 hours = 175
mcg/hour Duragesic™
675-764 mg morphine oral/24 hours = 113-127 mg morphine I.M./24 hours = 200
mcg/hour Duragesic™
765-854 mg morphine oral/24 hours = 128-142 mg morphine I.M./24 hours = 225
mcg/hour Duragesic™
855-944 mg morphine oral/24 hours = 143-157 mg morphine I.M./24 hours = 250
mcg/hour Duragesic™
945-1034 mg morphine oral/24 hours = 158-172 mg morphine I.M./24 hours = 275
mcg/hour Duragesic™
1035-1124 mg morphine oral/24 hours = 173-187 mg morphine I.M./24 hours = 300
mcg/hour Duragesic™
*Product information, Duragesic™ - Janssen
Pharmaceutica, January, 1991.
The dosage should not be titrated more frequently than every 3 days after the
initial dose or every 6 days thereafter. The majority of patients are controlled
on every 72-hour administration, however, a small number of patients require
every 48-hour administration.
Elderly >65 years: Transmucosal: Dose should be reduced to 2.5-5 mcg/kg;
elderly have been found to be twice as sensitive as younger patients to the
effects of fentanyl
Dosing adjustment in renal impairment:
Clcr 10-50 mL/minute: Administer at 75% of normal dose
Clcr <10 mL/minute: Administer at 50% of normal dose
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Dietary
Considerations |
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Alcohol: Additive CNS effects, avoid or limit alcohol; watch for sedation
Food: Glucose may cause hyperglycemia; monitor blood glucose concentrations
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Monitoring
Parameters |
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Respiratory and cardiovascular status, blood pressure, heart
rate |
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Mental Health: Effects
on Mental Status |
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Drowsiness, sedation, and depression are common; may rarely cause paradoxical
CNS excitement or delirium |
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Mental Health:
Effects on Psychiatric
Treatment |
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Concurrent use with low potency antipsychotics and TCAs may produce additive
hypotension |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |
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Patient
Information |
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While using this medication, do not use alcohol and other prescription or OTC
medications (especially sedatives, tranquilizers, antihistamines, or pain
medications) without consulting prescriber. Maintain adequate hydration (2-3
L/day of fluids unless instructed to restrict fluid intake). May cause
hypotension, dizziness, drowsiness, impaired coordination, or blurred vision
(use caution when driving, climbing stairs, or changing position - rising from
sitting or lying to standing, or when engaging in tasks requiring alertness
until response to drug is known); nausea or vomiting (frequent mouth care, small
frequent meals, chewing gum, or sucking lozenges may help); constipation
(increased exercise, fluids, or dietary fruit and fiber may help - if
constipation remains an unresolved problem, consult prescriber about use of
stool softeners). Report acute dizziness, chest pain, slow or rapid heartbeat,
acute headache; confusion or changes in mentation; changes in voiding frequency
or amount, swelling of extremities, or unusual weight gain; shortness of breath
or difficulty breathing; or changes in vision. Pregnancy/breast-feeding
precautions: Inform prescriber if you are or intend to be pregnant. Consult
prescriber if breast-feeding. |
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Nursing
Implications |
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May cause rebound respiratory depression postoperatively
Patients with increased temperature may have increased fentanyl absorption
transdermally, observe for adverse effects, dosage adjustment may be needed
Pharmacologic and adverse effects can be seen after discontinuation of
transdermal system, observe patients for at least 12 hours after transdermal
product removed; keep transdermal product (both used and unused) out of the
reach of children
Do not use soap, alcohol, or other solvents to remove transdermal gel
if it accidentally touches skin as they may increase transdermal absorption, use
copious amounts of water. For patients who have received transmucosal product
within 6-12 hours, it is recommended that if other narcotics are required, they
should be used at starting doses
1/4
to 1/3
those usually recommended. |
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Dosage Forms |
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Injection, as citrate: 0.05 mg/mL (2 mL, 5 mL, 10 mL, 20 mL, 50 mL)
Lozenge, oral transmucosal (raspberry flavored):
Fentanyl Oralet®: 100 mcg, 200 mcg, 300 mcg, 400 mcg,
600 mcg, 800 mcg, 1200 mcg, 1600 mcg
Actiq®: 100 mcg, 200 mcg, 300 mcg, 400 mcg
Transdermal system: 25 mcg/hour [10 cm2]; 50 mcg/hour [20
cm2]; 75 mcg/hour [30 cm2]; 100 mcg/hour [40
cm2] (all available in 5s) |
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References |
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Baraka A,
"Fentanyl-Induced Laryngospasm Following Tracheal Extubation in a Child,"
Anaesthesia, 1995, 50(4):375.
Bedforth NM and Lockey DJ,
"Raynaud's Syndrome Following Intravenous Induction of Anaesthesia,"
Anaesthesia, 1995, 50(3):248-9.
Billmire DA, Neale HW, and Gregory RO,
"Use of I.V. Fentanyl in the Outpatient Treatment of Pediatric Facial Trauma,"
J Trauma, 1985, 25(11):1079-80.
Chaturvedi AK, Rao NG, and Baird JR,
"A Death Due to Self-Administered Fentanyl," J Anal Toxicol, 1990,
14(6):385-7.
"Drugs for Pain," Med Lett Drugs Ther, 1998, 40(1033):79-84.
Fine PG, "Fentanyl in the Treatment of Cancer Pain," Semin Oncol,
1997, 24(5 Suppl 16):S16-20-7.
Furuya H and Okumura F,
"Hemolysis After Administration of High Dose Fentanyl," Anesth Analg,
1986, 65(2):207-8.
Jeal W and Benfield P,
"Transdermal Fentanyl. A Review of Its Pharmacological Properties and Therapeutic Efficacy in Pain Control,"
Drugs, 1997, 53(1):109-38.
Katz R, Kelly HW, and Hsi A,
"Prospective Study on the Occurrence of Withdrawal in Critically Ill Children Who Receive Fentanyl by Continuous Infusion,"
Crit Care Med, 1994, 22(5):763-7.
Leuschen MP, Willett LD, Hoie EB, et al,
"Plasma Fentanyl Levels in Infants Undergoing Extracorporeal Membrane Oxygenation,"
J Thorac Cardiovasc Surg, 1993, 105(5):885-91.
Maurer PM and Bartkowski RR,
"Drug Interactions of Clinical Significance With Opiad Analgesics," Drug
Saf, 1993, 8(1):30-48.
Poklis A, "Fentanyl: A Review for Clinical and Analytical Toxicologists,"
J Toxicol Clin Toxicol, 1995, 33(5):439-47.
Roth B, Schlunder C, Houben F, et al,
"Analgesia and Sedation in Neonatal Intensive Care Using Fentanyl by Continuous Infusion,"
Dev Pharmacol Ther, 1991, 17(3-4):121-7.
Schechter NL, Weisman SJ, Rosenblum M, et al,
"The Use of Oral Transmucosal Fentanyl Citrate for Painful Procedures in Children,"
Pediatrics, 1995, 95(3):335-9.
Scholz J, Steinfath M, and Schulz M,
"Clinical Pharmacokinetics of Alfentanil, Fentanyl, and Sufentanil. An Update,"
Clin Pharmacokinet, 1996, 31(4):275-92.
Stoukides CA and Stegman M,
"Diffuse Rash Associated With Transdermal Fentanyl," Clin Pharm, 1992,
11(3):222.
Zeltzer LK, Altman A, Cohen D, et al,
"Report of the Subcommittee on the Management of Pain Associated With Procedures in Children With Cancer,"
Pediatrics, 1990, 86(5 Pt 2):826-31.
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