Indications
Moderate to severe chronic pain in opioid-tolerant patients
requiring use of daily, around-the-clock longterm
opioid treatment and for which alternative treatment
options are inadequate (extended-release).
Transdermal fentanyl is not recommended for the control
of postoperative, mild, or intermittent pain, nor
should it be used for short-term pain relief.
Action
Binds to opiate receptors in the CNS, altering the response
to and perception of pain. Therapeutic Effects:
Decrease in severity of chronic pain.
Pharmacokinetics
Absorption: Well absorbed (92% of dose) through
skin surface under transdermal patch, creating a depot
in the upper skin layers. Release from transdermal system
into systemic circulationqgradually to a constant
rate, providing continuous delivery for 72 hr.
Distribution: Crosses the placenta; enters breast
milk.Metabolism and Excretion: Mostly metabolized
by the liver (CYP3A4 enzyme system); 10–25% excreted
unchanged by the kidneys.
Half-life: 17 hr after removal of a single application
patch,qto 21 hr after removal of multiple patches (because
of continued release from deposition of drug in
skin layers).
TIME/ACTION PROFILE (p pain)
ROUTE ONSET PEAK DURATION
Transdermal 6 hr† 12–24 hr 72 hr‡
†Achievement of blood levels associated with analgesia.
Maximal response and dose titration may take up to 6 days.
‡While patch is worn.
Contraindications/Precautions
Contraindicated in: Hypersensitivity to fentanyl or
adhesives; Patients who are not opioid tolerant; Acute,
mild, intermittent, or postoperative pain; Significant
respiratory depression; Acute or severe bronchial
asthma; Paralytic ileus; Severe hepatic or renal impairment;
Alcohol intolerance (small amounts of alcohol
released into skin); OB: Not recommended during labor
and delivery; Lactation: Avoid use during breast
feeding; may cause infant sedation and/or respiratory
depression.
Use Cautiously in: Diabetes; Patients with severe
pulmonary disease; Mild or moderate hepatic or renal
impairment; CNS tumors;qintracranial pressure; Head
trauma; Adrenal insufficiency; Undiagnosed abdominal
pain; Hypothyroidism; Alcoholism; Cardiac disease
(particularly bradyarrhythmias); Fever or situations
thatqbody temperature (qrelease of fentanyl from delivery
system); Titration period (additional analgesics
may be required); Cachectic or debilitated patients
(dosepsuggested because of altered drug disposition);
OB: Use only if the potential benefit justifies the potential
risk to the fetus. Chronic maternal treatment with
opioids during pregnancy may result in neonatal abstinence
syndrome; Pedi: Children 2 yr (safety not established);
pediatric patients initiating therapy at 25
mcg/hr should be opioid tolerant and receiving at least
60 mg oral morphine equivalents per day; Geri:qrisk
of respiratory depression; dosepsuggested.
Adverse Reactions/Side Effects
CNS: confusion, sedation, weakness, dizziness, restlessness.
Resp: APNEA, bronchoconstriction, laryngospasm,
RESPIRATORY DEPRESSION. CV: bradycardia, hypotension.
GI: anorexia, constipation, dry mouth,
nausea, vomiting. Derm: sweating, erythema. Endo:
adrenal insufficiency. Local: application site reactions.
MS: skeletal and thoracic muscle rigidity. Misc:
physical dependence, psychological dependence.
Interactions
Drug-Drug: Avoid use in patients who have received
MAO inhibitors within the previous 14 days (may
produce unpredictable, potentially fatal reactions).
Concomitant use of CYP3A4 inhibitors including ritonavir,
ketoconazole, itraconazole, clarithromycin,
nelfinavir, nefazodone, amiodarone, diltiazem,
aprepitant, fluconazole, fosamprenavir,
verapamil, and erythromycin may result inqplasma
levels andqrisk of CNS and respiratory depression.
Levels and effectiveness may bepby CYP3A4 inducers
including rifampin, carbamazepine, and phenytoin.
Use with benzodiazepines or other CNS depressants
including other opioids,
non-benzodiazepine sedative/hypnotics, anxiolytics,
general anesthetics, muscle relaxants, antipsychotics,
and alcohol may cause profound sedation,
respiratory depression, coma, and death; reserve concurrent
use for when alternative treatment options are
inadequate. Drugs that affect serotonergic neurotransmitter
systems, including tricyclic antidepressants,
SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol,
trazodone, mirtazapine, 5–HT3 receptor antagonists,
linezolid, methylene blue, and triptansq
risk of serotonin syndrome.
Drug-Natural Products: Concomitant use of
kava-kava, valerian, or chamomile canqCNS depression.
Drug-Food: Grapefruit juice is a moderate inhibitor
of the CYP3A4 enzyme system; concurrent use may
qblood levels and the risk of respiratory and CNS depression.
Careful monitoring and dose adjustment is
recommended.
Route/Dosage
Transdermal (Adults): 25 mcg/hr is the initial dose;
patients who have not been receiving opioids should receive
not more than 25 mcg/hr. To calculate the dose of
transdermal fentanyl required in patients who are already
receiving opioid analgesics, assess the 24-hr requirement
of currently used opioid. Using the equianalgesic
table in Appendix J, convert this to an equivalent
amount of morphine/24 hr. Conversion to fentanyl
transdermal may be accomplished by using the fentanyl
conversion table (Appendix J). During dose titration,
additional short-acting opioids should be available for
any breakthrough pain that may occur. Morphine 10
mg IM or 60 mg PO q 4 hr (60 mg/24 hr IM or 360 mg/
24 hr PO) is considered to be approximately equivalent
to transdermal fentanyl 100 mcg/hr. Transdermal patch
lasts 72 hr in most patients. Some patients require a
new patch every 48 hr.
Transdermal (Adults 60 yr, Debilitated, or Cachectic
Patients): Initial dose should be 25 mcg/hr
unless previous opioid use was 135 m g morphine
PO/day (or other opioid equivalent).
Hepatic Impairment
Transdermal (Adults): Mild-to-moderate hepatic
impairment—12 mcg/hr is the initial dose.
Renal Impairment
Transdermal (Adults): Mild-to-moderate renal impairment—
12 mcg/hr is the initial dose.
Availability (generic available)
Transdermal systems: 12.5 mcg/hr, 25 mcg/hr, 50
mcg/hr, 75 mcg/hr, 100 mcg/hr. Cost: Generic—12
mcg/hr $101.51/5, 25 mcg/hr $72.17/5, 50 mcg/hr
$131.92/5, 75 mcg/hr $201.23/5, 100 mcg/hr
$267.07/5.
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