A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Actiq Warnings, Precautions, Pregnancy, Nursing, Abuse - Fentanyl Citrate
Actiq Warnings, Precautions, Pregnancy, Nursing, Abuse - Fentanyl Citrate
WARNINGS
See BOXED WARNING.
May be habit forming.
The concomitant use of other CNS depressants, including other opioids,
sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers,
skeletal muscle relaxants, sedating antihistamines, potent inhibitors
of cytochrome P450 3A4 isoform (e.g., erythromycin, ketoconazole, and
certain protease inhibitors), and alcoholic beverages may produce increased
depressant effects. Hypoventilation, hypotension, and profound sedation
may occur.
Actiq is not recommended for use in patients who have received
MAO inhibitors within 14 days, because severe and unpredictable potentiation
by MAO inhibitors has been reported with opioid analgesics.
Pediatric Use
The appropriate dosing and safety Actiq in opioid tolerant children
with breakthrough cancer pain have not been established below the age
of 16 years.
Patients and their caregivers must be instructed that Actiq
contains a medicine in an amount which can be fatal to a child. Patients
and their caregivers must be instructed to keep both used and unused dosage
units out of the reach of children. While all units should be disposed
of immediately after use, partially consumed units represent a special
risk to children. In the event that a unit is not completely consumed
it must be properly disposed as soon as possible. (See DOSAGE
AND ADMINISTRATION: SAFETY AND HANDLING, PRECAUTIONS
,
and PATIENT LEAFLET for specific patient instructions.)
Physicians and dispensing pharmacists must specifically question patients
or caregivers about the presence of children in the home on a full time
or visiting basis and counsel them regarding the dangers to children from
inadvertent exposure.
PRECAUTIONS
General
The initial dose of Actiq to treat episodes of breakthrough cancer
pain should be 200 mcg. Each patient should be individually titrated to
provide adequate analgesia while minimizing side effects.
Opioid analgesics impair the mental and/or physical ability required
for the performance of potentially dangerous tasks (e.g., driving a car
or operating machinery). Patients taking Actiq should be warned
of these dangers and should be counseled accordingly.
The use of concomitant CNS active drugs requires special patient care
and observation. (See WARNINGS
.)
Hypoventilation (Respiratory Depression)
As with all opioids, there is a risk of clinically significant hypoventilation
in patients using Actiq. Accordingly, all patients should be followed
for symptoms of respiratory depression. Hypoventilation may occur more
readily when opioids are given in conjunction with other agents that depress
respiration.
Chronic Pulmonary Disease
Because potent opioids can cause hypoventilation, Actiq should
be titrated with caution in patients with chronic obstructive pulmonary
disease or pre-existing medical conditions predisposing them to hypoventilation.
In such patients, even normal therapeutic doses of Actiq may further
decrease respiratory drive to the point of respiratory failure.
Head Injuries and Increased Intracranial Pressure
Actiq should only be administered with extreme caution in patients
who may be particularly susceptible to the intracranial effects of C02
retention such as those with evidence of increased intracranial pressure
or impaired consciousness. Opioids may obscure the clinical course of
a patient with a head injury and should be used only if clinically warranted.
Cardiac Disease
Intravenous fentanyl may produce bradycardia. Therefore, Actiq
should be used with caution in patients with bradyarrhythmias.
Hepatic or Renal Disease
Actiq should be administered with caution to patients with liver
or kidney dysfunction because of the importance of these organs in the
metabolism and excretion of drugs and effects on plasma binding proteins
(see CLINICAL PHARMACOLOGY: Pharmacokinetics).
Information for Patients and Their Caregivers
See PATIENT INFORMATION section.
Laboratory Tests
The effects of Actiq on laboratory tests have not been evaluated.
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Because animal carcinogenicity studies have not been conducted with fentanyl
citrate, the potential carcinogenic effect of Actiq is unknown.
Standard mutagenicity testing of fentanyl citrate has been conducted.
There was no evidence of mutagenicity in the Ames Salmonella or
Escherichia mutagenicity assay, the in-vitro mouse lymphoma
mutagenasis assay, and the in-vivo micronucleus cytogenetic assay
in the mouse.
Reproduction studies in rats revealed a significant decrease in the pregnancy
rate of all experimental groups. This decrease was most pronounced in
the high dose group (1.25 mg/kg subcutaneously) in which one of twenty
animals became pregnant.
Pregnancy - Category C
Fentanyl has been shown to impair fertility and to have an embryocidal
effect with an increase in resorptions in rats when given for a period
of 12 to 21 days in doses of 30 mcg/kg IV or 160 mcg/kg subcutaneously.
No evidence of teratogenic effects has been observed after administration
of fentanyl citrate to rats. There are no adequate and well-controlled
studies in pregnant women. Actiq should be used during pregnancy
only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery
Actiq is not indicated for use in labor and delivery.
Nursing Mothers
Fentanyl is excreted in human milk; therefore Actiq should not
be used in nursing women because of the possibility of sedation and/or
respiratory depression in their infants.
Pediatric Use
See WARNINGS
.
Geriatric Use
Of the 257 patients in clinical studies of Actiq in breakthrough
cancer pain, 61 (24%) were 65 and over, while 15 (6%) were 75 and over.
Those patients over the age of 65 titrated to a mean dose that was about
200 mcg less than the mean dose titrated to by younger patients. Previous
studies with intravenous fentanyl showed that elderly patients
are twice as sensitive to the effects of fentanyl as the younger population.
No difference was noted in the safety profile of the group over 65 as
compared to younger patients in Actiq clinical trials. However,
greater sensitivity in older individuals cannot be ruled out. Therefore
caution should be exercised in individually titrating Actiq in
elderly patients to provide adequate efficacy while minimizing risk.
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