PRECAUTIONS
DELAYED RESPIRATORY DEPRESSION, RESPIRATORY ARREST,
BRADYCARDIA, ASYSTOLE, ARRHYTHMIAS AND HYPOTENSION HAVE ALSO BEEN REPORTED.
THEREFORE, VITAL SIGNS MUST BE MONITORED CONTINUOUSLY.
General
The initial dose of alfentanil should be appropriately
reduced in elderly and debilitated patients. The effect of the initial dose
should be considered in determining supplemental doses. In obese patients (more
than 20% above ideal total body weight), the dosage of alfentanil should be
determined on the basis of lean body weight.
In one clinical trial, the dose of alfentanil required to
produce anesthesia, as determined by appearance of delta waves in EEG, was 40%
lower in geriatric patients than that needed in healthy young patients.
In patients with compromised liver function and in
geriatric patients, the plasma clearance of alfentanil may be reduced and
postoperative recovery may be prolonged.
Induction doses of alfentanil should be administered
slowly (over three minutes). Administration may produce loss of vascular tone
and hypotension. Consideration should be given to fluid replacement prior to
induction.
Diazepam administered immediately prior to or in
conjunction with high doses of alfentanil may produce vasodilation, hypotension
and result in delayed recovery.
Bradycardia produced by alfentanil may be treated with
atropine. Severe bradycardia and asystole have been successfully treated with
atropine and conventional resuscitative methods.
The hemodynamic effects of a particular muscle relaxant
and the degree of skeletal muscle relaxation required should be considered in
the selection of a neuromuscular blocking agent.
Following an anesthetic induction dose of alfentanil,
requirements for volatile inhalation anesthetics or alfentanil infusion are
reduced by 30 to 50% for the first hour of maintenance.
Alfentanil infusions should be discontinued at least
10-15 minutes prior to the end of surgery during general anesthesia. During
administration of alfentanil for Monitored Anesthesia Care (MAC), infusions may
be continued to the end of the procedure.
Respiratory depression caused by opioid analgesics can be
reversed by opioid antagonists such as naloxone. Because the duration of
respiratory depression produced by alfentanil may last longer than the duration
of the opioid antagonist action, appropriate surveillance should be maintained.
As with all potent opioids, profound analgesia is accompanied by respiratory depression
and diminished sensitivity to CO2 stimulation which may persist into or recur
in the postoperative period. Intraoperative hyperventilation may further alter
postoperative response to CO2. Appropriate postoperative monitoring should be
employed, particularly after infusions and large doses of alfentanil, to ensure
that adequate spontaneous breathing is established and maintained in the
absence of stimulation prior to discharging the patient from the recovery area.
Head Injuries
Alfentanil should be used with caution in patients with
head injury or increased intracranial pressure, due to the increased risk of
respiratory depression. As with all opioids, alfentanil may obscure the
clinical course of patients with head injuries and should be used only if
clinically indicated.
Impaired Respiration
Alfentanil should be used with caution in patients with
pulmonary disease, decreased respiratory reserve or potentially compromised
respiration. In such patients, opioids may additionally decrease respiratory
drive and increase airway resistance. During anesthesia, this can be managed by
assisted or controlled respiration.
Impaired Hepatic Or Renal Function
In patients with liver or kidney dysfunction, alfentanil
should be administered with caution due to the importance of these organs in
the metabolism and excretion of alfentanil.
Carcinogenesis, Mutagenesis And Impairment Of Fertility
No long-term animal studies of alfentanil have been
performed to evaluate carcinogenic potential. No structural chromosome
mutations were produced in the in vivo micronucleus test in female rats at
single intravenous doses of alfentanil as high as 20 mg/kg body weight (approximately
40 times the upper human dose), equivalent to a dose of 103 mg/m² body surface
area. No dominant lethal mutations were produced in the in vivo dominant lethal
test in male and female mice at the maximum intravenous dose of 20 mg/kg (60
mg/m²). No mutagenic activity was revealed in the in vitro Ames Salmonella
typhimurium test, with and without metabolic activation.
Pregnancy Category C
Alfentanil has been shown to
have an embryocidal effect in rats and rabbits when given in doses 2.5 times
the upper human dose for a period of 10 days to over 30 days. These effects
could have been due to maternal toxicity (decreased food consumption with
increased mortality) following prolonged administration of the drug.
No evidence of teratogenic effects has been observed
after administration of alfentanil in rats or rabbits.
There are no adequate and well-controlled studies in
pregnant women. Alfentanil should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Labor And Delivery
There are insufficient data to support the use of
alfentanil in labor and delivery. Placental transfer of the drug has been
reported; therefore, use in labor and delivery is not recommended.
Nursing Mothers
In one study of nine women undergoing postpartum tubal
ligation, significant levels of alfentanil were detected in colostrum four
hours after administration of 60 mcg/kg of alfentanil, with no detectable
levels present after 28 hours. Caution should be exercised when alfentanil is
administered to a nursing woman.
Pediatric Use
Adequate data to support the use of alfentanil in
children under 12 years of age are not presently available.