WARNINGS
FENTANYL CITRATE SHOULD BE ADMINISTERED ONLY BY PERSONS SPECIFICALLY TRAINED IN THE USE OF INTRAVENOUS ANESTHETICS AND MANAGEMENT OF THE RESPIRATORY EFFECTS OF POTENT OPIOIDS.
AN OPIOID ANTAGONIST, RESUSCITATIVE AND INTUBATION EQUIPMENT, AND OXYGEN SHOULD BE READILY AVAILABLE.
See also discussion of narcotic antagonists in PRECAUTIONS and OVERDOSAGE.
If fentanyl is administered with a tranquilizer such as droperidol, the user should become familiar with the special properties of each drug, particularly the widely differing duration of action. In addition, when such a combination is used, fluids and other countermeasures to manage hypotension should be available.
As with other potent narcotics, the respiratory depressant effect of fentanyl may persist longer than the measured analgesic effect. The total dose of all narcotic analgesics administered should be considered by the practitioner before ordering narcotic analgesics during recovery from anesthesia. It is recommended that narcotics, when required, should be used in reduced doses initially, as low as 1/4 to 1/3 those usually recommended.
Fentanyl may cause muscle rigidity, particularly involving the muscles of respiration. In addition, skeletal muscle movements of various groups in the extremities, neck, and external eye have been reported during induction of anesthesia with fentanyl; these reported movements have, on rare occasions, been strong enough to pose patient management problems. This effect is related to the dose and speed of injection and its incidence can be reduced by: 1) administration of up to 1/4 of the full paralyzing dose of a nondepolarizing neuromuscular blocking agent just prior to administration of fentanyl citrate; 2) administration of a full paralyzing dose of a neuromuscular blocking agent following loss of eyelash reflex when fentanyl is used in anesthetic doses titrated by slow intravenous infusion; or, 3) simultaneous administration of fentanyl citrate and a full paralyzing dose of a neuromuscular blocking agent when fentanyl citrate is used in rapidly administered anesthetic dosages. The neuromuscular blocking agent used should be compatible with the patient’s cardiovascular status.
Adequate facilities should be available for postoperative monitoring and ventilation of patients administered anesthetic doses of fentanyl. Where moderate or high doses are used (above 10 mcg/kg), there must be adequate facilities for postoperative observation, and ventilation if necessary, of patients who have received fentanyl. It is essential that these facilities be fully equipped to handle all degrees of respiratory depression.
Fentanyl may also produce other signs and symptoms characteristic of narcotic analgesics including euphoria, miosis, bradycardia, and bronchoconstriction.
Severe and unpredictable potentiation by MAO inhibitors has been reported for other narcotic analgesics. Although this has not been reported for fentanyl, there are insufficient data to establish that this does not occur with fentanyl. Therefore, when fentanyl is administered to patients who have received MAO inhibitors within 14 days, appropriate monitoring and ready availability of vasodilators and beta-blockers for the treatment of hypertension is indicated.
Head Injuries and Increased Intracranial Pressure — Fentanyl should be used with caution in patients who may be particularly susceptible to respiratory depression, such as comatose patients who may have a head injury or brain tumor. In addition, fentanyl may obscure the clinical course of patients with head injury.
PRECAUTIONS
General
The initial dose of fentanyl citrate should be appropriately reduced in elderly and debilitated patients. The effect of the initial dose should be considered in determining incremental doses.
Nitrous oxide has been reported to produce cardiovascular depression when given with higher doses of fentanyl.
Certain forms of conduction anesthesia, such as spinal anesthesia and some peridural anesthetics, can alter respiration by blocking intercostal nerves. Through other mechanisms (see CLINICAL PHARMACOLOGY) fentanyl can also alter respiration. Therefore, when fentanyl is used to supplement these forms of anesthesia, the anesthetist should be familiar with the physiological alterations involved, and be prepared to manage them in the patients selected for these forms of anesthesia.
When a tranquilizer such as droperidol is used with fentanyl, pulmonary arterial pressure may be decreased. This fact should be considered by those who conduct diagnostic and surgical procedures where interpretation of pulmonary arterial pressure measurements might determine final management of the patient. When high dose or anesthetic dosages of fentanyl are employed, even relatively small dosages of diazepam may cause cardiovascular depression.
When fentanyl is used with a tranquilizer such as droperidol, hypotension can occur. If it occurs, the possibility of hypovolemia should also be considered and managed with appropriate parenteral fluid therapy. Repositioning the patient to improve venous return to the heart should be considered when operative conditions permit. Care should be exercised in moving and positioning of patients because of the possibility of orthostatic hypotension. If volume expansion with fluids plus other countermeasures do not correct hypotension, the administration of pressor agents other than epinephrine should be considered. Because of the alpha-adrenergic blocking action of droperidol, epinephrine may paradoxically decrease the blood pressure in patients treated with droperidol.
Elevated blood pressure, with and without preexisting hypertension, has been reported following administration of fentanyl citrate combined with droperidol. This might be due to unexplained alterations in sympathetic activity following large doses; however, it is also frequently attributed to anesthetic and surgical stimulation during light anesthesia.
When droperidol is used with fentanyl and the EEG is used for postoperative monitoring, it may be found that the EEG pattern returns to normal slowly.
Vital signs should be monitored routinely.
Respiratory depression caused by opioid analgesics can be reversed by opioid antagonists such as naloxone. Because the duration of respiratory depression produced by fentanyl 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 to ensure that adequate spontaneous breathing is established and maintained in the absence of stimulation prior to discharging the patient from the recovery area.
Impaired Respiration: Fentanyl should be used with caution in patients with chronic obstructive pulmonary disease, patients with decreased respiratory reserve, and others with potentially compromised respiration. In such patients, narcotics 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: Fentanyl citrate should be administered with caution to patients with liver and kidney dysfunction because of the importance of these organs in the metabolism and excretion of drugs.
Cardiovascular Effects: Fentanyl may produce bradycardia, which may be treated with atropine. Fentanyl should be used with caution in patients with cardiac bradyarrhythmias.
Drug Interactions:
Other CNS depressant drugs (e.g., barbiturates, tranquilizers, narcotics, and general anesthetics) will have additive or potentiating effects with fentanyl. When patients have received such drugs, the dose of fentanyl required will be less than usual. Following the administration of fentanyl citrate, the dose of other CNS depressant drugs should be reduced.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
No carcinogenicity or mutagenicity studies have been conducted with fentanyl citrate. Reproduction studies in rats revealed a significant decrease in the pregnancy rate of all experimental groups. This decrease was most pronounced in the high dosed group (1.25 mg/kg-12.5X human dose) in which one of twenty animals became pregnant.
Pregnancy – Category C:
Fentanyl citrate has been shown to impair fertility and to have an embryocidal effect in rats when given in doses 0.3 times the upper human dose for a period of 12 days. No evidence of teratogenic effects have been observed after administration of fentanyl citrate to rats. There are no adequate and well-controlled studies in pregnant women. Fentanyl 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 fentanyl in labor and delivery. Therefore, such use is not recommended.
Nursing Mothers:
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when fentanyl citrate is administered to a nursing woman.
Pediatric Use:
The safety and efficacy of fentanyl citrate in children under two years of age has not been established.
Rare cases of unexplained clinically significant methemoglobinemia have been reported in premature neonates undergoing emergency anesthesia and surgery which included combined use of fentanyl, pancuronium, and atropine. A direct cause and effect relationship between the combined use of these drugs and the reported cases of methemoglobinemia has not been established.
|
