Fentanyl Citrate

Fentanyl Citrate Injection is indicated for:

• •analgesic action of short duration during the anesthetic periods, premedication, induction and maintenance, and in the immediate postoperative period (recovery room) as the need arises.
• •use as an opioid analgesic supplement in general or regional anesthesia.
• •administration with a neuroleptic as an anesthetic premedication, for the induction of anesthesia and as an adjunct in the maintenance of general and regional anesthesia.
• •use as an anesthetic agent with oxygen in selected high-risk patients, such as those undergoing open heart surgery or certain complicated neurological or orthopedic procedures.

• •Fentanyl Citrate Injection should be administered only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids.
• •Ensure that an opioid antagonist, resuscitative and intubation equipment, and oxygen are readily available. (
  2.1 Important Dosage and Administration Instructions

  Fentanyl Citrate Injection should be administered only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids.

  • •Ensure that an opioid antagonist, resuscitative and intubation equipment, and oxygen are readily available.
  • •Individualize dosage based on factors such as age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and the surgical procedure involved.
  • •Monitor vital signs routinely.

  As with other potent opioids, the respiratory depressant effect of fentanyl may persist longer than the measured analgesic effect. The total dose of all opioid agonists administered should be considered by the practitioner before ordering opioid analgesics during recovery from anesthesia.

  If Fentanyl Citrate Injection is administered with a CNS depressant, become familiar with the properties of each drug, particularly each product's duration of action. In addition, when such a combination is used, fluids and other countermeasures to manage hypotension should be available

  [see

  Warnings and Precautions (5.3)

  ]

  .

  Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
  )
• •Individualize dosing based on the factors such as age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and the surgical procedure involved. (
  2.1 Important Dosage and Administration Instructions

  Fentanyl Citrate Injection should be administered only by persons specifically trained in the use of intravenous anesthetics and management of the respiratory effects of potent opioids.

  • •Ensure that an opioid antagonist, resuscitative and intubation equipment, and oxygen are readily available.
  • •Individualize dosage based on factors such as age, body weight, physical status, underlying pathological condition, use of other drugs, type of anesthesia to be used, and the surgical procedure involved.
  • •Monitor vital signs routinely.

  As with other potent opioids, the respiratory depressant effect of fentanyl may persist longer than the measured analgesic effect. The total dose of all opioid agonists administered should be considered by the practitioner before ordering opioid analgesics during recovery from anesthesia.

  If Fentanyl Citrate Injection is administered with a CNS depressant, become familiar with the properties of each drug, particularly each product's duration of action. In addition, when such a combination is used, fluids and other countermeasures to manage hypotension should be available

  [see

  Warnings and Precautions (5.3)

  ]

  .

  Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
  )
• •Initiate treatment in adults with 50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL). (
  2.2 Dosage

  50 mcg = 0.05 mg = 1 mL

  Premedication in Adults

  50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly 30 to 60 minutes prior to surgery.

  Adjunct to General Anesthesia

  See Dosage Range Charts below.

  Table 1: Dosage Range Chart

  TOTAL DOSAGE (expressed as fentanyl base)
  Low Dose –	Moderate Dose –	High Dose –
  2 mcg/kg (0.002 mg/kg) (0.04 mL/kg). For use in minor, but painful, surgical procedures. May also provide some pain relief in the immediate postoperative period.	2–20 mcg/kg (0.002–0.02 mg/kg) (0.04–0.4 mL/kg). For use in major surgical procedures, in addition to adequate analgesia, may abolish some of the stress response. Expect respiratory depression requiring artificial ventilation during anesthesia and careful observation of ventilation postoperatively is essential.	20–50 mcg/kg (0.02–0.05 mg/kg) (0.4–1 mL/kg). For open heart surgery and certain more complicated neurosurgical and orthopedic procedures where surgery is more prolonged, and the stress response to surgery would be detrimental to the wellbeing of the patient. In conjunction with nitrous oxide/oxygen has been shown to attenuate the stress response as defined by increased levels of circulating growth hormone, catecholamine, ADH and prolactin. Expect the need for postoperative ventilation and observation are essential due to extended postoperative respiratory depression.
  MAINTENANCE DOSE (expressed as fentanyl base)
  Low Dose –	Moderate Dose –	High Dose –
  2 mcg/kg (0.002 mg/kg) (0.04 mL/kg). Additional dosages are infrequently needed in these minor procedures.	2–20 mcg/kg (0.002–0.02 mg/kg) (0.04–0.4 mL/kg). 25 to 100 mcg (0.025 to 0.1 mg) (0.5 to 2 mL) Administer intravenously or intramuscularly as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia.	20–50 mcg/kg (0.02–0.05 mg/kg) (0.4–1 mL/kg). Maintenance dosage [ranging from 25 mcg (0.025 mg) (0.5 mL) to one half the initial loading dose] as needed based on vital signs changes indicative of stress and lightening of analgesia. Individualize dosage especially if the anticipated remaining operative time is short.

  Adjunct to Regional Anesthesia

  50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly or slowly intravenously, over one to two minutes, when additional analgesia is required.

  Postoperatively (recovery room)

  50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly for the control of pain, tachypnea and emergence delirium. The dose may be repeated in one to two hours as needed.

  For Induction and Maintenance in Children 2 to 12 Years of Age

  A reduced dose as low as 2 to 3 mcg/kg is recommended.

  As a General Anesthetic

  As a technique to attenuate the responses to surgical stress without the use of additional anesthetic agents, doses of 50 to 100 mcg/kg (0.05 to 0.1 mg/kg) (1 to 2 mL/kg) may be administered with oxygen and a muscle relaxant. In certain cases, doses up to 150 mcg/kg (0.15 mg/kg) (3 mL/kg) may be necessary to produce this anesthetic effect. It has been used for open heart surgery and certain other major surgical procedures in patients for whom protection of the myocardium from excess oxygen demand is particularly indicated, and for certain complicated neurological and orthopedic procedures.
  )
• •Initiate treatment in children 2 to 12 years of age with a reduced dose as low as 2 to 3 mcg/kg. (
  2.2 Dosage

  50 mcg = 0.05 mg = 1 mL

  Premedication in Adults

  50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly 30 to 60 minutes prior to surgery.

  Adjunct to General Anesthesia

  See Dosage Range Charts below.

  Table 1: Dosage Range Chart

  TOTAL DOSAGE (expressed as fentanyl base)
  Low Dose –	Moderate Dose –	High Dose –
  2 mcg/kg (0.002 mg/kg) (0.04 mL/kg). For use in minor, but painful, surgical procedures. May also provide some pain relief in the immediate postoperative period.	2–20 mcg/kg (0.002–0.02 mg/kg) (0.04–0.4 mL/kg). For use in major surgical procedures, in addition to adequate analgesia, may abolish some of the stress response. Expect respiratory depression requiring artificial ventilation during anesthesia and careful observation of ventilation postoperatively is essential.	20–50 mcg/kg (0.02–0.05 mg/kg) (0.4–1 mL/kg). For open heart surgery and certain more complicated neurosurgical and orthopedic procedures where surgery is more prolonged, and the stress response to surgery would be detrimental to the wellbeing of the patient. In conjunction with nitrous oxide/oxygen has been shown to attenuate the stress response as defined by increased levels of circulating growth hormone, catecholamine, ADH and prolactin. Expect the need for postoperative ventilation and observation are essential due to extended postoperative respiratory depression.
  MAINTENANCE DOSE (expressed as fentanyl base)
  Low Dose –	Moderate Dose –	High Dose –
  2 mcg/kg (0.002 mg/kg) (0.04 mL/kg). Additional dosages are infrequently needed in these minor procedures.	2–20 mcg/kg (0.002–0.02 mg/kg) (0.04–0.4 mL/kg). 25 to 100 mcg (0.025 to 0.1 mg) (0.5 to 2 mL) Administer intravenously or intramuscularly as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia.	20–50 mcg/kg (0.02–0.05 mg/kg) (0.4–1 mL/kg). Maintenance dosage [ranging from 25 mcg (0.025 mg) (0.5 mL) to one half the initial loading dose] as needed based on vital signs changes indicative of stress and lightening of analgesia. Individualize dosage especially if the anticipated remaining operative time is short.

  Adjunct to Regional Anesthesia

  50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly or slowly intravenously, over one to two minutes, when additional analgesia is required.

  Postoperatively (recovery room)

  50 to 100 mcg (0.05 to 0.1 mg) (1 to 2 mL) may be administered intramuscularly for the control of pain, tachypnea and emergence delirium. The dose may be repeated in one to two hours as needed.

  For Induction and Maintenance in Children 2 to 12 Years of Age

  A reduced dose as low as 2 to 3 mcg/kg is recommended.

  As a General Anesthetic

  As a technique to attenuate the responses to surgical stress without the use of additional anesthetic agents, doses of 50 to 100 mcg/kg (0.05 to 0.1 mg/kg) (1 to 2 mL/kg) may be administered with oxygen and a muscle relaxant. In certain cases, doses up to 150 mcg/kg (0.15 mg/kg) (3 mL/kg) may be necessary to produce this anesthetic effect. It has been used for open heart surgery and certain other major surgical procedures in patients for whom protection of the myocardium from excess oxygen demand is particularly indicated, and for certain complicated neurological and orthopedic procedures.
  )

• •Injection: 50 mcg (0.05 mg)/mL in single-dose Fliptop vial.
• •Injection: 50 mcg (0.05 mg)/mL in single-dose ampule.

• •
  Pregnancy
  : May cause fetal harm. (
  8.1 Pregnancy

  Risk Summary

  Use of opioid analgesics for an extended period of time during pregnancy may cause Neonatal Opioid Withdrawal Syndrome. Available data with Fentanyl Citrate Injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage ‎or adverse maternal outcomes‎. There are adverse outcomes reported with fetal exposure to opioid analgesics

  (see Clinical Considerations)

  .‎

  In animal reproduction studies, fentanyl administration to pregnant rats during organogenesis was embryocidal at doses within the range of the human recommended dosing. No evidence of malformations was noted in animal studies completed to date [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

  The background risk of major birth defects and miscarriage for the indicated population is unknown. All ‎pregnancies have a background risk of birth defect, loss, or other adverse outcomes.‎ In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

  Clinical Considerations

  Fetal/Neonatal Adverse Reactions

  Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

  Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly.

  Labor or Delivery

  Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Fentanyl Citrate Injection is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Fentanyl Citrate Injection, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

  Data

  Animal Data

  Fentanyl has been shown to embryocidal in pregnant rats at doses of 30 mcg/kg intravenously (0.05 times the human dose of 100 mcg/kg on a mg/m²basis) and 160 mcg/kg subcutaneously (0.26 times the human dose of 100 mcg/kg on a mg/m²basis). There was no evidence of teratogenicity reported.

  No evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered fentanyl continuously via subcutaneously implanted osmotic minipumps at doses of 10, 100, or 500 mcg/kg/day starting 2-weeks prior to breeding and throughout pregnancy. The high dose was approximately 0.81 times the human dose of 100 mcg/kg on a mg/m²basis.
  )
• •
  Lactation
  : Infants exposed to Fentanyl Citrate Injection through breast milk should be monitored for excess sedation and respiratory depression. (
  8.2 Lactation

  Risk Summary

  Fentanyl is present in breast milk. However, there is insufficient information to determine the effects of fentanyl on the breastfed infant and the effects of fentanyl on milk production.

  The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Fentanyl Citrate Injection and any potential adverse effects on the breastfed infant from Fentanyl Citrate Injection or from the underlying maternal condition.

  Clinical Considerations

  Monitor infants exposed to Fentanyl Citrate Injection through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
  )
• •
  Geriatric Patients
  : Titrate slowly and monitor for CNS and respiratory depression. (
  8.5 Geriatric Use

  Elderly patients (aged 65 years or older) may have increased sensitivity to fentanyl. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

  Respiratory depression is the chief risk for elderly patients treated with opioids and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Fentanyl Citrate Injection slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression

  [see Warnings and Precautions (5.2)]

  .

  Fentanyl is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
  )