NEODOSE

INDICATIONS

• Analgesia: A consensus of the International Evidence-Based Group for Neonatal Pain recommends the use of IV fentaNYL in newborns, using intermittent doses of 0.5 to 3 mcg/kg or a continuous infusion of 0.5 to 2 mcg/kg/hour. Investigators of one clinical trial in preterm neonates (32 weeks or younger) suggested bolus doses only when ventilation will be of short duration and before major painful procedures and to reserve continuous infusions when ventilation is expected to be of longer duration. A continuous infusion of fentaNYL 1 mcg/kg/hr, plus bolus doses of 1 mcg/kg prior to painful procedures, or as needed for severe pain, reduced the incidence of severe, acute procedural pain and severe prolonged pain compared with intermittent 1 mcg/kg bolus doses alone in a randomized, double-blind, placebo-controlled study of use initiated within 72 hours of birth in preterm newborns on mechanical ventilation (n=131; gestational age 22 to 32 weeks). However, no clinically significant difference was demonstrated for prolonged pain. Side effects, including longer duration of mechanical ventilation, longer time to first meconium passage, and higher mean airway pressure levels, were more common in the infusion versus bolus dose only group. Follow-up in 78 newborns (39 in both the fentaNYL and placebo groups) at 2 years of corrected age demonstrated a significant decrease in eye and hand coordination skills in the newborns administered fentaNYL continuous infusion versus bolus only. No difference was demonstrated for locomotor, personal and social skills, hearing and language, and performance.
• Sedation:
• Anesthesia:

PRECAUTIONS

• Addiction:
  • Abuse, misuse, or opioid addiction may occur; increased risk in patients with a personal or family history of substance abuse or mental illness; monitoring recommended.
• Cardiovascular:
  • Bradyarrhythmias may occur; monitoring recommended, particularly when initiating therapy.
  • Severe hypotension, including orthostatic hypotension and syncope, may occur in ambulatory patients, especially those with decreased blood volume or concurrent use of CNS depressants (eg, phenothiazides, general anesthetics). Avoid use in patients with circulatory shock.
  • Increased blood pressure may occur when coadministered with a neuroleptic agent; monitoring recommended.
• Concomitant use:
  • Avoid use with mixed agonists/antagonists and partial agonist analgesics.
  • Use not recommended within 14 days of MAOI administration.
  • Potentially life-threatening serotonin syndrome may occur with concomitant use of serotonergic drugs. In general, symptom onset occurs within several hours to a few days of concomitant use, but may occur later.
• Endocrine:
  • Adrenal insufficiency, typically with more than 1 month of use, has been reported. If adrenal insufficiency is suspected, perform diagnostic testing, treat with corticosteroids if confirmed, wean patient off of opioid if appropriate, and continue to assess adrenal function.
• Gastrointestinal:
  • Spasm of sphincter of Oddi may occur. Serum amylase may increase; monitoring recommended.
• Hepatic:
  • Biliary tract disease, including acute pancreatitis; use may cause spasm of the sphincter of Oddi and exacerbate symptoms; monitoring recommended.
  • Clearance may be decreased in patients with hepatic impairment; dose adjustments recommended in patients with mild to moderate hepatic impairment ; monitoring recommended.
  • Avoid use in patients with severe hepatic impairment.
• Nuromuscular:
  • Increased frequency of seizures may occur; monitoring recommended.
  • Decreased respiratory drive and subsequent carbon dioxide retention may occur, which may further increase intracranial pressure in susceptible patients (eg, brain tumors, elevated intracranial pressure); monitoring recommended especially at initiation.
  • Avoid use in patients with coma or impaired consciousness; opioids may obscure clinical course of head injury.
• Musculoskeletal:
  • Dose-related and rate-of-administration-related muscular rigidity, particularly involving muscles of respiration, has been reported with fentanyl injection; management protocol advised.
• Renal:
  • Clearance may be decreased in patients with renal impairment ; dose adjustments as needed ; monitoring recommended.
• Respiratory:
  • Decreased respiratory drive or apnea may occur in patients with chronic pulmonary disease (eg, chronic obstructive pulmonary disease, cor pulmonale, those with decreased respiratory reserve, hypoxia, hypercapnia, or respiratory depression); monitoring recommended, especially when given with other agents which depress respiration; consider nonopioid alternatives.
  • Sleep-related breathing disorders including central sleep apnea and sleeprelated hypoxemia may occur and risk increases in a dose-dependent fashion; dose reduction may be necessary.
  • Cachectic, or debilitated patients have an increased risk for respiratory depression; monitoring recommended, especially when given with other agents which depress respiration; consider nonopioid alternatives.
• Withdrawal:
  • Serious withdrawal symptoms, including uncontrolled pain, psychological distress, and suicide, may occur upon sudden dose decrease or discontinuation in patients who are physically dependent on opioid medications; do not discontinue abruptly and create a patient-specific plan to taper the opioid gradually.

ADVERSE EFFECTS

Respiratory depression occurs when anesthetic doses (greater than 5 mcg/kg) are used and may also occur unexpectedly because of redistribution. Chest wall rigidity has occurred in 4% of neonates who received 2.2 to 6.5 mcg/kg per dose, occasionally associated with laryngospasm. This was reversible with administration of naloxone. Urinary retention may occur when using continuous infusions. Tolerance may develop to analgesic doses with prolonged use. Significant withdrawal symptoms have been reported in patients treated with continuous infusion for 5 days or longer.

BLACK BOX WARNING

Warnings: Addiction, abuse, and misuse; live-threatening respiratory depression; CYP450 3A4 interaction; and risks from concomitant use of benzodiazepines or other CNS depressants.

• Addiction, Abuse, and Misuse
  • Fentanyl exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing, and monitor regularly for these behaviors or conditions.
• Life-threatening Respiratory Depression
  • Serious, life-threatening, or fatal respiratory depression may occur. Monitor for respiratory depression, especially during initiation of fentanyl or following a dose increase. Because of the risk of respiratory depression, fentanyl is contraindicated for use as an as-needed analgesic, in non-opioid tolerant patients, in acute pain, and in postoperative pain.
• Cytochrome P450 3A4 Interaction
  • The concomitant use of fentanyl with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in fentanyl plasma concentration. Monitor patients receiving fentanyl and any CYP3A4 inhibitor or inducer.
• Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
  • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
  • Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

ADMINISTRATION

• Intravenous: For continuous infusion, further dilute in compatible solution to a concentration of 10 mcg/mL. For intermittent infusions, administer over 15 to 30 minutes at concentrations of 10 mcg/mL.

MONITORING

Monitor respiratory and cardiovascular status closely. Observe for abdominal distention, loss of bowel sounds, and muscle rigidity..