Fentanyl parenteral

Generic name
Fentanyl parenteral
Brand name
ATC Code
N01AH01
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Fentanyl parenteral

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

The following pharmacokinetic parameters are reported by the SmPC:

  Cl (ml/kg/min)* Vss (l/kg)* T½ (h)*
Infants 48-71 days post partum 21,9 - 32,3 6,0 - 9,5 3,1 - 15,5
Children 3,17 ± 0,68 years 11,5 ± 4,19 3,06 ± 1,02 4,1 ± 1,3
Adolescents 12 ± 1,73 years 7,05 ± 1,24 1,92 ± 1,04 3,5 ± 1,2
Adults   5,7 6-8

* Steady-state clearance and volume of distribution values have been normalized for body weight.

Farmacokinetic parameters in neonates:

Reference Gestational age Postnatal age Dose (i.v.) Cl VdSS (L/kg)  T½ (hour) 
SmPC ( Fentanyl Kalceks and Fentanyl Piramal) Unknown 1-26 days unknown 3,4-58,7 ml/kg/min 1,3-30.,3 1,3-15,9
Saarenmaa 2000 (n = 38) 26-42 weeks, median 32 weeks Median 10 hours Loading dose: 10,5 mcg/kg over 1 hour, followed by continuous infusion 1,5 mcg/kg/hour Mean 11,5 ± 4,0  (range: 4,6-18,5) ml/kg/min - -
Abiramalatha 2019 (CI: n-53) (IB:  n=47) Mean: CI: 36,5 (SD 4,6) weeks  IB: 35,4 (SD 4,0) weeks  Median: CI: 1 day; IB:2 days  CI: 1 mcg/kg loading dose, followed by 1 mcg/kg/hour
IB: 6 mcg/kg/day in 6 doses, dosing intervals 4 hours		 Median CI: 4,1 (2.0-6.4) L/hour . This equals appr. 28,1 ml/kg/min. - Median CI: 8,4 (Range 7,9-9,7) hours 
IB: 26,7 (8,1 - 65,2) hours 
Völler 2019 (n  = 98) Median 26,9 weeks (range: 23,9-31,9) Median: 3 days (range: 0-68) PNA 0-4 days: 0,5 mcg/kg/hour
PNA 5-9 days: 0,8 mcg/kg/hour (dose recommendations derived from popPK model)		 Estimated: 0,415 L/hour .This equals appr. 6,9 ml/kg/min. Estimated V in central compartment: 8,68 L -
Wu 2022 (pooled data from Völler 2019 and Saarenmaa 2000) (n = 164) median: 28,95 weeks (range: 23,90-42,30 weeks) median: 1,1 day (range: 0-68 days) See Saarenmaa 2000 and Völler 2019 Estimated: 0,573 L/hourThis equals appr. 8,2 ml/kg/min.    

CI = Continuous infusion; IB= Intermittent bolus

The clearance (11.5 ml/min/kg) in neonates is correlated significantly with gestational age and birthweight. (Saarenmaa 2000: continuous IV, N=38, gestational age 26-42 weeks)

 

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

General Dose Info

In obese children, use adjusted body weight to calculate initial dose, thereafter increase or decrease dose based on efficacy and safety.

Dosages

Pain
  • Intravenous
    • Term neonate
      • Initial dose: 0.5 - 3 microg./kg/dose, bolus.
      • Maintenance dose: 0.5 - 2 microg./kg/hour, continuous infusion.
    • 2 years up to 18 years
      • 1.25 microg./kg/dose every 30-45 minutes.

      • ALTERNATIVE: Continuous infusion: 1 mcg/kg/hour

    • Preterm neonates Gestational age < 37 weeks
      • Initial dose: 0.5 - 3 microg./kg/dose, bolus.
      • Maintenance dose: 0.5 - 3 microg./kg/hour, continuous infusion.
Analgesia in intubated patients (intensive care)
  • Intravenous
    • 1 month up to 2 years

      • Intermittent dosing: initial dose 1 mcg/kg/dose
        Continuous infusion: initial dose 1 mcg/kg/h, thereafter increase or decrease dose by 1 mcg/kg/h based on sedation and analgesia, as assessed every 4 hours. Max. 10 mcg/kg/h. If needed, administer extra bolus dose equivalent to the hourly dose.

    • 1 month up to 2 years
      [17] [18]

      • Intermittent dosing: initial dose 1 mcg/kg/dose
        Continuous infusion: initial dose 1 mcg/kg/h, thereafter increase or decrease dose by 1 mcg/kg/h based on sedation and analgesia, as assessed every 4 hours. Max. 10 mcg/kg/h. If needed, administer extra bolus dose equivalent to the hourly dose.

    • 12 years up to 18 years

      • Intermittent dosing: initial dose 0,7-1,4 mcg/kg/dose (max. 50-100 mcg/dose), repeat the injections. If necessary titrate to a higher dose. Max 0,35-1,8 mcg/kg/hour (max. 25-125 mcg/hour) 
        Continuous infusion: initial dose 1 mcg/kg/h, thereafter increase or decrease dose by 1 mcg/kg/h based on sedation and analgesia, as assessed every 4 hours. Max. 10 mcg/kg/h (max. 25-125 mcg/hour). If needed, administer extra bolus dose equivalent to the hourly dose.

    • 2 years up to 12 years

      • Intermittent dosing: initial dose 1-3 mcg/kg/dose (max. 50  mcg/dose), thereafter  repeat the injection at 1-1,25 mcg/kg/dose. (max. 25-125 mcg/hour) 
        Continuous infusion: initial dose 1 mcg/kg/h, thereafter increase or decrease dose by 1 mcg/kg/h based on sedation and analgesia, as assessed every 4 hours. Max. 10 mcg/kg/h (max. 25-125 mcg/hour). If needed, administer extra bolus dose equivalent to the hourly dose.
Analgesia as part of general anesthesia in intubated and ventilated patients
  • Intravenous
    • 1 month up to 18 years
      • Initial dose: Induction: 0.5 - 5 microg./kg/dose, once only. Max: 200 microg./dose. Usually 1-2 mcg/kg/dose is sufficient..
      • Maintenance dose: Intermitting: 30-35 minutes after initial dose 1 - 10 microg./kg/dose, as required every 30-35 minutes. Max: 50 microg./day. Or as a continuous infusion: 1-10 mcg/kg/hour, max. 420 mcg/hour.

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

After discontinuing prolonged infusions of fentanyl, children have experienced movement disorders, extraordinary sensitivity to stimuli and opiate-deprivation-like symptoms. [SmPC Fentanyl Hexal, SmPC Fentanyl-Piramal]

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Severe inhibitors of CYP3A4 such as erythromycin, ketoconazole, itraconazole, fluconazole or ritonavir can raise the plasma concentration of fentanyl.

Chest wall rigidity may occur in children under 2 years of age on low doses of fentanyl; (Dewhirst 2012)

Clearance of fentanyl is absent in neonates during the first 0-4 days of life. Cautious (low) dosing is indicated during the first week after birth, especially in premature neonates with gestational age < 32 weeks.

Repeated administration at short intervals over longer periods of time can lead to the development of a withdrawal syndrome after the end of treatment (SmPC).

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

ANESTHETICS, GENERAL

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Halogenated hydrocarbons
N01AB07
N01AB06
N01AB08
Barbiturates, plain
N01AF03
Opioid anesthetics
N01AH02
N01AH06
N01AH03
Other general anesthetics
N01AX01
N01AX14
N01AX07
N01AX10

References

  1. Anand KJ, et al., Consensus statement for the prevention and management of pain in the newborn, Arch Pediatr Adolesc Med, 2001, 155(2), 173-80
  2. Johnson KL, et al, Fentanyl pharmacokinetics in the pediatric population., Anesthesiology, 1984, 61, A441
  3. Mercadante S, Cancer pain management in children., Palliat Med, 2004, 18, 654-62
  4. Mukherjee K. et al, Adenotonsillectomy in children: a comparison of morphine and fentanyl for peri-operative analgesia., Anaesthesia, 2001, 56(12):, 1193-7
  5. Pasero C, Fentanyl for acute pain management., J Perianesth Nurs, 2005, 20(4), 279-84
  6. Rajamani A, et al, A comparison of bilateral infraorbital nerve block with intravenous fentanyl for analgesia following cleft lip repair in children, Paediatr Anaesth, 2007, 17(2), 133-9
  7. Saarenmaa E, et al, Gestational age and birth weight effects on plasma clearance of fentanyl in newborn infants, J Pediatr., 2000, 136(6), 767-70
  8. Santeiro ML, et al, Pharmacokinetics of continuous infusion fentanyl in newborns, J Perinatol, 1997, 17(2), 135-9
  9. Werkgroep Neonatale Farmacologie NVK sectie Neonatologie., Expert opinie, 13 november 2018
  10. Abiramalatha T, et al., Continuous infusion versus intermittent bolus doses of fentanyl for analgesia and sedation in neonates: an open-label randomised controlled trial., Archives of disease in childhood Fetal and neonatal edition, 2019, 104(4), F433-F9
  11. Kalceks, SmPC Fentanyl Kalceks 0,05 mg/ml, oplossing voor injectie (RVG 119760) 21-03-24, www.geneesmiddelinformatiebank.nl
  12. Piramal Critical Care BV., SmPC Fentanyl-Piramal oplossing voor injectie 0,05 mg/ml (RVG 04748) 22-03-2024, www.geneesmiddelinformatiebank.nl
  13. Wu Y, et al., Pre- and Postnatal Maturation are Important for Fentanyl Exposure in Preterm and Term Newborns: A Pooled Population Pharmacokinetic Study., Clin Pharmacokinet., 2022, 61(3), 401-12
  14. Abiramalatha T, et al., Continuous infusion versus intermittent bolus doses of fentanyl for analgesia and sedation in neonates: an open-label randomised controlled trial., Arch Dis Child Fetal Neonatal Ed., 2019, 104(4), F433-f9
  15. Völler S, et al., Rapidly maturing fentanyl clearance in preterm neonates. , Arch Dis Child Fetal Neonatal Ed., 2019, 104(6), 598-603
  16. Ancora G, et al., Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation., The Journal of pediatrics, 2013, 163(3), 645-51
  17. da Silva P, et al., Use of fentanyl and midazolam in mechanically ventilated children--Does the method of infusion matter?, Journal of critical care, 2016, 32, 108-13
  18. Hameln Pharma GmbH., SmPC Fentanyl hameln 50 microgram/ml, oplossing voor injectie, (RVG 25458) 01-03-2024, www.geneesmiddelinformatiebank.nl
  19. Simion C, et al., Postoperative pain control for primary cleft lip repair in infants: is there an advantage in performing peripheral nerve blocks?, Paediatr Anaesth, 2008, 18(11), 1060-5
  20. Ross EL, et al., Development of recommendations for dosing of commonly prescribed medications in critically ill obese children. , Am J Health Syst Pharm., 2015, 72(7), 542-56
  21. NHS, How should medicines be dosed in children who are obese?, 2021
  22. Dewhirst E, et al., Chest wall rigidity in two infants after low-dose fentanyl administration, 2012, Contract No.:5, Report No.: 1535-1815 (Electronic)
  23. Völler S, et al., Rapidly maturing fentanyl clearance in preterm neonates., Arch Dis Child Fetal Neonatal Ed., 2019, 104(6), 598-603
  24. Ross EL, et al., Development of recommendations for dosing of commonly prescribed medications in critically ill obese children., Am J Health Syst Pharm., 2015, 72(7), 542-56

Changes

Therapeutic Drug Monitoring


Overdose