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

Interactions
PK
Renal impairment
References

Fentanyl (transdermal and nasal)

Generic name
Fentanyl (transdermal and nasal)
Brand name
ATC Code
N02AB03

Pharmacokinetics in children

Fentanyl concentrations were measured in more than 250 children aged 2 to 17 years who were applied fentanyl patches in the dose range of 12.5 to 300 mcg/h. Adjusted for body weight, clearance appears to be approximately 80% higher in children 2 to 5 years old and 25% higher in children 6 to 10 years old when compared to children 11 to 16 years old, who are expected to have a similar clearance as adults. [SmPC Durogesic SMAT].

The increased clearance in children ought to result in a shorter t1/2 than adults which was also reported by Paut et al. Cmax was negatively correlated with patient age but not with body weight. These results suggest that the pharmacokinetics of transdermal fentanyl in children are similar to those in adults. (Paut 2000). Transdermal clearance in children with cancer was inversely related to body weight (Collins 1999).

Dose Age (weight) N Cmax(mean+SD) Tmax(mean+SD) T ½(mean+SD) Reference
25µg/h for 72 hrs 18-60 months (11-20kg) 8 1,7 (0,66) µg/L 18 (11) h 14,5 (6,2) h Paut 2000
25-200µg/h for 72h 7-18 years 11 0,91 - 39 µg/L 18 - >66 h   Collins 1999

For intranasal use in children no specific PK-Data is available.  

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

No information is present at this moment.

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Available formulations

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General Dose Info

Nasal administration: The IV fluid can be administered via a MAD (Mucosal Atomization Device).

Dosages

Chronic pain
  • Transdermal
    • < 2 years

      • No studies have been carried out into effective and safe doses for children aged less than 2 years

    • 2 years up to 16 years
      • Transdermal patch: 12 - 25 microg./hour dependent on the analgesic effect, replace the patch every 72 hours.

      • Use in children who are already receiving at least the equivalent of 30mg morphine per day.

        Calculation of the dose:

        1. Conversion of analgesic need/24 h to a equianalgesic oral morphine dose (click here for conversion table)
        2. Conversion of oral morphine /24 h to equianalgesic transdermal fentanyl dose:
        Oral morphine Transdermal fentanyl
        30-45 mg/day 12 mcg/hour
        45-90 mg/day 25 mcg/hour

        For converting doses of > 90 mg oral morphine/day, 45mg oral morphine/day corresponds roughly to Fentanyl 12 µg/hour transdermal

    • 16 years up to 18 years
      • Transdermal patch: 12 - 25 microg./hour dependent on the analgesic effect, replace the patch every 48-72 hours.

      • Calculation of the dose:

        1. Conversion of analgesic need/24 h to a equianalgesic oral morphine dose (click here for conversion table)
        2. Conversion of oral morphine /24 h to equianalgesic transdermal fentanyl dose:
          • Patients with need for opioid rotation, Clinically less stable patients:  Conversion ratio 150:1 - see SmPC Durogesic Table 2
          • Patients on stable and well tolerated opioid therapy: conversion ratio 100:1 -  see SmPC Durogesic Table 3

        If analgesia is insufficient during the first application only, the  patch may be replaced after 48 hours with a patch of the same dose, or the dose may be increased after 72 hours

         
Respiratory Distress in Palliative Care
  • Nasal
    • 1 month up to 18 years
      • 1 - 2 microg./kg/dose, as required repeat. Max single dose: 100 microg./dose.
    • Preterm neonates (GA < 37 weeks) and Term neonate
      • 0.5 - 2 microg./kg/dose, as required repeat. Max single dose: 100 microg./dose.
    • 1 month up to 18 years
      [10] [13]
      • 1 - 2 microg./kg/dose, as required repeat. Max single dose: 100 microg./dose.
    • Preterm neonates (GA < 37 weeks) and Term neonate
      [13]
      • 0.5 - 2 microg./kg/dose, as required repeat. Max single dose: 100 microg./dose.

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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.

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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

Transdermal use:

Based on the pooled safety data from the 3 paediatric clinical trials, the most commonly (i.e. ≥ 10% incidence) reported adverse events (with an incidence in %) were: vomiting (33,9%), nausea (23,5%), headache (16,3%), constipation (13,5%), diarrhea (12,8%) and pruritus (12,8%). Repeated use can lead to tolerance, physical and psychological dependence (SmPC Durogesic SMAT)

Most of the side effects reported after transdermal fentanyl have been due to the drug itself. However, adhesion problems (usually solved by additional application of medical tape) and pain on removal due to excessive adhesion have been reported (Delgado 2014)

Intranasal use:

Typical side effects of fentanyl such as sedation, nausea/Vomiting, dizziness, drowsiness reported. Due to intranasal use bad taste or nasal itching may occur (Serra et al. 2023).

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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

Strong  inhibitors of CYP3A4 such as erythromycin, ketoconazole, itraconazole, fluconazole or ritonavir can raise the plasma concentrations of fentanyl

Transdermal use:
When switching from other opioids to fentanyl transdermal or abrupt discontinuation of therapy, some patients may experience withdrawal symptoms such as nausea, vomiting, diarrhea, anxiety and tremors. Very rarely it has been reported that long-term use during pregnancy has led to withdrawal symptoms in the newborn. Cases of serotonin syndrome have been reported following simultaneously use of fentanyl with highly serotonergic drugs. [SmPC Durogesic SMAT]

Mainly non-intentional exposures (e.g. ingestion) in Children < 2 years were reported to a National Poison Data System (Thornton 2019)

Intranasal use can quickly lead to dependence. Be careful in prolonged use

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Interactions

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

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Natural opium alkaloids
N02AA03
N02AA01
N02AA05
N02AA59
Phenylpiperidine derivatives
N02AB03
N02AB02
Diphenylpropylamine derivatives
N02AC06
N02AC03
Oripavine derivatives
N02AE01
Morphinan derivatives
N02AF02
Other opioids
N02AX06
N02AX01
N02AX02
Opioids in combination with non-opioid analgesics
N02AJ13

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References

  1. Mercadante S., Cancer pain management in children, Palliat Med, 2004, 18, 654-62
  2. Finkel JC, Transdermal fentanyl in the management of children with chronic severe pain: results from an international study., Cancer, 2005, 104(12), 2847-57
  3. Zernikow B, et al., Transdermal fentanyl in childhood and adolescence: a comprehensive literature review, J Pain, 2007, 8(3), 187-207
  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. Collins JJ, et al., Transdermal fentanyl in children with cancer pain: feasibility, tolerability, and pharmacokinetic correlates, J Pediatr., 1999, 134(3), 319-23
  6. Hunt A, et al., Transdermal fentanyl for pain relief in a paediatric palliative care population., Palliat Med, 2001, 15(5), 405-12
  7. 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
  8. Paut O, et al, Pharmacokinetics of transdermal fentanyl in the peri-operative, Anaesthesia, 2000, 55, 1202-1207
  9. Johnson KL, et al, Fentanyl pharmacokinetics in the pediatric population, Anesthesiology, 1984, 61, A441
  10. Pieper L et al, Intranasal fentanyl for respiratory distress in children and adolescents with life-limiting conditions, BMC Palliat Care, 2018, Sep 10;17(1), 106
  11. Mudd S et al, Intranasal fentanyl for pain management in children: a systematic review of the literature, J Pediatr Health Care, 2011, Sep-Oct;25(5), 316-22
  12. Herd D et al, Intranasal fentanyl paediatric clinical practice guidelines, Emerg Med Australa, 2009, Aug;21(4), 335
  13. Harlos MS et al, Intranasal fentanyl in the palliative care of newborns and infants, J Pain Symptom Manage, 2013, Aug;46(2, 265-74
  14. Hansen MS et al, Limited evidence for intranasal fentanyl in the emergency department and the prehospital setting--a systematic review,, Dan Med J, 2013, Jan;60(1), A4563
  15. Ku, L.C., et al., Intranasal midazolam and fentanyl for procedural sedation and analgesia in infants in the neonatal intensive care unit., J Neonatal Perinatal Med, 2019, 12(2), 143-148
  16. Prescott, M.G., et al., Intranasal analgesia for acute moderate to severe pain in children - a systematic review and meta-analysis. , BMC Pediatr,, 2023, 23(1), 405
  17. McNair, C., et al., A cohort study of intranasal fentanyl for procedural pain management in neonates, Paediatr Child Health, 2018, 23(8), e170-e175
  18. Serra, S., et al., Intranasal Fentanyl for Acute Pain Management in Children, Adults and Elderly Patients in the Prehospital Emergency Service and in the Emergency Department: A Systematic Review., J Clin Med, 2023, 12(7)
  19. Nemeth, M., et al., Intranasal Analgesia and Sedation in Pediatric Emergency Care-A Prospective Observational Study on the Implementation of an Institutional Protocol in a Tertiary Children's Hospital., Pediatr Emerg Care, 2019, 35(2), 89-95
  20. Snyers, D. et al, Intranasal Analgosedation for Infants in the Neonatal Intensive Care Unit: A Systematic Review., Neonatology, 2022, 119(3), 273-284
  21. Sindhur, M., et al., Intranasal fentanyl for pain management during screening for retinopathy of prematurity in preterm infants: a randomized controlled trial., J Perinatol,, 2020, 40(6), 881-887
  22. JANSSEN-CILAG GmbH, SmPC Durogesic SMAT® transdermales Pflaster (60415.00.00), 2023/03
  23. Herd D et al, Intranasal fentanyl paediatric clinical practice guidelines, Emerg Med Australa, 2009, Aug;21(4), 335
  24. Ku, L.C., et al., Intranasal midazolam and fentanyl for procedural sedation and analgesia in infants in the neonatal intensive care unit., J Neonatal Perinatal Med, 2019, 12(2), 143-148
  25. Prescott, M.G., et al., Intranasal analgesia for acute moderate to severe pain in children - a systematic review and meta-analysis., BMC Pediatr,, 2023, 23(1), 405

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Changes

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