What is the recommended dose of Tofacitinib (Janus kinase inhibitor) as per the British National Formulary for Children (BNFC)?

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Tofacitinib Dosing in the British National Formulary for Children (BNFC)

The British National Formulary for Children (BNFC) does not currently include specific dosing recommendations for tofacitinib in pediatric patients, as there is limited evidence supporting its routine use in children.

Available Evidence on Pediatric Dosing

Based on the available research evidence, tofacitinib has been studied in pediatric populations with the following dosing approaches:

Weight-Based Dosing in Clinical Trials

  • In juvenile idiopathic arthritis (JIA) studies, weight-based dosing has been used 1, 2:
    • For children 2 to <6 years: median dose of 3.0 mg twice daily
    • For children 6 to <12 years: median dose of 2.5 mg twice daily
    • For children 12 to <18 years: median dose of 5.0 mg twice daily

Dose Adjustments for Special Populations

  • Renal impairment: For severe renal disease (CrCl <30 mL/min), dose reduction to 5 mg once daily is recommended 3
  • Hepatic impairment 4:
    • Mild hepatic impairment: Standard dosing with careful monitoring
    • Moderate hepatic impairment: Reduced dose of 5 mg once daily
    • Severe hepatic impairment (Child-Pugh C): Not recommended

Important Monitoring Considerations

When administering tofacitinib to pediatric patients, the following monitoring should be implemented:

  • Baseline assessments:

    • Complete blood count
    • Liver function tests
    • Renal function tests
    • Screening for tuberculosis and other infections
  • Ongoing monitoring:

    • Complete blood count every 3 months
    • Liver function tests monthly for first 3 months, then every 3 months
    • Renal function tests every 3 months

Safety Considerations

Important safety considerations when using tofacitinib in pediatric patients:

  • Infection risk: Tofacitinib is associated with increased risk of serious infections, particularly herpes zoster 5

  • Laboratory abnormalities: Discontinue if 3:

    • Lymphocyte count <500 cells/mm³
    • Absolute neutrophil count <500 cells/mm³
    • Hemoglobin decreases by ≥2 g/dL or is <8.0 g/dL
  • Drug interactions: Dose reduction to 5 mg once daily when used with CYP3A4 inhibitors or medications that inhibit both CYP3A4 and CYP2C19 3

Formulations

Tofacitinib is available in:

  • Immediate-release tablets
  • Extended-release tablets (for once-daily dosing in adults) 6
  • Oral solution (grape flavor) for pediatric use 2

Clinical Efficacy in Pediatric Populations

In clinical trials for JIA, tofacitinib has shown efficacy:

  • In a phase 3 trial, tofacitinib significantly reduced flare rates compared to placebo (29% vs 53%) 1
  • Long-term extension studies show maintained efficacy up to 48 months 5

Conclusion

While tofacitinib has been studied in pediatric populations, particularly for JIA, it is important to note that specific BNFC dosing recommendations are not currently established. Clinicians considering tofacitinib for pediatric patients should refer to the weight-based dosing used in clinical trials and apply appropriate dose adjustments for special populations.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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