Infantile hemangiomas (IHs) are the most common vascular tumours occurring in children. The incidence and prevalence of IH in Canada is uncertain; however, the manufacturer has estimated that the incidence of IH ranges from 4.5% to 10.0%. Hemangiol is an oral solution containing 3.75 mg/mL propranolol that is indicated for the treatment of proliferating IH requiring systemic therapy in the following circumstances: life- or function-threatening hemangioma; ulcerated hemangioma with pain and/or lack of response to simple wound care measures; or hemangioma with a risk of permanent scarring or disfigurement. The manufacturer has requested that propranolol oral solution receive a recommendation to reimburse in accordance with the Health Canada–approved indication.

Propranolol oral solution is the first treatment specifically indicated for the treatment of patients with IH in Canada. The product monograph states that treatment should be initiated in infants aged five weeks to five months and the age for treatment initiation should be corrected in cases of premature birth. The recommended therapeutic dosage of propranolol for the treatment of IH is 3 mg/kg/day (administered as 1.5 mg/kg twice daily). The product monograph recommends that the first dose and each dose escalation should be administered in a clinical setting where there are adequate facilities for handling adverse events, including events that require urgent measures.

The CADTH Common Drug Review (CDR) conducted a systematic review to evaluate the beneficial and harmful effects of propranolol oral solution for the treatment of proliferating IH requiring systemic therapy. The CDR review focused on the use of propranolol at the Health Canada–approved dosage regimen of 3 mg/kg/day for six months.

Contents

• Clinical Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Introduction
    • Results and Interpretation
    • Place in Therapy
    • Conclusions
  • 1. INTRODUCTION
    • 1.1. Disease Prevalence and Incidence
    • 1.2. Standards of Therapy
    • 1.3. Drug
  • 2. OBJECTIVES AND METHODS
    • 2.1. Objectives
    • 2.2. Methods
  • 3. RESULTS
    • 3.1. Findings from the Literature
    • 3.2. Included Studies
    • 3.3. Patient Disposition
    • 3.4. Exposure to Study Treatments
    • 3.5. Critical Appraisal
    • 3.6. Efficacy
    • 3.7. Harms
  • 4. DISCUSSION
    • 4.1. Summary of Available Evidence
    • 4.2. Interpretation of Results
    • 4.3. Potential Place in Therapy
  • 5. CONCLUSIONS
  • APPENDIX 1. PATIENT INPUT SUMMARY
    • 1. Brief Description of Patient Group Supplying Input
    • 2. Condition-Related Information
    • 3. Current Therapy-Related Information
    • 4. Expectations About the Drug Being Reviewed
  • APPENDIX 2. LITERATURE SEARCH STRATEGY
  • APPENDIX 3. EXCLUDED STUDIES
  • APPENDIX 4. DETAILED OUTCOME DATA
  • APPENDIX 5. SUMMARY OF STUDY 201 EXTENSION PHASE
    • Objective
    • Limitations
    • Summary
  • APPENDIX 6. SUMMARY OF COMPASSIONATE USE PROGRAM
    • Objective
    • Study Design
    • Patient Characteristics
    • Exposure to Propranolol in the CUP
    • Efficacy and Discontinuation from the CUP
    • Regrowth and Retreatment
    • Harms Data from the CUP
    • Critical Appraisal
    • Conclusion
  • REFERENCES
• Pharmacoeconomic Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Background
    • Summary of Identified Limitations and Key Results
    • Conclusions
  • INFORMATION ON THE PHARMACOECONOMIC SUBMISSION
    • 1. SUMMARY OF THE MANUFACTURER’S PHARMACOECONOMIC SUBMISSION
    • 2. MANUFACTURER’S BASE CASE
    • 3. SUMMARY OF MANUFACTURER’S SENSITIVITY ANALYSES
    • 4. LIMITATIONS OF MANUFACTURER’S SUBMISSION
      • Incorrect primary comparator
      • Modelled patient population differs from the indicated patient population
      • Uncertainty associated with the magnitude of treatment effect
      • Rate of spontaneous involution is associated with uncertainty
      • Duration of treatment appears to be underestimated
      • Uncertainty with utility values
    • 5. CADTH COMMON DRUG REVIEW REANALYSES
    • 6. ISSUES FOR CONSIDERATION
    • 7. PATIENT GROUP INPUT
    • 8. CONCLUSIONS
  • APPENDIX 1. COST COMPARISON
    • CADTH Cost Calculation for Compounded Propranolol
  • APPENDIX 2. SUMMARY OF KEY OUTCOMES
  • APPENDIX 3. ADDITIONAL INFORMATION
  • APPENDIX 4. SUMMARY OF OTHER HTA REVIEWS OF DRUG
  • APPENDIX 5. REVIEWER WORKSHEETS
    • Manufacturer’s Model Structure
    • Manufacturer’s Results
    • CADTH Common Drug Review Reanalyses
  • REFERENCES
• CDEC FINAL RECOMMENDATION
  • Recommendation
  • Condition
  • Reasons for the Recommendation
  • Of Note
  • Other Discussion Points
  • Background
  • Summary of CDEC Considerations
  • Research Gaps

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