1. Unlicensed Medicines in Paediatrics Is there a problem ? Scottish Neonatal and Paediatric Pharmacist Group National Paediatric Pre- Registration Pharmacist Study Day January 2011

2. AIM To discuss the issues relating to the use of unlicensed medicines in paediatric patients and facilitate discussion of the implications in practice

3. Objectives describe the licensing process describe the licensing process identify problems of clinical trials in children identify problems of clinical trials in children examine the extent of the problem examine the extent of the problem discuss seamless care issues discuss seamless care issues pose questions for discussion!!! pose questions for discussion!!!

4. Kids’ medicine ‘danger’ shock SOME children’s medicines have not been approved for SOME children’s medicines have not been approved for consumption by youngsters according to a report published yesterday. It warns that most medicines either prescribed or sold direct are safe but a minority could do harm in the wrong doses. They are licensed, but only for adults.

5. Extent of unlicensed and off- label prescribing in children 90% of babies in neonatal intensive care 90% of babies in neonatal intensive care 70% of children in paediatric intensive care 70% of children in paediatric intensive care 67% of children in hospital across Europe 67% of children in hospital across Europe 11% of children treated at home by their GP 11% of children treated at home by their GP Must use a licensed product when it is suitable

6. Unlicensed and Off-label Medicine Definitions Unlicensed Unlicensed Extemporaneous dispensingExtemporaneous dispensing Pharmaceutical ‘specials’Pharmaceutical ‘specials’ Importing medicines licensed in other countriesImporting medicines licensed in other countries ‘Named patient’ supplies‘Named patient’ supplies Chemicals not licensed at all for human useChemicals not licensed at all for human use Off label Off label Dose Age of patient Indication Route of administration Contra-indications

7. Risk Assessment of Options Licensed products Licensed products Route of administration Route of administration Confidence in manufacturer Confidence in manufacturer Import licensed medicine from QC approved countryImport licensed medicine from QC approved country Pharmaceutical Special (Hospital / Commercial)Pharmaceutical Special (Hospital / Commercial) ExtemporaneousExtemporaneous Borderline substanceBorderline substance Labelling language/ PIL language Labelling language/ PIL language Finished product testing Finished product testing Certificate of AnalysisCertificate of Analysis Certificate of ConformityCertificate of Conformity QC Approved importers/ countries QC Approved importers/ countries (e.g. within EU, N America, Australia, Japan, Switzerland, New Zealand)(e.g. within EU, N America, Australia, Japan, Switzerland, New Zealand)

8. The licensing process To market a drug in the UK a pharmaceutical company must obtain a licence from the licensing authority (health ministers guided by the MHRA or EMA) To market a drug in the UK a pharmaceutical company must obtain a licence from the licensing authority (health ministers guided by the MHRA or EMA) The aim of a licence is to ensure that all medicines in the UK meet acceptable standards of safety, quality and efficacy The aim of a licence is to ensure that all medicines in the UK meet acceptable standards of safety, quality and efficacy

9. Extent of a product licence It allows a company to market a drug for; specified conditions specified conditions in an agreed dose range in an agreed dose range by a particular route by a particular route using a tested formulation using a tested formulation Based on clinical trial data

10. EMA / MHRA Product Licence Paediatric Investigation Plan (PIP) Paediatric Investigation Plan (PIP) Paediatric Regulation to submit a development plan for new medicinesPaediatric Regulation to submit a development plan for new medicines Specific class waiversSpecific class waivers Paediatric-Use Marketing Authorisation (PUMA) Paediatric-Use Marketing Authorisation (PUMA) Already authorise medicineAlready authorise medicine 10 years market protection10 years market protection

11. Paediatric clinical trials “ By an odd and unfortunate twist of fate, infants and children are becoming therapeutic orphans” Shirkey H 1968

12. Lack of Clinical trials 80% of new drugs had no info in paeds WHY ? 80% of new drugs had no info in paeds WHY ? ethics ethics long term effects long term effects micro-analytical techniques micro-analytical techniques return for investment return for investment

13. Directive 89/341/EEC all doctors can prescribe: there is no statutory requirement to disclose to a patient when a drug is unlicensed there is no statutory requirement to disclose to a patient when a drug is unlicensed all unlicensed prescribing / dispensing should be done knowingly(?) all unlicensed prescribing / dispensing should be done knowingly(?) the decision to prescribe unlicensed medicines the decision to prescribe unlicensed medicines should be in the best interest of the patientshould be in the best interest of the patient in accordance with a respectable body of professional opinionin accordance with a respectable body of professional opinion

14. Practical Implications Responsibility Responsibility Liability Liability Patient Information Patient Information Inappropriate prescribing? Inappropriate prescribing? Medication Errors Medication Errors Differing strengthsDiffering strengths Differing manufacturer’sDiffering manufacturer’s

15. Practical Issues Barrier to seamless care Barrier to seamless care Effective communication systems Effective communication systems Unlicensed manufacturer’s / suppliers cannot advertise products Unlicensed manufacturer’s / suppliers cannot advertise products

16. Dispensing Problems Lack of familiarity Lack of familiarity Calculations Calculations Lack of suitable products- risk assessment of options Lack of suitable products- risk assessment of options Only able to order from specific specials suppliers Only able to order from specific specials suppliers Medication Errors Medication Errors Professional check Professional check Cost Cost

17. How Extensive is the problem? Over to you - some audience participation please Over to you - some audience participation please

18. Consider the licensing status of the following medicines for children and neonates Buccal midazolam for seizures Buccal midazolam for seizures Paraldehyde for seizures (rectal) Paraldehyde for seizures (rectal) Spironolactone for liver ascites Spironolactone for liver ascites Paracetamol for pyrexia Paracetamol for pyrexia Phenobarbitone for epilepsy Phenobarbitone for epilepsy EMLA cream for topical anaesthesia EMLA cream for topical anaesthesia Melatonin for sleep disorders in children Melatonin for sleep disorders in children Ibuprofen for pyrexia Ibuprofen for pyrexia