Unlicensed Medicines in Unlicensed Medicines in PaediatricsPaediatrics

Is there a problem Is there a problem ??

Scottish Neonatal and Paediatric Pharmacist Group

National Paediatric Pre-Registration Pharmacist Study Day January 2011

AIMAIM

To discuss the issues relating to To discuss the issues relating to thethe

use of unlicensed medicines inuse of unlicensed medicines in

paediatric patients and facilitate paediatric patients and facilitate

discussion of the implicationsdiscussion of the implications

in practicein practice

ObjectivesObjectives

describe the licensing describe the licensing processprocess

identify problems of identify problems of clinical trials in childrenclinical trials in children

examine the extent of examine the extent of the problemthe problem

discuss seamless care discuss seamless care issuesissues

pose questions for pose questions for discussion!!!discussion!!!

Kids’ medicineKids’ medicine

‘‘danger’ shockdanger’ 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 consumption by youngsters according to a report

published yesterday.published yesterday.

It warns that most medicines either prescribed or sold direct It warns that most medicines either prescribed or sold direct

are safe but a minority could do harm in the wrongare safe but a minority could do harm in the wrong doses.doses.

They are licensed , but only for adults.They are licensed , but only for adults.

Extent of unlicensed and Extent of unlicensed and off-label prescribing in off-label prescribing in

childrenchildren 90% of babies in neonatal intensive care90% of babies in neonatal intensive care 70% of children in paediatric intensive care70% of children in paediatric intensive care 67% of children in hospital across Europe67% of children in hospital across Europe 11% of children treated at home by their GP11% of children treated at home by their GP

Must use a licensed product when it is Must use a licensed product when it is suitable suitable

Unlicensed and Off-label Unlicensed and Off-label Medicine DefinitionsMedicine Definitions

UnlicensedUnlicensed• Extemporaneous Extemporaneous

dispensingdispensing• Pharmaceutical Pharmaceutical

‘specials’‘specials’• Importing medicines Importing medicines

licensed in other licensed in other countriescountries

• ‘‘Named patient’ Named patient’ suppliessupplies

• Chemicals not licensed Chemicals not licensed at all for human useat all for human use

Off labelOff label• DoseDose• Age of patientAge of patient• IndicationIndication• Route of administrationRoute of administration• Contra-indicationsContra-indications

Risk Assessment of Risk Assessment of OptionsOptions

Licensed productsLicensed products Route of administrationRoute of administration Confidence in manufacturerConfidence 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 testingFinished 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, (e.g. within EU, N America, Australia, Japan, Switzerland,

New Zealand)New Zealand)

The licensing processThe licensing process

To To marketmarket a drug in the UK a a drug in the UK a pharmaceutical company must pharmaceutical company must obtain a licence from the obtain a licence from the licensing authority (health licensing authority (health ministers guided by the MHRA ministers guided by the MHRA or EMA)or EMA)

The aim of a licence is to The aim of a licence is to ensure that all medicines in the ensure that all medicines in the UK meet acceptable standards UK meet acceptable standards of safety, quality and efficacyof safety, quality and efficacy

Extent of a product Extent of a product licencelicence

It allows a company to It allows a company to

marketmarket a drug for; a drug for; specified conditions specified conditions in an agreed dose range in an agreed dose range by a particular routeby a particular route using a tested formulation using a tested formulation

Based on clinical trial Based on clinical trial datadata

EMA / MHRA Product EMA / MHRA Product LicenceLicence

Paediatric Investigation Plan (PIP)Paediatric Investigation Plan (PIP)• Paediatric Regulation to submit a Paediatric Regulation to submit a

development plan for new medicinesdevelopment plan for new medicines• Specific class waiversSpecific class waivers

Paediatric-Use Marketing Paediatric-Use Marketing Authorisation (PUMA)Authorisation (PUMA)• Already authorise medicineAlready authorise medicine• 10 years market protection10 years market protection

Paediatric clinical trialsPaediatric clinical trials

““By an odd and unfortunate twist of fate, By an odd and unfortunate twist of fate, infants and children are becoming infants and children are becoming

therapeutic orphans”therapeutic orphans”

Shirkey H 1968Shirkey H 1968

Lack of Clinical trialsLack of Clinical trials

80% of new drugs had no 80% of new drugs had no info in paedsinfo in paedsWHY ?WHY ?

ethicsethics long term effectslong term effects micro-analytical techniquesmicro-analytical techniques return for investmentreturn for investment

DirectiveDirective89/341/EEC89/341/EEC

all doctors can prescribe:all doctors can prescribe: there is no statutory requirement to there is no statutory requirement to

disclose to a patient when a drug is disclose to a patient when a drug is unlicensedunlicensed

all unlicensed prescribing / all unlicensed prescribing / dispensing should be done dispensing should be done knowingly(?)knowingly(?)

the decision to prescribe unlicensed the decision to prescribe unlicensed medicines medicines • should be in the best interest of the should be in the best interest of the

patientpatient• in accordance with a respectable in accordance with a respectable

body of professional opinionbody of professional opinion

Practical ImplicationsPractical Implications

Responsibility Responsibility LiabilityLiability Patient InformationPatient Information Inappropriate Inappropriate

prescribing?prescribing? Medication ErrorsMedication Errors

• Differing strengthsDiffering strengths• Differing Differing

manufacturer’smanufacturer’s

Practical IssuesPractical Issues

Barrier to seamless Barrier to seamless carecare

Effective Effective communication communication systemssystems

Unlicensed Unlicensed manufacturer’s / manufacturer’s / suppliers cannot suppliers cannot advertise productsadvertise products

Dispensing ProblemsDispensing Problems Lack of familiarityLack of familiarity CalculationsCalculations Lack of suitable Lack of suitable

products- risk products- risk assessment of optionsassessment of options

Only able to order Only able to order from specific specials from specific specials supplierssuppliers

Medication ErrorsMedication Errors Professional checkProfessional check CostCost

How Extensive is the How Extensive is the problemproblem??

Over to youOver to you - -

some audience some audience participation pleaseparticipation please

Consider the licensing status of Consider the licensing status of the following medicines for the following medicines for

children and neonateschildren and neonates Buccal midazolam for seizuresBuccal midazolam for seizures Paraldehyde for seizures (rectal)Paraldehyde for seizures (rectal) Spironolactone for liver ascitesSpironolactone for liver ascites Paracetamol for pyrexiaParacetamol for pyrexia Phenobarbitone for epilepsyPhenobarbitone for epilepsy EMLA cream for topical anaesthesiaEMLA cream for topical anaesthesia Melatonin for sleep disorders in childrenMelatonin for sleep disorders in children Ibuprofen for pyrexiaIbuprofen for pyrexia