1. Safe Supply of Paediatric Unlicensed Medicines
Steve Tomlin
Consultant Paediatric Pharmacist
Honorary Clinical Reader

2. Every Dose Is Different
Is dosing in adults logical?
One size fits all – useful for tablets
Paracetamol, ranitidine
When does a child become an adult?
Mg/kg
When can doses be rounded up or down?
Paracetamol, cefuroxime
Is Licensing Logical?
Aciclovir

3. What do children take? Dose (mg) 30 60 120 250 500 Dosage form? Drops
Liquid/melt
Liquid/melt/ tablet
Tablet/ capsule

4. Therapeutic Orphans
Europe - >50% of medicines used in children have never been tested in children.
Conroy S, Br Med J. 2000, 320:79-82
Australia - 25% of medicines licensed in children do not have appropriate formulations for children.
Tan E, Med J Aust. 2003, 179(4):195-8
1/3 of research papers into children’s medicines did not allow for the work to be reproduced / 51% did not use a paediatric formulation.
Standing J, Paediatrics. 2005, 116(4):
Pandit S, Arch Dis Child. 2010, 95:

5. Unlicensed & Off-Label Medication
Proportion of medicines used not licensed:
80% Neonatal Intensive Care Unit (NICU)
40% Paediatric Intensive Care (PICU)
25% general paediatric in-patients
11% children at home
Nunn A, 2003, Arch Dis Child :

6. Policy statement Joint RCPCH/NPPG Standing Committee on Medicines
‘it is not necessary to take additional steps, beyond those taken when prescribing licensed medicines, to obtain the consent of parents, carers and child patients to prescribe or administer unlicensed medicines or licensed medicines for unlicensed applications.’
Treatment Should Be The Best You Can Give!

7. Paediatric Patient Needs
Age-appropriate formulations
Type of formulation (liquid / solid)
Dose flexibility
Excipients and levels
Ease of dosing and compliance
Palatability
Frequency of dosing
Ease of manipulation (by carer)
Perceptions of parent / carer?

8. What medicine are you getting?
Licensed In Some Children
Licensed Adult Medicine
Import
Special
Extemporaneously Prepared
Product aligned to Clinical Need

9. Intravenous Preparations
Hospital Neonatal Unit
31% of prescriptions < 1/10 vial
4.8% of prescriptions <1/100 vial
Arch Dis Child. 2000; 834:92-6
Dose calculations often involve decimal points
Units often have to change – how to label
Standard Concentrations

10. IV Formulation Benzyl alcohol harmful in infants
contained in e.g. amiodarone and lorazepam injections
Shehab N, Pediatr Crit Care Med (2):
Phenobarbital injection – 90% propylene glycol  hyperosmolality in infants, pH 11
Ibuprofen – lignocaine in premature babies
Paracetamol – 10 x overdoses
Phenytoin – need to dilute, but it precipitates

11. Oral Formulations Phenobarbital elixir BP – 38% alcohol
Sugar or Sorbitol?
Dispersible Tablets (aspirin and diclofenac)
The history of nifedipine
Tuleu C, J of Drug Delivery Science & Tech (4):
Captopril – bioequivalence?
Mulla H, Arch Dis Child :
Clobazam – what’s left in the bottle
Glass ampoules for oral solutions?
(vitamin K, Caffeine)

12. Import/export of captopril oral liquid
10578 miles each way
BMS, UK
No MA for children
Not bioequivalent to:
tablets
compounded liquids
BMS, Victoria, Australia 12

13. Changing Medicines Crushing tablets can change profile
Increase side effects
Decrease duration

14. Pharmaceutical Issues when Crushing, Opening or Splitting Oral Dosage Forms June 2011
Changing the way in which a dosage form is presented can alter its absorption characteristics, result in medicines instability, produce local irritant effects, cause failure to reach the site of action, may produce occupational health and safety issues, and could result in a preparation with an unacceptable taste.
.. In most circumstances in which no appropriate licensed medicine is available, the prime objective should be to provide patients with a ready-to-use unlicensed medicine.

15. Other Routes INTRANASAL TOPICAL RECTAL Midazolam – why do they cry?
Chlorhexidine – it just cleans the skin!!
RECTAL
Glycerine Chips
Paracetamol / Morphine

16. The Future Standardisation / Formulary BP? BNF-C? Directed Prescribing
Defined Drop down boxes
Tighter Tariff