critical excipients

Question 1

what type of medication will children require?

Answer 1

children will require a liquid medication

Question 2

why are tablets inappropriate?

Answer 2

mg/kg dose makes tablets inappropriate inability to swallow tablets

Question 3

how can we increase tablet usage

Answer 3

through tablet training

Question 4

why will some older children still require liquids

Answer 4

medical conditions / still unable to swallow

Question 5

are dispersible tablets available?

Answer 5

yes they are , dispersible aciclover (£1 per box of 200mg tablets)

Question 6

does patient have an NG tube?

Answer 6

fine bore so eg. omeprazole mups will block tubes

nasojejunal feeds/ ketogenic diet may dictate liquids not suitable

Question 7

if tablets are not suitable what next

Answer 7

is licensed liquid commercially available?

is an unlicensed liquid available?

is there a soluble preparation?

can the injection be given orally?

can tablets be crushed and dispersed?

Question 7

are all medicines suitable for children?

Answer 7

suspensions solutions injections and creams

Question 7

examples of critical excipients

Answer 7

ethanol, propylene glycol, parabéns, benzyl alcohol/ benzoates
sugar
sweeteners
often used in suspensions / solutions/injections

Question 8

ethanol

Answer 8

synonym- alcohol
solvent
component of flavoured vehicles
antimicrobial preservatives
bacteriostatic, bactericidal, fungicidal and virucidal activity

newborn cutaneous absorption of ethanol is significant in Neonates due to the newborn’s immature skin

Question 9

risks associated with the use of ethanol

Answer 9

risk of acute intoxication with accidental overdose and chronic toxicity with long-term use

children especially under 6 are more vulnerable to the effects of alcohol

drowsiness behavioural changes and impaired ability to concentrate and participate in school activities

Question 10

in January 2014 what did the EMA propose?

Answer 10

the EMA proposed the inclusion more detailed information on alcohol content in patient information leaflets PILAs as well as alcohol content thresholds for different age groups in a draft for the guideline on excipients in the label and package leaflet of medicinal products for human use

Question 10

examples of medicines in which ethanol is used in

Answer 10

ranitidine phenobarbitone , furosemide and some morphine preparations

Question 10

what does EMA provide?

Answer 10

guidance as to acceptable limits for medications

Question 11

limits of ethanol used in the USA

Answer 11

for >12 years =max of 10% alcohol
for 6-12 years =max of 5% alcohol
for <6 years =max of 0.5%

Question 12

potential limitations of the limits used in the USA

Answer 12

doesn’t account for actual volume of medicine child is taking if patient took 1ml of a 10% solution then they would be taking 10mg of alcohol
if they took 10ml of a 5% solution then they would be taking 500mg of alcohol

Question 13

blood alcohol concentration

Answer 13

blood alcohol concentration=

Question 14

what do the AAP recommend?

Answer 14

the AAP recommend that the max blood alco0hol concentration that a single dose of a medicine should contribute is 25mg/100ml
the 0.79 can be disregarded if %is expressed as w/v

Question 15

phenobarbitone

Answer 15

Phenobarbital elixir 15mg/5ml
contins 38% alcohol
no warning on bottle
updated SPC has warning in CBNF has warning in it
alcohol free unlicensed suspension is available phenobarbitone 10mg/ml

Question 16

what should not be given to a child?

Answer 16

never ever give out licensed phenobarbitone to a child

tablets can be crushed and supersede
use alcohol free liquid

Question 17

propylene glycol

Answer 17

propane-1,2-diol
used in formulation of lipid soluble oral , topical and IV drugs - used as a co-solvent
accumulation of propylene glycol can occur in neonates and young children as they cannot adequately metabolise and eliminate the excipient

reduced metabolism and elimination can lead to depression of the central nervous system which can then cause lactic acidosis , seizures cardiac arythmiaswith high dose , long term usage

Question 18

propylene glycol emax levels

Answer 18

neonates upto 28 days : 1mg/kg
1 month- 4 years : 50mg/1kg
5-17 years : 500mg/kg
who max recommend levels
25mg/kg body weightmax daily intake
contraindicated in neonates and children under 4 years

Question 19

higher PG load

Answer 19

despite clinical date demonstrating that higher PG load may be safely administered to children older than 4 years and adults , a more cautious approach is still recommended for children under 5 years old because of a lack of clinical data

Question 20

awnings when using propylene glycol

Answer 20

propylene glycol might be used to facilitate the preparation of a solution rather than a suspension and hence ensure uniformity of a dose

if such medicine were re-formulated to exclude the propylene glycol there is a risk that the alternative product might inadvertently be of a poorer uniformity of dose

Question 20

is melatonin liquid licensed?

Answer 20

yes melatonin 1mg/ml liquid receives licence colonis Pharma says

Question 22

parabens

Answer 22

synonym-methyl parahydroxybenzoate , propyl parahydroxybenzoate infact a combination

primarily used as a solvent and preservatives who limit 10mg/kg body weight max daily intake

can cause hypersensitivity reactions avoided in critically ill neonates with jaundice, kernicterus and hyperbilirubinaemia

their metabolism and excretion pathways could cause displacement of bilirubin from albumin

get accumulation of bilirubin in the body

Question 23

benzyl alcohol synonyms

Answer 23

benzoic acid, sodium benzoate, benzenemethanol

Question 24

what’s benzyl alcohol used for ?

Answer 24

added as a preservative to IV formulations

Question 25

what is the acceptable daly intake of benzyl alcohol?

Answer 25

daily intake of 5mg /kg body weight

Question 26

what the EMEA guidance for benzyl alcohol

Answer 26

EMEA guidance
directive for excipients in the label and package leaflet of medicinal products for human use

contents of benzyl alcohol should be listed in medicines

exposures to less than 90mg/kg/day
must not be given to premature babies or neonates. May cause toxic reactions and allergic reactions in infants and children up to 3 years old

exposures to more than 90mg /kg/day

this product should not be used in infants and children up to 3 years

Question 27

problems with sugar/sweetners

Answer 27

all linked to tooth decay

Question 27

why can children not have benzyl alcohol?

Answer 27

young children cannot metabolise it quick enough leading to an accumulation of benzoic acid

Question 28

what are the side effects of benzyl alcohol?

Answer 28

metabolic acidosis , vasodilation n, paralysis , epileptic seizures , respiratory depression, death

causes gasping syndrome in neonates Amiodarone injection- exceeds limits but lack of alternative

Question 29

do sugar alcohols contribute to tooth decay?

Answer 29

they do not

Question 29

give examples of sugar sweeteners

Answer 29

sucrose glucose

Question 29

give some examples of sugar alcohols

Answer 29

sorbitol mannitol xylitol

Question 29

sugars and sweetners limitations

Answer 29

can have osmotic laxative and reduce bioavailability of some drugs eg loperamide suspension

Question 30

side effects of sugars and sweetners

Answer 30

flatulence and diarrhoea