Novel Routes of Administration:
Getting the Drug to the Right Place in
Challenging Circumstances
Dr Emily HARROP
Consultant in Paediatric Palliative Care
Introduction
• Setting the scene – why be ‘novel’?
• What routes do we use?
•
•
•
•
Subcutaneous infusion (briefly, as Lynda covering too)
Buccal / Sublingual – inc. data on current practice
Transdermal administration (patches)
Drugs via Gastrostomies / NG tubes / Jejunal tubes
• Case studies – how might we hunt for solutions to
administration barriers?
• What about the future…?
Setting the Scene
• Children cared for in a variety of settings
• May need background medication delivery and ‘top up‘ strategy
• Carers from a variety of backgrounds
• NO NEEDLES!
Practical Issues
 Small evidence base and extrapolation
from adult studies.
 Many drugs used are unlicensed in
children or “off label”
 Consider who is administering drug,
route and compliance
Rational and empirical approach
to prescribing
Prescribing Decisions Matrix
Palliative
Population
Subcutaneous Infusions
6
Continuous subcutaneous syringe driver
infusions
Indications:
•persistent nausea and vomiting
•dysphagia
•intestinal obstruction
•coma
•poor absorption of oral drugs
•patient preference
•NOT 4th step of the WHO pain ladder
Mixing Drugs
• To date there has been NO major issue reported related
to this practice
• ‘allowing the administration of medicines necessary for
maintaining life or managing symptoms when parentral
access is limited and / or alternative routes present
significant risk or patient discomfort’
Mixing drugs in a driver...?
Palliative
Population
Buccal Administration
10
Transmucosal Administration
Administration of a drug via a mucosal surface,
directly in to the systemic circulation
Drug absorption generally efficient:
•
No stratum corneum (unlike skin)
•
Rich blood supply to move drug to circulation
•
Avoids first pass metabolism
•
Avoids degradation in the GI tract
Buccal route
Pros
Cons
• Avoid the need for entral
absorption
• No first pass metabolism
• Rapid onset of action
• Better compliance than injectable
therapy
• No active input needed from the
patient
• Very few licensed products
• Mouth dryness / salivation can
affect
• ‘mouth feel’ is an issues
• Taste
• Consistency
• Irritancy
• New technique for carers
Examples in Palliative Care
• Midazolam (seizures, agitation, anxiety)
• Fentanyl (breakthrough pain)
• Morphine (breakthrough pain)
• Diamorphine (breakthrough pain)
• Ketamine (breakthrough neuropathic pain)
• Levomapromazine (nausea / vomiting)
• Buscopan (colicky pain bowel / urinary tract)
Often done using the parentral product
Novel Buccal drug use....?
Palliative
Population
Current Practice with Buccal opiods
• Electronic Questionnaire
• Survey Monkey system
• Members of the APPM who are know to be prescribers (N=99)
• Two reminders sent after the initial invitation
• 48% response rate
Results
Problems encountered included:
•
Drawing up small doses (35%)
•
Uncertainty about effectiveness (30%)
•
Taste (10%)
•
Sharps in the home
•
Confusion /resistance from user
Results
• 65% of responders prescribed
buccal opioids for use in patient’s
homes (83% for hospice use and
49% for hospital use)
• 75% of responders prescribed drugs
to be administered by family
members
Current Practice with Buccal Opioids
• 70% of those who responded used some form of buccal breakthrough
analgesia other than licensed preparations
• This is often undertaken using the parentral preparations available,
despite some practical difficulties being encountered
• Much of the administration occurs in patient’s own homes, often
given by non-medical carers
• Alternative treatments tended to be more invasive or technology
dependent
Better preparations are needed !
Transdermal Administration
19
Patch Delivery
• Transdermal delivery system (TDDS)
•
•
•
•
Hyoscine
Buprenorphine
Fentanyl
Clonidine
• Patch size governed by adult dosing regimes, can limit use in paediatrics
Margetts L, Sawyer R. Transdermal drug delivery: principles and opioid therapy. Continuing Education
in Anaesthesia, Critical Care and Pain. 2007; 7(5): 171-175.
Types of patches
• Reservoir Patch
• Drug in gel / solution
• Delivery determined by rate
controlling membrane between
reservoir and skin
• Damage to patch causes sudden
increase in drug release and
overdose
• Matrix Patch
• Drug incorporated in to adhesive
polymer matrix
• Dose dependent on the amount
of drug within the matrix and
the surface area in contact with
the skin - CAN be cut to
required surface area
Cutting a ‘patch’
Enteral Tube Administration
23
Enteral tube administration
• Nasogastric,
gastrostomy and
jejunostomy tubes may
be used to feed /
hydrate patients
• Administration of
medication by this route
is an unlicensed use
Practical Aspects
• Important to consider:
• Size of tube
• Risk of blockage
• Site of tube
• Jejunal should be sterile
• Absorption may be significantly different jejunally
• Formulation
• See ladder from PCF – always reflect on the safest product
• Properties of the drug itself
• Interactions (chemical & physical) – antibiotics & anti-epilpetics
• Absorption at the level administered
• Relationship with feed
• Need for separation? – stopping feed / flushes
McIntyre CM, Monk HM. Medication absorption considerations in patients with postpyloric enteral feeding tubes.
Am J Health Syst Pharm. 2014 Apr 1; 71(7):549-556.
BAPN The British Pharmaceutical
Nutrition Group
www.bpng.co.uk
Administering drugs via Enteral feeding
tubes
Case Study – Ellie
29
Novel Subcutaneous Infusion
• Ellie had a rare mitochondrial disease with Parkinson’s-type features
• She is was longer absorbing feed, and was felt be approaching EoL
• Parents preferred care outside of PICU
• She was dependent on an IV infusion of clonidine and morphine for
relief of dystonia / pain
• How can we achieve this?
• There is no specific data on clonidine subcutaneous infusion for
dystonia in children ….
• Can it be safely given subcutaneously?
• Can it be combined with morphine?
Solving the Mystery
• Subcutaneous infusions of clonidine are sometimes use in adult chronic
pain (as well as intra-thecal)
• Intra-thecal infusions sometimes contain morphine and clonidine
together
• Contacted adult pain specialist and adult palliative care colleagues for
information on their experience of use
• Conversion at 1:1 but approximately 10% increase needed compared to
previous stable dose
• Successfully given by subcutaneous infusion with good clinical effect and
no untoward local reaction
• EoLC delivered in Helen House
Case Study – Poppy
32
Novel Buccal Drug Use
• Four year old girl with rapidly progressively leukodystrophy
• Gut failure with very limited absorption and colicky abdominal pain
• Painful episodes respond to Buscopan SC (hyoscine butylbromide)
• Poppy developed a mild transient rash after SC dose
• Buscopan has limited enteral absorption even in healthy individuals
• Needle-free solution needed for ‘breakthrough’ episodes of acute
abdominal pain
• There is no published data on buccal ‘breakthrough’ with buscopan – could
this be an option?
Solving the Mystery
Buscopan – Hyoscine hydrobromide
• Small molecule
• Soluble in water
• Not very soluble in lipid
• Has very poor oral bioavailablily
• Traditional herbalist use - chewing leaves
• Patient unable to absorb well orally
• Repeated injections not acceptable
• Symptoms intermittent
Buscopan – Hyoscine Butylbromide
• Discussion with parents about trial of buccal buscopan using the
parentral preparation
• Discussion with a senior consultant colleague, agreed that there was
limited risk and significant potential benefit
• Decided to try to SC dose from the APPM Formulary as a starting
point
• This proved clinically effective and Poppy developed a similar, mild
transient rash!
Case Study - Hadi
37
Rationalising enteral tube drugs
• Hadi has large volumes of medication via his PEG and is often sick /
refluxes
• The Care Team / parents have already tried giving these staggered
and also more slowly – to limited avail
• He now has a PEG-J tube for his feed – how can we rationalise his
medication schedule to minimise reflux / vomits?
• He is on Movicol (Paed), baclofen, ranitidine and diazepam – what
would your approach be?
Solving the Mystery
• Movicol (Paed) – does not need to be absorbed, works locally in the
colon and has a large volume
• Ranitidine and benzodiazepines have ‘acceptable’ post-pyloric
absorption
• Baclofen is not at all well absorbed beyond the stomach
• Plan:
• Spacing out / slowing administration
• Giving Movicol PEG-J (use sterile water)
• Trying rantidine or benzodiazepines (one at a time) and monitoring clinical
effect
• Explain to parents that baclofen will need to go via PEG
In the future…?
• Better preparations of buccal medication?
• Clonidine gel as a variable dose break through strategy?