Novel Routes of Administration:Getting the Drug to the Right Place in
Challenging CircumstancesDr Emily HARROP
Consultant in Paediatric Palliative Care
• 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!
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
Continuous subcutaneous syringe driver infusions
•persistent nausea and vomiting•dysphagia•intestinal obstruction•coma•poor absorption of oral drugs•patient preference•NOT 4th step of the WHO pain ladder
• 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 parentralaccess is limited and / or alternative routes present significant risk or patient discomfort’
• Members of the APPM who are know to be prescribers (N=99)
• Two reminders sent after the initial invitation
• 48% response rate
Problems encountered included:
• Drawing up small doses (35%)
• Uncertainty about effectiveness (30%)
• Taste (10%)
• Sharps in the home
• Confusion /resistance from user
• 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 delivery system (TDDS)• Hyoscine
• 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
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
• 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 Groupwww.bpng.co.uk
Administering drugs via Enteral feeding tubes
Case Study – Ellie
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
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
Rationalising enteral tube drugs• Hadi has large volumes of medication via his PEG and is often sick /
• 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?