Guanfacine

Cite this article as:
Mary Hardimon. Guanfacine, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.13727

On 22nd August 2017, guanfacine hydrochloride (current sole brand name Intuniv) was accepted as a new chemical entity by the Therapeutic Goods Administration in Australia.1 Whilst new to Australia, guanfacine has been available within the United States of America and Europe since 20102 and 20153 respectively. The development of generic brands within these countries has seen increased uptake of this medication as an alternative to stimulant medications.

 

So what is it?

Guanfacine is an alpha 2 agonist. Unlike clonidine (which is non-selective and shows high affinity for all 3 subtypes of alpha 2 receptors – A, B and C), guanfacine has preferencial affinity for alpha 2A receptors. Stimulation of these receptors in the prefrontal cortex mimics noradreline/norepinephrine actions in this region, with current ADHD (Attention Deficit Hyperactivity Disorder) causal theories demonstrating noradrenergic dysfunction as underlying the cognitive and behavioural manifestations of ADHD.4

https://www.priory.com/psychiatry/clonidine.htm

 

Indications and Usage

Under current licensing in Australia, guanfacine is indicated for “the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents 6-17 years old, as monotherapy (when stimulants or atomoxetine are not suitable, not tolerated or have been shown to be ineffective) or as adjunctive therapy to psychostimulants (where there has been a sub-optimal response to psychostimulants).”

The use of guanfacine “must be used as part of a comprehensive ADHD management programme, typically including psychological, educational and social measures.1

These stipulations encourage prescribers to manage ADHD within a bio-psycho-social context, understanding that in the vast majority of cases, the condition whilst caused by a neurotransmitter imbalance may be attenuated by psychological and social strategies.

Shire Australia (whom is licensed for its distribution) recommends its use in children and adolescents 6 – 17 years of age.6 There are very limited studies7 surrounding guanfacine use in children younger than 6 years and whilst efficacy has been suggested, caution would be suggested in making ADHD diagnoses particularly in toddler years due to a great variety in “normal” in this period.

 

Dosage and Administration

Guanfacine will be released in 1mg, 2mg, 3mg and 4mg modified release tablets with administration once per day orally. Tablets should not be crushed or dissolved. Guanfacine should not be taken with high fat meals as this significantly affects absorption.

The recommended initial dose is 1mg (when used as either monotherapy or co-administered with stimulants). Dose adjustments are recommended by no more than 1mg/week with a target dose range (or based on therapeutic effect should it occur prior to this dose) of 0.05 – 0.12mg/kg/day. Doses exceeding 4mg (co-administration) and 7mg (when used as monotherapy) have not been evaluated.8

 

Recommended target dose range for maintenance therapy when guanfacine is sole agent8

Weight Target dose range (0.05 – 0.12 mg/kg/day)
25.0-33.9 kg 2-3 mg/day
34.0-41.4 kg 2-4 mg/day
41.5-49.4 kg 3-5 mg/day
49.5-58.4 kg 3-6 mg/day
58.5-91.0 kg 4-7 mg/day
≥91.0 kg 5-7 mg/day

 

Adverse effects

The most common adverse effects9 include:

  • Somnolence
  • Sedation
  • Abdominal pain
  • Dizziness
  • Hypotension
  • Dry mouth
  • Constipation

In contrast to stimulant medication, weight gain (mean of 0.5kg) is seen in patients using guanfacine.

Less common (although clinically significant) side effects10 include:

  • Atrioventricular block
  • Asthenia and chest pain
  • Increased ALT
  • Convulsion
  • Increased urinary frequency
  • Hypertension
  • Pallor

 

Drug interactions

CYP3A4 inhibitors (such as ketoconazole) and CYP3A4 inducers (such as rifampin) may affect guanfacine blood levels and subsequent clinical response.10

 

Cost

Since being introduced onto the PBS 1st September 2018, the previously prohibitive costs are now more affordable for families (although still quite expensive without a health care card) – ~$40 regular PBS price ~$6 concession PBS price.

 

References

1 https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia

2 https://www.drugs.com/newdrugs/shire-announces-fda-approval-once-daily-intuniv-guanfacine-extended-release-adhd-children-1599.html

3

4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676929/

5 https://stahlonline.cambridge.org/content/ep/images/85702c17_fig24.jpg

6 https://www.guildlink.com.au/gc/ws/zi/pi.cfm?product=zipintun10817

7 https://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291097-0355%28199723%2918:3%3C300::AID-IMHJ6%3E3.0.CO;2-Q/abstract

8 https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-02254-1&d=2017110516114622483

9 https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf

10 https://pi.shirecontent.com/PI/PDFs/Intuniv_USA_ENG.pdf

Additional useful websites:

  1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b972af81-3a37-40be-9fe1-3ddf59852528
  2. https://pi.shirecontent.com/PI/PDFs/Intuniv_USA_ENG.pdf
  3. https://www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-Education/Pharmacy-Education-Materials/Downloads/stim-pediatric-factsheet11-14.pdf
  4. https://www.guildlink.com.au/gc/ws/zi/pi.cfm?product=zipintun10817

Diana Egerton-Warbuton: Reducing alcohol related harm in adolescents at DFTB17

Cite this article as:
Team DFTB. Diana Egerton-Warbuton: Reducing alcohol related harm in adolescents at DFTB17, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.13984

This talk was recorded live on the opening plenary session of day two at DFTB17 in Brisbane.

The Quagmire

Cite this article as:
Natalie Thurtle. The Quagmire, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.13504

Our community is made up of health care folks that do hard things, go the extra mile, work on themselves and their knowledge so that patients get better outcomes. We’re not good all the time. We make mistakes, forget stuff, get grumpy or emotional, slide into tribal behaviour. But we’re working on it. So when someone comes along and shines a light on what’s happening outside our normal frame of practice, shows us patients that can’t get care, who are needlessly dying or suffering, it makes us uncomfortable. We want to do something.

Sometimes I get asked to be the person that turns on that torch, the person that makes everyone else uncomfortable, most recently at the excellent DFTB17. I try to do this with balance, to show another context, but also not to make people feel helpless or shocked. Sometimes I get it right, sometimes not. Without fail though, at least one person always asks me afterwards a variation of ‘What can I do?

Keeping little folk safe

Cite this article as:
Kristin Boyle. Keeping little folk safe, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.13844

If my house were a workplace, it would be an emergency department. We operate 24-7, there are frequent tears and sometimes blood, and always a little too much to do in the allocated time. We have also recently experienced a surge in workload, which has arrived in the form of a soft cheeked, downy haired, sweet smelling, all around delightful baby boy. We jokingly refer to him as The Royal Baby, for he is indeed a teeny dictator, but a benevolent one who bestows smiles generously upon his subjects, and is happy to converse with one and all, albeit with a limited vocabulary.

Aidan Baron: Crash course in LGBTQI+ at DFTB17

Cite this article as:
Team DFTB. Aidan Baron: Crash course in LGBTQI+ at DFTB17, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.13709

This talk was recorded live on the first day at DFTB17 in Brisbane. If you missed out in 2017 then why not book your leave for 2018 now. Tickets are on sale for the pre-conference workshops and the conference itself at www.dftb18.com.

Fetal Alcohol Spectrum Disorder – Management

Cite this article as:
Mary Hardimon. Fetal Alcohol Spectrum Disorder – Management, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.12615

After taking an extensive history and performing multiple clinical examinations in consultation with allied health staff, you come to the conclusion that Callum has a diagnosis of foetal alcohol spectrum disorder. His mother is mortified about the situation and isn’t sure what this will mean for Callum (both now and in the future) as well as the family.

Simon Craig: Acute asthma at DFTB17

Cite this article as:
Team DFTB. Simon Craig: Acute asthma at DFTB17, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.13122

This talk was recorded live at DFTB17 in Brisbane. We’ve got plenty more where this one came from so keep on checking in with us every week. If you think you’ve got the chops to pull it off next year then get in touch with us hello@dontforgetthebubbles.com.

Trust me, I’m a GP

Cite this article as:
Andrew Tagg. Trust me, I’m a GP, Don't Forget the Bubbles, 2017. Available at:
https://doi.org/10.31440/DFTB.12808

Here at DFTB we are keen to promote a culture that breaks down the silos of who can do what. We all care about one thing, above all else, the wellbeing of the children we treat. Working in a hospital environment sometimes gives us a skewed view of illness. Just like every neurosurgeon that sees a patient with a headache is concerned about a sub-arachnoid haemorrhage, every doctor in the paediatric emergency department is concerned about missing sepsis.