On 22 August 2017, the Therapeutic Goods Administration in Australia accepted guanfacine hydrochloride (current sole brand name Intuniv) as a new chemical entity. Whilst new to Australia, guanfacine has been available within the United States of America and Europe since 2010 and 2015, 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 guanfacine?
Guanfacine is an alpha 2 agonist. Unlike clonidine (which is non-selective and shows high affinity for all three subtypes of alpha 2 receptors – A, B and C), guanfacine has a preferential affinity for alpha 2A receptors. Stimulating these receptors in the prefrontal cortex mimics noradrenaline/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.
Indications for guanfacine
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 be ineffective) or as adjunctive therapy to psychostimulants (where there has been a sub-optimal response to psychostimulants).”
Guanfacine “must be used as part of a comprehensive ADHD management programme, typically including psychological, educational and social measures.
These stipulations encourage prescribers to manage ADHD within a bio-psycho-social context, understanding that, in most 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. There are minimal studies surrounding guanfacine use in children younger than six years, and whilst efficacy has been suggested, caution would be indicated in making ADHD diagnoses, particularly in toddler years, due to a great variety in “normal” in this period.
Dose 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 before this dose) of 0.05 – 0.12mg/kg/day. Amounts exceeding 4mg (co-administration) and 7mg (when used as monotherapy) have not been evaluated.
Recommended target dose range for maintenance therapy when guanfacine is sole agent
| 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 effects 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 effects 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.
Cost
Since being introduced onto the PBS on 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
https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia
https://www.drugs.com/newdrugs/shire-announces-fda-approval-once-daily-intuniv-guanfacine-extended-release-adhd-children-1599.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676929/
https://stahlonline.cambridge.org/content/ep/images/85702c17_fig24.jpg
https://www.guildlink.com.au/gc/ws/zi/pi.cfm?product=zipintun10817
https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-02254-1&d=2017110516114622483
https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf
https://pi.shirecontent.com/PI/PDFs/Intuniv_USA_ENG.pdf
Additional resources
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b972af81-3a37-40be-9fe1-3ddf59852528
https://pi.shirecontent.com/PI/PDFs/Intuniv_USA_ENG.pdf
https://www.guildlink.com.au/gc/ws/zi/pi.cfm?product=zipintun10817<
