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Scheduling delegate's final decisions, March 2017
Scheduling medicines and poisons
3.11 Guanfacine hydrochloride
Part A - Final decisions on matters referred to an expert advisory committee
3. Advisory Committee on Medicines Scheduling (ACMS #19)
3.11 Guanfacine hydrochloride
Referred scheduling proposal
The New Chemical Entity (NCE) delegate from the Therapeutic Goods Administration has referred the substance guanfacine hydrochloride, proposing that the substance be listed in Appendix K.
The proposed amendment to the Poisons Standard is as follows:
Schedule 4 – Proposed New Entry
Appendix K – Proposed New Entry
The reason provided by the clinical delegate is on the basis that guanfacine hydrochloride causes sedation.
Current scheduling status and relevant scheduling history
Guanfacine hydrochloride is not currently scheduled in Australia and has not been previously considered for scheduling; a scheduling history is therefore not available.
International regulatory information
Guanfacine hydrochloride is not classified in New Zealand. In the USA and Canada, Guanfacine hydrochloride is classified as a Prescription Only medicine.
Guanfacine hydrochloride is a central alpha2A-adrenergic receptor agonist and is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in paediatric patients (children and adolescents 6-17 years old inclusive).
Guanfacine hydrochloride is not a central nervous system (CNS) stimulant, a monoamine transporter inhibitor or releaser of presynaptic dopamine or norepinephrine. The mode of action of guanfacine hydrochloride in ADHD is not fully established. Preclinical research suggests guanfacine hydrochloride modulates signalling in the prefrontal cortex and basal ganglia through direct modification of synaptic norepinephrine transmission at the alpha 2-adrenergic receptors. The INN is guanfacine31.
There is a USP 36 monograph for guanfacine hydrochloride, but no BP 2016 monograph.
|Chemical name||N-amidino-2-(2,6-dichlorophenyl)acetamide monohydrochloride|
|Australian Approved Name (AAN)||guanfacine hydrochloride (reference USP, USAN)|
|Molecular weight||282.6 g/mol (for the hydrochloride salt)|
|Form||White to off-white powder (single polymorphic form)|
|Solubility||sparingly soluble in water and alcohol and slightly soluble in acetone|
|partition coefficient (logP)||2-octanol/water: 0.10|
|pH||~4 when dissolved in water|
Pre-meeting public submissions
No pre-meeting submissions were received for guanfacine.
Summary of ACMS advice to the delegate
The Committee advised that guanfacine should be entered in Schedule 4 with an Appendix K listing.
The recommended wording for the guanfacine entry is as follows:
Schedule 4 –New Entry
Appendix K –New Entry
The Committee also recommended an implementation date of 1 June 2017.
The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included: (a) the risks and benefits of the use of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (f) any other matters that the Secretary considers necessary to protect the public health.
The reasons for the advice comprised the following:
- Guanfacine is a central alpha2A-adrenergic receptor agonist used in the treatment of ADHD in children and adolescents.
- Guanfacine hydrochloride carries a significant risk of causing sedation and somnolence in humans exhibited by a medicine in normal use. Data demonstrates impairment of critical motor reflexes and cognitive skills applicable to driving or the operation of machinery with guanfacine hydrochloride use and therefore there is a need to warn users of any potential danger of the medication.
- There are no products containing guanfacine hydrochloride currently registered in the ARTG. This is a prescription-only medicine and Appendix K sedation warning is appropriate.
- Guanfacine hydrochloride has no known potential for abuse or dependence. The current sedation warning statements are more appropriate for a medication used in adults rather than children and adolescents.
The delegate considered the following in regards to this application:
- Scheduling proposal
- ACMS advice
- Section 52E of the Therapeutic Goods Act 1989
- Scheduling Policy Framework (SPF 2015)
- Other relevant information.
Delegate’s interim decision
The delegate’s interim decision is that a new Schedule 4 entry for guanfacine with an Appendix K listing is appropriate.
The proposed wording for the schedule and appendix entries is as follows:
Schedule 4 – New Entry
Appendix K – New Entry
The proposed implementation date is 1 June 2017.
The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (a) the risks and benefits of the use of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; (f) any other matters that the Secretary considers necessary to protect the public health.
The reasons for the interim decision are the following:
- The delegate acknowledges the committee’s advice.
- Guanfacine hydrochloride has a significant risk of causing sedation.
Public submissions on the interim decision
No public submissions were received in response to the interim decision for guanfacine hydrochloride.
Delegate’s final decision
The delegate has confirmed the interim decision and reasons for the decision as no evidence has been received to alter the interim decision. The delegate’s final decision is to create new Schedule 4 and Appendix K entries for guanfacine with an implementation date of 1 June 2017.