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Scheduling delegate's final decisions, March 2017

23 March 2017

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1.4 Sodium phenylbutyrate

Part B - Final decisions on matters not referred to an expert advisory committee

New Chemical Entities – medicines for human therapeutic use

1.4 Sodium phenylbutyrate

Scheduling proposal

The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of sodium phenylbutyrate, a new chemical entity (NCE) for a human therapeutic medicine.

Substance summary

Sodium phenylbutyrate is a pro-drug and is rapidly metabolised to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine which is then excreted by the kidneys.

Sodium phenylbutyrate is indicated as adjunctive therapy in the chronic management of urea cycle disorders and should be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, and protein-free calorie supplements). Sodium phenylbutyrate is indicated in all patients with neonatal-onset presentation (complete enzyme deficiencies, presenting within the first 28 days of life). It is also indicated in patients with late-onset disease (partial enzyme deficiencies, presenting after the first month of life) who have a history of hyperammonaemic encephalopathy. Sodium phenylbutyrate has not been studied in the geriatric (> 65 years of age) population.

Australian Approved Name (AAN) and International Non-Proprietary Name (INN): Sodium phenylbutyrate.

Scheduling status

Sodium phenylbutyrate is not specifically scheduled and is not captured by any entry in the current Poisons Standard.

International regulations

Sodium phenylbutyrate is classified as a prescription medicine in New Zealand, Canada and USA.

Delegate's consideration

The delegate decided to make a delegate-only decision. The Advisory Committee on Medicines Scheduling was not consulted.

The delegate considered the following in regards to this application for scheduling:

  • Subsection 52E(1) of the Therapeutic Goods Act 1989;
  • The Scheduling Policy Framework (2015) scheduling factors;
  • The TGA evaluation report; and
  • The new drug application.

The delegate noted that currently there are no issues of concern that require additional control other than by inclusion in Schedule 4.

Delegate's final decision

The delegate has made a final decision to amend the Poisons Standard to include Sodium phenylbutyrate in Schedule 4, with an implementation date of 1 June 2017.

The delegate has decided that the wording for the schedule entry will be as follows:

Schedule 4 - New Entry

SODIUM PHENYLBUTYRATE.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are: (a) the risks and benefits of the use of a substance; (b) the purpose and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse.

The delegate decided that the reasons for the final decision comprise the following:

  • Sodium phenylbutyrate is an NCE with no marketing experience in Australia.
  • The risks and benefits of Sodium phenylbutyrate have been considered and are outlined in the Product Information (PI) and the TGA evaluation reports.
  • Sodium phenylbutyrate has been used for more than a decade internationally but there is no marketing experience in Australia.
  • Sodium phenylbutyrate has risks that require medical intervention, evaluation and monitoring by the medical practitioner.
  • Treatment should only be initiated and monitored by a health professional experienced in the treatment of urea cycle disorders.
  • It does not appear to produce dependency and the abuse potential appears low

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