You are here

Scheduling delegate's interim decisions and invitation for further comment: ACCS/ACMS, February 2016

Scheduling medicines and poisons

3 February 2016

Book pagination

2.4 Piracetam

Part A - Interim decisions on matters referred to an expert advisory committee

2. Scheduling proposals referred to the November 2015 meeting of the Advisory Committee on Medicines Scheduling (ACMS#16)

2.4 Piracetam

Scheduling proposal

The medicines scheduling delegate has referred the following scheduling proposal for consideration by the Advisory Committee on Medicines Scheduling (ACMS):

  • To reschedule piracetam and its analogues and derivatives from Schedule 4 to unscheduled (exempt).
Substance summary

The applicant has provided the following information regarding Piracetam:

Piracetam acts on the central nervous system (CNS) and has been described as a nootropic; it is said to protect the cerebral cortex against hypoxia. It is also reported to inhibit platelet aggregation and reduce blood viscosity at high doses. Piracetam is used as an adjunct in the treatment of myoclonus of cortical origin, and has also been used in dementia. Other disorders or states in which it has been tried (on the basis of a supposed 'cerebrocortical insufficiency' responsive to piracetam) include alcoholism, vertigo, cerebrovascular accidents, dyslexia, behavioural disorders in children, and after trauma or surgery.

In cortical myoclonus, piracetam is given in oral doses of 7.2 g daily, increasing by 4.8 g daily every three or four days up to a maximum of 24 g daily. It is given in two or three divided doses. Once the optimal dose of piracetam has been established, attempts should be made to reduce the dose of other drugs.

Piracetam has been given for various other disorders in a usual oral dose of up to 2.4 g daily in 2 or 3 divided doses; doses of up to 4.8 g daily or higher have been used in severe cases. In severe disorders it has also been given by intramuscular or intravenous injection.

Although piracetam is used in some countries in the management of cognitive impairment and dementia, a systematic (Cochrane) review concluded that the evidence from the published literature did not support this use.

Piracetam is reported to produce insomnia or somnolence, weight gain, hyperkinesia, nervousness and depression. Other reported adverse effects include gastrointestinal disorders such as abdominal pain, diarrhoea, nausea and vomiting, hypersensitivity reactions, ataxia, vertigo, confusion, hallucinations, angioedema and rashes. Piracetam should not be given to patients with hepatic impairment or with severe renal impairment (creatinine clearance less than 20 mL/minute); dosage reduction is recommended for those with mild to moderate renal impairment. Therapy with piracetam should not be withdrawn abruptly in myoclonic patients due to the risk of inducing seizures. When used to treat cortical myoclonus, piracetam is contraindicated in patients with cerebral haemorrhage, and should be used with caution after major surgery and in those with haemostatic disorders or severe haemorrhage.

Piracetam is rapidly and extensively absorbed from the gastrointestinal tract; peak plasma concentrations are reached within 1.5 hours after oral doses. The plasma half-life is reported to be five hours, and piracetam crosses the blood-brain barrier. Piracetam is excreted almost completely in the urine. It crosses the placenta and is distributed into breast milk.

Scheduling status

Piracetam is currently listed in Schedule 4.

Scheduling history
National Drugs and Poisons Schedule Committee (NDPSC): October 2006

The NDPSC agreed to include piracetam in Schedule 4, on the grounds of harmonisation with New Zealand.

The New Zealand Medicines Classification Committee (MCC) considered the classification of a number of new chemical entities, including piracetam, at its meeting on 17 May 2001. The MCC agreed that, in view of the indications and as it was a new chemical entity, piracetam should be classified as prescription medicine.

Pre-meeting public submissions

Two public submissions were received. These were opposed to the proposal.

They made the following main points:

  • Piracetam has been used in dementia or cognitive impairment, but its mechanism of action is not well defined, and evidence for efficacy has not been demonstrated consistently.
  • Possible adverse effects of piracetam include insomnia, weight gain, hyperkinesia and depression. Other reported effects include gastrointestinal symptoms (e.g. abdominal pain, diarrhoea), ataxia, confusion, hallucinations, angioedema, confusion, bleeding problems, vertigo and worsening of epilepsy.
  • Although the purpose of the current proposal is not clear, the documented characteristics and side effect profile of piracetam would suggest that less restricted availability could pose unacceptable risks to consumers.
  • Dietary supplements containing piracetam were the subject of compliance actions by the United States Food and Drug Administration.
  • Removing piracetam completely from the poisons schedule could potentially lead to products containing this substance to be sold in a general retail setting (or online) which is not in the interests of public health.
  • Piracetam does not have a TGA pregnancy rating but consumers are advised to avoid it during pregnancy due to insufficient data.
  • The onus of proof rests with the applicants to show why removing piracetam from the Poisons Standard (thus allowing products containing this substance to be sold in general retail outlets) does not pose a risk to public health.

The public submissions are available at Public submissions on scheduling matters.

ACMS advice to the delegates

The ACMS recommended that the current scheduling of piracetam remains appropriate.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate included: a) the risks and benefits of the use of the substance; b) the purposes for which a substance is to be used and the extent of use of a substance; c) the toxicity of the substance; d) the dosage, formulation, labelling, packaging and presentation of a substance; e) the potential for abuse of a substance; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the recommendation comprised the following:

  • Piracetam is not used therapeutically in Australia.
  • Its risks outweigh the benefits.
  • No Australian data is available on marketing.
  • Some of the conditions that piracetam would be used for require medical supervision.
  • Piracetam (and its derivatives) is widely marketed as a cognitive enhancement agent. In UK it is prescribed for myoclonus and other off-label conditions. In Switzerland it is prescribed for myoclonus, cognitive disorders and dyslexia. No piracetam containing products are listed on the ARTG.
  • Piracetam has low toxicity in short (high-dose) & long-term trials.
  • Unexpected effects of the substance may only become evident after widespread use (SPF criteria 8).
  • The potential for abuse of Piracetam is low.
  • The ailments or symptoms that the substance is used for require medical intervention (SPF criteria 1).
  • The experience of the use of the substances under normal clinical conditions is limited (SPF criteria 8).
Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • Public submissions received;
  • ACMS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors19;
  • Other relevant information.
Delegate's interim decision

The delegate's interim decision is that the current scheduling of piracetam remains appropriate.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate included: a) the risks and benefits of the use of the substance; b) the purposes for which a substance is to be used and the extent of use of a substance; c) the toxicity of the substance; d) the dosage, formulation, labelling, packaging and presentation of a substance; e) the potential for abuse of a substance; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the recommendation comprised the following:

  • Piracetam is not used therapeutically in Australia. Risks outweigh the benefits. No Australian data available on marketing. Some of the conditions that piracetam would be used for require medical supervision.
  • Piracetam (and its derivatives) is widely marketed as a cognitive enhancement agent. In UK it is prescribed for myoclonus and other off-label conditions. In Switzerland it is prescribed for myoclonus, cognitive disorders and dyslexia. No piracetam containing products are listed on the ARTG.
  • Low toxicity in short (high-dose) and long-term trials. Unexpected effects of the substance may only become evident after widespread use (SPF criteria 8).
  • Piracetam is not used therapeutically in Australia. Risks outweigh the benefits. No Australian data available on marketing. Some of the conditions that piracetam would be used for require medical supervision.
  • Low potential for abuse.
  • The ailments or symptoms that the substance is used for require medical intervention (SPF criteria 1).
  • The experience of the use of the substances under normal clinical conditions is limited (SPF criteria 8).

Footnotes

  1. Scheduling Policy Framework for Medicines and Chemicals (SPF, 2015)

Book pagination