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

Scheduling medicines and poisons

15 September 2016

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1.5 Piper methysticum (kava)

Note

  • Red strikethrough text indicates text that has been deleted.
  • Green italicised text indicates text that has been added.
Referred scheduling proposal

An application was submitted to amend part a) of the Schedule 4 entry for piper methysticum (kava) to exempt powdered and liquid preparations of piper methysticum (kava) dosage forms not exceeding 3 g, and where containing more than 25 mg of kavalactones per dose, compliant with the requirements of the Medicines Advisory Statements Specification. It is also proposed that there is the addition of the mandatory warning statement "Do not exceed recommended daily dose" to be added to all kava packaging.

Scheduling application

General application.

The applicant's proposed amendments to the SUSMP are as follows:

Schedule 4 - Amend entry

PIPER METHYSTICUM (kava) in preparations for human use except when included on the Australian Register of Therapeutic Goods in preparations:

  1. for oral use when present in tablet, capsule, powder, liquid or teabag form that is labelled with a recommended maximum daily dose of 250 mg or less of kavalactones and:
    1. the tablet or capsule form contains 125 mg or less of kavalactones per tablet or capsule; or
    2. the amount of dried whole or peeled rhizome in the teabag does not exceed 3 g; and, where containing more than 25 mg of kavalactones per dose, compliant with the requirements of the Required Advisory Statements for Medicine Labels; or
    3. the amount of dried whole or peeled rhizome in the unit dose of powder does not exceed 3 g; and

      where containing more than 25 mg of kavalactones per dose, compliant with the requirements of the Medicines Advisory Statements Specification 2014;

      and is packaged with a dose controlled measuring device (Scoop);

      and is limited to a maximum quantity of 200 g of powder per package; or

    4. the liquid form contains 125 mg or less of kavalactones per unit dose of liquid;

      and, where containing more than 25 mg of kavalactones per dose, compliant with the Medicines Advisory Statements Specification 2014;

      and is packaged in a single serve packaging.

  2. in topical preparations for use on the rectum, vagina or throat containing dried whole or peeled rhizome or containing aqueous dispersions or aqueous extracts of whole or peeled rhizome; or
  3. in dermal preparations.

It is also proposed that there is the addition of the mandatory warning statement "Do not exceed recommended daily dose" to be added to all kava packaging as follows:

Medicines Advisory Statements Specification - New warning statement

WARNING: Do not exceed recommended daily dose.

The applicant's reasons for the request are:

  • Current regulations in Australia pertaining to kava are the result of both the potential for hepatotoxicity and reported abuse in Indigenous communities in Australia;
  • The rhizome of piper methysticum (kava), indigenous to the South Pacific, has a proven history of use as an effective treatment for anxiety through folk and contemporary medicine;
  • The yearly state-of-the-nation survey Stress and wellbeing in Australia 2014, has highlighted a yearly incremental increase in the levels of stress and anxiety in the Australian population since it began in 2011;
  • This increase in stress and anxiety in the Australian population calls for assessment of effective strategies for helping to manage anxiety and promote greater health and wellbeing within the community;
  • Evidence suggests that some specific dosage forms are more difficult for members of the community suffering from stress and anxiety to adhere to due to difficulties swallowing tablets and capsules meaning less access to effective treatment;
  • Current exceptions to the SUSMP exclude powder and liquid preparations for kava;
  • The proposed new dosage form poses no further risk to the community than those currently approved for use; and
  • The use of kava as an effective anxiolytic is well established, with benefits to the community particularly in relation to stress and anxiety.
Substance summary

Kava is the rhizome of piper methysticum (piperaceae), a shrub indigenous to islands of the South Pacific.

The major chemical constituents of kava are kava lactones (also known as kava pyrones) with the major lactones being kawain (1.8%), methysticin (1.2%), dihydromethysticin (0.5%), emethyoxyyangonin (1.0%), yagonin (1.0%) and dihydrokawain (1.0%). At least 13 other lactones, two chalcones and a number of free aromatic acids are known.(1) The structures of the representative lactones are presented below in Figure 1.5.

Figure 1.5: Chemical structure of isolated kava lactones.

Figure 1.5: Chemical structure of isolated kava lactones.

There have been concerns over hepatotoxicity, which have lead to kava's use being restricted in Australia by way of addition to Schedule 4 of the SUSMP and it has also been withdrawn or restricted for use in other parts of the world.

Hepatotoxicity was not an established health issue of kava, over the centuries of traditional kava use, and it appears that the primary cause of toxicity is most likely attributable to poor quality of the raw material caused by bacterial and/or mould hepatotoxins. Other issues may be the forms, including plant parts and incorrect cultivars of kava and potential adulteration however further research is required to elucidate the exact cause and currently the most convincing argument is for a plan for rigorous testing of kava raw materials as well as kava standardisation and manufacturing quality standards put forward by kava researchers Teschke and Sarris (2011).

Kava is a psychotropic plant medicine that has anxiolytic activity. This effect is achieved through modulation of GABA activity via alteration of lipid membrane structure and sodium channel function, monoamine oxidase B inhibition, and noradrenaline and dopamine re-uptake inhibition.

Kava has been used in the South Pacific to produce an intoxicating beverage for recreational purposes and during convalescence. Traditionally, a beverage is prepared, then drunk before the evening meal. It is reported to have sedative, skeletal muscle relaxant, and anaesthetic properties. It is given in some anxiety and stress related disorders. Kawain has also been used for nervous disorders and as a tonic.

Specific questions raised by the delegate

The delegate asked the committee the following questions:

  1. Does the application provide any new information from that considered by ACMS in 2011?
  2. Is it appropriate for liquid and powder preparations of PIPER METHYSTICUM (kava) as in the proposal to be exempt from Schedule 4 of SUSMP?
  3. Does the risk of misuse and abuse of liquid and powder preparations of kava that are not for medicinal use fit an unscheduled product?
  4. Do the current jurisdictional controls still allow appropriate access for traditional use?
Current scheduling status

Piper methysticum is currently listed in Schedule 4 of the SUSMP.

Schedule 4

PIPER METHYSTICUM (kava) in preparations for human use except when included on the Australian Register of Therapeutic Goods in preparations:

  1. for oral use when present in tablet, capsule or teabag form that is labelled with a recommended maximum daily dose of 250 mg or less of kavalactones and:
    1. the tablet or capsule form contains 125 mg or less of kavalactones per tablet or capsule; or
    2. the amount of dried whole or peeled rhizome in the teabag does not exceed 3 g;

      and, where containing more than 25 mg of kavalactones per dose, compliant with the requirements of the Required Advisory Statements for Medicine Labels;

  2. in topical preparations for use on the rectum, vagina or throat containing dried whole or peeled rhizome or containing aqueous dispersions or aqueous extracts of whole or peeled rhizome; or
  3. in dermal preparations.
Relevant scheduling history
National Drugs and Poisons Schedule Committee: October 2003

The committee noted a safety evaluation report prepared by the Kava Evaluation Group/ Office of Complementary Medicines on kava containing medicines, which made recommendations on the regulation of kava as an ingredient in Listed Medicines. Due to the potential risk of liver toxicity from use of non-aqueous extracts of kava plants at high doses, the committee considered there was a need to restrict the use of alcohol/acetone extracts of kava, including those for bulk supply to health care practitioners for use in extemporaneous compounding.

National Drugs and Poisons Schedule Committee: February 2004

The committee was advised that the Complementary Medicines Evaluation Committee (CMEC) Recommendation 41.3 regarding the listing and registration of kava had been included in Schedule 4 of the Therapeutic Goods Regulations 1990 (TG Regulations). This recommendation only allowed specified concentrations of aqueous kava extracts in Listed Medicines and required that all other kava products be cancelled from the ARTG. The committee agreed to foreshadow the inclusion of kava in Schedule 4 of the SUSDP with exemptions consistent with those specified in the TG Regulations.

National Drugs and Poisons Schedule Committee: June 2004

The committee, on the grounds of public health and safety, agreed to include kava in Schedule 4, as well as adopting exemptions as specified in the TGA Regulations 1990. The decision made all kava Schedule 4 except dried whole or peeled rhizome, its aqueous dispersions or extracts, tablets of 125 mg or less of kavalactones per tablet, teabags of up to 3 g kava, and not more than 25 mg of kavalactones per dose.

National Drugs and Poisons Schedule Committee: October 2005

The committee confirmed that all parts of the Schedule 4 exemption for oral use for kava required the mandatory warning statement. The committee agreed that the only exception to this should be for preparations containing less than 25 mg kavalactones and agreed to amend the Schedule 4 entry for kava to clarify this ambiguity.

National Drugs and Poisons Schedule Committee: October 2007

The committee considered a proposal from the Office of Chemical Safety (OCS) which requested the removal of the current exemption from scheduling for the whole or peeled rhizome of kava. This request was part of the Australian Government's efforts to reduce the abuse of the substance in some indigenous communities. The committee agreed to foreshadow consideration of this issue at the February 2008 NDPSC Meeting.

National Drugs and Poisons Schedule Committee: February 2008

The committee considered the Schedule 4 entry for piper methysticum (kava). In light of an Australian Government kava policy decision, the committee reconsidered the restrictions for kava and concluded that the potential for abuse and the hazard to public health of the whole or peeled rhizome meant that this form of kava should no longer be exempt from scheduling. The committee therefore amended the Schedule 4 entry so that only some products on the ARTG were not captured.

National Drugs and Poisons Schedule Committee: June 2009

The committee considered the scheduling of piper methysticum (kava) and decided that the current scheduling for piper methysticum remains appropriate.

Pre-meeting public submissions

Four (4) public submissions were received.

All 4 submissions supported amendment (iii) of the proposal. The main points were that kava has a long history of use, well-researched toxicity, low relative potential for abuse, and very significant positive benefits, both demonstrated and potential.

Two (2) submissions provided alternative wording for amendment (iv) and the additional mandatory warning label. The main points were:

  • Consideration regarding ability to provide packs for extemporaneous dispensing larger than the proposed limitation; and
  • Mandatory warning label potentially problematic as it is unclear if it refers to bulk supplies or dispensed product in the extemporaneous context.

The public submissions are available on the TGA website.

Summary of ACMS advice to the delegate

The committee advised that the delegate that the current scheduling remains appropriate.

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; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity 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 advice comprised the following:

  • Cultural use has a long history where the drink is consumed for sense of relaxation, tranquillity and to manifest sociable attitude, however there is a high potential of recreational misuse in localised communities;
  • Liver toxicity is a known adverse effect with kava. Elevated liver enzymes on exposure return to normal levels upon ceasing or reducing kava consumption;
  • Long term consumption of kava can lead to toxic effects, such as dry and scaly skin which is reversible on cessation;
  • There are serious concerns that kava powder and liquid forms would be misused and does not support down-scheduling of kava powder from Schedule 4. Several jurisdictions have had historical problems with misuse, especially with the powder forms and liquid form, but the latter to a lesser extent;
  • There are concerns that people ingesting drinks prepared from either liquid or powdered forms would not know the level of kava contained in the preparations. In comparison, an individual would be able to readily identify the number of tablets they consume;
  • Pre-packaged liquid doses might promote the mixing of the liquid dose in other drinks, and this may lead to serious concerns about the ability of children to access mixed drinks;
  • In 2008, the whole or peeled rhizomes and aqueous dispersions of kava were removed from the SUSMP, and despite reconsideration by the scheduling committee in 2011, the scheduling of kava has remained unchanged. In this proposal, no further information was provided to support a change in the scheduling of kava; and
  • Kava would be more open to misuse, with no particular health benefit, by permitting kava to become available in powder or liquid form.
Delegate's considerations

The delegate considered the following in regards to this application:

  • Scheduling proposal;
  • Public submissions received;
  • ACMS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling Policy Framework (SPF 2015); and
  • Other relevant information.
Delegate's interim decision

The delegate notes and accepts the ACMS advice and reasons that the current Schedule 4 entry for piper methysticum (kava) remains appropriate. The scheduling application has presented no further information to support a change in the scheduling of kava. There is a long history of cultural use for piper methysticum (kava) where the drink is consumed for sense of relaxation, tranquillity and to manifest sociable attitude. However, there is a high potential of recreational misuse in localised communities. Long term consumption of kava can lead to toxic effects, such as liver toxicity and dry/scaly skin, which is reversible on cessation. There are serious concerns that kava would be more open to misuse, with no particular health benefit, by permitting kava to become available in powder or liquid form. Several jurisdictions have had historical problems with misuse, especially with the powder and liquid (to a lesser extent) forms. While an individual would be able to readily identify the number of kava tablets they consume, there are concerns that people ingesting drinks prepared from either liquid or powdered kava forms would not know the level of kava contained in the preparations. Furthermore, pre-packaged liquid doses might promote the mixing of the liquid dose in other drinks, and this leads to serious concerns about the ability of children to access mixed drinks.

An implementation date is not relevant given there will be no change to the SUSMP as a result of this interim decision.

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; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity 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.

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