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Scheduling delegate's interim decisions and invitation for further comment: ACMS, October 2015

Scheduling medicines and poisons

1 October 2015

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Interim decisions on matters referred to an expert advisory committee (1.5-1.8)

1.5 2-Hydroxyethyl methacrylate

Scheduling proposal

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

  • Noting the Chemical Delegate's interim decision to create a new Schedule 5 entry, 2-hydroxyethyl methacrylate except when in nail preparations labelled "Avoid contact with skin", should therapeutic and/or dental use of this substance be exempt from scheduling or have a cut-off of strength? If a cut-off of strength is to be applied, is the previously proposed implementation date of 1 February 2016 appropriate for therapeutic and/or dental use?

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

2-Hydroxyethyl methacrylate is a methacrylate ester. It is used in cosmetic products (including in artificial nail builders, in finger paints and as a film-forming agent) and in domestic products (e.g. adhesives and sealants; paint, thinners and paint removers; washing and cleaning products; anti-freeze products). Uses at concentrations up to 10% in cosmetic products and up to 80% in domestic products have been identified in Australia. The substance also has commercial, site-limited and non-industrial uses. The main toxicity concerns relate to skin sensitisation potential, eye irritation and skin irritation. Please refer to the NICNAS IMAP human health Tier II assessment report for 2-propenoic acid, 2-methyl-, 2-hydroxyethyl ester - this report is publicly available on the NICNAS website: NICNAS IMAP-assessment ID 11875.

2-Hydroxyethyl methacrylate is also used in dental restorative products in Australia.

Scheduling status

2-Hydroxyethyl methacrylate is not currently scheduled. Following the March 2015 meeting of the Advisory Committee on Chemicals Scheduling, a new Schedule 5 entry was proposed for 2-hydroxyethyl methacrylate except when in nail preparations labelled “Avoid contact with skin”. New Appendix E and Appendix F entries were also proposed for 2-hydroxyethyl methacrylate when in Schedule 5. The proposed implementation date was 1 February 2016.

The scheduling delegate subsequently became aware that 2-hydroxyethyl methacrylate is also used in dental restorative products for human use.

Scheduling history
2-Hydroxyethyl methacrylate

Advisory Committee on Chemicals Scheduling: March 2015

The ACCS considered a proposal to create a new Schedule 5 entry for 2-hydroxyethyl methacrylate (primarily for use in cosmetics or domestic products). Concerns regarding skin sensitisation potential and evidence of eye irritation with 2-hydroxyethyl methacrylate were noted. The ACCS recommended inclusion of 2-hydroxyethyl methacrylate in Schedule 5, except when in nail preparations labelled "Avoid contact with skin". Appendix E and Appendix F statements were also proposed.

Other methacrylate esters

2-Hydroxyethyl methacrylate belongs to a group of chemicals known as methacrylate esters, and other chemicals in this group have been considered by National Drugs and Poisons Scheduling Committee (NDPSC) and Advisory Committee on Chemicals Scheduling (ACCS), for the same use and due to the same hazardous property of skin sensitisation. Two other chemicals belonging to this group of chemicals, namely ethyl methacrylate and methyl methacrylate are listed in the Poisons Standard.

National Drugs and Poisons Scheduling Committee: 2006-2008

The NDPSC considered ethyl methacrylate and methyl methacrylate several times over the period 2006-2008. The NDPSC decided to include ethyl methacrylate in Schedule 5 at concentrations above 1% as the low irritancy and skin sensitisation risks of ethyl methacrylate could be appropriately reduced through including a new Schedule 5 entry for cosmetic use, and to create an Appendix F entry providing appropriate warning statements and safety directions and that these risks are sufficiently reduced when there is ≤ 1% monomer present as a residue in a polymer as to warrant exclusion from the requirements of scheduling.

The NDPSC decided to include methyl methacrylate (MMA) in Schedule 6 for non-cosmetic uses at concentrations above 1% and Appendix C for all cosmetic uses. The NDPSC noted that the severe dermal irritancy, moderate respiratory irritancy and evidence of moderate sensitising potential of methyl methacrylate constituted a moderate potential for causing harm (when for non-cosmetic uses), the extent of which could be reduced through the use of appropriate packaging and labelling and that these risks are sufficiently reduced when there is ≤ 1% monomer present as a residue in a polymer as to warrant exclusion from the requirements of scheduling. However, the cosmetic use of MMA posed sufficient danger as to warrant prohibition of sale, supply and use through inclusion in Appendix C.

Advisory Committee on Chemicals Scheduling: July 2014

Another methacrylate ester, 2-hydroxypropyl methacrylate, was considered by the ACCS. The chemicals delegate's decision was to add the substance to schedule 5 in nail preparations except when labelled 'avoid contact with skin'. The chemicals delegate noted the toxicity of 2-hydroxypropyl methacrylate appears to be less severe than the methyl- and ethylmethacrylates currently listed in Schedule 5, 6 and Appendix C, although there is some potential for cross sensitisation to occur between these methacrylate derivatives when used in nail preparations. The implementation date for this decision is 1 January 2016. The final decision of 2-hydroxypropyl methacrylate is available at 1.4 2-hydroxypropyl methacrylate.

Pre-meeting public submissions

No submissions were received.

ACMS advice to the delegate

The ACMS recommended that 2-hydroxyethyl methacrylate be included in Schedule 5 except when included in dental restorative preparations for therapeutic use when labelled "Avoid contact with skin" (this is in addition to the previously agreed exemption for nail preparations labelled "Avoid contact with skin").

The ACMS recommended an implementation date for the new Schedule 5 entry of 1 February 2016.

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; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the recommendation comprised the following:

  • Risks: irritation and skin sensitisation; and lower risk due to inhalation of the chemical.
  • 2-Hydroxyethyl methacrylate is used in therapeutic goods for dental use that are regulated by the TGA.
  • There were some concerns regarding the potential for occupational exposure of dental technicians.
  • Labels of products containing 2-hydroxyethyl methacrylate should be required to include a warning statement regarding skin sensitisation.
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 factors6;
  • Other relevant information.
Delegate's interim decision

The delegate's interim decision is that 2-hydroxyethyl methacrylate be included in Schedule 5 except when included in dental restorative preparations for therapeutic use when labelled "Avoid contact with skin" (this is in addition to the previously agreed exemption for nail preparations labelled "Avoid contact with skin").

The proposed implementation date is 1 February 2015.

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; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the decision comprised the following:

  • The main risks with 2-hydroxyethyl methacrylate are irritation and skin sensitisation. There were some concerns regarding the potential for occupational exposure of dental technicians.
  • 2-Hydroxyethyl methacrylate is used in therapeutic goods for dental use that are regulated by the TGA.
  • The SUSMP Appendix A general exemption does not apply to dental restorative compounds, as they are not Class III medical devices.
  • Exemption of 2-hydroxyethyl methacrylate from scheduling in products for therapeutic or dental use is appropriate. Dental restorative compounds are used by highly trained people and the 2-hydroxyethyl methacrylate is converted to the polymer form (cured by UV light). There is a low risk of deliberate or accidental misuse.
  • There were some concerns regarding the potential for occupational exposure of dental technicians.
  • The only effect of exempting dental restoratives from Schedule 5 (with products required to be labelled "Avoid contact with the skin") is that product labels would not require a "CAUTION" heading.
  • Insufficient information is available to support any specific concentration cut-off for a scheduling exemption for 2-hydroxyethyl methacrylate in dental preparations. Therefore, dental products should be scheduled in the same way as nail preparations.
  • Labels of products containing 2-hydroxyethyl methacrylate should be required to include a warning statement regarding skin sensitisation.
Schedule entry
Schedule 5 - New entry

2-HYDROXYETHYL METHACRYLATE except when included in dental restorative preparations for therapeutic use or in nail preparations when labelled "Avoid contact with skin".

Appendix E, Part 2 - New entry
Poison Standard statements
2-hydroxyethyl methacrylate

A - For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once).

E1 - If in eyes wash out immediately with water.

S1 - If skin or hair contact occurs, remove contaminated clothing and flush skin and hair with running water.

Appendix F, Part 3 - New entry
Poison Warning statement Safety direction
2-hydroxyethyl methacrylate 28. (Over) (Repeated) exposure may cause sensitisation. 4. Avoid contact with skin

1.6 Esomeprazole

Scheduling proposal

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

  • To amend the scheduling of esomeprazole to include oral preparations containing 20 mg or less of esomeprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than seven days' supply from Schedule 3 to Schedule 2.

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

Esomeprazole is the S-isomer of the proton pump inhibitor (PPI), omeprazole, and is used similarly in the treatment of peptic ulcer disease and NSAID-associated ulceration, in gastro-oesophageal reflux disease, and in Zollinger-Ellison syndrome. Esomeprazole is given as the magnesium, sodium, or strontium salts but doses are calculated in terms of esomeprazole. Esomeprazole magnesium 22.2 mg, esomeprazole sodium 21.3 mg, and esomeprazole strontium 24.7 mg are each equivalent to about 20 mg of esomeprazole.

Scheduling status

Esomeprazole is currently listed in Schedules 3 and 4.

Schedule 3

ESOMEPRAZOLE in oral preparations containing 20 mg or less per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 14 days’ supply.

Schedule 4

ESOMEPRAZOLE except when included in Schedule 3.

Scheduling history
National Drugs and Poisons Schedule Committee: November 2000

The New Zealand Ministry of Health requested that the NDPSC consider scheduling esomeprazole to harmonise with New Zealand’s inclusion of the substance in Schedule 1, Part 1 (equivalent to Schedule 4 in the SUSMP). The NDPSC supported harmonisation and included esomeprazole in Schedule 4.

Advisory Committee on Medicines Scheduling: November 2013

The ACMS considered an application to down-schedule from Schedule 4 to Schedule 3 esomeprazole in in oral preparations containing 20 mg or less per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 14 days' supply. The ACMS advised the delegate to down-schedule esomeprazole to Schedule 3, as requested.

Pre-meeting public submissions

Seven submissions were received.

Three submissions supported the applicant's proposal to reschedule esomeprazole from Schedule 3 to Schedule 2 when in packs containing not more than seven days' supply.

Main points:

  • Esomeprazole is available OTC in the USA.
  • Recommend appropriate warning statements.

Three submissions opposed the rescheduling proposal. Main points:

  • No monitoring of ongoing/long-term use of PPIs which may lead to adverse reactions.
  • Need to ensure appropriate consultation and review by pharmacists.

One submission did not state a position. Main points:

  • If esomeprazole down-scheduled then recommend all PPIs have new Schedule 2 entry.
ACMS advice to the delegate

The ACMS recommended that esomeprazole in oral preparations containing 20 mg or less per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than seven days' supply, be down-scheduled from Schedule 3 to Schedule 2.

The committee also recommended to the delegate that consideration be given to down-scheduling the other OTC PPIs (i.e. lansoprazole, omeprazole and rabeprazole) from Schedule 3 to Schedule 2 in packs containing not more than seven days' supply.

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; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the recommendation comprised the following:

  • Esomeprazole is a safe and effective first line treatment for consumers with frequent symptoms of gastro-oesophageal reflux disease.
  • Heartburn and other symptoms of gastro-oesophageal reflux disease are common.
  • Esomeprazole has very low toxicity with short-term use.
  • The proposed Schedule 2 pack size (seven days' supply), labelling (including Required Advisory Statements for Medicine Labels (RASML) warning statements) and provision of Consumer medicine information will help ensure appropriate use of esomeprazole as a Schedule 2 medicine.
  • The current RASML label warnings for all OTC PPIs would apply to esomeprazole in Schedule 2 or Schedule 3.
  • Esomeprazole may be more effective in the treatment of gastro oesophageal reflux disease than ranitidine which is currently available as an unscheduled medicine (seven days' supply) and as a Schedule 2 medicine (14 days' supply).
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 factors7;
  • Other relevant information.
Delegate's interim decision

The delegate's interim decision is that esomeprazole, in oral preparations containing 20 mg or less per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than seven days’ supply, be down-scheduled from Schedule 3 to Schedule 2.

The proposed implementation date is 1 February 2016.

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; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the decision comprised the following:

  • Esomeprazole is a safe and effective first line treatment for consumers with frequent symptoms of gastro-oesophageal reflux disease.
  • Heartburn and other symptoms of gastro-oesophageal reflux disease are common.
  • Esomeprazole has very low toxicity with short-term use.
  • The proposed Schedule 2 pack size (seven days' supply), labelling (including RASML warning statements) and provision of Consumer medicine information will help ensure appropriate use of esomeprazole as a Schedule 2 medicine.
  • The current RASML label warnings for all OTC PPIs would apply to esomeprazole in Schedule 2 or Schedule 3.
  • Esomeprazole may be more effective in the treatment of gastro oesophageal reflux disease than ranitidine which is currently available as an unscheduled medicine (seven days' supply) and as a Schedule 2 medicine (14 days' supply).
Schedule entry
Schedule 2 - New entry

ESOMEPRAZOLE in oral preparations containing 20 mg or less of esomeprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 7 days' supply.

Schedule 3 - Amendment

ESOMEPRAZOLE in oral preparations containing 20 mg or less of esomeprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 14 days' supply except when included in Schedule 2.

Schedule 4 - Amendment

ESOMEPRAZOLE except when included in Schedule 2 or 3.

1.7 Proton pump inhibitors

Scheduling proposal

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

  • To create new Appendix H entries for the following Schedule 3 proton pump inhibitors (PPIs):
    • lansoprazole;
    • omeprazole;
    • pantoprazole; and
    • rabeprazole.

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

Lansoprazole, omeprazole, pantoprazole and rabeprazole are PPIs. PPIs are used in the treatment of peptic ulcer disease and NSAID-associated ulceration, in gastro-oesophageal reflux disease, and in Zollinger-Ellison syndrome.

Scheduling status

Lansoprazole, omeprazole and rabeprazole are currently listed in Schedules 3 and 4.

Pantoprazole is currently listed in Schedules 2, 3 and 4.

Lansoprazole

Schedule 3

LANSOPRAZOLE in oral preparations containing 15 mg or less of lansoprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 14 days' supply.

Schedule 4

LANSOPRAZOLE except when included in Schedule 3.

Omeprazole

Schedule 3

OMEPRAZOLE in oral preparations containing 20 mg or less of omeprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 14 days' supply.

Schedule 4

OMEPRAZOLE except when included in Schedule 3.

Raberazole

Schedule 3

RABEPRAZOLE in oral preparations containing 10 mg or less of rabeprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 14 days' supply.

Schedule 4

RABEPRAZOLE except when included in Schedule 3.

Pantoprazole

Schedule 2

PANTOPRAZOLE in oral preparations containing 20 mg or less of pantoprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 7 days' supply.

Schedule 3

PANTOPRAZOLE in oral preparations containing 20 mg or less of pantoprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 14 days' supply except when included in Schedule 2.

Schedule 4

PANTOPRAZOLE except when included in Schedule 2 or 3.

Scheduling history
National Drugs and Poisons Schedule Committee: June 2005

The NDPSC included pantoprazole in Schedule 3, in oral preparations containing 20 mg or less of pantoprazole for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 14 days’ supply (the NDPSC subsequently amended the implementation date until 1 May 2008). The NDPSC did not consider Appendix H listing at that time.

National Drugs and Poisons Schedule Committee: June 2009

The NDPSC agreed to down-schedule rabeprazole to Schedule 3 (with pack size and indication restrictions similar to those for pantoprazole). A request for Appendix H listing was rejected.

National Drugs and Poisons Schedule Committee: February 2010

The NDPSC decided that inclusion of pantoprazole in Appendix H listing was not appropriate.

Lansoprazole and omeprazole were scheduled similarly to pantoprazole and rabeprazole, to harmonise with New Zealand. In both cases, the NDPSC agreed that a consistent approach for all PPIs should be undertaken in relation to Appendix H listing, i.e. lansoprazole and omeprazole were not included in Appendix H.

National Drugs and Poisons Schedule Committee: June 2010

The NDPSC again rejected a proposal to include rabeprazole in Appendix H. The NDPSC generally agreed that an Appendix H listing was not appropriate at this time and that it would be beneficial for pharmacists to first become accustomed to having rabeprazole available as a Schedule 3 medicine.

Advisory Committee on Medicines Scheduling: November 2014

The ACMS recommended a new entry in Schedule 2 for pantoprazole when supplied in oral preparations containing 20 mg or less of pantoprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 7 days of supply.

Advisory Committee on Medicines Scheduling: March 2015

The ACMS recommended inclusion of esomeprazole in Appendix H. The ACMS also proposed that the medicines delegate consider initiating a proposal to list all Schedule 3 proton pump inhibitors (PPIs) in Appendix H.

Pre-meeting public submissions

Three submissions were received.

All three submissions supported the scheduling proposal with one on the condition that all advertisements for these products highlight the mandatory role of the pharmacist in determining the suitability of the product for consumers.

ACMS advice to the delegate

The ACMS recommended that new Appendix H entries be created for the following Schedule 3 proton pump inhibitors: Lansoprazole, Omeprazole, Pantoprazole and Rabeprazole.

The ACMS recommended an implementation date of 1 February 2016.

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; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the recommendation comprised the following:

  • The ACMS, at its March 2015 meeting, had recommended inclusion of esomeprazole in Appendix H.
  • The delegate decided that esomeprazole would be included in Appendix H as of 1 October 2015.
  • There are no relevant clinical differences between esomeprazole and the other over-the-counter (OTC) PPI medications that would affect their listing in Appendix H.
  • All the OTC PPIs have similar mechanisms of action and similar efficacy and safety profiles.
  • The same indications and Required Advisory Statements for Medicine Labels (RASML) label statement requirements apply to all OTC PPIs.
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 factors8;
  • Other relevant information.
Delegate's interim decision

The delegate's interim decision is that new Appendix H entries be created for the following Schedule 3 proton pump inhibitors: Lansoprazole, Omeprazole, Pantoprazole and Rabeprazole.

The proposed implementation date is 1 February 2016.

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; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the decision comprised the following:

  • The ACMS, at its March 2015 meeting, had recommended inclusion of esomeprazole in Appendix H.
  • The delegate decided that esomeprazole would be included in Appendix H as of 1 October 2015.
  • There are no relevant clinical differences between esomeprazole and the other over-the-counter (OTC) PPI medications that would affect their listing in Appendix H.
  • All the OTC PPIs have similar mechanisms of action and similar efficacy and safety profiles.
  • The same indications and Required Advisory Statements for Medicine Labels (RASML) label statement requirements apply to all OTC PPIs.
Schedule entry
Appendix H - New entries

Lansoprazole.

Omeprazole.

Pantoprazole.

Rabeprazole.

1.8 Levocetirizine

Scheduling proposal

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

  • Although levocetirizine is covered by the schedule entries for cetirizine, it is proposed to include specific entries for levocetirizine in Schedule 2, Schedule 4 and Appendix K in the Poisons Standard.

Consideration should include:

  • whether all levocetirizine preparations for oral use should be in Schedule 2; or
  • whether levocetirizine should be exempt from scheduling in divided preparations for oral use for the treatment of seasonal allergic rhinitis in adults and children 12 years of age and over when: (a) in a primary pack containing not more than five days' supply; and (b) labelled with a recommended daily dose not exceeding 5 mg of levocetirizine (i.e. consistent with the scheduling exemption for cetirizine).

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

Levocetirizine is the active enantiomer of cetirizine (5 mg of levocetirizine is equivalent to 10 mg of cetirizine).

Levocetirizine is an antihistamine, and is used for relief of symptoms of allergic conditions such as allergic rhinitis and chronic idiopathic urticaria. In Australia, levocetirizine is approved for use in adults and children aged 2 years and over. In some other countries, levocetirizine is approved for use in children from 6 months of age (e.g. in the US, levocetirizine is approved for relief of symptoms of seasonal allergic rhinitis in adults and children aged from 2 years, and for relief of symptoms of perennial allergic rhinitis and chronic idiopathic urticaria in adults and children aged from 6 months).

Cetirizine is a piperazine derivative and metabolite of hydroxyzine. It is a long-acting, low-sedating antihistamine with some mast-cell stabilising activity.

Scheduling status

Levocetirizine is not currently listed in the Poisons Standard, but would be covered by the Schedule 2 and 4 entries for cetirizine.

The Standard for Uniform Scheduling of Medicines and Poisons (SUSMP) Part 1, Interpretation, point 1(2) states: "Unless the contrary intention appears a reference to a substance in a Schedule or an Appendix to this Standard includes: ... (c) every salt, active principle or derivative of the substance, including esters and ethers, and every salt of such an active principle or derivative; ... (e) every stereoisomer of the substance and every salt of such a stereoisomer; ...".

Cetirizine is currently listed in Schedules 2 and 4.

Schedule 2

CETIRIZINE in preparations for oral use except in divided preparations for the treatment of seasonal allergic rhinitis in adults and children 12 years of age and over when:

  1. in a primary pack containing not more than 5 days' supply; and
  2. labelled with a recommended daily dose not exceeding 10 mg of cetirizine.
Schedule 4

CETIRIZINE except:

  1. when included in Schedule 2; or
  2. in divided preparations for oral use for the treatment of seasonal allergic rhinitis in adults and children 12 years of age and over when:
    1. in a primary pack containing not more than 5 days' supply; and
    2. labelled with a recommended daily dose not exceeding 10 mg of cetirizine.

Cetirizine is also listed in Appendix K.

Scheduling history
Levocetirizine

No previous scheduling considerations. DPSSC, NDPSC and ACMS considerations of cetirizine make no mention of levocetirizine.

Cetirizine

Drugs and Poisons Schedule Standing Committee: May 1993

The DPSSC decided to include cetirizine in Schedule 4 and in Appendix K (Drugs required to be labelled with a sedation warning).

National Drugs and Poisons Scheduling Committee: May 1997

The NDPSC decided to include cetirizine in Schedule 3 as the only therapeutically active substance in divided preparations for oral use containing 10 mg or less of cetirizine. A limit on pack size was not considered necessary. Cetirizine remained in Schedule 4 except when included in Schedule 3.

National Drugs and Poisons Scheduling Committee: February 1998

The NDPSC decided to amend the Schedule 3 entry for cetirizine to include all oral formulations of cetirizine, when it was the only active substance in the preparation (the Schedule 3 entry was no longer to be restricted to divided preparations and the maximum dosage unit size was deleted).

National Drugs and Poisons Scheduling Committee: November 1999

The NDPSC decided to reschedule cetirizine in all preparations for oral use to Schedule 2. The Appendix H entry for cetirizine was deleted.

Advisory Committee on Medicines Scheduling: June 2012

The ACMS recommended that cetirizine should be exempt from scheduling, when in divided forms for oral use containing 10 mg or less of cetirizine hydrochloride per dose, in packs containing not more than 5 days' supply for the treatment of seasonal allergic rhinitis.

Pre-meeting public submissions

Two submissions were received.

One submission supported the proposal to include separate schedule entries for levocetirizine, but did not support a scheduling exemption of levocetirizine.

Main points:

  • Risk of sedation and its potential impact on driving capacity.
  • Levocetirizine is six times more likely to result in sedation than other non-sedating antihistamines.
  • Combination with other impairing drugs (including alcohol) increases the opportunity for impairment.
  • Inclusion of warnings on medicine packs is insufficient.

One submission supported the proposal to schedule levocetirizine as for cetirizine.

ACMS advice to the delegate

The ACMS recommended that a separate schedule entry in the Poisons Standard for levocetirizine be included in Schedule 2 and Appendix K, and that levocetirizine should be scheduled as for cetirizine.

The ACMS recommended an implementation date of 1 February 2016.

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; and d) the dosage, formulation, labelling, packaging and presentation of a substance.

The reasons for the recommendation comprised the following:

  • Levocetirizine is the active isomer of cetirizine. The risks and benefits of levocetirizine and cetirizine will be the same, so the scheduling outcomes for the two substances should also be the same, taking the 1:2 dose ratio into account. Scheduling exemption would be similar to other less-sedating antihistamines.
  • The indications for levocetirizine are as for cetirizine.
  • Levocetirizine has the same efficacy and safety profiles as cetirizine.
  • Schedule entries for levocetirizine and cetirizine should therefore have the same outcome.
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 factors9;
  • Other relevant information.
Delegate's interim decision

The delegate's interim decision is that separate schedule entries be included in the Poisons Standard for levocetirizine in Schedule 2, Schedule 4 and Appendix K, and that levocetirizine should be scheduled as for cetirizine.

The proposed implementation date is 1 February 2016.

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; and d) the dosage, formulation, labelling, packaging and presentation of a substance.

The reasons for the decision comprised the following:

  • Levocetirizine is the active isomer of cetirizine. The risks and benefits of levocetirizine and cetirizine will be the same, so the scheduling outcomes for the two substances should also be the same, taking the 1:2 dose ratio into account. Scheduling exemption would be similar to other less-sedating antihistamines.
  • The indications for levocetirizine are as for cetirizine.
  • Levocetirizine has the same efficacy and safety profiles as cetirizine.
  • Schedule entries for levocetirizine and cetirizine should therefore have the same outcome.
Schedule entry
Schedule 2 - New entry

LEVOCETIRIZINE in preparations for oral use except in divided preparations for the treatment of seasonal allergic rhinitis in adults and children 12 years of age and over when:

  1. in a primary pack containing not more than 5 days' supply; and
  2. labelled with a recommended daily dose not exceeding 5 mg of levocetirizine.
Schedule 4 - New entry

LEVOCETIRIZINE except:

  1. when included in Schedule 2; or
  2. in divided preparations for oral use for the treatment of seasonal allergic rhinitis in adults and children 12 years of age and over when:
    1. in a primary pack containing not more than 5 days' supply; and
    2. labelled with a recommended daily dose not exceeding 5 mg of levocetirizine.
Appendix K - New entry

Levocetirizine


Footnotes

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