Publication of interim decisions proposing to amend, or not amend, the current Poisons Standard, September 2018

Scheduling medicines and poisons

10 September 2018

Book pagination

1.3 Alkyl nitrites

1. Advisory Committee on Medicines Scheduling (ACMS #24)

Delegate's interim decision

The delegate's interim decision under regulation 42ZCZN of the Therapeutic Goods Regulations 1990 (the Regulations) is to amend the current Poisons Standard in relation to alkyl nitrites and lubricants as follows:

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Deleted text is shown as red, smaller font, with a strikethrough.

Schedule 4 - Delete Entries

AMYL NITRITE.

BUTYL NITRITE.

ISOAMYL NITRITE.

ISOBUTYL NITRITE.

OCTYL NITRITE.

Schedule 9 - New Entries

ALKYL NITRITES except those specifically listed elsewhere in these Schedules.

ISOPROPYL NITRITE.

PROPYL NITRITE.

CYCLOHEXANE NITRITE.

Schedule 9 - Entries moved from Schedule 4

AMYL NITRITE.

BUTYL NITRITE.

ISOAMYL NITRITE.

ISOBUTYL NITRITE.

OCTYL NITRITE.

Appendix A - Amend Entry

LUBRICANTS in preparations that provide a lubricating action between machinery parts, except soluble oils and solvent-deposited lubricating agents.

Proposed implementation date: 1 February 2019

Reasons

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate for the decision include:

  1. the risks and benefits of the use of a substance:
    • There are numerous risks of harm associated with alkyl nitrites.
    • Risks associated with the use of alkyl nitrites include illicit use for euphoric (perceived due to dilation of blood vessels in brain and periphery), analgesic and muscle relaxant effects.[21]
    • Adverse events associated with the use of alkyl nitrites include methaemoglobinaemia and maculopathy.[21],[22],[23] Complete recovery of visual function even after drug use is ceased is rare.[24] According to a 2016 UK government report (Advisory Council on the Misuse of Drugs) there are around 30 published cases of ophthalmological damage associated with use of alkyl nitrites.
    • Alkyl nitrites are toxic via inhalation. Toxicity includes tachycardia, hypotension, headache, flushing, dizziness, nausea, and syncope.[25] Co-use with phosphodiesterase type 5 (PDE-5) inhibitors can lead to severe hypotension.
    • Increased risk of cardiovascular harm when used in conjunction with other vasodilators.
    • Alkyl nitrites are sweet-smelling liquids and pose a risk to child safety through cases of accidental ingestion.
    • There appears to be an increasing trend with time in the use and abuse of volatile alkyl nitrites, with a 56% increase in exposures from 2009 to 2014 according to statistics collected from Australian Poisons Information Centres.
    • Over an eleven year period (2004-2014), Australian Poisons Information Centres received 273 calls about alkyl nitrite exposures:
      • 3.7% of calls (10 cases) which involved accidental paediatric exposures.
      • Hospitalisation was required in 72.5% of all cases with almost all of these requiring a clinical toxicology consultant, indicating high perceived risk or severity.
      • 15% (41 cases) of the hospital admitted patients presented with methaemoglobinaemia, with 14 requiring treatment with the antidote, methylene blue.
    • There are no therapeutic benefits associated with the use of alkyl nitrites other than amyl nitrite, which may be used as an alternative antidote for cyanide poisoning in the event that IV access or first line antidotes are not immediately available.
    • Industry stakeholders have not identified any current use of alkyl nitrites and have indicated that the proposed changes to the Poisons Standard with respect to alkyl nitrites and lubricants will therefore not impact their current products.
  2. the purposes for which a substance is to be used and the extent of use of a substance:
    • Commonly misused alkyl nitrites include amyl nitrite, butyl nitrite and isobutyl nitrite, with more recent variations including isopropyl and cyclohexyl nitrite.
    • Alkyl nitrites have little to no therapeutic use. There are no products on the Australian Register of Therapeutic Goods (ARTG) that contain alkyl nitrites. There are no agricultural products or veterinary medicines containing any nitrite listed on the Australian Pesticides and Veterinary Medicines Authority's PubCRIS database.
    • Volatile nitrites were historically used to treat angina[26] however they have been replaced by other medications.
    • There is limited and superseded therapeutic use for amyl nitrite as an antidote for cyanide poisoning. Current alternative treatment recommendations for cyanide poisoning include sodium thiosulfate plus hydroxocobalamin, or sodium nitrite plus sodium thiosulfate.[27]
    • Alkyl nitrites are largely used recreationally as 'party drugs'. There has been an increase in the use and abuse of alkyl nitrites in Australia over recent years. According to the most recent 2017 report of the Ecstasy and Related Drugs Reporting System (EDRS)[28] recent users of alkyl nitrites was reported in 25% of study participants.
  3. the toxicity of a substance:
    • Alkyl nitrites are toxic via inhalation. Toxicity includes tachycardia, hypotension, headache, flushing, dizziness, nausea, and syncope.[29] Co-use with phosphodiesterase type 5 (PDE-5) inhibitors can lead to severe hypotension.
    • Increased risk of cardiovascular harm when used in conjunction with other vasodilators.
    • Inhalation of alkyl nitrites can lead to methaemoglobinaemia and even death, with significantly increased risk if ingested. Methaemoglobinaemia is potentially life threatening if not treated appropriately.[23]
    • Alkyl nitrites can cause chemical burns to the skin and eyes on direct contact. Other risks of alkyl nitrites include maculopathy and skin lesions.
  4. the potential for abuse of a substance:
    • There is a high potential for misuse and abuse of alkyl nitrites for euphoric properties, and as sex aids due to their muscle relaxant properties.
    • The misuse and abuse of alkyl nitrites appears to be in particular sections of the community rather than widespread.
  5. any other matters that the Secretary considers necessary to protect public health:
    • Exemptions from scheduling for lubricants were first proposed in 1965 and in 1969 and 'motor fuels and lubricants' were included in the list of exemptions at this time. Amendments to the Appendix A lubricant entry will clarify its intent, restricting the Appendix A exemption under the Poisons Standard to machinery use, not personal care use.
    • Feedback from those supplying industrial machinery lubricants did not identify any problems with the proposed new wording for the Appendix A entry.

Delegate's considerations

The delegate considered the following in regards to this interim decision:

  • The application to amend the current Poisons Standard with respect to alkyl nitrites;
  • The advice received from the Advisory Committee on Medicines Scheduling (ACMS#24);
  • The public submissions received before the first closing date;
  • The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
  • Section 52E of the Therapeutic Goods Act 1989, in particular: (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 and (f) any other matters that the Secretary considers necessary to protect public health.

Scheduling proposal

The pre-meeting scheduling proposal was published on the TGA website on 12 April 2018 at Consultation: Proposed amendments to the Poisons Standard being referred to the June 2018 meetings of the ACCS, ACMS and Joint ACCS/ACMS.

Background information for alkyl nitrites

Delegate's referral to ACMS

An application was submitted to amend the Poisons Standard with respect to alkyl nitrites. The application proposed to amend the Appendix A listing for lubricants and to create a new Schedule 4 group entry for alkyl nitrites.

Applicant's scheduling proposal and reasons

The applicant's proposed amendments to the Poisons Standard were:

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Schedule 4 - New Entry

ALKYL NITRITES except those specifically listed elsewhere in these Schedules.

Appendix A - Amend Entry

LUBRICANTS in preparations that provide a lubricating action between machinery parts, except soluble oils and solvent-deposited lubricating agents.

The applicant's reasons for the proposal were:

  • There are increasing reports of misuse and abuse of 'poppers' containing short chain volatile alkyl nitrites in the clubbing/dance scene in Australia and globally for the purposes of recreational use alongside narcotics.
  • Information received indicates that some suppliers of 'poppers' containing various short chain volatile alkyl nitrites, although not usually amyl nitrite, are claiming that their products are exempt from the Poisons Standard on the basis that they are marketed as 'lubricants'. A lubricating action is unlikely due to the volatility of the alkyl nitrites contained in these products. The products are generally labelled as 'leather cleaners' or 'room odorisers' but there is no credible evidence they are actually used for either of these purposes. Rather the contents of the little bottles are inhaled and cost about $30 to $50.
  • Ophthalmologists in Australia are reporting an increase in the number of cases of maculopathies (retinal damage) caused by recreational use of 'poppers'/'lubricants' containing alkyl nitrites. These reports have been observed elsewhere in the world, with the first cases reported in The New England Journal of Medicine in 2010.
  • Proposed amendments to the Poisons Standard include either specific listing of these alternative alkyl nitrites or creating a new entry to ensure clarity of the intent of capturing any volatile alkyl nitrite in Schedule 4.

Current scheduling status

Five (5) alkyl nitrites are listed in Schedule 4 of the Poisons Standard as follows:

Schedule 4

AMYL NITRITE.

BUTYL NITRITE.

ISOAMYL NITRITE.

ISOBUTYL NITRITE.

OCTYL NITRITE.

Scheduling history

Amyl nitrite

In January 1955, the Committee of Poisons Schedules placed amyl nitrite in Schedule 3 of the newly created Poisons Standard. In February 1989, following reports of recreational abuse of amyl nitrite and other nitrites a change to Schedule 4 was foreshadowed. Members considered that the substance had no use in contemporary medicine, although anecdotally it was being used by the mining industry as a cyanide antidote. The Schedule 3 entry was deleted and a new Schedule 4 entry created in February 1990.

In November 1993 (deferred from August 1993), the National Drugs and Poisons Committee (NDPSC) considered a proposal to create new Appendix D (Possession of this drug without authority should be illegal) entries for amyl and butyl nitrites owing to their reported use by paedophiles, who administer it to children for anal dilation. The committee decided that due to the lack of precise information about widespread misuse by paedophiles, this proposal was not warranted at this time and that more attention should be paid to policing the illegal supply of a Schedule 4 substance.

In August 1995, the National Drugs and Poisons Committee (NDPSC) considered the use of amyl nitrite as a first-aid treatment for cyanide poisoning. The Committee considered that the use of amyl nitrite as a first aid treatment for cyanide poisoning could not be supported in view of concerns with its safety and efficacy. Consequently, it would not support any change to its current Schedule 4 status. The committee agreed that if amyl nitrite were to be used as an antidote, existing mechanisms were available in each of the States and Territories to permit such use.

In May 1999, the National Drugs and Poisons Committee (NDPSC) considered harmonisation between Australia and New Zealand for amyl nitrite. At the time the committee noted that amyl nitrite is scheduled in NZ as Part III, but is exempted from scheduling in NZ when sold as an antidote for cyanide poisoning associated with the use of sodium cyanide for vertebrate control. The committee was advised that the Working Party while considering Schedule 4 was appropriate for amyl nitrite recognised the need for an exemption in the NZ entry to allow its availability as an antidote.

Butyl nitrite

In November 1978 a new Schedule 3 entry was created for butyl nitrite, owing to concerns that there were no controls over the substance, which was anecdotally being used as a sex stimulant. In February 1989 an amendment to Schedule 4 was foreshadowed for butyl nitrite and other nitrites. The Schedule 3 entry was deleted and a new Schedule 4 entry created in February 1990.

In November 1993 (deferred from August 1993), the National Drugs and Poisons Committee (NDPSC) considered a proposal to create new Appendix D (Possession of this drug without authority should be illegal) entries for amyl and butyl nitrites owing to their reported use by paedophiles, who administer it to children for anal dilation. The committee decided that due to the lack of precise information about widespread misuse by paedophiles, this proposal was not warranted at this time and that more attention should be paid to policing the illegal supply of a Schedule 4 substance.

In May 1999, the National Drugs and Poisons Committee (NDPSC) considered harmonisation between Australia and New Zealand for butyl nitrite, octyl nitrite, isoamyl nitrite and isobutyl nitrite. The committee noted that the Working Party did not support adoption of the NZ scheduling for two reasons. In Australia, this group of drugs has been abused with severe adverse effects, and the NDPSC decision to shift the group in Schedule 4 in 1993 was related to reports of administration of nitrites to assist anal penetration in children by paedophiles.

Isoamyl nitrite

In May 1999, the National Drugs and Poisons Committee (NDPSC) considered harmonisation between Australia and New Zealand for butyl nitrite, octyl nitrite, isoamyl nitrite and isobutyl nitrite. The committee noted that the Working Party did not support adoption of the NZ scheduling for two reasons. In Australia, this group of drugs has been abused with severe adverse effects, and the NDPSC decision to shift the group in Schedule 4 in 1993 was related to reports of administration of nitrites to assist anal penetration in children by paedophiles.

Isobutyl nitrite

In February 1989, isobutyl nitrite was among a number of alkyl nitrites being considered for inclusion in Schedule 4 following reports of recreational abuse. A Schedule 4 entry for isobutyl nitrite was created in February 1990.

In May 1999, the National Drugs and Poisons Committee (NDPSC) considered harmonisation between Australia and New Zealand for butyl nitrite, octyl nitrite, isoamyl nitrite and isobutyl nitrite. The committee noted that the Working Party did not support adoption of the NZ scheduling for two reasons. In Australia, this group of drugs has been abused with severe adverse effects, and the NDPSC decision to shift the group in Schedule 4 in 1993 was related to reports of administration of nitrites to assist anal penetration in children by paedophiles.

Octyl nitrite

In May 1956 the PSC created a new Schedule 3 entry for octyl nitrite. This scheduling was confirmed for all jurisdictions in February 1985. In February 1989, following reports of recreational abuse of amyl nitrite and other nitrites an amendment to a Schedule 4 entry was foreshadowed. The Schedule 3 entry was deleted and a new Schedule 4 entry created in February 1990. In May 1999, the National Drugs and Poisons Committee (NDPSC) considered harmonisation between Australia and New Zealand for butyl nitrite, octyl nitrite, isoamyl nitrite and isobutyl nitrite. The committee noted that the Working Party did not support adoption of the NZ scheduling for two reasons. In Australia, this group of drugs has been abused with severe adverse effects, and the NDPSC decision to shift the group in Schedule 4 in 1993 was related to reports of administration of nitrites to assist anal penetration in children by paedophiles.

Nitrites

When considering a proposal to delete Schedule 3 entries for amyl, butyl and octyl nitrite and to create new Schedule 4 entries for these substances and also for isobutyl nitrite, the committee decided against making a generic entry for 'ALIPHATIC DERIVATIVES OF NITROUS ACID' as there was a trend away from generic scheduling entries, with specific entries being preferred.

Isopropyl nitrite, Isopentyl nitrite, propyl nitrite, cyclohexyl nitrite

Isopropyl nitrite, Isopentyl nitrite, propyl nitrite and cyclohexyl nitrite are not currently scheduled and has not been previously considered for scheduling. Therefore a scheduling history is not available.

Lubricants

Exemptions from scheduling were first proposed at the December 1965 Poisons Schedule Sub-Committee (PSSC) meeting. The original listing was for purposes that in some substances a poison is not likely to be released to cause poisoning. 'Motor fuels and lubricants unless specified in Schedule 5' was first among the first list of exemptions. It was not until the January 1969 PSSC meeting that the recommendation was made to include the list of exemptions, which included 'motor fuels and lubricants'.

Australian regulations

The Australian Register of Therapeutic Goods (ARTG) has no products that contain the alkyl nitrites isopentyl nitrite, 2-pentyl and N-propyl nitrite or cyclohexyl nitrite.

Alkyl nitrites do not appear in the current Therapeutic Goods (Permissible Indications) Determination No. 2 of 2018.

According to the TGA Ingredient Database, amyl nitrite, octyl nitrite and nitrite are:

  • Available for use as an Active Ingredient in Biologicals, Devices (amyl nitrite only) and Prescription Medicines;
  • Available for use as an Excipient Ingredients in Biologicals, Devices and Prescription Medicines; and
  • Not available as an Equivalent Ingredient in any application.

There are no agricultural and veterinary chemicals containing any nitrite listed on the APVMA's PubCRIS.

International regulations

The international legal status of alkyl nitrites is unclear. In the European Union (EU), isobutyl nitrite was classified as a class 2 carcinogen under the EU Directive 76/769/EEC, making it illegal for shops to sell this variety of poppers.

In January 2016, the United Kingdom (UK) government included alkyl nitrites in a list of banned psychoactive substances, but this decision was set to be reviewed, and it is unclear whether this decision remains.

In New Zealand (NZ), amyl nitrite is a prescription medicine except when sold to a person who holds a controlled substances licence (issued under section 95B of the Hazardous Substances and New Organisms Act 1996) authorising the person to possess cyanide and except when sold to an exempt laboratory covered by a Hazardous Substances and New Organisms Act 1996 approved code of practice. Octyl nitrite, isobutyl nitrite, butyl nitrite and isoamyl nitrite are classified as prescription medicines.

Substance summary

Poppers' is the street term for various alkyl nitrites taken for recreational purposes through direct inhalation. In the past these included amyl nitrite, butyl nitrite and isobutyl nitrite, with more recent variations including isopropyl and cyclohexyl nitrite. Alkyl nitrites have a smooth muscle relaxant effect, and were first used therapeutically (amyl nitrite) to treat angina. They have been used as recreational drug for the reported sensations of head rush, euphoria, uncontrollable laughter or giggling, and other sensations that result from the hypotensive effect and increase sexual arousal and desire. In addition, the smooth muscles of the anus and vagina are relaxed. Adverse effects of short term use include severe headache, throat irritation, nose bleeds, nausea, erectile problems, sensations of spinning or falling and dyspnoea. According to St George's Hospital, University of London, there have been 14 deaths in the UK related to inhaling alkyl nitrites since 1971, three of which were in 2006.[30]

In Australia, the drugs are sold under the guise of room deodorisers and cleaning solvents, and are readily available in adult shops and online. National Drug and Alcohol Research Centre's (NDARC) Ecstasy and Related Drugs Reporting System (EDRS) shows use of amyl nitrite (and may include other alkyl nitrites) running at 27% of those who participated in the survey in 2016 (up from 21% in 2015).[31] The demographics of the survey group suggest popper use has expanded to the community more generally - it was once associated more with the lesbian, gay, bisexual, trans, and/or intersex (LGBTI) community.

Ophthalmologists in Australia are seeing an increase in cases of temporary and permanent macula damage caused by recreational drug use of alkyl nitrite compounds. Ophthalmologists believe that chronic use could lead to irreversible damage. Alkyl nitrite 'popper' maculopathy causes gradual vision loss and clinically is the equivalent of having a hole burned in the macula from gazing at the sun.

Table 1.3: Chemical information for volatile alkyl nitrites
Chemical CAS number IUPAC and/or common and/or other names Molecular formula and weight Chemical structure
General information for volatile alkyl nitrites N/A N/A R-NO2 General chemical structure for volatile alkyl nitrites
Amyl nitrite 110-46-3 3-Methylbutanol nitrite; isoamyl nitrite; nitrous acid, 3-methylbutyl ester; nitrous acid, isopentyl ester

C5H11NO2

117.1 g/mol

Chemical structure for amyl nitrite
Isopropyl nitrite 541-42-4 2-Propanol nitrite; isopropylester kyseliny dusite; nitrous acid, 1-methylethyl ester

C3H7NO2

89.1 g/mol

Chemical structure of isopropyl nitrite
N-Propyl nitrite 543-67-9 Nitrous acid, n-propyl ester; propanol nitrite; propyl nitrite

C3H7NO2

89.1 g/mol

Chemical structure of n-propyl nitrite
Cyclohexyl nitrite 5156-40-1 Nitrous acid, cyclohexyl ester; N-cyclohexyl nitrite; cyclohexyl alcohol nitrite; C-hexyl nitrite; O-nitrosocyclohexanol

C6H11NO2

129.2 g/mol

Chemical structure of cyclohexyl

Pre-meeting public submissions

Three (3) public submissions were received before the first closing date in response to an invitation published on 12 April 2018 under regulation 42ZCZK of the Regulations. Two (2) submissions were in support of the proposed amendments, and one (1) was in conditional support.

The main points provided in support of the amendment were:

  • Alkyl nitrites have a minimal therapeutic role:
    • Volatile nitrites (such as amyl nitrites) are no longer used as a first aid measure to induce methaemoglobinaemia after cyanide exposure. Current alternative treatment recommendations for this indication include sodium thiosulfate plus hydroxocobalamin, or sodium nitrite plus sodium thiosulfate.[32]
    • There is limited support for a Schedule 4 entry for alkyl nitrites to allow them to be used in cyanide antidote kits under the Special Access Scheme only.
    • Volatile nitrites were historically used to treat angina. However, they have been replaced by nitrates.
  • Abuse potential:
    • Evidence provided by poisons information centres (PIC) around Australia indicate increasing misuse and harms.
    • PIC data indicates that alkyl nitrites are often used as party drugs.
    • PIC data indicates alkyl nitrites are used at home recreationally for their euphoric properties and as sex aids.
    • To avoid detection by authorities, alkyl nitrites are often labelled and sold as leather cleaner, video head cleaner, incense or room-odorising products. This can result in misidentification and impair the risk assessment.
  • Alkyl nitrites toxicity:
    • Toxicity of alkyl nitrites is primary due to vasodilatory actions. This includes tachycardia, hypotension, headache, flushing, dizziness, nausea, and syncope.[33]
    • Methaemoglobinaemia is a relatively uncommon but potentially life threatening consequence of alkyl nitrite exposure.[34]

The main points provided in conditional support of the amendment were:

  • A Schedule 4 entry with an associated Appendix D entry for alkyl nitrites would be more appropriate than just a Schedule 4 entry. However, a Schedule 9 or Schedule 10 entry is preferred due to lack of therapeutic use, abuse potential and significant harms.

ACMS advice

The committee made the following recommendations:

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  1. that the Appendix A entry for LUBRICANTS be amended as follows:

    Appendix A - Amend Entry

    LUBRICANTS in preparations that provide a lubricating action between machinery parts, except soluble oils and solvent-deposited lubricating agents.

  2. that new Schedule 9 entries for alkyl nitrites, isopropyl nitrite, propyl nitrite and cyclohexane nitrite be created as follows:

    Schedule 9 - New Entries

    ALKYL NITRITES except those specifically listed elsewhere in these Schedules.

    ISOPROPYL NITRITE.

    PROPYL NITRITE.

    CYCLOHEXANE NITRITE.

  3. that amyl nitrite, butyl nitrite, isoamyl nitrite, isobutyl nitrite and octyl nitrite be up-scheduled from Schedule 4 to Schedule 9 as follows:

    Schedule 9 - New Entries moved from Schedule 4

    AMYL NITRITE.

    BUTYL NITRITE.

    ISOAMYL NITRITE.

    ISOBUTYL NITRITE.

    OCTYL NITRITE.

The committee also recommended an implementation date of 1 February 2019.

Members agreed that the relevant matters under Section 52E(1) of the Therapeutic Goods Act 1989 included: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the extent of use; (c) the toxicity 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 advice included:

  1. risks and benefits of the use of a substance:
    • Numerous risks of harms with little or no therapeutic benefit.
    • No benefits except possibly for the use of amyl nitrite as alternative antidote for cyanide poisoning if IV access or first line antidote not immediately available.
    • Risks include illicit use for euphoric and muscle relaxant effects, adverse events including maculopathy and methaemoglobinaemia.
  2. the purpose for which a substance is to be used and the extent of use:
    • Alkyl nitrites have little to no therapeutic use. Limited and superseded therapeutic use for amyl nitrite only, which is included in Schedule 4.
    • Largely recreational use as a 'party drug'.
    • No medicinal use.
  3. the toxicity of a substance:
    • Via inhalation includes tachycardia, hypotension, headache, flushing, dizziness, nausea, and syncope. Combination with other drugs like sildenafil can lead to severe hypotension.
    • Chemical burns to the skin and eyes on direct contact.
    • Can lead to methaemoglobinaemia via inhalation with significantly increased risk if ingested.
    • Can cause death - Methaemoglobinaemia can occur and is potentially life threatening if not treated appropriately. Fatalities have been recorded.
    • Other risks include maculopathy and skin lesions.
    • Also increased risk of cardiovascular harm when used in conjunction with other vasodilators such as sildenafil.
  4. the potential for abuse of a substance:
    • High potential for abuse for euphoric properties and as sex aids.
    • High risk of misuse and abuse - but tends to be in particular sections of the community rather than widespread use.
  5. any other matters that the Secretary considers necessary to protect public health:
    • Appendix A entry to clarify the meaning of lubricants under the SUSMP to manage the risk associated with the use of alkyl nitrites found in 'poppers'.

Footnotes

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  1. Docherty et al. (2017) '"Poppers Maculopathy": a case report and literature review', Canadian Journal of Ophthalmology, In press. DOI: https://doi.org/10.1016/j.jcjo.2017.10.036
  2. Tiew S, Choudhary A. (2015) 'Poppers maculopathy or retinopathy?' Eye. 29, 147-8
  3. Hunter, L. et al., (2011) 'Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: A review', British Journal of Clinical Pharmacology, 72(1), pp.18-26
  4. Audo, I. et al., 2011. Foveal damage in habitual poppers users. Archives of Ophthalmology, 129(6), pp.703-708.
  5. Romanelli, F. et al., (2004) 'Poppers: Epidemiology and Clinical Management of Inhaled Nitrite Abuse', Pharmacotherapy, 24(1), pp.69-78
  6. Fye WB, (1986) 'T Lauder Brunton and amyl nitrite: a Victorian vasodilator', Circulation, 74, 222-9
  7. Therapeutic Guidelines, Toxicology and Wilderness, Therapeutic Guidelines Ltd (eTG March 2018 edition)
  8. The Ecstasy and Related Drugs Reporting System (EDRS)
  9. Romanelli, F. et al., (2004) 'Poppers: Epidemiology and Clinical Management of Inhaled Nitrite Abuse', Pharmacotherapy, 24(1), pp.69-78
  10. http://www.re-solv.org/wp-content/uploads/2011/12/Poppers.pdf (pdf,106kb)
  11. Stafford J and Breen J (2016) 'Trends in ecstasy and related drug markets (pdf,3.37Mb)*', Australian Drug Trends Series No. 172
  12. Therapeutic Guidelines, Toxicology and Wilderness, Therapeutic Guidelines Ltd (eTG March 2018 edition)
  13. Romanelli, F. et al., 2004. Poppers: Epidemiology and Clinical Management of Inhaled Nitrite Abuse. Pharmacotherapy, 24(1), pp.69-78
  14. Hunter, L. et al., 2011. Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: A review. British Journal of Clinical Pharmacology, 72(1), pp.18-26.

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