Nitazenes dependence – withdrawal and induction to treatment

Consensus guide for clinicians

This page provides​ guidance for clinicians to manage opioid withdrawal and induction onto opioid dependence treatment for people with dependence on nitazenes or other high potency opioids who present with severe withdrawal. For broader advice, see Clinical guidance for withdrawal from alcohol and other drugs.

The advice guides recommended practice and provides a resource to assist decision-making, alongside clinician judgement and patient choice. The advice is based on clinical consensus, as additional research is required.

Services are encouraged to collect data on patient progress to assist refining treatment options.

 

Caution is advised in treatment

This consensus guidance is only to be used in the alcohol and other drugs (AOD) specialist setting, and/or or in ongoing consultation with an AOD specialist from whom advice is obtained and updated following regular reviews.

The risk of adverse reactions including opioid overdose must be considered.

There is wide variation in the potency of different nitazenes and no robust evidence regarding the half-life of nitazenes.

On this page

  1. Treatment setting considerations
  2. Patient assessment
  3. Medication options
  4. Sample testing
  5. Special considerations for children and young people
  6. Provision of take-home naloxone and overdose advice
  7. More information about circulating drugs of concern
  8. Need clinical support?
  9. Information for the community
  10. References

Treatment setting considerations

Ensure required resources are available to support the treatment of choice. For inpatient admissions, patients should be considered for admission into wards with enhanced monitoring, e.g. Short Stay or High Dependency Units.

  • Inpatient admissions may not always be locally available to manage withdrawal and induction to treatment. Consider transfer of care to a specialist unit or outpatient management.
  • For hospital inpatients, unless the inpatient stay exceeds 14 consecutive days, there is no requirement to obtain approval from NSW Pharmaceutical Services to prescribe or supply Schedule 8 drugs to a drug dependent person. To continue treatment beyond 14 days as an inpatient or following discharge, approval from NSW Pharmaceutical Services is required.
  • Applications to prescribe and supply methadone doses of >200mg/day or a dose equivalent to >32mg sublingual buprenorphine/day are not approved in real-time and may require additional review. If a higher dose is indicated, allow extra time for the application process and consider as part of discharge planning.

Patient assessment

The Clinical Opiate Withdrawal Scale (COWS)1 should be undertaken as part of a comprehensive assessment in all cases where nitazene withdrawal is suspected. Use the COWS at the beginning of treatment to assess response to medication and repeat as needed. When interpreting the COWS in this context, greater consideration should be given to clinical findings specific to opioid withdrawal, i.e. piloerection, lacrimation, rhinorrhoea, yawning, dilated pupils, diarrhoea, vomiting, and perspiration.

Additional sedating drugs, e.g. benzodiazepines, are best avoided unless there is a clinical need for additional supportive care and symptom relief. Short-acting benzodiazepines present fewer risks.

Medication options

Options provided below are presented in order of recommended approach. See also NSW Health Interim Clinical Guidance: Outpatient Transfer from Methadone to Buprenorphine Using the Micro-dosing or Bridging Methods2.

When appropriate, discuss long term management and patient preference for medication, which may be started once the patient is stabilised.

  • Three options are​​ provided.​

    ​​​​​1. SL buprenor​phine to LAIB (Sublocade) – as inpatient

    ​​Day 1
    • Patients may be started on SL buprenorphine 2mg test dose (based on clinical judgement)
    • Review every 1—2 hours, SL buprenorphine dose should be increased depending on effect, up to maximum of 32mg on day one
    • Use COWS to assist with clinical assessment of response with focus on objective opioid withdrawal signs i.e. piloerection, lacrimation, rhinorrhoea, yawning, dilated pupils, diarrhoea, vomiting, perspiration.

    Day 2 to 3

    • Continue S/L buprenorphine BP or commence Sublocade 300mg
    • Consider additional SL buprenorphine if ongoing objective opioid withdrawal

    Discharge and continuing care

    • Patient is usually ready to be discharged on day 3 or 4, with outpatient follow up.
    • Give Sublocade 300mg/100mg dose at usual time intervals, based on clinical assessment
    • Consider additional SL buprenorphine if ongoing objective opioid withdrawal


    2. SL Buprenorphine to LAIB (Buvidal) – as inpatient

    Day 1

    • Patients may be started on SL buprenorphine 2mg test dose (based on clinical judgement)
    • Review every 1—2 hours, SL buprenorphine dose should be increased depending on effect, up to maximum of 32mg on day one
    • Use COWS to assist with clinical assessment of response with focus on objective opioid withdrawal signs i.e. piloerection, lacrimation, rhinorrhoea, yawning, dilated pupils, diarrhoea, vomiting, perspiration.

    Day 2 to 3

    • Commence Buvidal Weekly 32mg or Buvidal Monthly 128mg as per LAIB Guidance
    • Consider additional Buvidal 8mg weekly if ongoing objective opioid withdrawal

    Discharge and continuing care

    • Patient is usually ready to be discharged on day 3 or 4, with outpatient follow up
    • Consider additional doses of Buvidal Weekly or Buvidal Monthly if ongoing objective opioid withdrawal. (Up to maximum dose of 40mg Buvidal Weekly/160mg Buvidal monthly)


    3. SL Buprenorphine as inpatient

    Day 1

    • Patients may be started on SL buprenorphine 2mg test dose (based on clinical judgement)
    • Review every 1—2 hours, SL buprenorphine dose should be increased depending on effect, up to maximum of 32mg on day one
    • Use COWS to assist with clinical assessment of response with focus on objective opioid withdrawal signs i.e. piloerection, lacrimation, rhinorrhoea, yawning, dilated pupils, diarrhoea, vomiting, perspiration.

    Day 2 to 4

    • Continue S/L buprenorphine 32mg
    • Consider additional SL buprenorphine if ongoing objective opioid withdrawal
    • Discharge once stable with minimal objective opioid withdrawal 


  • ​​Preferably use subcutaneous injection morphine. However, oral morphine or morphine infusion may be appropriate depending on the clinical resources available. Alternatively, if morphine not available or allergy/contraindication, oral immediate release oxycodone may be used.

    SC morphine

    Day 1

    • Commence on *SC morphine 5—10mg (use 5mg first dose if high clinical uncertainty – this dose will be highly sedating if the person is opioid naive)
    • Review every 1—2 hours, with further 5-10mg as required
    • Use COWS to assist with clinical assessment of response with focus on objective opioid withdrawal signs i.e. piloerection, lacrimation, rhinorrhoea, yawning, dilated pupils, diarrhoea, vomiting, perspiration.
    • Titrate until withdrawal symptoms relieved (may require 150mg—200mg daily dose)

    *Alternatively use IV morphine where appropriate facilities are available

    Day 2 to 4

    • Commence buprenorphine/methadone as per guidelines

    Oral morphine

    Day 1

    • Commence on oral morphine 20—30mg
    • Review every 1—2 hours, with further 30mg as required
    • Use COWS to assist with clinical assessment of response with focus on objective opioid withdrawal signs i.e. piloerection, lacrimation, rhinorrhoea, yawning, dilated pupils, diarrhoea, vomiting, perspiration.
    • Titrate until withdrawal symptoms relieved (may require 300—400mg oral daily dose)

    Day 2 to 4

    • ​Commence buprenorphine/methadone as per guidelines 


    • ​​Where a patient is still using the opioid of concern and admission is not possible, a planned induction to methadone or buprenorphine in the community may be considered.
    • The induction should be in line with current guidelines
    • Use daily supervised dosing and conduct frequent follow up 

Sample testing

There is a risk of treating a patient for nitazene/another opioid withdrawal, when the presence of nitazenes/other novel opioids this has not been confirmed.

Analysis of patient samples for nitazenes is only available through one laboratory in NSW – NSW Health Pathology Forensic & Analytical Science Service (FASS) Forensic Toxicology Lab at Lidcombe (not to be confused with FASS Drug Toxicology Unit who perform urine drug screens). Analysis of whole blood (EDTA) or urine is possible but requires at least 2 business days following receipt of sample. Therefore, clinicians are likely to need to act without confirmatory testing.

If a suspected nitazene product is provided by the patient for testing, this can be done by FASS Illicit Drug Analysis Unit and results may be available within the same day, if provided to the lab by midday.

To access testing for product or patient samples please email MOH-PRISE@health.nsw.gov.au or call 9461 7178.

There is some evidence to suggest that currently available nitazene test strips may detect certain nitazene analogues in drug samples . However, data on the sensitivity and specificity of these tests remain limited, and concerns exist regarding their usability and the potential for misinterpretation. These test strips may have a role within a clinical setting, where results contribute to a broader clinical assessment and are interpreted within the context of limited supporting evidence. At this time, there is insufficient evidence to recommend their clinical use to test biological patient samples, or consumer use to check drug samples.

Special considerations for children and young people

A second opinion from an addiction medicine specialist is required for the treatment of patients under 18 years. This second opinion should be saved in the patient's file.

Individual exemptions from the Child and Young Person's (Care and Protection) Act 1998 are no longer required, including for children under 16 years. This is due to be updated in the OTP Guidelines 2018.

Provision of take-home naloxone and overdose advice

Naloxone and overdose brief intervention should be provided to the patient (family and carers) as soon as feasible, in case the patient disengages. Do not wait until discharge.

Anecdotal evidence notes that some nitazene overdose cases required more than one dose of naloxone for initial reversal or for ongoing management. There is very limited experience with intranasal naloxone for nitazene overdose, but it is expected to be effective. Standard doses of 400-800 micrograms naloxone IV/IM appear effective from a series of 9 patients involving single nitazene exposures of metonitazene, isotonitazepyne, protonitazene, protonitazepyne, etodesnitazene.3

Nitazenes can have a longer duration of action compared to other opioids, so toxicity can recur despite initial reversal with naloxone, and can pose a higher risk of respiratory depression.

Services that provide take home naloxone interventions can supply up to two units of Nyxoid® or Prenoxad® to patients per PBS-subsidised intervention. If more doses of naloxone might be needed, additional interventions should be offered to the person.

In services where the NSW Take Home Naloxone Program is not available, naloxone access can be facilitated via existing channels – on a prescriber's order or over the counter at community pharmacies. Drug & Alcohol Consultation Liaison teams may also be available to provide take home naloxone interventions.

More information about circulating drugs of concern

The Ministry of Health will continue to send public health messaging and warnings.

See Safety Notice 023/24 Cases of dependence and overdose linked to nitazenes (strong opioids) in refillable vape liquids. All safety notices are available on the NSW Health Safety Alert Broadcast System (SABS).

Need clinical support?

Call the Drug and Alcohol Specialist Advisory Service (DASAS) on 1800 023 687.

They are a 24/7, free, specialist phone advisory service for all health professionals

Information for the community

NSW Users and AIDS Association (NUAA) is a peer-based drug user organisation that is governed, staffed and led by people with lived or living experience of drug use. NUAA has lots of good information about opioid dependence treatment and other resources.

You can learn more about different drugs, and find out what support is available to you at Your Room.

References

  1. Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs. 2003 Apr-Jun;35(2):253-9
  2. Interim Clinical Guidance: Outpatient Transfer from Methadone to Buprenorphine Using the Micro-dosing or Bridging Methods
  3. Cases reported to Prescription, Recreational and Illicit Substance Evaluation program as of 29 October 2024


Current as at: Friday 6 December 2024
Contact page owner: Centre for Alcohol and Other Drugs