The government is now operating in accordance with the Guidance on Caretaker Conventions, pending the outcome of the 2025 federal election.
Health professionals are advised that the Product Information (PI) documents for bupropion-containing products have been updated to include a warning about the risk of serotonin syndrome when this drug is co-administered with other drugs known to be associated with serotonin syndrome, including selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with other serotonergic agents is clinically warranted, careful observation of the patient is advised.
Bupropion is a selective inhibitor of the neuronal re-uptake of catecholamines (noradrenaline and dopamine) with minimal effect on the re-uptake of indolamines (serotonin) and no inhibitory effect on monoamine oxidase.
There are two products containing bupropion currently included on the Australian Register of Therapeutic Goods - Zyban SR and Contrave 8/90.
Zyban SR is indicated as a short-term adjunctive therapy for the treatment of nicotine dependence in those who are committed to quitting smoking, when used in conjunction with counselling for smoking cessation/abstinence. The mechanism by which bupropion enhances the ability of patients to abstain from smoking is unknown. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms.
Contrave 8/90, which contains bupropion in combination with naltrexone, is indicated, as an adjunct to a reduced-calorie diet and increased physical activity, for the management of weight in adult patients (≥18 years) with an initial Body Mass Index (BMI) of:
- ≥ 30 kg/m2 (obese), or
- ≥ 27 kg/m2 to < 30 kg/m2 (overweight) in the presence of one or more weight-related comorbidities (for example, type 2 diabetes, dyslipidaemia, or controlled hypertension).
The 'Special Warnings and Precautions for Use' sections of the PI documents of bupropion products - external site have been updated to add the following information:
Serotonin syndrome
Serotonin syndrome has been reported when bupropion is co-administered with drugs known to be associated with serotonin syndrome, including selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). If concomitant treatment with other serotonergic agents is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see Section 4.5 INTERACTIONS WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTIONS).
Serotonin syndrome has also been reported with overdosage (see Section 4.9 OVERDOSE).
The 'Interactions with Other Medicines and Other Forms of Interactions' section has been updated to add the following information:
Post-marketing data show a possible pharmacodynamics interaction between bupropion and SSRIs and SNRIs resulting in an increased risk of serotonin syndrome (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE, Serotonin syndrome).
Adverse event reports in Australia
As of 17 June 2021, six cases of serotonin syndrome associated with bupropion have been reported to the Therapeutic Goods Administration.
Information for health professionals
If concomitant treatment with other serotonergic agents, including SSRIs and SNRIs, is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
Signs and symptoms of serotonin syndrome may include:
- mental-status changes (for example, agitation, hallucinations, coma)
- autonomic instability (for example, tachycardia, labile blood pressure, hyperthermia)
- neuromuscular abnormalities (for example, hyperreflexia, incoordination, rigidity)
- gastrointestinal symptoms (for example, nausea, vomiting, diarrhoea).
If treating patients concomitantly with other drugs known to be associated with the serotonin syndrome, you should educate them about the signs and symptoms of serotonin syndrome and instruct them to see you or another health professional if they suspect that they are experiencing any of these effects.
What to report? You don't need to be certain, just suspicious!
The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.
We particularly request reports of:
- all suspected reactions to new medicines (look for the Black Triangle in PI and CMI documents - this symbol identifies medicines that are new or being used differently)
- all suspected medicines interactions
- suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.
Reports may be submitted:
- online at www.tga.gov.au
- by fax to 02 6232 8392
- by email to ADR.Reports@tga.gov.au
For more information about reporting, visit www.tga.gov.au or contact the TGA's Pharmacovigilance and Special Access Branch ADR.Reports@tga.gov.au.
Disclaimer
Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.
© Commonwealth of Australia 2021
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For correspondence or further information about Medicines Safety Update, contact the TGA's Pharmacovigilance and Special Access Branch at ADR.Reports@tga.gov.au.
Medicines Safety Update is written by staff from the Pharmacovigilance and Special Access Branch.
Acting Editor: Dr Catherine Brogan
Deputy Editor: Mr Michael Pittman
Contributor: Mr Gilbert Yeap