Published: 5 June 2025

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Spotlight on Contrave (naltrexone + bupropion)

Published: 5 June 2025
Prescriber Update 46(2): 21–23
June 2025

This article on Contrave continues the spotlight series where Medsafe reviews the safety information on a specific medicine. Contrave is a fixed dose combination product containing naltrexone (an opioid receptor antagonist) and bupropion (a moderately weak inhibitor of neuronal reuptake of dopamine and noradrenaline).¹

When used individually, naltrexone is approved for treatment of opioid and alcohol dependence and bupropion as an aid in smoking cessation.^2,3 There is evidence that naltrexone and bupropion individually supress hunger. Using them together may have a synergistic effect.⁴

What is Contrave (naltrexone + bupropion) indicated for?

Contrave is indicated, as an adjunct to a reduced-calorie diet and increased physical activity, for the management of weight in adults with an initial body mass index (BMI) of:

• ≥30 kg/m² (obese) or
• 27 to 29 kg/m² (overweight) in the presence of one or more weight-related comorbidities (eg, type 2 diabetes, dyslipidaemia or controlled hypertension).¹

Considerations for use¹

The following section describes some significant safety issues associated with Contrave. This is not a comprehensive description of all safety information – refer to the data sheet for full prescribing information.

Psychiatric symptoms

Suicidal events and panic attacks have been reported with the use of Contrave.

Counsel patients and their caregivers about the need to monitor for any clinical worsening, suicidal behavioural or thoughts and unusual changes in behaviour. Immediate medical attention should be sought if they occur.

Use Contrave with caution in patients with a history of mania. Activation of mania and hypomania has been reported in patients with mood disorders treated with other similar products.

Contrave is contraindicated in patients with a history of bipolar disorder. It is also contraindicated in patients with a current or previous diagnosis of bulimia or anorexia nervosa.

Seizures

There is a risk of seizures from the bupropion component. Use Contrave with caution in patients with risk factors for seizures, such as those taking concomitant medicines that can lower the seizure threshold or with a history of head trauma. Patients who experience a seizure while taking Contrave should discontinue treatment.

Contrave is contraindicated in patients with a history of or current seizure disorder or a known central nervous system tumour. It is also contraindicated in patients undergoing acute alcohol or benzodiazepine withdrawal.

Cardiovascular effects

Patients may develop elevated blood pressure or heart rate with Contrave. Hypertensive crisis has also been reported during the initial titration phase.

Check the patient’s blood pressure and pulse prior to starting therapy and monitor this at regular intervals. Discontinue Contrave if there are clinically relevant and sustained increases in blood pressure or heart rate.

Use Contrave with caution in patients with controlled hypertension. Contrave is contraindicated in patients with uncontrolled hypertension.

Use with opioids

Serious life-threatening reactions have been observed with co-administration of Contrave and opioids. Contrave must not be used in patients currently dependent on opioids (including on opioid analgesics, opioid substitution therapy or in acute opioid withdrawal). To prevent withdrawal symptoms, wait at least 7 to 10 days after ceasing the opioid and use Contrave with caution. If opioid therapy is required later, stop Contrave treatment.

The effectiveness of opioid-containing medicines (eg, opioid based analgesics, anti-diarrhoeal, and cough suppressants) may be reduced with Contrave. For example, insufficient intra-/post-operative opioid analgesia during treatment with Contrave has been reported.

Patients requiring intermittent treatment with opioids (eg, due to a planned surgery) should stop Contrave for a minimum of 3 days before starting opioid treatment. The opioid dose should not be increased above the standard dose.

Serotonin syndrome

Serotonin syndrome has been reported when the bupropion component was co-administered with serotonergic medicines (eg, selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors and opioids).

Contrave is contraindicated in patients taking concomitant monoamine oxidase inhibitors.

Pharmacokinetic drug-drug interactions

Bupropion is an inhibitor of cytochrome P450 (CYP) 2D6. Medicines that are substrates of CYP2D6 may need a dose reduction, particularly if they have a narrow therapeutic index.

Bupropion is primarily metabolised by CYP2B6. Concomitant use with CYP2B6 inhibitors or inducers may increase or decrease bupropion levels respectively.¹

Contrave can interact with a variety of other medicines. Refer to the data sheet for more information.

New Zealand case reports

Contrave was approved for use in New Zealand on 1 October 2020. As of 31 March 2025, there were 39 case reports where Contrave was reported to be the suspect medicine.

The most frequently reported reactions were nausea (7 reports), dizziness (6), tinnitus (4), urticaria (4), upper abdominal pain (3), headache (3), pruritus (3), tremor (3) and vomiting (3).

There were also two reports of seizures, one report of drug withdrawal syndrome associated with concomitant use of methadone, and one report of serotonin syndrome associated with concomitant use of a serotonergic medicine.

More information

• See the Contrave data sheet and consumer medicine information.
• New Zealand Formulary monograph for naltrexone + bupropion.
• Healthify has information for consumers about Contrave.

References

1. iNova Pharmaceuticals (New Zealand) Limited. 2025. Contrave New Zealand Data Sheet 29 April 2025. URL: www.medsafe.govt.nz/profs/datasheet/c/Contravetab.pdf (accessed 9 May 2025).
2. GlaxoSmithKline NZ Limited. 2024. Zyban New Zealand Data Sheet 22 March 2024 URL: www.medsafe.govt.nz/profs/datasheet/z/zybantab.pdf (accessed 8 April 2025).
3. Teva Pharma (New Zealand) Limited. 2019. Naltraccord New Zealand Data Sheet 28 February 2019. URL: www.medsafe.govt.nz/profs/datasheet/n/naltraccordtab.pdf (accessed 8 April 2025).
4. Schimiedel O and Proietto J. 2021. Naltexone/Bupropion (Contrave) for the treatment of obseity. In: Research Review. URL: www.researchreview.co.nz/getmedia/1f4d8209-5445-4b9b-9c88-b74b4a57f597/Product-Review-Contrave-for-Obesity-treatment.pdf.aspx?ext=.pdf (accessed 8 April 2025).