Data from EMA (European Medicines Agency) - Curated by EPG Health - Last updated 09 April 2018
• Patients with uncontrolled hypertension (see section 4.4)
• Patients with a current seizure disorder or a history of seizures (see section 4.4)
• Patients with a known central nervous system tumour
• Patients undergoing acute alcohol or benzodiazepine withdrawal
• Patients with a history of bipolar disorder
• Patients receiving any concomitant treatment containing bupropion or naltrexone
• Patients with a current or previous diagnosis of bulimia or anorexia nervosa
• Patients currently dependent on chronic opioids (see sections 4.4 and 4.5) or opiate agonists (e.g., methadone), or patients in acute opiate withdrawal
• Patients receiving concomitant administration of monoamine oxidase inhibitors (MAOI). At least 14 days should elapse between discontinuation of MAOI and initiation of treatment with naltrexone / bupropion (see section 4.5)
• Patients with severe hepatic impairment (see sections 4.2 and 5.2)
• Patients with end-stage renal failure (see sections 4.2 and 5.2)
Upon initiating treatment, the dose should be escalated over a 4-week period as follows:
• Week 1: One tablet in the morning
• Week 2: One tablet in the morning and one tablet in the evening
• Week 3: Two tablets in the morning and one tablet in the evening
• Week 4 and onwards: Two tablets in the morning and two tablets in the evening
The maximum recommended daily dose of Mysimba is two tablets taken twice daily for a total dose of 32 mg naltrexone hydrochloride and 360 mg bupropion hydrochloride.
The need for continued treatment should be evaluated after 16 weeks (see section 4.1) and reevaluated annually.
If a dose is missed, patients should not take an additional dose, but take the prescribed next dose at the usual time.
Naltrexone / bupropion should be used with caution in patients over 65 years of age and is not recommended in patients over 75 years of age (see sections 4.4, 4.8 and 5.2).
Patients with renal impairment
Naltrexone / bupropion is contraindicated in patients with end-stage renal failure (see section 4.3). In patients with moderate or severe renal impairment, the maximum recommended daily dose for naltrexone / bupropion is two tablets (one tablet in the morning and one tablet in the evening) (see sections 4.4, 4.8 and 5.2). Dose reduction is not necessary in patients with mild renal impairment. For individuals who are at elevated risk for renal impairment, in particular patients with diabetes or elderly individuals, estimated glomerular filtration rate (eGFR) should be assessed prior to initiating therapy with naltrexone / bupropion.
Patients with hepatic impairment
Naltrexone / bupropion is contraindicated in patients with severe hepatic impairment (see sections 4.3, 4.4 and 5.2). Naltrexone / bupropion is not recommended in patients with mild or moderate hepatic impairment.
The safety and efficacy of naltrexone / bupropion in children and adolescents below 18 have not yet been established. Therefore, naltrexone / bupropion should not be used in children and adolescents below 18.
There are no or limited amounts of data from the use of naltrexone / bupropion in pregnant women.
The combination has not been tested in reproductive toxicity studies. Studies with naltrexone in animals have shown reproductive toxicity (see section 5.3); animal studies with bupropion show no clear evidence of reproductive harm. The potential risk for humans is unknown.
Naltrexone / bupropion should not be used during pregnancy or in women currently attempting to become pregnant.
Naltrexone and bupropion and their metabolites are excreted in human milk.
Since there is limited information on the systemic exposure to naltrexone and bupropion in infants/newborns being breast-fed, a risk to the newborns/infants cannot be excluded.
Naltrexone / bupropion should not be used during breast-feeding.
There are no data on fertility from the combined use of naltrexone and bupropion. No effect on fertility in reproductive toxicity studies have been observed with bupropion. Naltrexone administered orally to rats caused a significant increase in pseudopregnancy and a decrease in pregnancy rates at approximately 30 times the naltrexone dose provided by naltrexone / bupropion. The relevance of these observations to human fertility is not known (see section 5.3).
|Agency product number||EMEA/H/C/003687|
|Date First Approved||26-03-2015|
|Type||Medicinal product subject to medical prescription|
|Marketing authorisation holder||Orexigen Therapeutics Ireland Limited|
|Warnings||This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions|