Mysimba

Posology 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.

1) and re- evaluated annually. The cardiovascular risks of Mysimba when given for longer than a year have not been fully determined. 1). 4) and maintenance of weight loss as defined in this section. Missed dose If a dose is missed, patients should not take an additional dose, but take the prescribed next dose at the usual time.

2). 3). 2). It is recommended that patients with moderate or severe renal impairment initiate treatment with one tablet in the morning for the first week of treatment, and escalate to one tablet in the morning and one tablet in the evening from week 2 onwards.

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.

3). 2). 2). It is recommended that patients with mild hepatic impairment initiate treatment with one tablet in the morning for the first week of treatment, and escalate to one tablet in the morning and one tablet in the evening from week 2 onwards.

Degree of hepatic impairment should be assessed using the Child-Pugh score. Paediatric population 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.

Method of administration Oral use. The tablets should be swallowed whole with some water. 2). The tablets should not be cut, chewed, or crushed.

9% of subjects receiving placebo discontinued treatment due to an adverse reaction. The most frequent adverse reactions for naltrexone/bupropion are nausea (very common), constipation (very common), vomiting (very common), dizziness (common), and dry mouth (common).

The most frequent adverse reactions leading to discontinuation with naltrexone/bupropion were nausea (very common), headache (very common), dizziness (common) and vomiting (very common). The list of terms in Table 2 provides information on the adverse reactions of the individual components naltrexone (N) and bupropion (B) identified in their respective approved SmPCs for different indications.

12 The frequencies of adverse reactions are ranked according to the following: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Table 1. 4). 1% (1/1,000). 4). *** Toothache and dental caries, while not meeting the criteria for inclusion in this table, are listed based on the subset of patients with dry mouth, in which a higher incidence of toothache and dental caries was observed in subjects treated with NB versus placebo.

5). *****Post-marketing cases of hypertensive crisis have been reported during the initial titration phase. As NB is a fixed combination of two active ingredients, in addition to the terms listed in Table 1, additional adverse reactions seen with one of the active substances may potentially occur.

The additional undesirable effects occurring with either of the individual components (bupropion or naltrexone) when used for non-obesity indications are summarized in Table 2. Table 2. Adverse reactions of the individual components naltrexone and bupropion identified in the respective approved SmPCs.

The safety and tolerability of naltrexone/bupropion should be assessed at regular intervals. 8). Suicide and suicidal behaviour Naltrexone/bupropion contains bupropion. Bupropion is indicated for the treatment of depression in some countries.

A meta-analysis of placebo-controlled clinical trials of antidepressants in adult subjects with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in subjects less than 25 years old.

Although in placebo-controlled clinical trials with naltrexone/bupropion for the treatment of obesity in adult subjects, no suicides or suicide attempts were reported in studies up to 56 weeks duration with naltrexone/bupropion, suicidality events (including suicidal ideation) have been reported in subjects of all ages treated with naltrexone/bupropion post-marketing.

Close supervision of patients, particularly those at high risk, should accompany therapy with naltrexone/bupropion especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

1%. Plasma concentrations of bupropion and metabolites of bupropion following single-dose administration of 180 mg of bupropion as naltrexone/bupropion tablets are comparable to concentrations observed after single-dose administration of bupropion SR 150 mg; however, no study has been conducted that determined the concentrations of bupropion and metabolites of bupropion after repeated dosing of naltrexone/bupropion tablets compared to bupropion SR tablets.

As it is unknown whether the risk for seizure with bupropion is related to bupropion or a metabolite of bupropion, and there are no data demonstrating comparability of plasma concentrations with repeated dosing, there is uncertainty whether repeated-dose administration naltrexone/bupropion may be associated with a similar rate of seizures as bupropion SR 300 mg.

1. 5) • Patients receiving concomitant administration of monoamine oxidase inhibitors (MAOI). 2)