Special Warning : אזהרת שימוש

4.4.     Special warnings and precautions for use

Paediatric population
Reboxetine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

As reboxetine has not been tested in patients with convulsive disorders in clinical studies and since rare cases of seizures have been reported in clinical studies, it should be given under close supervision to subjects with a history of convulsive disorders and it must be discontinued if the patient develops seizures.

Serotonin syndrome
The development of potentially life-threatening serotonin syndrome has been reported with serotonin-norepinephrine reuptake inhibitors [SNRIs], including reboxetine alone, and with concomitant use of other serotonergic drugs (e.g., selective serotonin reuptake inhibitors [SSRIs], other SNRIs, triptans, tricyclic and tetracyclic antidepressants, lithium, opioids [e.g., buprenorphine], tryptophan, buspirone, monoamine oxidase inhibitors [MAOIs], and St. John’s Wort) (see section 4.5).

Serotonin syndrome may include mental status changes (e.g., confusion, agitation, hallucinations, delirium, and coma); autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia, diaphoresis, and flushing); neuromuscular abnormalities (e.g., tremor, rigidity, clonus, and hyperreflexia); gastrointestinal signs and symptoms (e.g., nausea, vomiting, diarrhoea). Patients should be monitored for the emergence of serotonin syndrome.


Concomitant use of MAO-inhibitors (including linezolid (an antibiotic which is a reversible non-selective MAOI) and methylene blue) and reboxetine should be avoided in view of the potential risk (tyramine-like effect) based on their mechanisms of action.

Concomitant use of reboxetine with other antidepressants (tricyclics, MAO inhibitors, SSRIs and lithium) has not been evaluated during clinical trials.

If concomitant use of reboxetine with other serotonergic drugs is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see section 4.5). Patients should be made aware of the potential risk of serotonin syndrome.
Treatment with reboxetine and any concomitant serotonergic agents should be discontinued immediately if the above events occur, and supportive symptomatic treatment should be initiated.
2021-0070817, 2024-0091157                              Page: 2 of 10


As with all antidepressants, switches to mania/hypomania have occurred during the clinical studies. Close supervision of bipolar patients is, therefore, recommended.

Suicide/suicidal thoughts or clinical worsening:
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy 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.

Clinical experience with reboxetine in patients affected by serious concomitant systemic illnesses is limited. Close supervision should be applied in patients with current evidence of urinary retention, prostatic hypertrophy, glaucoma and history of cardiac disease.

At doses higher than the maximum recommended, orthostatic hypotension has been observed with greater frequency than that observed at recommended doses. Particular attention should be paid when administering reboxetine with other drugs known to lower blood pressure.

Clinical experience with reboxetine in the long-term treatment of elderly patients is, at present, limited. In this population, lowering of mean potassium levels was found starting from week 14; the magnitude of this reduction did not exceed 0.8 mmol/litre and potassium levels never dropped below normal limits.

Mydriasis has been reported in association with reboxetine; therefore, caution should be used when prescribing reboxetine to patients with increased intraocular pressure or those at risk of acute narrow-angle glaucoma.

Effects on Driving