|Over 2100 patients received reboxetine in clinical studies, approximately 250 of which received reboxetine for at least 1 year.
The information provided in Table 1 below is a summary of adverse events observed in patients treated with reboxetine in placebo-controlled clinical studies of 8 weeks duration or less. In addition, the table also includes adverse events observed from postmarketing experience (frequency not known).Table 1: Adverse Events|
* these adverse events also occurred in postmarketing experience** Cases of suicidal ideation and suicidal behaviours have been reported during reboxetine therapy or early after treatment discontinuation (see section 4.4).
In placebo-controlled studies of 8 weeks duration or less, adverse events were reported in approximately 80% of reboxetine-treated patients and in approximately 70% of placebo-treated patients. Discontinuation rates for adverse events were approximately 9% and 5% for reboxetine-and placebo-treated patients, respectively.
As for long-term tolerability, 143 reboxetine-treated and 140 placebo-treated adult patients participated in a long term placebo controlled study. Adverse events newly emerged on long term treatment in 28% of the reboxetine treated patients and 23% of the placebo-treated patients and caused discontinuation in 4% and 1% of the cases respectively. There was a similar risk of the development of individual events with reboxetine and placebo. In the long term studies, no individual events were seen which have not been seen on short term treatment.
In short-term controlled studies of patients with depression, no clinically significant between-gender differences were noted in the frequency of treatment emergent symptoms, with the exception of urologic events (such as the sensation of incomplete bladder emptying, dysuria and urinary frequency), which were reported in a higher percentage of reboxetine-treated male patients (31.4% [143/456]) than reboxetine-treated female patients (7.0% [59/847]). In contrast, the frequency of urologic-related events was similar among male (5.0% [15/302]) and female (8.4% [37/440]) placebo-treated patients. In the elderly population, frequency of total adverse events, as well as of individual events, was no higher than that reported above.
In pre-marketing clinical studies, signs and symptoms newly reported following discontinuation occurred in approximately (5%) of the reboxetine treated patients and approximately (4%) of placebo-treated patients. In post-marketing experience, there have been a few spontaneous reports of withdrawal symptoms including headache, dizziness, nervousness and nausea; however, no consistent pattern of events on cessation of treatment with reboxetine was evident in these reports.In those short-term studies in depression where heart rate was assessed with ECG, reboxetine was associated with mean increases in heart rate, compared to placebo, of 6 to 12 beats per minute.In all short-term controlled studies in depression, the mean change in pulse (in beats per minute) for reboxetine-treated patients was 3.0, 6.4 and 2.9 in the standing, sitting and supine positions respectively, compared with 0, 0, and 0.5 for placebo-treated patients in the corresponding positions. In these same studies, 0.8% of reboxetine-treated patients discontinued the drug because of tachycardia compared with 0.1% of placebo-treated patients.
|Very common(≥ 1/10)||Common (≥ 1/100 to < 1/10)||Uncommon (≥1/1000 to < 1/100)||Frequency not Known|
|Metabolism and nutrition disorders|
| ||Decreased appetite|| ||Hyponatraemia|
|Insomnia||Agitation*, Anxiety*|| ||Aggressive behaviour, Hallucination, Suicidal Ideation/behaviour**|
|Nervous system disorders|
| ||Headache, Dizziness, Paraesthesia*, Akathisia, Dysguesia|| || |
| ||Accommodation disorder|| || |
|Ear and labyrinth disorders|
| || ||Vertigo|| |
| ||Tachycardia, Palpitations|| || |
| ||Vasodilatation, Hypotension, Hypertension*|| ||Peripheral coldness, Raynaud`s phenomenon|
|Dry mouth, Constipation, Nausea*||Vomiting*|| || |
|Skin and subcutaneous tissue disorders|
|Hyperhidrosis||Rash*|| ||Allergic dermatitis|
|Renal and urinary disorders|
| ||Sensation of incomplete bladder emptying, Urinary tract infection, Dysuria, Urinary retention || || |
|Reproductive system and breast disorders|
| ||Erectile dysfunction , Ejaculatory pain , Ejaculatory delay || ||Testicular pain|
|General disorders and administration site conditions|
| ||Chills|| ||Irritability|