Adverse reactions : תופעות לוואי

4.8.     Undesirable effects
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 reactions observed in patients treated with reboxetine in placebo-controlled clinical studies of 8 weeks duration or less.
In addition, the table also includes adverse reactions observed from postmarketing experience (frequency not known).


Table 1: Adverse reactions
Very               Common                 Uncommon           Rare             Not known Common             (≥1/100 to <1/10)      (≥1/1000 to        (≥1/10000 to     (Frequency cannot (≥1/10)                                   <1/100)            <1/1000)         be estimated from the available data)

Metabolism and nutrition disorders
Decreased appetite                                          Hyponatraemia Psychiatric disorders
Insomnia          Agitation*,                                                 Aggressive Anxiety*                                                    behaviour, 2021-0070817, 2024-0091157                               Page: 5 of 10
Hallucination,
Suicidal
Ideation/behaviour**
Nervous system disorders
Dizziness        Headache,                                                 Serotonin syndrome* Paraesthesia*,
Akathisia,
Dysguesia
Eye disorders
Accommodation           Mydriasis*        Glaucoma*       Intraocular pressure disorder                                                  increased
Ear and labyrinth disorders
Vertigo
Cardiac disorders
Tachycardia,
Palpitations
Vascular disorders
Vasodilatation,                                  Peripheral coldness, Hypotension,                                     Raynaud`s
Hypertension*                                    phenomenon
Gastrointestinal disorders
Dry mouth,         Vomiting*
Constipation,
Nausea*
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                                         Testicular pain dysfunction,
Ejaculatory pain,
Ejaculatory delay
General disorders and administration site conditions
Chills                                           Irritability
* these adverse reactions 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 2021-0070817, 2024-0091157                             Page: 6 of 10
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.


Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/