Reboxetine

No clinical trial data on exposure to reboxetine during pregnancy are available. However, postmarketing safety data on a very limited number of exposed pregnancies indicate no adverse effects of reboxetine on pregnancy or on the health of the foetus/newborn child.

Animal studies in general do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development or parturition. Some impairment of growth and development has been noted in rat neonates.

Reboxetine should only be used in pregnancy if the potential benefits of treatment to the mother outweigh the possible risks to the developing foetus.

Reboxetine is known to be excreted in breast milk. The level of active substance transferred in breast milk is anticipated to be very low, however there is insufficient information to exclude a risk to the nursing infant. The use of reboxetine during breastfeeding can be considered if the potential benefits outweigh the risk for the child.

Fertility

There is no clinical trial data on fertility. However, in animal studies no effect on fertility parameters was observed.

Although reboxetine has been shown to have negligible effect on psychomotor performance in healthy volunteers, any psychoactive drug can impair judgement or skills. Patients should be cautioned about driving or operating hazardous machinery until reasonably certain that their performance has not been affected.

Over 2100 patients received reboxetine in clinical studies, approximately 250 of which received reboxetine for at least 1 year.

The information provided 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).

Adverse Events:

Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1000 to <1/100)
Rare (≥1/10000 to <1/1000)
Frequency not known

Metabolism and nutrition disorders

Common: Decreased appetite

Frequency not known: Hyponatraemia

Psychiatric disorders

Very common: Insomnia

Common: Agitation*, Anxiety*

Frequency not known: Aggressive behaviour, Hallucination, Suicidal Ideation/behaviour**

Nervous system disorders

Very common: Dizziness

Common: Headache, Paraesthesia*, Akathisia, Dysguesia

Eye disorders

Common: Accommodation disorder

Uncommon: Mydriasis*

Rare: Glaucoma*

Frequency not known: Intraocular pressure increased

Ear and labyrinth disorders

Uncommon: Vertigo

Cardiac disorders

Common: Tachycardia, Palpitations

Vascular disorders

Common: Vasodilatation, Hypotension, Hypertension*

Frequency not known: Peripheral coldness, Raynaud’s phenomenon

Gastrointestinal disorders

Very common: Dry mouth, Constipation, Nausea*

Common: Vomiting*

Skin and subcutaneous tissue disorders

Very common: Hyperhidrosis

Common: Rash*

Frequency not known: Allergic dermatitis

Renal and urinary disorders

Common: Sensation of incomplete bladder emptying, Urinary tract infection, Dysuria, Urinary retention

Reproductive system and breast disorders

Common: Erectile dysfunction, Ejaculatory pain, Ejaculatory delay

Frequency not known: Testicular pain

General disorders and administration site conditions

Common: Chills

Frequency not known: Irritability

* 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.

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.