Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The most common adverse reaction was nausea.
Tabulated list of adverse reactions

Adverse reactions are listed below using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
The list is based on information from clinical trials and post-marketing experience.

SYSTEM ORGAN CLASS                               FREQUENCY            ADVERSE REACTION Immune system disorders                          Not known*           Anaphylactic reaction Endocrine disorders                              Not known*           Hyperprolactinaemia, in some cases associated with galactorrhea
Metabolism and nutrition disorders
Not known *          Hyponatraemia
Psychiatric disorders                            Common               Abnormal dreams Not known *          Insomnia
Not known *          Agitation, aggression (see section
4.4)
Nervous system disorders                         Common               Dizziness Uncommon             Tremor
Not known *          Serotonin Syndrome,
Headache,
Akathisia,
Bruxism,
Trismus,
Restless leg syndrome
Eye disorders                                    Uncommon             Blurred vision Rare                 Mydriasis (which may lead to acute narrow angle glaucoma - see section 4.4)
Vascular disorders                               Uncommon             Flushing 
Not known*            Haemorrhage (including contusion, ecchymosis, epistaxis,
gastrointestinal or vaginal bleeding)
Gastrointestinal disorders                      Very common           Nausea Common                Diarrhoea,
Constipation,
Vomiting,
Dyspepsia
Skin and subcutaneous tissue disorders          Common                Pruritus, including pruritus generalised
Hyperhidrosis
Uncommon              Night sweats
Not known*            Angioedema,
Urticaria
Rash
General disorder and administration site        Not known*            Discontinuation syndrome conditions
* Based on post-marketing cases

Description of selected adverse reactions

Nausea
Nausea was usually mild or moderate and occurred within the first two weeks of treatment. The reactions were usually transient and did not generally lead to cessation of therapy. Gastrointestinal adverse reactions, such as nausea, occurred more frequently in women than men.

Elderly patients
For doses ≥10 mg vortioxetine once daily, the withdrawal rate from the studies was higher in patients aged ≥65 years.
For doses of 20 mg vortioxetine once daily, the incidences of nausea and constipation were higher in patients aged ≥65 years (42% and 15%, respectively) than in patients aged <65 years (27% and 4%, respectively)(see section 4.4).

Sexual dysfunction
In clinical studies, sexual dysfunction was assessed using the Arizona Sexual Experience Scale (ASEX). Doses of 5 to 15 mg showed no difference to placebo. However, the 20 mg dose of vortioxetine was associated with an increase in sexual dysfunction (TESD)(see section 5.1) .
In the post-marketing setting cases of sexual dysfunction have also been reported with doses of vortioxetine below 20 mg.


Class effect
Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving a medicinal product from related pharmacological classes of antidepressants (SSRIs or TCAs). The mechanism behind this risk is unknown, and it is not known if this risk is also relevant for vortioxetine.

Symptoms upon discontinuation of vortioxetine treatment
In the clinical studies, discontinuation symptoms were systematically evaluated following abrupt cessation of vortioxetine treatment. There was no clinically relevant difference to placebo in the incidence or nature of the discontinuation symptoms after treatment with vortioxetine (see section 5.1). Cases describing discontinuation symptoms have been reported in the post-marketing setting and have included symptoms such as dizziness, headache, sensory disturbances (including paraesthesia, electric shock sensations), sleep disturbances (including insomnia), nausea and/or vomiting, anxiety, 
irritability, agitation, fatigue and tremor. These symptoms may occur within the first week of vortioxetine discontinuation.

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/