Adverse reactions : תופעות לוואי

4.8         Undesirable effects
 a. Summary of the safety profile
The most commonly reported adverse reactions in patients treated with fluoxetine were headache, nausea, insomnia, fatigue and diarrhea. Undesirable effects may decrease in intensity and frequency with continued treatment and do not generally lead to cessation of therapy.
 b. Tabulated list of adverse reactions

The table below gives the adverse reactions observed with fluoxetine treatment in adult and pediatric populations. Some of these adverse reactions are in common with other SSRIs.

The following frequencies have been calculated from clinical trials in adults (n = 9,297) and from spontaneous reporting.


Frequency estimate: 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), not known (cannot be estimated from the available data).

Very Common                 Common                   Uncommon                      Rare                   Not Known Blood and lymphatic system disorders
Thrombocytopenia
Neutropenia
Leucopenia
Immune system disorders
Anaphylactic reaction
Serum sickness
Endocrine disorders
Inappropriate antidiuretic hormone secretion
Metabolism and nutrition disorders
Decreased appetite1                                  Hyponatraemia

Psychiatric disorders
Insomnia2                 Anxiety                   Depersonalization         Hypomania Nervousness               Elevated mood             Mania
Restlessness              Euphoric mood             Hallucinations
Tension                   Thinking abnormal         Agitation
Libido decreased3         Orgasm abnormal5          Panic attacks
Sleep disorder            Bruxism                   Confusion
Abnormal dreams4          Suicidal thoughts and     Dysphemia behavior6                 Aggression


Nervous system disorders
Headache                 Disturbance in attention   Psychomotor               Convulsion Dizziness                  hyperactivity             Akathisia
Dysgeusia                  Dyskinesia                Buccoglossal syndrome Lethargy                   Ataxia                    Serotonin syndrome Somnolence7                Balance disorder
Tremor                     Myoclonus
Memory impairment

Eye disorders
Vision blurred            Mydriasis
Ear and labyrinth disorders
Tinnitus
Cardiac disorders
Palpitations                                        Ventricular arrhythmia Electrocardiogram QT                                including torsades de prolonged (QTcF                                     pointes
≥450 msec)8
Vascular disorders
Flushing9                 Hypotension               Vasculitis
                                                                            Vasodilatation
Respiratory, thoracic and mediastinal disorders
Yawning                   Dyspnea                 Pharyngitis
Epistaxis               Pulmonary events
(inflammatory processes of varying histopathology and/or fibrosis) 10

Gastrointestinal disorders
Diarrhea                   Vomiting                 Dysphagia               Oesophageal pain Nausea                     Dyspepsia                Gastrointestinal
Dry mouth                hemorrhage11

Hepato-biliary disorders
Idiosyncratic hepatitis
Skin and subcutaneous tissue disorders
Rash12                    Alopecia                Angioedema
Urticaria                 Increased tendency to   Ecchymosis
Pruritus                  bruise                  Photosensitivity
Hyperhidrosis             Cold sweat              reaction
Purpura
Erythema multiforme
Stevens-Johnson syndrome
Toxic Epidermal
Necrolysis (Lyell
Syndrome)

Musculoskeletal and connective tissue disorders
Arthralgia                  Muscle twitching        Myalgia
Renal and urinary disorders
Frequent urination13       Dysuria                 Urinary retention
Micturition disorder

Reproductive system and breast disorders
Gynecological               Sexual dysfunction16   Galactorrhea              Postpartum 14 bleeding                                           Hyperprolactinemia        hemorrhage17 Erectile dysfunction                               Priapism
Ejaculation disorder15
General disorders and administration site conditions
Fatigue18                Feeling jittery             Malaise                Mucosal hemorrhage Chills                      Feeling abnormal
Feeling cold
Feeling hot

Investigations
Weight decreased         Transaminases increased
                                      Gamma- glutamyltransferase increased
1
Includes anorexia
2
Includes early morning awakening, initial insomnia, middle insomnia
3
Includes loss of libido
4
Includes nightmares
5
Includes anorgasmia
6
Includes completed suicide, depression suicidal, intentional self-injury, self-injurious ideation, suicidal behavior, suicidal ideation, suicide attempt, morbid thoughts, self-injurious behavior.
These symptoms may be due to underlying disease
7
Includes hypersomnia, sedation
8
Based on ECG measurements from clinical trials
9
Includes hot flush
10
Includes atelectasis, interstitial lung disease, pneumonitis
11
Includes most frequently gingival bleeding, hematemesis, hematochezia, rectal hemorrhage, diarrhea hemorrhagic, melaena, and gastric ulcerhemorrhage
12
Includes erythema, exfoliative rash, heat rash, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash macular-papular, rash morbilliform, rash papular, rash pruritic, rash vesicular, umbilical erythema rash
13
Includes pollakiuria
14
Includes cervix hemorrhage, uterine dysfunction, uterine bleeding, genital hemorrhage, menometrorhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal hemorrhage, uterine hemorrhage, vaginal hemorrhage
15
Includes ejaculation failure, ejaculation dysfunction, premature ejaculation, ejaculation delayed, retrograde ejaculation
16
Occasionally persisting after treatment discontinuation
17
This event has been reported for the therapeutic class of SSRIs/SNRIs (see sections 4.4, 4.6).
18
Includes asthenia
 c. Description of selected adverse reactions

Suicide/suicidal thoughts or clinical worsening: Cases of suicidal ideation and suicidal behavior have been reported during fluoxetine therapy or early after treatment discontinuation (see section 4.4).

Bone fractures: Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to the risk is unknown.

Withdrawal symptoms seen on discontinuation of fluoxetine treatments: Discontinuation of fluoxetine commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paresthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or anxiety, nausea and/or vomiting, tremor and headache are the most commonly reported reactions.
Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged (see section 4.4). It is therefore advised that when Prozac treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).
 d. Pediatric population (see sections 4.4 and 5.1)

Adverse reactions that have been observed specifically or with a different frequency in this population are described below. Frequencies for these events are based on pediatric clinical trial exposures (n = 610).

In pediatric clinical trials, suicide-related behaviors (suicide attempt and suicidal thoughts), hostility (the events reported were: anger, irritability, aggression, agitation, activation syndrome), manic reactions, including mania and hypomania (no prior episodes reported in these patients) and epistaxis, were commonly reported and were more frequently observed among children and adolescents treated with antidepressants compared to those treated with placebo.

Isolated cases of growth retardation have been reported from clinical use (See also section 5.1).

In pediatric clinical trials, fluoxetine treatment was also associated with a decrease in alkaline phosphatase levels.

Isolated cases of adverse events potentially indicating delayed sexual maturation or sexual dysfunction have been reported from pediatric clinical use (see also section 5.3).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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