Adverse reactions : תופעות לוואי

4.8   Undesirable effects
Nausea is the most common undesirable effect. In the treatment of social anxiety disorder, sexual dysfunction (ejaculation failure) in men occurred in 14% for sertraline vs 0% in placebo. These undesirable effects are dose dependent and are often transient in nature with continued treatment.

Table 1 displays adverse reactions observed from post-marketing experience (frequency not known) and placebo-controlled clinical trials (comprising a total of 2542 patients on sertraline and 2145 on placebo) in depression, OCD, panic disorder, PTSD and social anxiety disorder.
Some adverse drug reactions listed in Table 1 may decrease in intensity and frequency with continued treatment and do not generally lead to cessation of therapy.
Table 1: Adverse Reactions
Frequency of adverse reactions observed from placebo-controlled clinical trials in depression, OCD, panic disorder, PTSD and social anxiety disorder. Pooled analysis and post-marketing experience.
System Organ        Very            Common                 Uncommon                  Rare                            Frequency Class               Common          (≥1/100 to             (≥1/1,000 to              (≥1/10,000 to                   Not Known (≥1/10)          <1/10)                <1/100)                   <1/1,000)                       (Cannot be Estimated
From the
Available
Data)

Infections and                     upper respiratory        gastroenteritis, otitis   diverticulitis§ infestations                       tract infection,         media pharyngitis, rhinitis
Neoplasms                                                   neoplasm benign,
malignant and unspecified
(including cysts and polyps)
Blood and                                                                             lymphadenopathy, lymphatic                                                                             thrombocytopenia*§, system disorders                                                                      leukopenia*§ Immune system                                               hypersensitivity,        anaphylactoid reaction disorders                                                   seasonal allergy Endocrine                                                   hypothyroidism           hyperprolactinaemia§, disorders                                                                             inappropriate antidiuretic hormone secretion§

Metabolism and                     decreased appetite,                                hypercholesterolaemia, diabetes nutrition                          increased appetite*                                mellitus, hypoglycaemia, disorders                                                                             hyperglycaemia§, hyponatraemia§

Psychiatric        insomnia        anxiety*, depression*,   suicidal                  conversion disorder§, disorders                          agitation*,              ideation/behaviour,       paroniria§, drug dependence, libido decreased*,       psychotic disorder,      sleep walking, premature nervousness,             thinking abnormal,        ejaculation depersonalisation,       apathy,hallucination*,
nightmare, bruxism*      aggression*, euphoric mood*, paranoia
Nervous system     dizziness,      tremor, movement         amnesia,                  coma*, akathisia (see section disorders          headache*,      disorders (including     hypoaesthesia*, muscle    4.4), dyskinesia, hyperaesthesia, somnolence      extrapyramidal           contractions              cerebrovascular spasm symptoms such as         involuntary*, syncope*,   (including reversible cerebral hyperkinesia,            hyperkinesia*,            vasoconstriction syndrome and hypertonia, dystonia,    migraine*, convulsion*,   Call-Fleming syndrome)§, teeth grinding or gait   dizziness postural,       psychomotor restlessness§ (see abnormalities),          coordination abnormal,    section 4.4), sensory paraesthesia*,           speech disorder           disturbance, choreoathetosis§, hypertonia*,                                       also reported were signs and disturbance in                                     symptoms associated with attention, dysgeusia                               serotonin syndrome or neuroleptic malignant syndrome:
In some cases associated with concomitant use of serotonergic drugs that included agitation,
confusion, diaphoresis,
diarrhoea, fever, hypertension,
rigidity and tachycardia§
Table 1: Adverse Reactions
Frequency of adverse reactions observed from placebo-controlled clinical trials in depression, OCD, panic disorder, PTSD and social anxiety disorder. Pooled analysis and post-marketing experience.
System Organ        Very            Common                 Uncommon                  Rare                            Frequency Class               Common          (≥1/100 to <1/10)      (≥1/1,000 to <1/100)      (≥1/10,000 to <1/1,000)         Not Known (≥1/10)                                                                                          (Cannot be Estimated
From the
Available
Data)

Eye disorders                        visual disturbance       mydriasis                  scotoma, glaucoma, diplopia,          maculopathy photophobia, hyphaema§, pupils unequal§, vision abnormal§,
lacrimal disorder
Ear and labyrinth                    tinnitus                 ear pain disorders
Cardiac                              palpitations             tachycardia, cardiac       myocardial infarction§, Torsade disorders                                                      disorder                    de Pointes§ (see sections 4.4, 4.5 and 5.1), bradycardia, QTc prolongation (see sections 4.4,
4.5 and 5.1)
Vascular                             hot flush                abnormal bleeding           peripheral ischaemia disorders                                                      (such as gastrointestinal bleeding),
hypertension, flushing,
haematuria
Respiratory,                         yawning                  dyspnoea, epistaxis,       hyperventilation, interstitial lung thoracic and                                                   bronchospasm*               disease§, eosinophilic mediastinal                                                                                pneumonia*§, laryngospasm, disorders                                                                                  dysphonia, stridor§, hypoventilation, hiccups
Gastrointestinal    nausea,          dyspepsia,                melaena, tooth disorder,    mouth ulceration, pancreatitis§,     colitis disorders           diarrhoea, dry   constipation*,            oesophagitis, glossitis,    haematochezia, tongue                 microscopic* mouth            abdominal pain*,          haemorrhoids, salivary      ulceration, stomatitis vomiting*, flatulence     hypersecretion,
dysphagia, eructation,
tongue disorder


Hepatobiliary                                                                              hepatic function abnormal, disorders                                                                                  serious liver events (including hepatitis, jaundice and hepatic failure)
Skin and                             hyperhidrosis, rash*      periorbital oedema*,        rare reports of severe cutaneous subcutaneous                                                   urticaria*, alopecia*,      adverse reactions (SCAR): e.g.
tissue disorders                                               pruritus*, purpura*,        Stevens-Johnson syndrome and dermatitis, dry skin,       epidermal necrolysis§, skin face oedema, cold           reaction§, photosensitivity§,
sweat                       angioedema, hair texture abnormal, skin odour abnormal,
dermatitis bullous, rash follicular
Musculoskeletal                      back pain, arthralgia,   osteoarthritis, muscle      rhabdomyolysis§, bone disorder       trismus* and connective                       myalgia                   twitching, muscle tissue disorders                                               cramps, muscular weakness
Renal and                                                      pollakiuria, micturition    urinary hesitation*, oliguria urinary disorders                                              disorder, urinary retention,
urinary incontinence*,
polyuria, nocturia
Table 1: Adverse Reactions
Frequency of adverse reactions observed from placebo-controlled clinical trials in depression, OCD, panic disorder, PTSD and social anxiety disorder. Pooled analysis and post-marketing experience.
System Organ        Very                Common                  Uncommon                   Rare                               Frequency Class               Common              (≥1/100 to <1/10)       (≥1/1,000 to <1/100)       (≥1/10,000 to <1/1,000)            Not Known (≥1/10)                                                                                                   (Cannot be Estimated
From the
Available
Data)
Reproductive        ejaculation         menstruation            sexual dysfunction (see galactorrhoea*, atrophic              postpartum system and          failure             irregular, erectile    section 4.4),              vulvovaginitis, genital discharge, haemorrhage*† breast disorders                        dysfunction             menorrhagia, vaginal       balanoposthitis§, haemorrhage, female        gynaecomastia, priapism* sexual dysfunction (see section 4.4)
General             fatigue*            malaise*,               oedema peripheral*,        hernia, drug tolerance decreased disorders and                           chest pain*,            chills, gait disturbance*, administration                          asthenia, pyrexia     thirst site conditions
Investigations                          weight increased*       alanine                    blood cholesterol increased, aminotransferase           abnormal clinical laboratory increased*, aspartate      results, semen abnormal, altered aminotransferase           platelet function§ increased*, weight decreased*
Injury, poisoning                       injury and procedural complications
Surgical and                                                                               vasodilation procedure medical procedures

ADR identified post-marketing
§
ADR frequency represented by the estimated upper limit of the 95% confidence interval using “The Rule of 3”.
†
This event has been reported for the therapeutic class of SSRIs/SNRIs (see sections 4.4, 4.6).

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

Elderly population
SSRIs or SNRIs including sertraline have been associated with cases of clinically significant hyponatraemia in elderly patients, who may be at greater risk for this adverse event (see section 4.4).

Class effects
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 this risk is unknown.

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.