Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Oedema, hypertension and heart failure have been reported in association with NSAIDs treatment.
Clinical studies and epidemiological data suggest that the use of some NSAIDs (especially at high doses and for long-term treatments) may be associated with a moderate increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section 4.4).
As for other substances with a similar action, some patients showed increases in blood urea nitrogen that do not exceed a certain level with prolonged treatment; once therapy is discontinued the values return to baseline.

Undesirable side effects are listed in the table below according to the MedDRA System Organ Class, defined 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 (the frequency cannot be defined based on the available data).

Classification according Adverse Reaction                                Frequency to MedDRA
System Organ Class
Anaemia                                       Common
Hemolymphopoietic          Aplastic anaemia, hemolitic anaemia,          Rare system diseases            thrombocytopenia, leucopenia,
eosinophilia, pancytopenia
Serum disease, anaphylaxis, allergic          Rare oedema (of face and hands)
Immune system disorders
Hypersensitivity                              Not known

Fluid retention, hypoglycaemia,
Metabolism and nutrition hyperglycaemia, abnormal weight gain, Not known disorders                loss of appetite, anorexia

Depression, strange dreams,               Not known
Psychiatric disorders      hallucinations, insomnia, confusion, mood swings, nervousness, erethism
Headache                                      Common
Nervous system diseases
Dizziness, drowsiness                         Uncommon

Blurred vision                                Uncommon
Eye disorders
Sight impairment                              Rare

Ear and labyrinth          Vertigo, tinnitus                             Common disorders                  Ear impairment                                Not known Vasculitis, shock (warning symptoms)          Not known

Vascular disorders         Stroke, hypertension                          Not known 
Henoch-Schonlein purpura                      Rare

Respiratory, thoracic and Bronchospasm, epistaxis                        Not known mediastinal disorders
Gastrointestinal disorders Abdominal distress, abdominal pain,           Common constipation, diarrhoea, epigastric pain or distress, flatulence, nausea, vomiting,
dyspepsia
Ulcerative stomatitis                         Uncommon
Gastritis, gastrointestinal bleeding,         Not known gastrointestinal perforation, melaena,
haematemesis, peptic ulcer, pancreatitis,
dry mouth
Exacerbation of colitis*, Crohn’s disease*   Not known
Hepatobiliary disorders   Jaundice (rare cases of fatal hepatitis)     Rare Hepatitis                                    Not known
Skin and subcutaneous     Skin rash, pruritus                          Common tissue disorders
Photosensitivity reaction, urticaria,        Rare angioedema, non-thrombocytopenic purpura,
Severe cutaneous adverse reactions           Very rare
(SCARs): Stevens-Johnson syndrome
(SJS), toxic epidermal necrolysis (TEN)
(see section 4.4)
Alopecia, skin desquamation, erythema        Not known multiforme, ecchymosis, sweating,
abnormal nail growth
Fixed drug eruption (see section 4.4)        Not known
Renal and urinary         Interstitial nephritis, renal papillary     Rare disorders                 necrosis, nephrotic syndrome, renal failure Vesicular dysfunction                        Very rare
Haematuria, dysuria                          Not known
Acute renal failure                          Not known
Systemic disorders and    Oedema                                       Rare administration site
Malaise, asthenia                            Not known conditions
Cardiac disorders         Myocardial infarction, heart failure         Not known Reproductive system and Female infertility                             Not known breast disorders
Diagnostic tests          Increased liver function tests               Rare Increased transaminase levels, weight gain, Not known positive antinuclear antibody, abnormal haematology test, decreased haemoglobin,
decreased haematocrit

* see section 4.4

The most commonly observed adverse events are gastrointestinal. Peptic ulcers, gastrointestinal perforation or bleeding, may occur, and are sometimes fatal, especially in the elderly (see section 4.4).

BREXIN has the prerequisites for being better tolerated than plain piroxicam in the gastrointestinal tract; in fact, the shorter persistence of the active substance in the gastrointestinal tract reduces the risk of contact irritation.

Piroxicam therapy should be discontinued if clinical signs and symptoms of hepatic disturbances occur.
Some cases of acute renal failure, water retention, which can occur as oedema especially in the peripheral regions of the lower limbs or as cardiovascular disorders (hypertension, decompensation) have been reported.

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/