Adverse reactions : תופעות לוואי

4.8   Undesirable effects

The most commonly reported serious adverse reactions reported with fondaparinux are bleeding complications (various sites including rare cases of intracranial/ intracerebral and retroperitoneal bleedings) and anaemia. Fondaparinux should be used with caution in patients who have an increased risk of haemorrhage (see section 4.4).

The safety of fondaparinux 2.5 mg has been evaluated in:
- 3,595 patients undergoing major orthopaedic surgery of the lower limbs treated up to 9 days - 327 patients undergoing hip fracture surgery treated for 3 weeks following an initial prophylaxis of 1 week
- 1,407 patients undergoing abdominal surgery treated up to 9 days
- 425 medical patients who are at risk for thromboembolic complications treated up to 14 days - 10,057 patients undergoing treatment of UA or NSTEMI ACS
- 6,036 patients undergoing treatment of STEMI ACS.

For the prevention of VTE, the adverse reactions reported by the investigator as at least possibly related to fondaparinux are presented within each frequency grouping (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) and system organ class by decreasing order of seriousness; these adverse reactions should be interpreted within the surgical and medical context.

System organ class          Adverse reactions in patients       Adverse reactions in medical undergoing major orthopaedic        patients
MedDRA surgery of lower limbs and/or abdominal surgery


Infections and              Rare: post-operative        wound infestations                infection
Blood and lymphatic         Common: post-operative              Common: bleeding system disorders            haemorrhage, anaemia                (haematoma, haematuria, Uncommon: bleeding (epistaxis,      haemoptysis, gingival bleeding) gastrointestinal, haemoptysis,      Uncommon: anaemia haematuria, haematoma) thrombocytopenia, purpura,
thrombocythaemia, platelet abnormal, coagulation disorder


Immune system disorders Rare: allergic reaction (including Rare: allergic reaction very rare reports of angioedema, (including very rare reports anaphylactoid/anaphylactic         of angioedema,
reaction)                          anaphylactoid/anaphylactic reaction
Metabolism and nutrition Rare: hypokalaemia disorders

Nervous system disorders Rare: anxiety, somnolence,
vertigo, dizziness, headache,
confusion


Vascular disorders           Rare: hypotension

Respiratory, thoracic and Rare: dyspnoea, coughing                Uncommon: dyspnoea mediastinal disorders

Gastrointestinal             Uncommon: nausea, vomiting disorders                    Rare: abdominal pain, dyspepsia,
gastritis, constipation, diarrhoea

Hepatobiliary disorders      Uncommon: hepatic enzymes increased, hepatic function abnormal
Rare: bilirubinaemia
Skin and subcutaneous        Uncommon: rash, pruritus             Uncommon: rash, pruritus tissue disorders

General disorders and        Uncommon: oedema, oedema           Uncommon: chest pain administration site          peripheral, fever, wound conditions                   secretion
Rare: chest pain, fatigue, hot flushes, leg pain, oedema genital,
flushing, syncope


In other studies or in post-marketing experience, rare cases of intracranial / intracerebral and retroperitoneal bleedings have been reported.

The adverse event profile reported in the ACS program is consistent with the adverse drug reactions identified for VTE prophylaxis.

Bleeding was a commonly reported event in patients with UA/NSTEMI and STEMI. The incidence of adjudicated major bleeding was 2.1% (fondaparinux) vs. 4.1% (enoxaparin) up to and including Day 9 in the Phase III UA/NSTEMI study, and the incidence of adjudicated severe haemorrhage by modified TIMI criteria was 1.1% (fondaparinux) vs. 1.4% (control [UFH/placebo]) up to and including Day 9 in the Phase III STEMI study.

In the Phase III UA/NSTEMI study, the most commonly reported non-bleeding adverse events (reported in at least 1% of subjects on fondaparinux) were headache, chest pain and atrial fibrillation.

In the Phase III study in STEMI patients, the most commonly reported non-bleeding adverse events (reported in at least 1% of subjects on fondaparinux) were atrial fibrillation, pyrexia, chest pain, headache, ventricular tachycardia, vomiting, and hypotension.

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
Additionally, you can also report via the following address: Padagis.co.il