Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

Dabigatran etexilate has been evaluated in clinical trials overall in approximately 64,000 patients; thereof approximately 35,000 patients were treated with dabigatran etexilate.


Pradaxa 75                                                                          Prescribing Information Boehringer Ingelheim                                                                          January 2022 In actively controlled VTE prevention trials 6,684 patients were treated with 150 mg or 220 mg dabigatran etexilate daily.

The most commonly reported events are bleedings occurring in approximately 14 % of patients; the frequency of major bleeds (including wound site bleedings) is less than 2 %.

Although rare in frequency in clinical trials, major or severe bleeding may occur and, regardless of location, may lead to disabling, life-threatening or even fatal outcomes.

Tabulated list of adverse reactions

Table 8 shows the adverse reactions ranked under headings of System Organ Classes (SOC) and frequency 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).

Table 8: Adverse reactions

SOC / Preferred term                                                     Frequency Blood and lymphatic system disorders
Haemoglobin decreased                                                   Common Anaemia                                                                Uncommon Haematocrit decreased                                                  Uncommon Thrombocytopenia                                                          Rare Neutropenia                                                            Not known Agranulocytosis                                                        Not known Immune system disorder
Drug hypersensitivity                                                  Uncommon Anaphylactic reaction                                                    Rare Angioedema                                                               Rare Urticaria                                                                Rare Rash                                                                     Rare Pruritus                                                                 Rare Bronchospasm                                                           Not known Nervous system disorders
Intracranial haemorrhage                                                   Rare Vascular disorders
Haematoma                                                              Uncommon Wound haemorrhage                                                      Uncommon Haemorrhage                                                              Rare Respiratory, thoracic and mediastinal disorders
Epistaxis                                                              Uncommon Haemoptysis                                                              Rare Gastrointestinal disorders
Gastrointestinal haemorrhage                                           Uncommon Rectal haemorrhage                                                     Uncommon Haemorrhoidal haemorrhage                                              Uncommon Diarrhoea                                                              Uncommon 
Pradaxa 75                                                                         Prescribing Information Boehringer Ingelheim                                                                          January 2022 Nausea                                                                 Uncommon Vomiting                                                               Uncommon Gastrointestinal ulcer, including oesophageal                            Rare ulcer
Gastroesophagitis                                                          Rare Gastroesophageal reflux disease                                            Rare Abdominal pain                                                             Rare Dyspepsia                                                                  Rare Dysphagia                                                                  Rare Hepatobiliary disorders
Hepatic function abnormal/ Liver function Test                           Common abnormal
Alanine aminotransferase increased                                     Uncommon Aspartate aminotransferase increased                                   Uncommon Hepatic enzyme increased                                               Uncommon Hyperbilirubinaemia                                                    Uncommon Skin and subcutaneous tissue disorder
Skin haemorrhage                                                       Uncommon Alopecia                                                               Not known Musculoskeletal and connective tissue disorders
Haemarthrosis                                                          Uncommon Renal and urinary disorders
Genitourological haemorrhage, including                                Uncommon haematuria
General disorders and administration site conditions
Injection site haemorrhage                                                 Rare Catheter site haemorrhage                                                  Rare Bloody discharge                                                           Rare Injury, poisoning and procedural complications
Traumatic haemorrhage                                                  Uncommon Post procedural haematoma                                              Uncommon Post procedural haemorrhage                                            Uncommon Post procedural discharge                                              Uncommon Wound secretion                                                        Uncommon Incision site haemorrhage                                                Rare Anaemia postoperative                                                    Rare Surgical and medical procedures
Wound drainage                                                             Rare Post procedural drainage                                                   Rare 
Description of selected adverse reactions

Bleeding reactions
Due to the pharmacological mode of action, the use of dabigatran etexilate may be associated with an increased risk of occult or overt bleeding from any tissue or organ. The signs, symptoms, and severity (including fatal outcome) will vary according to the location and degree or extent of the bleeding and/or anaemia. In the clinical studies mucosal bleedings (e.g. gastrointestinal, genitourinary) were seen more frequently during long term dabigatran etexilate treatment compared with VKA treatment. Thus, in addition to adequate clinical Pradaxa 75                                                                          Prescribing Information Boehringer Ingelheim                                                                           January 2022 surveillance, laboratory testing of haemoglobin/haematocrit is of value to detect occult bleeding. The risk of bleedings may be increased in certain patient groups e.g. those patients with moderate renal impairment and/or on concomitant treatment affecting haemostasis or strong P-gp inhibitors (see section 4.4 Haemorrhagic risk).
Haemorrhagic complications may present as weakness, paleness, dizziness, headache or unexplained swelling, dyspnoea, and unexplained shock.

Known bleeding complications such as compartment syndrome and acute renal failure due to hypoperfusion and anticoagulant-related nephropathy in patients with predisposing risk factors have been reported for dabigatran etexilate. Therefore, the possibility of haemorrhage is to be considered in evaluating the condition in any anticoagulated patient. For adult patients, a specific reversal agent for dabigatran, idarucizumab, is available in case of uncontrollable bleeding (see Section 4.9).

The table 9 shows the number (%) of patients experiencing the adverse reaction bleeding during the treatment period in the indication primary VTE prevention after hip or knee replacement surgery in the two pivotal clinical trials, according to dose.

Table 9: Number (%) of patients experiencing the adverse reaction bleeding 
Dabigatran etexilate    Dabigatran etexilate     Enoxaparin
150 mg                  220 mg
N (%)                   N (%)                    N (%)
Treated                           1,866(100.0)            1,825(100.0)             1,848(100.0) Major bleeding                      24 (1.3)                33 (1.8)                 27 (1.5) Any bleeding                       258(13.8)                251(13.8)                247(13.4) 
Agranulocytosis and neutropenia

Agranulocytosis and neutropenia have been reported very rarely during post approval use of dabigatran etexilate. Because adverse reactions are reported in the postmarketing surveillance setting from a population of uncertain size, it is not possible to reliably determine their frequency. The reporting rate was estimated as 7 events per 1 million patient years for agranulocytosis and as 5 events per 1 million patient years for neutropenia.



Reporting of suspected adverse reactions

You can report side effects to the Ministry of Health by following the link ‘Reporting Side Effects of Drug Treatment' on the Ministry of Health home page (www.health.gov.il) which links to an online form for reporting side effects. You can also use this link: https://sideeffects.health.gov.il