The BRUKINSA®▼ safety profile is based on pooled data from 1550 patients with B-cell malignancies, including patients with CLL (N=938), Waldenström’s macroglobulinemia (N=249), mantle cell lymphoma (N=140), marginal zone lymphoma (N=93), follicular lymphoma (N=59) and other types of B-cell malignancies (N=71), treated with BRUKINSA in clinical studies with a median duration of exposure of 34.41 months.1
The most commonly occurring adverse reactions (≥20%) were upper respiratory tract infection* (36%), bruising* (32%), haemorrhage/haematoma* (30%), neutropenia* (30%), musculoskeletal pain* (27%) , rash* (25%), pneumonia* (24%), diarrhoea (21%) and cough* (21%).1
The most commonly occurring investigations (based on laboratory measurements) were neutrophil count decreased (52%), platelets decreased (39%) and haemoglobin decreased (26%).1
The most common Grade 3 or higher adverse reactions (>3%) were neutropenia* (21%), pneumonia* (14%), hypertension* (8%), thrombocytopenia* (6%), anaemia (6%) and haemorrhage/haematoma* (4%).1
Of the 1550 patients treated with BRUKINSA, 4.8% of patients discontinued treatment due to adverse reactions. The most frequent adverse reaction leading to treatment discontinuation was pneumonia* (2.6%). Adverse reactions leading to dose reduction occurred in 5.0% of patients.1
*Includes multiple adverse reaction terms.
Table 1. Adverse reactions reported in clinical studies in patients with B-cell malignancies.1
| MedDRA SOC | MedDRA Terms | All Grades* (%) | Grade 3 or higher (%) |
|---|---|---|---|
| Infections and infestations | Upper respiratory tract infection§ | Very Common (36) | 2 |
| Pneumonia§|| | Very Common (24) | 12 | |
| Pneumonia | Very Common (15) | 8 | |
| Lower respiratory tract infection | Common (5) | <1 | |
| Urinary tract infection§ | Very Common (14) | 2 | |
| Bronchitis | Common (4) | <1 | |
| Hepatitis B reactivation | Uncommon (<1) | <1 | |
| Blood and lymphatic system disorders | Neutropenia§ | Very Common (30) | 21 |
| Febrile neutropenia | Common (2) | 2 | |
| Thrombocytopenia§ | Very Common (18) | 6 | |
| Anaemia§ | Very Common (16) | 6 | |
| Nervous system disorder | Dizziness§ | Very Common (12) | <1 |
| Cardiac disorders | Atrial fibrillation and flutter | Common (5) | 2 |
| Vascular disorders | Bruising§ | Very Common (32) | <1 |
| Contusion | Very Common (20) | 0 | |
| Petechiae | Common (7) | <1 | |
| Purpura | Common (5) | <1 | |
| Ecchymosis | Common (3) | <1 | |
| Haemorrhage/haematoma§|| | Very Common (30) | 4 | |
| Haematuria | Very common (11) | <1 | |
| Epistaxis | Common (8) | <1 | |
| Gastrointestinal haemorrhage | Uncommon (<1) | <1 | |
| Hypertension§ | Very Common (17) | 8 | |
| Gastrointestinal disorders | Diarrhoea | Very Common (21) | 2 |
| Constipation | Very Common (14) | <1 | |
| Skin and subcutaneous tissue disorders | Rash§ | Very Common (25) | <1 |
| Pruritus | Common (8) | <1 | |
| Dermatitis exfoliative general | Unknown | Unknown | |
| Musculoskeletal and connective tissue disorders | Musculoskeletal pain§ | Very Common (27) | 2 |
| Arthralgia | Very Common (15) | <1 | |
| Back pain | Very Common (12) | <1 | |
| General disorders and administration site conditions | Fatigue§ | Very common (18) | 1 |
| Fatigue | Very common (14) | 1 | |
| Asthenia | Common (4) | <1 | |
| Oedema peripheral | Common (8) | <1 | |
| Respiratory, thoracic and mediastinal disorders | Cough | Very Common (21) | <1 |
| Metabolism and nutrition disorders | Tumour lysis syndrome§|| | Uncommon (<1) | <1 |
| Investigations† | Neutrophil count decreased†‡ | Very common (52) | 22 |
| Platelets decreased†‡ | Very common (39) | 8 | |
| Haemoglobin decreased†‡ | Very common (26) | 4 |
*Grades were evaluated based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. †Based on laboratory measurements. ‡Percentages are based on number of patients with both baseline and at least one post-baseline assessment available. §Includes multiple adverse reaction terms. ||Includes events with fatal outcome.
Other special populations1
Elderly patients
Of the 1550 patients treated with BRUKINSA, 61.3% were 65 years of age or older. The incidence of Grade 3 or higher adverse events was slightly higher among elderly patients treated with BRUKINSA (69.6% of patients age ≥65 versus 62.7% of patients <65 years of age). No clinically relevant differences in safety were observed between patients ≥65 years and younger.
Paediatric patients
The safety and efficacy of BRUKINSA in children and adolescents below 18 years of age have not been established.
Special warnings and
precautions for use1
The BRUKINSA Summary of Product Characteristics list the following special warnings and precautions for use. Please see the Summary of Product Characteristics for full details.
Haemorrhage
Serious and fatal haemorrhagic events have occurred in patients treated with BRUKINSA. Grade 3 or higher bleeding events including intracranial and gastrointestinal haemorrhage, haematuria and haemothorax have been reported in patients. Bleeding events of any grade including purpura and petechiae occurred in patients with haematological malignancies. The mechanism for the bleeding events is not well understood.
BRUKINSA may increase the risk of haemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Dose modification may be necessary for Grade 3 or greater adverse reactions as recommended. Warfarin or other vitamin K antagonists should not be administered concomitantly with BRUKINSA. Patients should be monitored for signs and symptoms of bleeding and monitor complete blood counts. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with BRUKINSA. Consider the benefit-risk of withholding BRUKINSA for 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.
Infections
Fatal and non-fatal infections (including bacterial, viral, fungal infections, or sepsis) and opportunistic infections (e.g., herpes viral, cryptococcal, aspergillus, and pneumocystis jirovecii infections have occurred in patients treated with BRUKINSA. Grade 3 or higher infections occurred in patients. The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have also occurred. Before initiating treatment with BRUKINSA, patients’ HBV status should be established. Consultation with a liver disease expert physician is recommended for patients who test positive for HBV or have positive HBV serology, before initiating treatment. Patients should be monitored and managed according to the medical standards to prevent HBV reactivation. Consider prophylaxis according to standard of care in patients who are at increased risk for infections. Patients should be monitored for signs and symptoms of infection and treat appropriately.
Cytopenia
Grade 3 or 4 cytopenias including neutropenia, thrombocytopenia, and anaemia based on laboratory measurements were reported in patients treated with BRUKINSA. Monitor complete blood counts monthly during treatment.
Second primary malignancies
Second primary malignancies, including non-skin carcinoma have occurred in patients treated with BRUKINSA. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin). Advise patients to use sun protection.
Atrial fibrillation and flutter
Atrial fibrillation and atrial flutter have occurred in patients treated with BRUKINSA, particularly in patients with cardiac risk factors, hypertension, acute infections and elderly (≥65 years). Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.
Tumour lysis syndrome
Tumour lysis syndrome has been infrequently reported with BRUKINSA monotherapy, particularly in patients who were treated for CLL. Assess relevant risks (e.g., high tumour burden or blood uric acid level) and take appropriate precautions. Monitor patients closely and treat as appropriate.
Women of childbearing potential
Women of childbearing potential must use a highly effective method of contraception while taking BRUKINSA.
Based on findings in animals, BRUKINSA may cause foetal harm when administered to pregnant women. Women should avoid becoming pregnant while taking BRUKINSA and for up to 1 month after ending treatment. Therefore, women of childbearing potential must use highly effective contraceptive measures while taking BRUKINSA and for up to 1 month after stopping treatment. It is currently unknown whether BRUKINSA may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method. Pregnancy testing is recommended for women of reproductive potential prior to initiating therapy.
Pregnancy
BRUKINSA should not be used during pregnancy. There are no data from the use of BRUKINSA in pregnant women. Studies in animals have shown reproductive toxicity.
Breast-feeding
It is not known whether BRUKINSA or its metabolites are excreted in human milk and no non-clinical studies were conducted. A risk to breast-fed children cannot be excluded. Breast-feeding should be discontinued during treatment with BRUKINSA.
Fertility
No effect on male or female fertility was noted in rats but morphological abnormalities in sperm and increased post-implantation loss were noted at 300 mg/kg/day.
BRUKINSA contains sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say ‘essentially sodium-free’.
Please refer to the BRUKINSA Summary of Product Characteristics for further information.