Alunbrig

Alunbrig Adverse Reactions

brigatinib

Manufacturer:

Takeda

Distributor:

Zuellig Pharma
Full Prescribing Info
Adverse Reactions
Summary of the safety profile: The most common adverse reactions (≥ 25%) reported in patients treated with Alunbrig at the recommended dosing regimen were increased AST, increased CPK, hyperglycaemia, increased lipase, hyperinsulinaemia, diarrhoea, increased ALT, increased amylase, anaemia, nausea, fatigue, hypophosphataemia, decreased lymphocyte count, cough, increased alkaline phosphatase, rash, increased APTT, myalgia, headache, hypertension, decreased white blood cell count, dyspnoea, and vomiting.
The most common serious adverse reactions (≥ 2%) reported in patients treated with Alunbrig at the recommended dosing regimen other than events related to neoplasm progression were pneumonia, pneumonitis, dyspnoea and pyrexia.
Tabulated list of adverse reactions: The data described as follows reflect exposure to Alunbrig at the recommended dosing regimen in three clinical trials: a Phase 3 trial (ALTA 1L) in patients with advanced ALK-positive NSCLC previously not treated with an ALK-inhibitor (N = 136), a Phase 2 trial (ALTA) in patients treated with Alunbrig with ALK-positive NSCLC who previously progressed on crizotinib (N = 110), and a phase 1/2 dose escalation/expansion trial in patients with advanced malignancies (N = 28). Across these studies, the median duration of exposure in patients receiving Alunbrig at the recommended dosing regimen was 21.8 months.
Adverse reactions reported are presented in Table 7 and are listed by system organ class, preferred term and frequency. Frequency categories are very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100). Within each frequency grouping, undesirable effects are presented in order of frequency. (See Table 7.)

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Description of selected adverse reactions: Pulmonary Adverse Reactions: In ALTA 1L, 2.9% of patients experienced any Grade ILD/pneumonitis early in treatment (within 8 days), with Grade 3-4 ILD/pneumonitis in 2.2% of patients. There were no fatal ILD/pneumonitis. Additionally, 3.7% of patients experienced pneumonitis later in treatment.
In ALTA, 6.4% of patients experienced pulmonary adverse reactions of any grade, including ILD/pneumonitis, pneumonia and dyspnoea, early in treatment (within 9 days, median onset: 2 days); 2.7% of patients had Grade 3-4 pulmonary adverse reactions and 1 patient (0.5%) had fatal pneumonia. Following Grade 1-2 pulmonary adverse reactions, treatment with Alunbrig was either interrupted and then restarted or the dose was reduced. Early pulmonary adverse reactions also occurred in a dose escalation study in patients (N = 137) (Study 101) including three fatal cases (hypoxia, acute respiratory distress syndrome and pneumonia). Additionally, 2.3% of patients in ALTA experienced pneumonitis later in treatment, with 2 patients having Grade 3 pneumonitis (see Dosage & Administration and Precautions).
Elderly: Early pulmonary adverse reaction was reported in 10.1% of patients ≥ 65 years of age compared with 3.1% of patients < 65 years of age.
Hypertension: Hypertension was reported in 30% of patients treated with Alunbrig at the 180 mg regimen with 11% having Grade 3 hypertension. Dose reduction for hypertension occurred in 1.5% at the 180 mg regimen. Mean systolic and diastolic blood pressure, in all patients, increased over time (see Dosage & Administration and Precautions).
Bradycardia: Bradycardia was reported in 8.4% of patients treated with Alunbrig at the 180 mg regimen.
Heart rates of less than 50 beats per minute (bpm) were reported in 8.4% of patients at the 180 mg regimen (see Dosage & Administration and Precautions).
Visual disturbance: Visual disturbance adverse reactions were reported in 14% of patients treated with Alunbrig at the 180 mg regimen. Of these, three Grade 3 adverse reactions (1.1%) including macular oedema and cataract were reported.
Dose reduction for visual disturbance occurred in two patients (0.7%) at the 180 mg regimen (see Dosage & Administration and Precautions).
Peripheral neuropathy: Peripheral neuropathy adverse reactions were reported in 20% of patients treated at the 180 mg regimen. Thirty-three percent of patients had resolution of all peripheral neuropathy adverse reactions. The median duration of peripheral neuropathy adverse reactions was 6.6 months, with a maximum duration of 28.9 months.
Creatine phosphokinase (CPK) elevation: In ALTA 1L and ALTA, elevations of CPK were reported in 64% of patients treated with Alunbrig at the 180 mg regimen. The incidence of Grade 3-4 elevations of CPK was 18%. The median time to onset for CPK elevations was 28 days.
Dose reduction for CPK elevation occurred in 10% of patients at the 180 mg regimen (see Dosage & Administration and Precautions).
Elevations of pancreatic enzymes: Elevations of amylase and lipase were reported in 47% and 54% of patients treated with Alunbrig, respectively at the 180 mg regimen. For elevations to Grade 3 and 4, the incidences for amylase and lipase were 7.7% and 15%, respectively. The median time to onset for amylase elevations and lipase elevations was 17 days and 29 days, respectively.
Dose reduction for elevation of lipase and amylase occurred in 4.7% and 2.9% of patients, respectively at the 180 mg regimen (see Dosage & Administration and Precautions).
Elevation of hepatic enzymes: Elevations of ALT and AST were reported in 49% and 68% of patients treated with Alunbrig, respectively at the 180 mg regimen. For elevations to Grade 3 and 4, the incidences for ALT and AST were 4.7% and 3.6%, respectively.
Dose reduction for elevation of ALT and AST occurred in 0.7% and 1.1% of patients, respectively at the 180 mg regimen (see Dosage & Administration and Precautions).
Hyperglycaemia: Sixty one percent of patients experienced hyperglycaemia. Grade 3 hyperglycemia occurred in 6.6% of patients.
No patients had dose reductions due to hyperglycaemia.
Photosensitivity and photodermatosis: A pooled analysis from seven clinical trials with data from 804 patients, treated with Alunbrig at different dosing regimens, showed that photosensitivity and photodermatosis was reported in 5.8% of patients and Grade 3-4 occurred in 0.7% of patients. Dose reduction occurred in 0.4% of patients (see Dosage & Administration and Precautions).
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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
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