On November 29, 2018 Takeda Pharmaceutical Company Limited ( TSE: 4502 ) reported that the European Commission (EC) has granted marketing authorization for ALUNBRIG (brigatinib) as monotherapy for the treatment of adult patients with advanced anaplastic lymphoma (ALK +) positive non-small cell lung cancer (NSCLC) previously treated with crizotinib (Press release, Takeda, NOV 29, 2018, View Source [SID1234531721]). The decision follows a favorable opinion from the Committee for Medicinal Products for Human Use (CHMP) dated 20 September 2018.
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"The advent of targeted therapies has significantly improved the treatment of ALK + NSCLC. Despite this, for the approximately 70 percent of crizotinib-treated patients with progression with brain metastases, additional treatment options are needed, "says Enriqueta Felip, MD, PhD, head of the Chest Oncology Unit, oncology department at the Vall d’Hebron University Hospital in Barcelona. "The ALTA ALUNBRIG trial data demonstrated long-lasting results in terms of systemic and intracranial efficacy, as well as a manageable safety profile, which resulted in longer progression-free survival and better survival." overall survival in this context. This approval gives EU doctors an additional option for ALK + NSCLC patients previously treated with crizotinib. "
"The decision of the European Commission to approve ALUNBRIG for patients with NSCLC ALK + represents a significant step forward for European patients affected by this life-threatening disease," says Jesús Gómez-Navarro, MD, vice -President, Head of R & D in clinical oncology at Takeda. "This is the first time that a median progression-free survival of more than 16 months, assessed by an independent review committee, and a median overall survival of 34 months, has been demonstrated in a post-crizotinib setting, which underlines the reliability of the data from the ALTA trial. Authorization for ALUNBRIG in the EU exemplifies our ongoing commitment to developing innovative solutions to improve the quality of life of approximately 40,000 patients diagnosed each year worldwide. "
"Many people do not know about ALK + NSCLC and its nuances, including the fact that this type of lung cancer tends to affect people at a younger age, and is not associated with smoking. Says Stefania Vallone, President of Lung Cancer Europe. "These younger patients are often in the prime of life and raising their children, focusing on their careers and contributing to their community. The availability of new therapies with the potential to increase the duration of disease progression is very important and can not be underestimated. "
The European Commission’s approval is based on data from the ALTA Phase 2 global trial, in which patients were randomized to follow one of two ALUNBRIG dosing regimens: 90 mg once daily (n = 112) or the recommended dosage of 180 mg once daily after a preparatory period of seven days at 90 mg once daily (n = 110). The results demonstrated that among the patients who followed the recommended dosing regimen, 56 percent achieved an objective response rate (ORR), and the median duration response (DR) was 15.7 months, according to the evaluation. an Independent Review Committee (IRC). ALUNBRIG demonstrated a median progression-free survival (PFS) of 16.7 months, according to
hypertension, decreased blood count, myalgia and peripheral neuropathy. The most common (≥ 2 percent) serious adverse reactions reported in patients treated with ALUNBRIG at the recommended regimen other than the manifestations of neoplasm progression are pneumonitis, pneumonia and dyspnea.
This decision from the European Commission means that ALUNBRIG is now approved for the placing on the market of this indication in the 28 Member States of the European Union, and applicable in Norway, Liechtenstein and Iceland. For more information on the European Commission’s decision, please visit the website of the European Medicines Agency: www.ema.europe.eu/ema .
About ALTA study
ALTA study ( A LK in L ung Cancer T rial of AP26113) Phase 2 for ALUNBRIG in adults is an open-label, open-label, multi-center, global trial with 222 patients with locally advanced or metastatic ALK + NSCLC for whom crizotinib is not available. is more effective. Patients received either 90 mg of ALUNBRIG as a single daily dose (n = 112) or 180 mg as a single daily dose after a 7-day preparation period of 90 mg as a single daily dose (n = 110). The primary endpoint is the objective response rate (OLR) confirmed, in accordance with RECIST v1.1, and evaluated by an independent review committee. Evaluated by this committee, the secondary criteria include the ORT, the duration of the response (DR),
Les résultats de l’essai ALTA ont démontré que chez les patients ayant reçu une dose de 180 mg, 56 pour cent ont atteint un TRO selon l’évaluation d’un chercheur, et 56 pour cent selon l’évaluation du comité d’examen indépendant. La DR médiane est de 13,8 mois, selon l’évaluation d’un chercheur, et 15,7 mois selon l’évaluation du CEI. La SSP médiane est de 15,6 mois selon l’évaluation d’un chercheur, contre 16,7 mois selon l’évaluation du comité d’examen indépendant. De plus, parmi les patients présentant des métastases cérébrales mesurables au niveau de base (n=18), 67 pour cent ont atteint un TRO intracrânien selon l’évaluation du comité d’examen indépendant ; et une durée médiane de la réponse intracrânienne de 16,6 mois selon l’évaluation de ce comité. La survie globale médiane est de 34,1 mois.
Of the patients who followed the 90 mg dosing regimen, 46 percent achieved a TRB as assessed by a researcher, and 51 percent according to the assessment of an IRC. The median DR is 12.0 months as assessed by a researcher and 16.4 months as assessed by an IRC. The median PFS is 9.2 months as assessed by a researcher and an IEC. In addition, among patients with baseline measurable brain metastases (n = 26), 50 percent achieved intracranial ORT according to the evaluation of an ILC; the median duration of intracranial response is 9.4 months as assessed by an ARC. The median overall survival is 29.5 months.
About NSCLC ALK +
Non-Small Cell Lung Cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the 1.8 million new cases of lung cancer diagnosed each year worldwide. according to the World Health Organization. Genetic studies indicate that chromosomal rearrangements in the anaplastic lymphoma kinase (ALK) are the main drivers in a subset of NSCLC patients. About three to five percent of patients with metastatic NSCLC present a rearrangement of the ALK gene.
Takeda is committed to continuing research and development in NSCLC to improve the lives of approximately 40,000 new patients each year affected by this rare and serious form of lung cancer worldwide.
About ALUNBRIG (brigatinib)
ALUNBRIG is a targeted anti-cancer drug discovered by ARIAD Pharmaceuticals, Inc., which was acquired by Takeda in February 2017. In April 2017, ALUNBRIG received an accelerated approval process from the Food and Drug Administration ( FDA) for patients with ALK + metastatic NSCLC whose disease has progressed or who are intolerant to crizotinib. This indication is approved as part of the accelerated approval procedure based on tumor response rate and duration of response. The extension of approval for this indication may depend on the verification and description of the clinical benefit in a confirmatory trial. In July 2018, Health Canada has approved ALUNBRIG for the treatment of adult patients with ALK + metastatic NSCLC whose disease has progressed or who are intolerant to an ALK inhibitor (crizotinib). FDA and Health Canada approvals for ALUNBRIG are based primarily on the results of the pivotal ALTA Phase 2 trial (A LK in L ung Cancer T rial of A P26113).
ALUNBRIG has received the FDA’s pioneering therapy designation for the treatment of patients with ALK + CKRNA whose tumors are crizotinib-resistant, and the FDA’s orphan drug designation for the treatment of ALK +, ROS1 + NSCLC and NSCLC EGFR +.
The clinical development program of brigatinib reinforces Takeda’s ongoing commitment to innovative therapies for patients with ALCN + NSCLC worldwide and to the healthcare professionals who care for them. This comprehensive program includes the following clinical trials:
Phase 1/2 trial, designed to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of ALUNBRIG
ALTA Phase 2 pivotal trial investigating the efficacy and safety of ALUNBRIG in two dosing regimens in patients with locally advanced or metastatic ALK + NSCLC who experienced disease progression with crizotinib
Phase 3 ALTA-1L Assay, a global randomized trial evaluating the efficacy and safety of ALUNBRIG compared to crizotinib in patients with locally advanced or metastatic ALK + NSCLC never previously treated with an inhibitor. ALK
Single Group, Multicenter Phase 2 Study in Japanese Patients with ALK + NSCLC, Focused on Patients With Alectinib Progression
Single Group Global Phase 2 Study Evaluating ALUNBRIG in Patients with Advanced ALK + NSCLC Having Disease Progression with Alectinib or Ceritinib
Global Phase 3 Randomized Trial Comparing the Efficacy and Safety of ALUNBRIG Versus Alectinib in Participants With ALK + NSCLC Increased Disease With Crizotinib
For more information on clinical trials with brigatinib, please visit www.clinicaltrials.gov .
ALUNBRIG (brigatinib): IMPORTANT INFORMATION ON SAFETY FOR EUROPE
WARNINGS AND USE PRECAUTIONS
Unwanted pulmonary reactions :serious, life-threatening or life-threatening pulmonary reactions, including those suggestive of interstitial lung disease (IPD) / pneumonitis, may occur. Most adverse pulmonary reactions were observed during the first seven days of treatment. Grade 1-2 adverse pulmonary reactions have been resolved with discontinuation or dose modification. Older age and a shorter interval (less than seven days) between the last dose of crizotinib and the first dose of ALUNBRIG were independently associated with an increased incidence of these adverse pulmonary reactions. These factors must be taken into account when start treatment with ALUNBRIG. Some patients had pneumonitis later in ALUNBRIG treatment. Monitor patients for the onset or worsening of respiratory symptoms (eg dyspnoea, cough, etc.), especially during the first week of treatment. Rapidly evaluate any signs of pneumonitis in a patient with worsening respiratory symptoms. In case of suspected pneumonitis, ALUNBRIG should be discontinued and the patient should be examined for other symptomatic causes (eg pulmonary embolism, tumor progression and infectious pneumonia). Adjust the dose accordingly. Some patients had pneumonitis later in ALUNBRIG treatment. Monitor patients for the onset or worsening of respiratory symptoms (eg dyspnoea, cough, etc.), especially during the first week of treatment. Rapidly evaluate any signs of pneumonitis in a patient with worsening respiratory symptoms. In case of suspected pneumonitis, ALUNBRIG should be discontinued and the patient should be examined for other symptomatic causes (eg pulmonary embolism, tumor progression and infectious pneumonia). Adjust the dose accordingly. Some patients had pneumonitis later in ALUNBRIG treatment. Monitor patients for the onset or worsening of respiratory symptoms (eg dyspnoea, cough, etc.), especially during the first week of treatment. Rapidly evaluate any signs of pneumonitis in a patient with worsening respiratory symptoms. In case of suspected pneumonitis, ALUNBRIG should be discontinued and the patient should be examined for other symptomatic causes (eg pulmonary embolism, tumor progression and infectious pneumonia). Adjust the dose accordingly. worsening of respiratory symptoms (eg dyspnea, cough, etc.), especially during the first week of treatment. Rapidly evaluate any signs of pneumonitis in a patient with worsening respiratory symptoms. In case of suspected pneumonitis, ALUNBRIG should be discontinued and the patient should be examined for other symptomatic causes (eg pulmonary embolism, tumor progression and infectious pneumonia). Adjust the dose accordingly. worsening of respiratory symptoms (eg dyspnea, cough, etc.), especially during the first week of treatment. Rapidly evaluate any signs of pneumonitis in a patient with worsening respiratory symptoms. In case of suspected pneumonitis, ALUNBRIG should be discontinued and the patient should be examined for other symptomatic causes (eg pulmonary embolism, tumor progression and infectious pneumonia). Adjust the dose accordingly. ALUNBRIG should be discontinued and the patient should be examined for other symptomatic causes (eg, pulmonary embolism, tumor progression and infectious pneumonia). Adjust the dose accordingly. ALUNBRIG should be discontinued and the patient should be examined for other symptomatic causes (eg, pulmonary embolism, tumor progression and infectious pneumonia). Adjust the dose accordingly.
Hypertension: Cases of hypertension have been reported. Blood pressure should be monitored regularly during treatment with ALUNBRIG. Hypertension should be treated according to standard standards of blood pressure control. Monitor patients’ heart rate more frequently if concomitant use of a drug known to cause bradycardia can not be avoided. For cases of severe hypertension (≥ Grade 3), discontinue ALUNBRIG until hypertension returns to Grade 1 or baseline. Adjust the dose accordingly.
Bradycardia: cases of bradycardia have been reported. Use caution when administering ALUNBRIG in combination with other agents known to cause bradycardia. Regularly monitor heart rate and blood pressure. Discontinue ALUNBRIG treatment with symptomatic bradycardia. Evaluate the concomitant use of drugs known to cause bradycardia. After recovery, change the doses accordingly. In case of life-threatening bradycardia, definitively discontinue ALUNBRIG if no concomitant medicinal product is identified as a contributing factor, or in case of recurrence. If a concomitant drug is identified as a contributing factor,
Visual disturbances: cases of visual disturbances have been reported with ALUNBRIG. Advise patients to report any visual symptoms. In case of onset or aggravation of severe visual symptoms, consider ophthalmologic evaluation and dose reduction.
Elevation of Creatine Phosphokinase (CPK): Cases of elevation of creatine phosphokinase have been reported. Advise patients to report any muscle pain, tenderness, or fatigue. Regularly monitor CPK levels during treatment. Depending on the severity of CPK elevation, discontinue ALUNBRIG therapy and change the dose accordingly.
Elevation of Pancreatic Enzyme Levels: Cases of elevations of amylase and lipase have been reported. Regularly monitor lipase and amylase levels during ALUNBRIG treatment. Depending on the severity of laboratory abnormalities, stop taking ALUNBRIG and change the dose accordingly.
Hepatotoxicity: Cases of elevated liver enzymes (aspartate aminotransferase, alanine aminotransferase) and bilirubin have been reported. Assess liver function, including AST, ALT, and total bilirubin, before starting ALUNBRIG, then every two weeks for the first three months of treatment. Then proceed to periodic monitoring. Depending on the severity of laboratory abnormalities, stop taking ALUNBRIG and change the doses accordingly.
Hyperglycaemia: Cases of serum glucose elevations have been reported. Evaluate fasting serum glucose before starting ALUNBRIG and monitor periodically. Initiate or optimize an antihyperglycaemic treatment, if any. If adequate hyperglycemic control can not be achieved with optimal medical management, discontinue ALUNBRIG until adequate hyperglycemic control is obtained. After recovery, consider reducing the dose or permanently discontinuing ALUNBRIG.
Drug Interactions : Concomitant use of ALUNBRIG with potent CYP3A inhibitors should be avoided. If concomitant use of potent CYP3A inhibitors can not be avoided, reduce the dose of ALUNBRIG from 180 mg to 90 mg, or from 90 mg to 60 mg. After discontinuation of a potent CYP3A inhibitor, ALUNBRIG may be restarted at the dose that was tolerated prior to initiation of the potent CYP3A inhibitor. Concomitant use of ALUNBRIG with potent or moderate inducers of CYP3A should be avoided.
Fertility : Counsel women of childbearing potential to use an effective non-hormonal contraceptive during treatment with ALUNBRIG and for at least four months after the last dose. Advise men with female partners of childbearing potential to use an effective contraceptive during treatment and for at least 3 months after the last dose of ALUNBRIG.
Lactose : ALUNBRIG contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
ADVERSE REACTIONS
The most common adverse reactions (≥25%) reported in patients treated with ALUNBRIG with the recommended dosing regimen are elevated aspartate aminotransferase (AST), hyperglycaemia, hyperinsulinemia, anemia , increased levels of creatine phosphokinase (CPK), nausea, elevated lipase levels, decreased lymphocyte count, elevated alanine aminotransferase (ALT), diarrhea, elevated blood amylase levels, fatigue, cough, headache, elevated alkaline phosphatase, hypophosphatemia, increased activated partial thromboplastin time (APTT), rash, vomiting, dyspnea, hypertension,decreased blood count, myalgia and peripheral neuropathy.
The most common serious adverse reactions (≥ 2%) reported in patients treated with ALUNBRIG with the recommended dosing schedule, other than manifestations related to progression of neoplasms, are pneumonitis, pneumonia and dyspnea.
SPECIFIC POPULATIONS
Elderly patients: The limited safety and safety data for ALUNBRIG in patients 65 years of age and older suggest that dosage adjustment is not required in elderly patients. No data is available for patients over 85 years old.
Hepatic impairment: No dose adjustment of ALUNBRIG is required for patients with mild hepatic impairment (Child-Pugh classification A) or moderate hepatic impairment (Child-Pugh classification B). A reduced initial dose (60 mg) once daily for the first seven days, then 120 mg once daily for patients with severe hepatic impairment (Child-Pugh C-classification).
Renal Insufficiency: No dose adjustment of ALUNBRIG is required for patients with mild to moderate renal impairment (estimated glomerular filtration rate (eGFR) ≥ 30 mL / min). A reduced initial dose (60 mg) once daily for the first seven days, then 90 mg once daily is recommended for patients with severe renal impairment (eGFR <30 mL / min). Patients with severe renal impairment should be closely monitored for the onset or worsening of respiratory symptoms that may indicate IPD / pneumonitis (eg dyspnoea, cough, etc.), especially during the first week of life. .
Pediatric population: The safety and efficacy of ALUNBRIG in patients younger than 18 years of age have not been established. No data available.
IMPORTANT SAFETY INFORMATION (USA)
WARNINGS AND PRECAUTIONS
Interstitial lung disease (IPD) / pneumonitis: serious, life-threatening or life-threatening pulmonary-related adverse events suggestive of interstitial lung disease (ILD) / pneumonitis have occurred with ALUNBRIG. In ALTA (ALTA), MPI / pneumonitis occurred in 3.7% of patients in the 90 mg (90 mg once daily) group and in 9.1% of patients in the 90 to 180 mg (dose single daily 180 mg after a preparatory period of seven days to 90 mg as a single daily dose). Adverse reactions suggestive of possible MPI / pneumonitis occurred early (within 9 days of starting ALUNBRIG, median onset of onset of two days) in 6.4% of patients, with grade 3 or 4 reactions occurring in 2.7% of them. Monitor for the onset or worsening of respiratory symptoms (eg, dyspnea, cough, etc.) especially during the first week of ALUNBRIG. Discontinue ALUNBRIG in patients with new or worsening respiratory symptoms and evaluate promptly for MPI / pneumonitis or other causes of respiratory symptoms (eg, pulmonary embolism, tumor progression, and infectious pneumonia). For MPI / pneumonitis grade 1 or 2, ALUNBRIG may be restarted by reducing the dose after returning to baseline, or permanently discontinuing ALUNBRIG.
Hypertension: in the ALTA trial, hypertension was reported in 11% of patients in the 90 mg ALUNBRIG group and 21% in the 90 → 180 mg group. Level 3 hypertension occurred in 5.9% of patients in total. Monitor blood pressure before any treatment with ALUNBRIG. Monitor blood pressure after 2 weeks, then at least once a month during ALUNBRIG treatment. Discontinue administration of ALUNBRIG for Level 3 hypertension despite optimal antihypertensive therapy. After resolution or improvement to grade 1, resume administration of ALUNBRIG by reducing the dose. Consider a definite cessation of treatment with ALUNBRIG in case of
Bradycardia: Bradycardia can occur with ALUNBRIG. In the ALTA trial, heart rates of less than 50 beats per minute (bpm) occurred in 5.7% of patients in the 90 mg group and in 7.6% of the 90 to 180 mg group. Level 2 bradycardia occurred in 1 (0.9%) patients in the 90 mg group. Monitor heart rate and blood pressure during treatment with ALUNBRIG. Monitor patients more frequently if concomitant use of a drug known to cause bradycardia can not be avoided. In symptomatic bradycardia, discontinue ALUNBRIG and evaluate concomitant medications known to cause bradycardia. If any of these drugs are identified and discontinued or adjusted, restart ALUNBRIG at the same dose after symptomatic bradycardia has resolved; otherwise, reduce the dose of ALUNBRIG after symptomatic bradycardia disappears. Discontinue ALUNBRIG for life-threatening bradycardia if no concomitant medicinal product contributing to it is identified.
Visual disturbances: durant l’étude ALTA, des réactions indésirables conduisant à des troubles visuels, notamment une vision floue, une diplopie et une acuité visuelle réduite, ont été signalées chez 7,3 % des patients traités par ALUNBRIG du groupe 90 mg et chez 10 % des patients du groupe 90→180 mg. Un œdème maculaire de niveau 3 et une cataracte se sont produits chez un patient du groupe 90→180 mg. Conseiller aux patients de signaler tout symptôme visuel. Interrompre l’administration d’ALUNBRIG et procéder à une évaluation ophtalmologique des patients présentant des symptômes visuels nouveaux ou s’aggravant, de niveau 2 ou d’une gravité supérieure. Après retour du niveau de gravité 2 ou 3 au niveau 1 ou au niveau de base, reprendre l’administration d’ALUNBRIG en réduisant la dose. Cesser définitivement le traitement à l’ALUNBRIG en cas de troubles visuels de niveau 4.
Elevation of creatine phosphokinase (CPK): in the ALTA study, elevation of creatine phosphokinase (CPK) occurred in 27% of ALUNBRIG patients in the 90 mg group and in 48% of patients in the 90 → 180 mg group. The incidence of 3-4 CPK elevation was 2.8% in the first group, compared to 12% in the second group. Dose reduction due to elevated CPK was achieved in 1.8% of patients in the 90 mg group and in 4.5% of patients in the 90 → 180 mg group. Advise patients to report unexplained muscle pain, tenderness or weakness. Monitor CPK levels during treatment with ALUNBRIG. Interrupt administration of ALUNBRIG if CPK level 3 or level 4 is elevated.
Elevation of pancreatic enzyme levels: in the ALTA trial, amylase elevation occurred in 27% of patients in the 90 mg group compared to 39% of patients in the 90 → 180 mg group. Lipase elevation occurred in 21% of patients in the first group, compared with 45% in the second group. Elevation of amylase level 3 or 4 occurred in 3.7% of patients in the first group, compared to 2.7% of those in the second group. Level 3 or 4 lipase elevation occurred in 4.6% of patients in the first group, compared with 5.5% in the second group. Monitor lipase and amylase levels during treatment with ALUNBRIG. Discontinue administration of ALUNBRIG if level 3 or 4 pancreatic enzymes are elevated..
Hyperglycemia: in the ALTA trial, 43% of patients who received ALUNBRIG had new or worsening hyperglycemia. Level 3 hyperglycemia, based on a laboratory assessment of fasting blood glucose levels, occurred in 3.7% of patients. Two in 20 (10%) patients with diabetes or glucose intolerance at baseline required insulin administration during ALUNBRIG therapy. Evaluate fasting blood glucose levels prior to administration of ALUNBRIG and monitor periodically thereafter. Start or optimize the administration of anti-hyperglycemic drugs, as needed. If proper hyperglycemic control can not be achieved with optimal medical management,
Embryonic and fetal toxicity: Based on its mechanism of action and results obtained in animals, ALUNBRIG can harm the fetus when administered to a pregnant woman. There are no clinical data on the use of ALUNBRIG in pregnant women. Inform pregnant women of the potential risk to the fetus. Advise women of childbearing potential to use effective non-hormonal contraception during treatment with ALUNBRIG and for at least four months after the final dose. Advise men with female partners of childbearing potential to use effective contraception during treatment and for at least 3 months after the last dose of ALUNBRIG.
ADVERSE REACTIONS
Serious adverse reactions occurred in 38% of patients in the 90 mg group compared to 40% of patients in the 90 to 180 mg group. The most common serious adverse reactions were pneumonia (5.5% of the total, 3.7% in the 90 mg group, compared to 7.3% in the 90 → 180 mg group) and MPI / pneumonitis (4.6% of the total, 1.8% in the first group, against 7.3% in the second group). Fatal adverse reactions occurred in 3.7% of patients, in the form of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis, and urinary tract infection (1 patient per case).
The most common adverse reactions (≥25%) in patients in the 90 mg group were nausea (33%), fatigue (29%), headache (28%) and dyspnea (27%) ; and nausea (40%), diarrhea (38%), fatigue (36%), cough (34%) and headache (27%) in the 90 → 180 mg group.
DRUGS INTERACTIONS
CYP3A Inhibitors : Avoid the concomitant use of ALUNBRIG with potent CYP3A inhibitors. Avoid grapefruit and grapefruit juice, which may also increase plasma concentrations of brigatinib. If concomitant use of a potent CYP3A inhibitor can not be avoided, reduce the dose of ALUNBRIG.
CYP3A inducers: Avoid the concomitant use of ALUNBRIG with potent CYP3A inducers.
CYP3A Substrates: Concomitant administration of ALUNBRIG with CYP3A substrates, including hormonal contraceptives, may result in reduced concentrations and loss of CYP3A substrate efficiency.
USE IN SPECIFIC POPULATIONS
Pregnancy: ALUNBRIG can harm the fetus. Inform women of reproductive age about the potential risk to the fetus.
Breast-feeding: There are no data on the secretion of brigatinib in breast milk, nor its effects on breastfed infants or milk production. Because of potential adverse reactions for the breastfeeding infant, advise breastfeeding women not to breastfeed while taking ALUNBRIG.
Women and men of childbearing age:
Contraception : To advise women of childbearing potential to use an effective non-hormonal contraceptive during ALUNBRIG treatment, and for at least four months after the last dose. Advise men with female partners of childbearing potential to use effective contraception while taking ALUNBRIG, and for at least 3 months after the last dose.
Infertility : ALUNBRIG may cause reduced fertility in humans.
Pediatric Use: The safety and efficacy of ALUNBRIG in pediatric patients have not been established.
Geriatric Use: Clinical studies with ALUNBRIG do not include sufficient numbers of patients aged 65 years or older to determine a possible difference in response compared to younger patients. Of the 222 patients in the ALTA trial, 19.4% were aged 65 to 74 years, and 4.1% were 75 years of age or older. There were no clinically significant differences in safety and efficacy between patients ≥ 65 years of age and younger patients.
Hepatic or Renal Insufficiency: No dose adjustment is recommended for patients with mild hepatic impairment or mild or moderate renal impairment. The safety of ALUNBRIG in patients with moderate or severe hepatic impairment, or severe renal impairment has not been studied.