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– ALUNBRIG resulted in an unprecedented median progression-free survival of 16.7 months and a total survival of 34.1 months after crizotinib treatment –
– Based on regulatory approvals in the United States and Canada, EU-wide approval could help bridge the coverage gap in patients with ALK-positive NSCLC in Europe,
As announced today by Takeda Pharmaceutical Company Limited (TSE: 4502), the European Commission has approved ALUNBRIG (brigatinib) monotherapy for the treatment of non-small cell lung cancer (ALK) positive for anaplastic lymphoma (ALK). ) positive. NSCLC) after treatment with crizotinib. This decision followed a recommendation from the Committee for Medicinal Products for Human Use (CHMP) of 20 September 2018.
"The introduction of targeted therapies has significantly improved the treatment of ALK + NSCLC, but approximately 70% of patients who develop disease progression during crizotinib treatment with brain metastases are in dire need of treatment." 39 additional treatment options, "said Dr. Felip Dr. Enriqueta, MD, PhD., Director of the Thoracic Oncology Unit, Department of Oncology at Vall University Hospital. from Hebron to Barcelona. "Data collected as part of the ALTA study on ALUNBRIG showed consistent results of systemic and intracranial efficacy and a manageable safety profile." The study demonstrated the longest survival Without progression and the longest overall survival in this regard.With this approval, doctors from the European Union will have another option to treat patients with ALK + CPN as a result of previous treatment with crizotinib. "
"The decision of the European Commission to authorize ALUNBRIG as a treatment for ALK + NSCLC patients represents significant progress for European patients with this life-threatening disease," said Dr. Jesús Gómez-Navarro, MD, Vice President, Head of Clinical Research and Development in Oncology, Takeda. "This is the first time that independent independent peer-reviewed median survival beyond 16 months and a total survival of 34 months after previous treatment with crizotinib has been reported – evidence of the strength of data from the community. ALTA study ALUNBRIG's endorsement in the EU underscores our continued commitment to developing innovative solutions that improve the quality of life of the approximately 40,000 patients worldwide diagnosed with this disease each year. "
"Many people do not know ALK + NSCLC and its variants.The fact that young patients often suffer from lung cancer and are not associated with smoking is also largely unknown," said Stefania Vallone, president of Lung cancer, Europe. "These young people are often in the middle of their lives, have started a family, are dedicated to their careers and participate in the life of their community.The availability of new treatments that can prolong the life expectancy without progression of the disease is very important and can not be underestimated. "
The European Commission's approval is based on the ALTA Phase 2 global data, in which patients were randomized to one of two ALUNBRIG regimens: 90 mg once daily (n = 112) or the recommended dose 180 mg once daily after treatment. initial phase of seven days with 90 mg once daily (n = 110). The results showed that 56% of patients receiving the recommended regimen had a confirmed total response rate (ORR) as judged by an independent review committee (IRC), while the median duration of response (DOR) was 15.7 months as assessed by the IRC. was. According to the evaluation of IRC, ALUNBRIG achieved a median progression-free survival (PFS) of 16.7 months and an overall survival of 34.1 months in patients with locally advanced or metastatic ALK-NSCLC. the disease had progressed under treatment with crizotinib.
The most common adverse reactions (≥ 25%) in patients treated with ALUNBRIG at the recommended dose of 180 mg were including an increase in aspartate aminotransferase (AST), hyperglycemia, hyperinsulinemia, anemia, increased creatine phosphokinase (CPK), nausea, increased lipase and decreased lipase levels. Number of lymphocytes, elevated alanine aminotransferase (ALT), diarrhea, increased amylase, fatigue, cough, headache, increased alkaline phosphatase, hypophosphatemia, abnormally high level of activated partial thromboplastin (aTT), rash , vomiting, dyspnea, dyspnea, hypertension, hypoglycemia, peripheral neuropathy. The most common serious adverse events (≥ 2%) in patients treated with ALUNBRIG at the recommended dose were, in addition to neoplastic changes, pneumonitis, pneumonia and respiratory distress.
The decision of the European Commission means that ALUNBRIG now has a marketing authorization for this indication in the 28 Member States of the European Union as well as in Norway, Liechtenstein and in Iceland. More information on the European Commission's decision is available on the website of the European Medicines Agency: www.ema.europe.eu/ema.
About the ALTA study The ALTA Phase 2 study (ATLK in TheCancer Trial of ATP26113) formed the basis of ALUNBRIG's approval for the treatment of adults. This global, ongoing, multi-center, open-label, two-component trial enrolled 222 patients with locally advanced or advanced metastatic NSCLC or whose disease had progressed with crizotinib treatment. Patients received either 90 mg of ALUNBRIG once daily (n = 112), or 180 mg once daily after a seven-day introductory phase with 90 mg once daily (n = 110). The primary endpoint of the efficacy study was the Confirmed Response Rate (CRR) v1.1 (Criteria for Evaluation of Response in Solid Tumors), which had been evaluated by the investigator. Other efficacy targets include the ORR, the Independent Response Committee (IRC), Duration of Response (DOR), Progression Free Survival (PFS), Intracranial ORM, and Intracranial ORD. , safety and tolerability.
The results of the ALTA study showed that among patients who received the 180 mg regimen, 56% achieved a total response rate according to the investigator's evaluation and 56%, the response rate to the evaluation according to the evaluation of the IRC. At the recommended dosage, the median duration of response was 13.8 months according to the assessment of the investigator and 15.7 months according to the evaluation of the IRC. The median progression-free survival was 15.6 months according to the researcher's assessment and 16.7 months according to the IRC evaluation. In addition, 67% of patients with initially measurable brain metastases (n = 18) had an overall intracranial response rate according to the IRC evaluation; the median duration of intracranial response rate was 16.6 months according to the IRC evaluation. The median overall survival rate was 34.1 months.
Forty-six percent of patients receiving the 90 mg regimen achieved ORR according to the investigator's assessment and 51% according to the IRC evaluation. The median duration of response was 12.0 months according to the assessment of the investigator and 16.4 months according to the evaluation of the IRC. The median PFS was 9.2 months, both according to the assessment of the investigator and according to the evaluation of the IRC. In addition, 50% of patients with initially measurable brain metastases (n = 26) had an overall intracranial response rate according to the IRC evaluation; the median duration of the intracranial response rate was 9.4 months according to the IRC evaluation. The median overall survival rate was 29.5 months.
About positive NSCLC for ALK Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. According to the World Health Organization, it accounts for about 85% of the 1.8 million new cases of lung cancer diagnosed each year worldwide. Genetic studies have suggested that chromosomal rearrangements affecting anaplastic lymphoma kinase (ALK) also play an important role in a subgroup of NSCLC patients. About three to five percent of patients with metastatic NSCLC have a rearrangement of the ALK gene.
Takeda is committed to continuing its research and development on non-small cell lung cancer to improve the quality of life of some 40,000 patients worldwide who are diagnosed each year with this type of lung cancer serious and rare.
About ALUNBRIG® (Brigatinib) ALUNBRIG is a targeted anti-cancer drug developed by ARIAD Pharmaceuticals, Inc., a company acquired by Takeda in February 2017. ALUNBRIG received accelerated FDA approval in April 2017 for the treatment of ALK + metastatic CPN patients with progression during treatment with crizotinib or for crizotinib intolerance. The approval of this indication was made as part of an accelerated approval procedure based on the tumor response rate and the duration of the response. Permanent approval for this indication may depend on the review and description of the clinical benefit in a confirmatory study. In July 2018, Health Canada approved ALUNBRIG for the treatment of adult patients with ALK + metastatic NSCLC who experienced progression or intolerance to crizotinib during treatment with an ALK inhibitor (crizotinib). The approval of ALUNBRIG by the FDA and Health Canada was based primarily on the results of the pivotal ALTA Phase 2 study (ATLK in TheCancer Trial of ATP26113).
ALUNBRIG has achieved FDA disruptive treatment status for the treatment of patients with ALK-positive NSCLC whose tumors are resistant to crizotinib. In addition, the FDA has assigned orphan drug designation to ALK-positive NSCLC and NSCLC positive for ROS1 and EGFR.
Brigatinib's Clinical Development Program reiterates Takeda's constant quest to develop innovative therapies for people with ALK-positive NSCLC and healthcare professionals they treat worldwide. The comprehensive study program includes the following clinical trials:
- Phase 1/2 trial to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of ALUNBRIG
- A pivotal Phase 2 study on ALTA aimed at evaluating the efficacy and safety of ALUNBRIG under two regimens in patients with ALK-positive, locally advanced or metastatic NSCLC and presenting a progression of the disease under crizotinib
- Phase 3 ALTA-1L, Randomized Global Trial to Assess Efficacy and Safety of ALUNBRIG Versus Crizotinib in Patients with Positive, Locally Advanced or Metastatic ALK NSCLC Without Pretreatment with Inhibitor d & # 39; ALK
- One-arm multicenter phase 2 study in Japanese patients with ALK-positive NSCLC, focused on patients whose disease course was undergoing alectinib treatment
- A global phase 2 study evaluating ALUNBRIG in patients with advanced NSCLC with ALK-positive and with disease progression under treatment with alectinib or ceritinib
- Randomized Phase 3 global trial to evaluate the efficacy and safety of ALUNBRIG versus alectinib in ALK-positive NSCLC patients with disease progression under crizotinib
For more information on clinical trials with Brigatinib, visit www.clinicaltrials.gov.
ALUNBRIG® (Brigatinib): IMPORTANT INFORMATION ON SECURITY (EUROPE)
SPECIAL WARNINGS AND USE PRECAUTIONS
pulmonary side effects: Severe, life-threatening and fatal pulmonary adverse events, such as interstitial lung disease (interstitial lung disease) or pneumonitis, may occur. Most pulmonary adverse events were observed during the first 7 days of treatment. Grade 1-2 adverse events were corrected after treatment interruption or dose modification. Increasing age or a shorter interval (less than 7 days) between the last administration of crizotinib and the first administration of ALUNBRIG were independently associated with an increase in pulmonary adverse events. Therefore, these factors must be taken into account when treating with ALUNBRIG. In some patients, pneumonitis occurred later during treatment with ALUNBRIG. Patients should be monitored to detect the onset or worsening of breathing difficulties (eg, dyspnea, cough, etc.), especially during the first week of treatment. In all patients with increased breathing difficulties, a clarification regarding pneumonitis should be given immediately. If pneumonia is suspected, ALUNBRIG therapy should be discontinued and the patient should be screened for other causes of the disease (eg, pulmonary embolism, tumor progression, and infectious pneumonia). The dosage should be adjusted accordingly.
hypertensiontook place. Blood pressure should be monitored regularly during treatment with ALUNBRIG. Hypertension should be treated according to standard guidelines for blood pressure control. Heart rate is more common in patients when the concomitant use of a drug known to cause bradycardia can not be avoided. In case of severe hypertension (≥ 3), treatment with ALUNBRIG should be discontinued until blood pressure is restored to level 1 or the initial level. The dosage should be adjusted accordingly.
bradycardiatook place. Caution is required when co-administering ALUNBRIG with other drugs known to cause bradycardia. Heart rate and blood pressure should be checked regularly. Symptomatic bradycardia should be discontinued with ALUNBRIG. Concomitant medications should be tested for agents known to cause bradycardia. The dose of ALUNBRIG should be adjusted accordingly after clarification. In case of life-threatening bradycardia, ALUNBRIG should be discontinued in the absence of concomitant co-medication or in the event of recurrent bradycardia. If concomitant concomitant treatment is determined, the dosage should be adjusted accordingly.
blurred visionoccurred during treatment with ALUNBRIG. Patients should be advised to report visual complaints. In case of new or exacerbated vision problems, ophthalmological examination and dose reduction should be considered.
Elevations of creatine phosphokinase (CPK) have been reported. Patients should be informed of any unexplained muscle pain, tenderness or weakness. During treatment with ALUNBRIG, the CPK level should be checked regularly. Depending on the degree of increase in CPK, treatment with ALUNBRIG should be discontinued and the dosage adjusted accordingly.
Increased pancreatic enzymes: Elevations of amylase and lipase have occurred. During treatment with ALUNBRIG, lipase and amylase levels should be monitored regularly. Depending on the degree of deviation of laboratory values, treatment with ALUNBRIG should be suspended and the dosage adjusted accordingly.
hepatotoxicity: Increases in liver enzyme levels (aspartate aminotransferase, alanine aminotransferase) and bilirubin have been observed. Liver function, including AST, ALT and total bilirubin, should be measured every 2 weeks before starting treatment with ALUNBRIG, and then within the first 3 months of treatment. Then the check should be done at regular intervals. Depending on the degree of deviation of laboratory values, treatment with ALUNBRIG should be suspended and the dosage adjusted accordingly.
hyperglycemia: An increase in blood glucose in the serum has occurred. Before treatment with ALUNBRIG, serum fasting glucose should be determined and monitored at regular intervals thereafter. If necessary, initiate a treatment with hypoglycemic drugs or optimize it. If, despite optimal treatment, adequate control of hyperglycemia can not be achieved, treatment with ALUNBRIG should be discontinued until adequate control of hyperglycemia is obtained. . After recovery, a reduction in ALUNBRIG dose or a definite ALUNBRIG discontinuation should be considered.
Interaction with other drugs: The concomitant use of ALUNBRIG and potent CYP3A inhibitors should be avoided. If concomitant use of a potent CYP3A inhibitor is unavoidable, ALUNBRIG should be reduced from 180 mg to 90 mg or from 90 mg to 60 mg. After discontinuation of a potent CYP3A inhibitor, ALUNBRIG therapy should be resumed at the tolerated dose prior to initiation of treatment with the potent CYP3A inhibitor. The simultaneous use of ALUNBRIG with potent and moderate inducers of CYP3A should be avoided.
fertility: Women of childbearing potential are advised to use an effective non-hormonal method of contraception while taking ALUNBRIG and to maintain it for at least 4 months after the last dose. Men with a partner of childbearing potential should use an effective method of contraception while taking ALUNBRIG and 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.
SIDE EFFECTS The most common adverse reactions (≥ 25%) in patients treated with ALUNBRIG at the recommended dose included an increase in AST, hyperglycemia, hyperinsulinemia, 39, anemia, increased CPK, nausea, increased lipase, decreased lymphocyte count, increased ALT, increased amylase, fatigue, cough, headache, increased alkaline phosphatase, hypophosphatemia, partial activated TCA increase, rash, vomiting, respiratory distress, hypertension, decreased white blood cell count, myalgia and peripheral neuropathy.
The most common serious adverse events (≥ 2%) in patients receiving ALUNBRIG at the recommended dose were pneumonia, pneumonia and dyspnea, in addition to neoplastic changes.
SPECIAL POPULATIONS OF PATIENTS
Elderly patients: Limited data on the safety and efficacy of ALUNBRIG in the treatment of patients over 65 years of age suggest that it may not be necessary. adjust the dosage in elderly patients. There is no data available for patients over 85 years old.
Limitation of liver function: No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh Class A) or moderate hepatic impairment (Child-Pugh Class B). In patients with severe hepatic impairment (Child-Pugh Class C), an initial dose of 60 mg daily for the first 7 days of treatment is recommended, followed by a daily dose of 120 mg.
renal failure: No dose adjustment is necessary in patients with mild or moderate renal impairment (estimated glomerular filtration rate (eGFR ≥ 30 ml / min)). In patients with severe renal impairment (eGFR <30 ml / min), an initial dose of 60 mg once daily for the first 7 days of treatment is recommended, followed by a dose of 90 mg once per day. Patients with severe renal impairment should be closely monitored for recurrence or exacerbation of respiratory symptoms that may indicate interstitial lung disease (eg, dyspnea, cough, etc.). , especially during the first week of treatment.
Children and adolescents: The safety and efficacy of ALUNBRIG in patients younger than 18 years have not been studied. Therefore, no data is available.
IMPORTANT SAFETY INFORMATION (USA) WARNINGS AND PRECAUTIONS
Interstitial pneumonitis (interstitial lung disease): Serious, fatal and fatal lung-related adverse events, such as interstitial lung disease (interstitial lung disease) and pneumonitis, have occurred with the use of ALUNBRIG. In the ALTA study (ALTA), ILD / pneumonitis occurred in 3.7% of patients in the 90 mg (90 mg once daily) group and 9.1% in the 90 to 180 mg group (180 once per day with an initial phase of 7 days with 90 mg once a day). Possible side effects of interstitial lung disease or interstitial lung disease occurred early (within 9 days of starting ALUNBRIG, median onset: 2 days) in 6.4% of patients, with adverse effects of grades 3 and 4 over 2.7% were observed. Patients should be monitored to detect the onset or worsening of breathing difficulties (eg, dyspnea, cough, etc.), especially during the first week. after starting treatment with ALUNBRIG. Treatment with ALUNBRIG should be discontinued in all patients with recent or increased respiratory distress, and details of interstitial lung disease or pneumonitis or other causes of respiratory distress (eg, pulmonary embolism, tumor progression). and infectious pneumonia) should be communicated promptly. In case of ILD / 1st or 2nd degree pneumopathy with ALUNBRIG, treatment should be resumed after recovery at a reduced dose or permanently stopped with ALUNBRIG. In cases of interstitial pneumonitis / grade 3 or 4 pneumonia or recurrent ILD / grade 1 or 2 pneumonia, ALUNBRIG must be permanently discontinued.
hypertension: In the ALTA study, hypertension was reported in 11% of patients in the 90 mg ALUNBRIG group and in 21% of patients in the 90 to 180 mg group. Grade 3 hypertension occurred in 5.9% of patients. Before starting treatment with ALUNBRIG, a blood pressure check is necessary. During treatment with ALUNBRIG, blood pressure should be monitored after 2 weeks, then at least once a month. In case of third-degree hypertension despite optimal antihypertensive treatment, treatment with ALUNBRIG should be suspended. When normalizing blood pressure or improving severity 1, treatment with ALUNBRIG should be resumed at a lower dose. In case of grade 4 hypertension or recurrence of grade 3 hypertension, definitive discontinuation of ALUNBRIG should be considered. Precautions should be taken when administering ALUNBRIG in combination with antihypertensives that cause bradycardia.
bradycardia: Bradycardia can occur during the administration of ALUNBRIG. In the ALTA study, heart rates below 50 beats per minute were observed in 5.7% of patients in the 90 mg group and in 7.6% of patients in the 90 to 180 mg group. Grade 2 bradycardia occurred in 1 patient (0.9%) in the 90 mg group. During treatment with ALUNBRIG, heart rate and blood pressure should be monitored. If co-administration with a drug known to cause bradycardia can not be avoided, patients should be monitored more closely. In symptomatic bradycardia, treatment with ALUNBRIG should be discontinued and concomitant therapy should be tested for agents that may cause bradycardia. If concomitant therapy known to cause bradycardia has been detected, stopped or administered, treatment with ALUNBRIG should be resumed at the same dose after cessation of symptomatic bradycardia. Otherwise, the dose of ALUNBRIG should be reduced after cessation of symptomatic bradycardia. In the event of life-threatening bradycardia, ALUNBRIG should be discontinued if no concomitant co-medication is found.
vision problems: In the ALTA study, adverse effects to blurred vision, such as blurred vision, diplopia, and decreased visual acuity, were reported in 7.3% of patients treated with ALUNBRIG in the 90 mg group and in 10% of patients in the range 90 → 180. mg group reported. Macular edema and grade 3 cataract occurred in one patient in the 90 to 180 mg group. Patients should be advised to report visual complaints. If new or existing second degree symptoms or larger vision symptoms occur, ALUNBRIG therapy should be discontinued and an ophthalmic consultation should be obtained. If Grade 2 or 3 symptoms decrease in Grade 1 or at the beginning of treatment, treatment with ALUNBRIG should be resumed at a lower dose. In cases of visual disturbances of the 4th degree, treatment with ALUNBRIG must be interrupted,
Increased creatine phosphokinase: In the ALTA study, 27% of patients treated with ALUNBRIG in the 90 mg and 48% of patients in the 90 to 180 mg group experienced an increase in creatine phosphokinase (CPK). The incidence of CPK grade 3 or 4 was 2.8% in the 90 mg group and 12% in the 90 to 180 mg group. Dose reduction due to elevated CPK was reported in 1.8% of patients in the 90 mg and 4.5% of 90 → 180 mg groups. Patients should be informed of any unexplained muscle pain, tenderness or weakness. During treatment with ALUNBRIG, the CPK rate should be monitored. Treatment with ALUNBRIG should be done with elevation of CPK at the 3rd or 4th degree. When the CPK level is normalized or decreases at grade 1 or baseline, treatment with ALUNBRIG should be resumed at the same dose or at a reduced dose.
Increased pancreatic enzymes: In the ALTA study, an increase in amylase was observed in 27% of patients in the 90 mg group and in 39% of patients in the 90 to 180 mg group. Elevations of lipases occurred in 21% of patients in the 90 mg and 45% of patients in the 90 → 180 mg group. Elevations of amylase at the 3rd or 4th degree were observed in 3.7% of patients in the 90 mg group and in 2.7% of patients in the 90 → 180 mg group. Elevations of grade 3 or 4 lipase levels were observed in 4.6% of patients in the 90 mg group and in 5.5% of patients in the 90 to 180 mg group. During treatment with ALUNBRIG, levels of lipase and amylase should be monitored. Treatment with ALUNBRIG should be associated with an increase in pancreatic enzymes in the 3rd or 4th degree. When normalizing or reducing to grade 1 or baseline, treatment with ALUNBRIG should be resumed at the same dose or at a reduced dose.,
hyperglycemia: In the ALTA study, it was observed that hyperglycemia was new or increased in 43% of patients receiving ALUNBRIG. Grade 3 hyperglycemia, determined by fasting plasma glucose levels in the laboratory serum, occurred in 3.7% of patients. In 2 out of 20 (10%) patients with diabetes or glucose intolerance at the start of treatment, insulin treatment was to be initiated with ALUNBRIG therapy. Before treatment with ALUNBRIG, serum fasting glucose should be determined and monitored at regular intervals thereafter. Si nécessaire, initiez un traitement avec des médicaments hypoglycémiants ou optimisez-le. Si un contrôle adéquat de l'hyperglycémie ne peut pas être atteint malgré un traitement optimal, le traitement par ALUNBRIG doit être interrompu jusqu'à ce qu'un contrôle adéquat de l'hyperglycémie soit obtenu. Une réduction de la dose d'ALUNBRIG ou un arrêt définitif d'ALUNBRIG doit être envisagé.
Toxicité embryo-fœtale: Le mécanisme d'action et les observations chez les animaux suggèrent qu'ALUNBRIG peut être nocif pour le fœtus lorsqu'il est utilisé pendant la grossesse. Il n’existe aucune donnée clinique sur l’utilisation d’ALUNBRIG pendant la grossesse. Les femmes enceintes doivent être informées des risques potentiels pour leur enfant à naître. Il est conseillé aux femmes en âge de procréer d’utiliser une méthode de contraception non hormonale efficace pendant le traitement par ALUNBRIG et de la maintenir pendant au moins 4 mois après la dernière dose. Les hommes ayant un partenaire en âge de procréer doivent utiliser une méthode de contraception efficace pendant le traitement par ALUNBRIG et au moins 3 mois après la dernière dose d'ALUNBRIG.,
RÉACTIONS INDÉSIRABLES
Des effets indésirables graves ont été observés chez 38% des patients du groupe 90 mg et 40% des patients du groupe 90 → 180 mg. Les réactions indésirables graves les plus courantes étaient la pneumonie (5,5% au total, 3,7% dans le groupe 90 mg et 7,3% dans le groupe 90 → 180 mg) et la pneumopathie interstitielle (4,6% au total). 1,8% dans le groupe 90 mg et 7,3% dans le groupe 90 → 180 mg). Des effets indésirables mortels sont survenus chez 3,7% des patients et ont inclus pneumonie (2 patients), mort subite, détresse respiratoire, défaillance respiratoire, embolie pulmonaire, méningite bactérienne et urosepsie (1 patient chacun).
Les réactions indésirables les plus courantes (≥ 25%) dans le groupe 90 mg ont été les nausées (33%), la fatigue (29%), les maux de tête (28%) et la détresse respiratoire (27%). Dans le groupe des 90 à 180 mg, nausées (40%), diarrhée (38%), fatigue (36%), toux (34%) et maux de tête (27%).
INTERACTIONS AVEC D'AUTRES MEDICAMENTS
CYP3A-Inhibitoren: Die gleichzeitige Anwendung von ALUNBRIG mit starken CYP3A-Inhibitoren ist zu vermeiden. Auf Grapefruit oder Grapefruitsaft ist zu verzichten, da diese auch zu einem Anstieg des Brigatinib-Plasmaspiegels führen können. Wenn die gleichzeitige Anwendung eines starken CYP3A-Inhibitors unvermeidlich ist, ist die ALUNBRIG-Dosis zu senken.
CYP3A-Induktoren: Die gleichzeitige Anwendung von ALUNBRIG mit starken CYP3A-Induktoren ist zu vermeiden.
CYP3A-Substrate: Die gemeinsame Verabreichung von ALUNBRIG mit CYP3A-Substraten, darunter hormonelle Kontrazeptiva, kann zu herabgesetzten Spiegeln und dem Verlust der Wirksamkeit von CYP3A-Substraten führen.
ANWENDUNG BEI SPEZIELLEN PATIENTENPOPULATIONEN
Schwangerschaft: ALUNBRIGkann zu einer Schädigung des ungeborenen Lebens führen. Gebärfähige Frauen sind auf das potenzielle Risiko für das Ungeborene hinzuweisen.
Stillzeit: Es liegen keine Daten zum Übertritt von Brigatinib in die Muttermilch, zu den Auswirkungen auf den gestillten Säugling oder die Beeinflussung der Milchproduktion vor. Wegen der möglichen unerwünschten Reaktionen beim gestillten Säugling ist stillenden Frauen davon abzuraten, während der Behandlung mit ALUNBRIG zu stillen.
Gebärfähige Frauen und zeugungsfähige Männer:
Schwangerschaftsverhütung: Gebärfähigen Frauen ist anzuraten, während der Behandlung mit ALUNBRIG eine wirksame nicht-hormonelle Verhütungsmethode anzuwenden und diese für mindestens 4 Monate nach Gabe der letzten Dosis beizubehalten. Männern mit Partnerinnen im gebärfähigen Alter ist anzuraten, während der Behandlung mit ALUNBRIG und mindestens 3 Monate nach der letzten ALUNBRIG-Dosis wirksame Methoden zur Schwangerschaftsverhütung anzuwenden.
Infertilität: ALUNBRIG kann bei Männern zu herabgesetzter Fertilität führen.
Kinder und Jugendliche: Zur Sicherheit und Wirksamkeit von ALUNBRIG bei pädiatrischen Patienten liegen keine Daten vor.
Ältere Patienten: In die klinischen Studien zu ALUNBRIG wurden nicht genügend Patienten im Alter von mindestens 65 Jahren aufgenommen, um einen Unterschied in deren Ansprechen im Vergleich zu jüngeren Patienten beurteilen zu können. Von den 222 Patienten in der ALTA-Studie waren 19,4 % in der Altersgruppe 65-74 Jahre und 4,1 % waren mindestens 75 Jahre alt. Es wurden keine klinisch relevanten Unterschiede hinsichtlich der Sicherheit oder Wirksamkeit zwischen Patienten ≥ 65 Jahre und jüngeren Patienten festgestellt.
Einschränkungen der Leber- oder Nierenfunktion: Eine Dosisanpassung wird bei Patienten mit leichten Einschränkungen der Leberfunktion oder leichten bis mittelschweren Einschränkungen der Nierenfunktion nicht empfohlenen. Die Sicherheit von ALUNBRIG bei Patienten mit mittelschweren bis schweren Einschränkungen der Leberfunktion oder schweren Einschränkungen der Nierenfunktion wurde nicht untersucht.
Die vollständigen US-Verschreibungsinformationen zu ALUNBRIG finden Sie unter www.ALUNBRIG.com
Über die Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited ist ein global tätiges, forschungs- und entwicklungsorientiertes Pharmaunternehmen, das sich für bessere Gesundheit und eine bessere Zukunft für Patienten einsetzt, indem es wissenschaftliche Erkenntnisse in lebensverändernde Medikamente umwandelt. Takeda konzentriert seine Forschungs- und Entwicklungsbemühungen auf Onkologie, Gastroenterologie, Impfstoffe und mit dem Zentralnervensystem zusammenhängende Therapiebereiche sowie Impfstoffe. Takeda führt sowohl intern als auch über Partner Forschungs- und Entwicklungsaufgaben aus, um dadurch bei Innovationen an vorderster Front zu bleiben. Neue innovative Produkte, insbesondere in der Onkologie und Gastroenterologie, sowie seine Präsenz in Wachstumsmärkten treiben das Wachstum von Takeda voran. Mehr als 30.000 Mitarbeiter setzen sich bei Takeda für die Verbesserung der Lebensqualität von Patienten ein und arbeiten in über 70 Ländern mit Partnern im dortigen Gesundheitswesen zusammen. Weitere Informationen finden Sie unter http://www.takeda.com/news.
Weitere Informationen über Takeda finden Sie auf der Unternehmenswebsite unter www.takeda.com. Weitere Informationen über Takeda Oncology, die Marke für die globale Onkologie-Sparte von Takeda Pharmaceutical Company Limited, finden Sie unter www.takedaoncology.com.
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Takeda Pharmaceutical Company Limited Japanische Medien Kazumi Kobayashi [email protected] +81 3 3 278 2095
Medien außerhalb Japans Amanda Loder [email protected] +1-212-259-0491
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