Alunbrig

brigatinib · Tablet, Film Coated · Oral

Uses

1 INDICATIONS AND USAGE ALUNBRIG is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test [see Dosage and Administration (2.1) ] . ALUNBRIG is a kinase inhibitor indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. ( 1 , 2.1 )

Dosage and administration

90 mg orally once daily for the first 7 days; then increase to 180 mg orally once daily. May be taken with or without food. ( 2.2 ) 2.1 Patient Selection Select patients for the treatment of metastatic NSCLC with ALUNBRIG based on the presence of ALK positivity in tumor specimens [see Clinical Studies (14) ] . Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosage for ALUNBRIG is: 90 mg orally once daily for the first 7 days; then increase the dose to 180 mg orally once daily. Administer ALUNBRIG until disease progression or unacceptable toxicity. If ALUNBRIG is interrupted for 14 days or longer for reasons other than adverse reactions, resume treatment at 90 mg once daily for 7 days before increasing to the previously tolerated dose. ALUNBRIG may be taken with or without food. Instruct patients to swallow tablets whole. Do not crush or chew tablets. If a dose of ALUNBRIG is missed or vomiting occurs after taking a dose, do not administer an additional dose and take the next dose of ALUNBRIG at the scheduled time. 2.3 Dosage Modifications for Adverse Reactions ALUNBRIG dosage reductions for adverse reactions are summarized in Table 1. Table 1: Recommended ALUNBRIG Dosage Reductions Dosage Reduction Dosage First Second Third 90 mg once daily 60 mg once daily permanently discontinue N/A Not applicable 180 mg once daily 120 mg once daily 90 mg once daily 60 mg once daily Once reduced for adverse reactions, do not subsequently increase the dosage of ALUNBRIG. Permanently discontinue ALUNBRIG if patients are unable to tolerate the 60 mg once daily dose. Recommendations for dosage modifications of ALUNBRIG for the management of adverse reactions are provided in Table 2. Table 2: Recommended ALUNBRIG Dosage Modifications for Adverse Reactions Adverse Reaction Severity Graded per National Cancer Institute Common Terminology Criteria for Adverse Events. Version 4.0 (NCI CTCAE v4). Dosage Modifications bpm = beats per minute; DBP = diastolic blood pressure; HR = heart rate; SBP = systolic blood pressure; ULN = upper limit of normal Interstitial Lung Disease (ILD) /Pneumonitis [see Warnings and Precautions (5.1 )] Grade 1 If new pulmonary symptoms occur during the first 7 days of treatment, withhold ALUNBRIG until recovery to baseline, then resume at same dose and do not escalate to 180 mg if ILD/pneumonitis is suspected. If new pulmonary symptoms occur after the first 7 days of treatment, withhold ALUNBRIG until recovery to baseline, then resume at same dose. If ILD/pneumonitis recurs, permanently discontinue ALUNBRIG. Grade 2 If new pulmonary symptoms occur during the first 7 days of treatment, withhold ALUNBRIG until recovery to baseline. Resume at next lower dose (Table 1) and do not dose escalate if ILD/pneumonitis is suspected. If new pulmonary symptoms occur after the first 7 days of treatment, withhold ALUNBRIG until recovery to baseline. If ILD/pneumonitis is suspected, resume at next lower dose (Table 1); otherwise, resume at same dose. If ILD/pneumonitis recurs, permanently discontinue ALUNBRIG. Grade 3 or 4 Permanently discontinue ALUNBRIG for ILD/pneumonitis. Hypertension [see Warnings and Precautions (5.2) ] Grade 3 hypertension (SBP greater than or equal to 160 mmHg or DBP greater than or equal to 100 mmHg, medical intervention indicated, more than one antihypertensive drug, or more intensive therapy than previously used indicated) Withhold ALUNBRIG until hypertension has recovered to Grade 1 or less (SBP less than 140 mmHg and DBP less than 90 mmHg), then resume ALUNBRIG at the same dose. Recurrence: withhold ALUNBRIG until recovery to Grade 1 or less, and resume at next lower dose (Table 1) or permanently discontinue treatment. Grade 4 hypertension (life-threatening consequences, urgent intervention indicated) Withhold ALUNBRIG until recovery to Grade 1 or less, and resume at next lower dose (Table 1) or permanently discontinue treatment. Recurrence: permanently discontinue ALUNBRIG for recurrence of Grade 4 hypertension. Bradycardia (HR less than 60 bpm) [see Warnings and Precautions (5.3) ] Symptomatic bradycardia Withhold ALUNBRIG until recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above. If a concomitant medication known to cause bradycardia is identified and discontinued or dose-adjusted, resume ALUNBRIG at same dose upon recovery to asymptomatic bradycardia or to resting heart rate of 60 bpm or above. If no concomitant medication known to cause bradycardia is identified, or if contributing concomitant medications are not discontinued or dose-adjusted, resume ALUNBRIG at next lower dose (Table 1) upon recovery to asymptomatic bradycardia or to resting heart rate of 60 bpm or above. Bradycardia with life-threatening consequences, urgent intervention indicated Permanently discontinue ALUNBRIG if no contributing concomitant medication is identified. If contributing concomitant medication is identified and discontinued or dose-adjusted, resume ALUNBRIG at next lower dose (Table 1) upon recovery to asymptomatic bradycardia or to a resting heart rate of 60 bpm or above, with frequent monitoring as clinically indicated. Recurrence: permanently discontinue ALUNBRIG. Visual Disturbance [see Warnings and Precautions (5.4) ] Grade 2 or 3 visual disturbance Withhold ALUNBRIG until recovery to Grade 1 or baseline, then resume at the next lower dose (Table 1). Grade 4 visual disturbance Permanently discontinue ALUNBRIG. Creatine Phosphokinase (CPK) Elevation [see Warnings and Precautions (5.5) ] Grade 3 or 4 CPK elevation (greater than 5× ULN) with Grade 2 or higher muscle pain or weakness Withhold ALUNBRIG until recovery to Grade 1 or less (less than or equal to 2.5× ULN) CPK elevation or to baseline, then resume ALUNBRIG at same dose.

Dosage forms and strengths

180 mg: oval, white to off-white film-coated tablets with "U13" debossed on one side and plain on the other side 90 mg: oval, white to off-white film-coated tablets with "U7" debossed on one side and plain on the other side 30 mg: round, white to off-white film-coated tablets with "U3" debossed on one side and plain on the other side Tablets: 180 mg, 90 mg, or 30 mg. ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

Interstitial Lung Disease (ILD)/Pneumonitis : Monitor for new or worsening respiratory symptoms, particularly during the first week of treatment. Withhold ALUNBRIG for new or worsening respiratory symptoms and promptly evaluate for ILD/pneumonitis. Upon recovery, either dose reduce or permanently discontinue ALUNBRIG. ( 2.3 , 5.1 ) Hypertension : Monitor blood pressure after 2 weeks and then at least monthly during treatment. For severe hypertension, withhold ALUNBRIG, then dose reduce or permanently discontinue. ( 2.3 , 5.2 ) Bradycardia : Monitor heart rate and blood pressure regularly during treatment. If symptomatic, withhold ALUNBRIG, then dose reduce or permanently discontinue. ( 2.3 , 5.3 ) Visual Disturbance : Advise patients to report visual symptoms. Withhold ALUNBRIG and obtain ophthalmologic evaluation, then dose reduce or permanently discontinue ALUNBRIG. ( 2.3 , 5.4 ) Creatine Phosphokinase (CPK) Elevation : Monitor CPK levels regularly during treatment. Based on the severity and with muscle pain or weakness, withhold ALUNBRIG, then resume or reduce dose. ( 2.3 , 5.5 ) Pancreatic Enzymes Elevation : Monitor lipase and amylase levels regularly during treatment. Based on the severity, withhold ALUNBRIG, then resume or reduce dose. ( 2.3 , 5.6 ) Hepatotoxicity : Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin levels regularly during treatment. Based on severity, withhold dose, then resume at lower level. ( 2.3 , 5.7 ) Hyperglycemia : Assess fasting serum glucose prior to starting ALUNBRIG and regularly during treatment. If not adequately controlled with optimal medical management, withhold ALUNBRIG, then consider dose reduction or permanently discontinue, based on severity. ( 2.3 , 5.8 ) Photosensitivity : Advise patients to limit sun exposure. Based on severity withhold ALUNBRIG, then resume at the same dose, reduce the dose, or permanently discontinue. ( 2.3 , 5.9 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.10 , 8.1 , 8.3 ) 5.1 Interstitial Lung Disease (ILD)/Pneumonitis Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with ALUNBRIG. In Trial ALTA 1L, ILD/pneumonitis occurred in 5.1% of patients receiving ALUNBRIG. ILD/pneumonitis occurred within 8 days of initiation of ALUNBRIG in 2.9% of patients, with Grade 3 to 4 reactions occurring in 2.2% of patients. In Trial ALTA, ILD/pneumonitis occurred in 3.7% of patients in the 90 mg group (90 mg once daily) and 9.1% of patients in the 90→180 mg group (180 mg once daily with 7-day lead-in at 90 mg once daily). Adverse reactions consistent with possible ILD/pneumonitis occurred within 9 days of initiation of ALUNBRIG (median onset was 2 days) in 6.4% of patients, with Grade 3 to 4 reactions occurring in 2.7%. Monitor for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), particularly during the first week of initiating ALUNBRIG. Withhold ALUNBRIG in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia). For Grade 1 or 2 ILD/pneumonitis, either resume ALUNBRIG with dose reduction according to Table 1 after recovery to baseline or permanently discontinue ALUNBRIG. Permanently discontinue ALUNBRIG for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis [see Dosage and Administration (2.3) , Adverse Reactions (6.1) ] . 5.2 Hypertension In ALTA 1L, hypertension was reported in 32% of patients receiving ALUNBRIG; Grade 3 hypertension occurred in 13% of patients. In ALTA, hypertension was reported in 11% of patients in the 90 mg group who received ALUNBRIG and 21% of patients in the 90→180 mg group. Grade 3 hypertension occurred in 5.9% of patients overall. Control blood pressure prior to treatment with ALUNBRIG. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 hypertension despite optimal antihypertensive therapy. Upon resolution or improvement to Grade 1, resume ALUNBRIG at the same dose. Consider permanent discontinuation of treatment with ALUNBRIG for Grade 4 hypertension or recurrence of Grade 3 hypertension [see Dosage and Administration (2.3) , Adverse Reactions (6.1) ] . Use caution when administering ALUNBRIG in combination with antihypertensive agents that cause bradycardia [see Warnings and Precautions (5.3) ] . 5.3 Bradycardia In ALTA 1L, heart rates less than 50 beats per minute (bpm) occurred in 8.1% of patients receiving ALUNBRIG. Grade 3 bradycardia occurred in 1 patient (0.7%). In ALTA, heart rates less than 50 beats per minute (bpm) occurred in 5.7% of patients in the 90 mg group and 7.6% of patients in the 90→180 mg group. Grade 2 bradycardia occurred in 1 (0.9%) patient in the 90 mg group. Monitor heart rate and blood pressure during treatment with ALUNBRIG. Monitor patients more frequently if concomitant use of drug known to cause bradycardia cannot be avoided [see Warnings and Precautions (5.2) ] . For symptomatic bradycardia, withhold ALUNBRIG and review concomitant medications for those known to cause bradycardia. If a concomitant medication known to cause bradycardia is identified and discontinued or dose adjusted, resume ALUNBRIG at the same dose following resolution of symptomatic bradycardia; otherwise, reduce the dose of ALUNBRIG following resolution of symptomatic bradycardia. Discontinue ALUNBRIG for life-threatening bradycardia if no contributing concomitant medication is identified [see Dosage and Administration (2.3) ] .

Side effects

The following adverse reactions are discussed in greater detail in other sections of the prescribing information: Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.1) ] Hypertension [see Warnings and Precautions (5.2) ] Bradycardia [see Warnings and Precautions (5.3) ] Visual Disturbance [see Warnings and Precautions (5.4) ] Creatine Phosphokinase (CPK) Elevation [see Warnings and Precautions (5.5) ] Pancreatic Enzymes Elevation [see Warnings and Precautions (5.6) ] Hepatotoxicity [see Warnings and Precautions (5.7) ] Hyperglycemia [see Warnings and Precautions (5.8) ] Photosensitivity [see Warnings and Precautions (5.9) ] The most common adverse reactions (≥25%) with ALUNBRIG were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, and dyspnea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-217-6468 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Advanced ALK-positive NSCLC Without Prior ALK-targeted Therapy In ALTA 1L, the safety of ALUNBRIG was evaluated in 136 patients with advanced ALK-positive NSCLC who had not previously received an ALK-targeted therapy [see Clinical Studies (14) ] . The median duration of treatment with ALUNBRIG when administered as 90 mg orally once daily for the first 7 days; then increased to 180 mg orally once daily, was 24.3 months. A total of 106 (78%) patients were exposed to ALUNBRIG for greater than or equal to 6 months including 92 (68%) patients exposed for greater than or equal to 1 year. The median relative dose intensity was 97% for ALUNBRIG. The study population (N = 275) characteristics were: median age 59 years (range: 27 to 89), age less than 65 years (68%), female (55%), White (59%), Asian (39%), Stage IV disease (93%), NSCLC adenocarcinoma histology (96%), never smoker (58%), ECOG Performance Status (PS) 0 or 1 (95%), and CNS metastases at baseline (30%) [see Clinical Studies (14) ] . Serious adverse reactions occurred in 33% of patients receiving ALUNBRIG. The most common serious adverse reactions were pneumonia (4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Fatal adverse reactions occurred in 2.9% of patients and included pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%). In ALTA 1L, 13% of patients receiving ALUNBRIG permanently discontinued ALUNBRIG for adverse reactions. The most frequent adverse reactions that led to discontinuation were ILD/pneumonitis (3.7%) and pneumonia (2.2%). In ALTA 1L, 38% of patients required a dose reduction due to adverse reactions. The most common adverse reaction that led to dose reduction was increased creatine phosphokinase (15%), increased lipase (6.6%), increased amylase (4.4%), increased aspartate aminotransferase (2.2%), ILD/pneumonitis (2.2%) and hypertension (2.2%). Table 3 and Table 4 summarize the common adverse reactions and laboratory abnormalities observed in ALTA 1L. Table 3: Adverse Reactions in ≥10% (All Grades Per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 ) or ≥2% (Grades 3-4) of Patients by Arm in ALTA 1L (N = 273) Adverse Reactions ALUNBRIG N = 136 Crizotinib N = 137 All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%) Gastrointestinal Disorders Diarrhea 53 2.2 57 2.9 Nausea 30 2.2 58 2.9 Abdominal pain Includes abdominal discomfort, abdominal distension, abdominal pain, abdominal pain lower, abdominal pain upper, and epigastric discomfort 24 0.7 33 3.6 Vomiting 21 0.7 44 2.2 Constipation 18 0 42 0 Stomatitis Includes aphthous ulcer, mouth ulceration, oral mucosal blistering and stomatitis 13 0.7 8.8 0 Dyspepsia 8 0 16 0.7 Gastroesophageal reflux disease 0.7 0 11 0 Skin and Subcutaneous Tissue Disorders Rash Includes dermatitis, dermatitis acneiform, dermatitis bullous, dermatitis contact, drug eruption, erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, toxic skin eruption, urticaria 40 2.9 17 0 Pruritus Included pruritus, allergic pruritus, and generalized pruritus 20 0.7 5.8 0.7 Respiratory, Thoracic and Mediastinal Disorders Cough 35 0 20 0 Dyspnea Include dyspnea and exertional dyspnea 25 2.9 22 Includes Grade 5 events 3.6 ILD/Pneumonitis 5.1 2.9 2.2 0.7 Pulmonary embolism 2.2 2.2 5.8 2.9 Vascular Disorders Hypertension Includes hypertension and systolic hypertension 32 13 8 2.9 General Disorders and Administration Site Conditions Fatigue Includes asthenia and fatigue 32 1.5 40 2.2 Edema Includes angioedema, eye swelling, eyelid edema, face edema, generalized edema, lip swelling, peripheral edema, periorbital edema, peripheral swelling, skin swelling, swelling and swelling face 18 0.7 48 0.7 Pyrexia 15 0.7 15 0 Musculoskeletal and Connective Tissue Disorders Myalgia Includes muscle spasms, muscle twitching, musculoskeletal discomfort, musculoskeletal pain, and myalgia 28 0 23 0 Back pain 21 0.7 17 1.5 Arthralgia 14 0 12 0 Pain in extremity 5.1 0 15 0.7 Nervous System Disorders Headache Includes headache and migraine 22 2.2 17 0 Dizziness 15 0.7 20 0.7 Peripheral neuropathy Includes burning sensation, dysesthesia, hyperesthesia, hypoesthesia, neuralgia, peripheral neuropathy, paraesthesia, peripheral sensory neuropathy and polyneuropathy 11 0.7 18 0 Dysgeusia 2.9 0 14 0 Investigations Increased Blood cholesterol Includes blood cholesterol increased, hypercholesterolaemia 13 0 0.7 0 Cardiac Disorders Bradycardia Includes bradycardia, heart rate decreased, sinus bradycardia 12 0.7 23 0 Infections and Infestations Pneumonia Inc…

Drug interactions

7 DRUG INTERACTIONS CYP3A Inhibitors : Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inhibitors. If coadministration of a strong or moderate CYP3A inhibitor is unavoidable, reduce the dose of ALUNBRIG. ( 2.4 , 7.1 ) CYP3A Inducers : Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inducers. If coadministration of a moderate CYP3A inducer is unavoidable, increase the dose of ALUNBRIG. ( 2.5 , 7.1 ) 7.1 Effect of Other Drugs on ALUNBRIG Strong or Moderate CYP3A Inhibitors Coadministration of ALUNBRIG with a strong or moderate CYP3A inhibitor increased brigatinib plasma concentrations, which may increase the incidence of adverse reactions [see Clinical Pharmacology (12.3) ] . Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inhibitors. If coadministration of strong or moderate CYP3A inhibitors cannot be avoided, modify dose as recommended [see Dosage and Administration (2.4) ] . Strong or Moderate CYP3A Inducers Coadministration of ALUNBRIG with a strong or moderate CYP3A inducer decreased brigatinib plasma concentrations, which may decrease the efficacy of ALUNBRIG [see Clinical Pharmacology (12.3) ] . Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inducers. If coadministration of moderate CYP3A inducers cannot be avoided, modify dose as recommended [see Dosage and Administration (2.5) ] .

Use in specific populations

Hepatic Impairment : Reduce the dose of ALUNBRIG for patients with severe hepatic impairment. ( 2.6 , 8.6 ) Renal Impairment : Reduce the dose of ALUNBRIG for patients with severe renal impairment. ( 2.7 , 8.7 ) Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action and findings in animals, ALUNBRIG can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no clinical data on the use of ALUNBRIG in pregnant women. Administration of brigatinib to pregnant rats during the period of organogenesis resulted in dose-related skeletal anomalies at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily) as well as increased post-implantation loss, malformations, and decreased fetal body weight at doses of 25 mg/kg/day (approximately 1.26 times the human exposure at 180 mg once daily) or greater (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study in which pregnant rats were administered daily doses of brigatinib during organogenesis, dose-related skeletal (incomplete ossification, small incisors) and visceral anomalies were observed at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily). Malformations observed at 25 mg/kg/day (approximately 1.26 times the human AUC at 180 mg once daily) included anasarca (generalized subcutaneous edema), anophthalmia (absent eyes), forelimb hyperflexion, small, short and/or bent limbs, multiple fused ribs, bent scapulae, omphalocele (intestine protruding into umbilicus), and gastroschisis (intestines protruding through a defect in the abdominal wall) along with visceral findings of moderate bilateral dilatation of the lateral ventricles. 8.2 Lactation Risk Summary There are no data regarding the secretion of brigatinib in human milk or its effects on the breastfed infant or milk production. Because of the potential for adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with ALUNBRIG and for 1 week following the final dose. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating ALUNBRIG [see Use in Specific Populations (8.1) ] . Contraception ALUNBRIG can cause fetal harm [see Use in Specific Populations (8.1) ] . Females Advise females of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 4 months after the final dose. Males Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 3 months after the final dose [see Nonclinical Toxicology (13.1) ] . Infertility Based on findings in male reproductive organs in animals, ALUNBRIG may cause reduced fertility in males [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use The safety and effectiveness of ALUNBRIG in pediatric patients have not been established. 8.5 Geriatric Use Of the 359 patients enrolled in the ALTA 1L ALUNBRIG arm and in ALTA, 26.7% were 65 and older and 7.5% were 75 and older. No overall differences in safety or effectiveness were observed between patients ≥65 years and younger patients. 8.6 Hepatic Impairment No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A) or moderate hepatic impairment (Child-Pugh B). Reduce the dose of ALUNBRIG for patients with severe hepatic impairment (Child-Pugh C) [see Dosage and Administration (2.6) , Clinical Pharmacology (12.3) ] . 8.7 Renal Impairment No dose adjustment is recommended for patients with mild or moderate renal impairment [creatinine clearance (CLcr) 30 to 89 mL/min by Cockcroft-Gault]. Reduce the dose of ALUNBRIG for patients with severe renal impairment (CLcr 15 to 29 mL/min) [see Dosage and Administration (2.7) , Clinical Pharmacology (12.3) ] .

Pregnancy

8.1 Pregnancy Risk Summary Based on its mechanism of action and findings in animals, ALUNBRIG can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no clinical data on the use of ALUNBRIG in pregnant women. Administration of brigatinib to pregnant rats during the period of organogenesis resulted in dose-related skeletal anomalies at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily) as well as increased post-implantation loss, malformations, and decreased fetal body weight at doses of 25 mg/kg/day (approximately 1.26 times the human exposure at 180 mg once daily) or greater (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In an embryo-fetal development study in which pregnant rats were administered daily doses of brigatinib during organogenesis, dose-related skeletal (incomplete ossification, small incisors) and visceral anomalies were observed at doses as low as 12.5 mg/kg/day (approximately 0.7 times the human exposure by AUC at 180 mg once daily). Malformations observed at 25 mg/kg/day (approximately 1.26 times the human AUC at 180 mg once daily) included anasarca (generalized subcutaneous edema), anophthalmia (absent eyes), forelimb hyperflexion, small, short and/or bent limbs, multiple fused ribs, bent scapulae, omphalocele (intestine protruding into umbilicus), and gastroschisis (intestines protruding through a defect in the abdominal wall) along with visceral findings of moderate bilateral dilatation of the lateral ventricles.

Pediatric use

8.4 Pediatric Use The safety and effectiveness of ALUNBRIG in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Of the 359 patients enrolled in the ALTA 1L ALUNBRIG arm and in ALTA, 26.7% were 65 and older and 7.5% were 75 and older. No overall differences in safety or effectiveness were observed between patients ≥65 years and younger patients.

Description

Brigatinib is a kinase inhibitor. The chemical name for brigatinib is 5-chloro-N 4 -[2-(dimethylphosphoryl)phenyl]-N 2 -{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine. The molecular formula is C 29 H 39 ClN 7 O 2 P which corresponds to a formula weight of 584.10 g/mol. Brigatinib has no chiral centers. The chemical structure is shown below: Brigatinib is an off-white to beige/tan solid. The pK a s were determined to be: 1.73 ± 0.02 (base), 3.65 ± 0.01 (base), 4.72 ± 0.01 (base), and 8.04 ± 0.01 (base). ALUNBRIG is supplied for oral use as film-coated tablets containing 180 mg, 90 mg or 30 mg of brigatinib and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate (Type A), magnesium stearate, and hydrophobic colloidal silica. The tablet coating consists of talc, polyethylene glycol, polyvinyl alcohol, and titanium dioxide. Chemical Structure

Mechanism of action

12.1 Mechanism of Action Brigatinib is a tyrosine kinase inhibitor (TKI) with in vitro activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. Brigatinib also inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice. At clinically achievable concentrations (≤500 nM), brigatinib inhibited the in vitro viability of cells expressing EML4-ALK and 17 mutant forms associated with resistance to ALK inhibitors including crizotinib, as well as EGFR-Del (E746-A750), ROS1-L2026M, FLT3-F691L, and FLT3-D835Y. Brigatinib exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib. Brigatinib also reduced tumor burden and prolonged survival in mice implanted intracranially with an ALK-driven tumor cell line.

How supplied

180 mg tablets: oval, white to off-white film-coated tablets with "U13" debossed on one side and plain on the other side; available in: Bottle of 23 tablets NDC 63020-180-23 Bottle of 30 tablets NDC 63020-180-30 90 mg tablets: oval, white to off-white film-coated tablets with "U7" debossed on one side and plain on the other side; available in: Bottle of 7 tablets NDC 63020-090-07 Bottle of 30 tablets NDC 63020-090-30 30 mg tablets: round, white to off-white film-coated tablets with "U3" debossed on one side and plain on the other side; available in: Bottle of 30 tablets NDC 63020-113-30 90 mg / 7 count tablets (NDC 63020-090-07) and 180 mg / 23 count tablets (NDC 63020-180-23) are also available in a single carton as a one-month initiation pack: One carton containing one bottle of 90 mg tablets (7 count) and one bottle of 180 mg tablets (23 count) NDC 63020-198-30 Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) (see USP).

Storage

Store at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) (see USP).

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Interstitial Lung Disease (ILD)/Pneumonitis Inform patients of the symptoms and risks of serious pulmonary adverse reactions such as ILD/pneumonitis. Advise patients to immediately report any new or worsening respiratory symptoms [see Warnings and Precautions (5.1) ] . Hypertension Advise patients of risks of hypertension and to promptly report signs or symptoms of hypertension [see Warnings and Precautions (5.2) ] . Bradycardia Advise patients to report any symptoms of bradycardia and to inform their healthcare provider about the use of heart and blood pressure medications [see Warnings and Precautions (5.3) ] . Visual Disturbance Advise patients to inform their healthcare provider of any new or worsening vision symptoms [see Warnings and Precautions (5.4) ] . Creatine Phosphokinase (CPK) Elevation Inform patients of the signs and symptoms of creatine phosphokinase (CPK) elevation and the need for monitoring during treatment. Advise patients to inform their healthcare provider of any new or worsening symptoms [see Warnings and Precautions (5.5) ] . Pancreatic Enzymes Elevation Inform patients of the signs and symptoms of pancreatitis and the need to monitor for amylase and lipase elevations during treatment [see Warnings and Precautions (5.6) ] . Hepatotoxicity Inform patients of the signs and symptoms of hepatotoxicity, and the need to monitor for aspartate aminotransferase (AST), alanine animotransferase (ALT) and total bilirubin elevations during treatment. Advise patients to inform their healthcare provider of any new or worsening symptoms [see Warnings and Precautions (5.7) ] . Hyperglycemia Inform patients of the risks of new or worsening hyperglycemia and the need to periodically monitor glucose levels. Advise patients with diabetes mellitus or glucose intolerance that antihyperglycemic medications may need to be adjusted during treatment with ALUNBRIG [see Warnings and Precautions (5.8) ] . Photosensitivit y Inform patients of the signs and symptoms of photosensitivity. Advise patients to limit sun exposure while taking ALUNBRIG and for at least 5 days after the final dose. Advise patients to wear a hat, protective clothing, and to use a broad-spectrum Ultraviolet A (UVA)/ Ultraviolet B (UVB) sunscreen and lip balm (SPF ≥30) to protect against sunburn [see Warnings and Precautions (5.9) ] . Females and Males of Reproductive Potential Embryo-Fetal Toxicity Advise females and males of reproductive potential that ALUNBRIG can cause fetal harm [see Warnings and Precautions (5.10) , Use in Specific Populations (8.1) ] . Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy and to use effective contraception during treatment with ALUNBRIG and for at least 4 months after the final dose [see Use in Specific Populations (8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 3 months after the final dose [see Use in Specific Populations (8.3) ] . Lactation Advise females not to breastfeed during treatment with ALUNBRIG and for at least 1 week following the final dose [see Use in Specific Populations (8.2) ] . Infertility Advise males of reproductive potential of the potential for reduced fertility from ALUNBRIG [see Use in Specific Populations (8.3) , Nonclinical Toxicology (13.1) ] . Drug Interactions Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products. Inform patients to avoid grapefruit or grapefruit juice while taking ALUNBRIG [see Drug Interactions (7) ] . Dosing and Administration Instruct patients to start with 90 mg of ALUNBRIG once daily for the first 7 days and if tolerated, increase the dose to 180 mg once daily. Advise patients to take ALUNBRIG with or without food [see Dosage and Administration (2.2) ] . Missed Dose Advise patients that if a dose of ALUNBRIG is missed or if the patient vomits after taking a dose of ALUNBRIG, not to take an extra dose, but to take the next dose at the regular time [see Dosage and Administration (2.2) ] .

Label text from the FDA structured product label by Takeda Pharmaceuticals America, Inc. (revised Jan 12, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Brigatinib in 3 products

Alunbrig NDC products (4)

NDC	Strength & form	Labeler	Type
63020-090	Brigatinib 90 mg/1 Tablet, Film Coated	Takeda Pharmaceuticals America, Inc.	NDA
63020-113	Brigatinib 30 mg/1 Tablet, Film Coated	Takeda Pharmaceuticals America, Inc.	NDA
63020-180	Brigatinib 180 mg/1 Tablet, Film Coated	Takeda Pharmaceuticals America, Inc.	NDA
63020-198	Kit	Takeda Pharmaceuticals America, Inc.	NDA

Frequently asked questions

What is Alunbrig used for?

What are the side effects of Alunbrig?

Who makes Alunbrig?

Alunbrig is listed by 1 labeler in the FDA NDC directory, including Takeda Pharmaceuticals America, Inc..