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Alunbrig is a brand name for Brigatinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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…
Verbatim from this product's FDA label. Tap a section to expand.
2 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. 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) ] .
gov/CompanionDiagnostics. 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.
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. 0 (NCI CTCAE v4). 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.
9) ] The most common adverse reactions (≥25%) with ALUNBRIG were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, and dyspnea. gov/medwatch. 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) ] .
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. 2%). 7%). In ALTA 1L, 13% of patients receiving ALUNBRIG permanently discontinued ALUNBRIG for adverse reactions. 2%). In ALTA 1L, 38% of patients required a dose reduction due to adverse reactions.
2%). Table 3 and Table 4 summarize the common adverse reactions and laboratory abnormalities observed in ALTA 1L. 7%). ALK-positive Advanced or Metastatic NSCLC Previously Treated with Crizotinib The safety of ALUNBRIG was evaluated in 219 patients with locally advanced or metastatic ALK-positive NSCLC who received at least 1 dose of ALUNBRIG in ALTA after experiencing disease progression on crizotinib.
5 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. 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 ) Bradycardia : Monitor heart rate and blood pressure regularly during treatment. If symptomatic, withhold ALUNBRIG, then dose reduce or permanently discontinue. 3 ) Visual Disturbance : Advise patients to report visual symptoms. Withhold ALUNBRIG and obtain ophthalmologic evaluation, then dose reduce or permanently discontinue ALUNBRIG.
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. 5 ) Pancreatic Enzymes Elevation : Monitor lipase and amylase levels regularly during treatment.
Based on the severity, withhold ALUNBRIG, then resume or reduce dose. 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.
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.
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. 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.
4 CONTRAINDICATIONS None. None. ( 4 )
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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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. 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. 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. 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.
5× ULN) CPK elevation or to baseline, then resume ALUNBRIG at same dose. 5× ULN) CPK elevation or to baseline, then resume ALUNBRIG at the next lower dose (Table 1). 5× ULN) or to baseline, then resume ALUNBRIG at same dose. 5× ULN) or to baseline, then resume ALUNBRIG at next lower dose (Table 1).
5× ULN) or to baseline, then resume ALUNBRIG at next lower dose (Table 1). 7) ] Grade 3 or 4 elevation (greater than 5 × ULN) of either ALT or AST with bilirubin less than or equal to 2 × ULN Withhold ALUNBRIG until recovery to Grade 1 or less (less than or equal to 3× ULN) or to baseline, then resume ALUNBRIG at next lower dose (Table 1).
Grade 2 to 4 elevation (greater than 3 × ULN) of ALT or AST with concurrent total bilirubin elevation greater than 2 × ULN in the absence of cholestasis or hemolysis Permanently discontinue ALUNBRIG. 9 mmol/L) or 4 If adequate hyperglycemic control cannot be achieved with optimal medical management, withhold ALUNBRIG until adequate hyperglycemic control is achieved and resume at the next lower dose (Table 1) or permanently discontinue ALUNBRIG.
Other Grade 3 Withhold ALUNBRIG until recovery to baseline, then resume at same dose. Recurrence: withhold ALUNBRIG until recovery to baseline, then resume at next lower dose or discontinue ALUNBRIG (Table 1). Grade 4 Withhold ALUNBRIG until recovery to baseline and resume at next lower dose (Table 1).
Recurrence:
Permanently discontinue ALUNBRIG. 3) ] . , from 180 mg to 90 mg, or from 90 mg to 60 mg). , from 180 mg to 120 mg, 120 mg to 90 mg, or from 90 mg to 60 mg). After discontinuation of a strong or moderate CYP3A inhibitor, resume the ALUNBRIG dose that was tolerated prior to initiating the CYP3A inhibitor.
3) ] . If coadministration of a moderate CYP3A inducer cannot be avoided, increase the ALUNBRIG once daily dose in 30 mg increments after 7 days of treatment with the current ALUNBRIG dose as tolerated, up to a maximum of twice the ALUNBRIG dose that was tolerated prior to initiating the moderate CYP3A inducer.
After discontinuation of a moderate CYP3A inducer, resume the ALUNBRIG dose that was tolerated prior to initiating the moderate CYP3A inducer. 3) ] . 3) ] .
Patients received ALUNBRIG 90 mg once daily continuously (90 mg group) or 90 mg once daily for 7 days followed by 180 mg once daily (90→180 mg group). 8 months in the 90→180 mg group. A total of 150 (68%) patients were exposed to ALUNBRIG for greater than or equal to 6 months and 42 (19%) patients were exposed for greater than or equal to 1 year.
The study population (N = 222) characteristics were: median age 54 years (range: 18 to 82), age less than 65 years (77%), female (57%), White (67%), Asian (31%), Stage IV disease (98%), NSCLC adenocarcinoma histology (97%), never or former smoker (95%), ECOG Performance Status (PS) 0 or 1 (93%), and CNS metastases at baseline (69%) [see Clinical Studies (14) ] .
Serious adverse reactions occurred in 38% of patients in the 90 mg group and 40% of patients in the 90→180 mg group. 3% in the 90→180 mg group). 7% of patients and consisted of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis and urosepsis (1 patient each).
2% of patients in the 90→180 mg group permanently discontinued ALUNBRIG for adverse reactions. 8% in the 90→180 mg group only). 3% in the 90 mg group and 20% in the 90→180 mg group). 5% in the 90→180 mg group). Table 5 and Table 6 summarize the common adverse reactions and laboratory abnormalities observed in ALTA.
9%). 1%).
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. 1% of patients receiving ALUNBRIG.
2% of patients. 1% of patients in the 90→180 mg group (180 mg once daily with 7-day lead-in at 90 mg once daily). 7%. ), particularly during the first week of initiating ALUNBRIG. , 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. 1) ] . 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. 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. 1) ] . 3) ] . 1% of patients receiving ALUNBRIG. 7%). 6% of patients in the 90→180 mg group.
9%) patient in the 90 mg group. Monitor heart rate and blood pressure during treatment with ALUNBRIG. 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.
3) ] . 4% of patients receiving ALUNBRIG. 3% of patients receiving ALUNBRIG in the 90 mg group and 10% of patients in the 90→180 mg group. Grade 3 macular edema and cataract occurred in 1 patient each in the 90→180 mg group. Advise patients to report any visual symptoms.
Withhold ALUNBRIG and obtain an ophthalmologic evaluation in patients with new or worsening visual symptoms of Grade 2 or greater severity. Upon recovery of Grade 2 or Grade 3 visual disturbances to Grade 1 severity or baseline, resume ALUNBRIG at a reduced dose.
1) ] . 5 Creatine Phosphokinase (CPK) Elevation In ALTA 1L, creatine phosphokinase (CPK) elevation occurred in 81% of patients who received ALUNBRIG. The incidence of Grade 3 or 4 CPK elevation was 24%. Dose reduction for CPK elevation occurred in 15% of patients.
In ALTA, CPK elevation occurred in 27% of patients receiving ALUNBRIG in the 90 mg group and 48% of patients in the 90 mg→180 mg group. 8% in the 90 mg group and 12% in the 90→180 mg group. 5% in the 90→180 mg group. Advise patients to report any unexplained muscle pain, tenderness, or weakness.
Monitor CPK levels during ALUNBRIG treatment. Withhold ALUNBRIG for Grade 3 or 4 CPK elevation with Grade 2 or higher muscle pain or weakness. 1) ] . 8% of patients. Lipase elevations occurred in 59% of patients and Grade 3 or 4 lipase elevation occurred in 17% of patients.
In ALTA, amylase elevation occurred in 27% of patients in the 90 mg group and 39% of patients in the 90→180 mg group. Lipase elevations occurred in 21% of patients in the 90 mg group and 45% of patients in the 90→180 mg group. 7% of patients in the 90→180 mg group.
5% of patients in the 90→180 mg group. Monitor lipase and amylase during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 or 4 pancreatic enzyme elevation. 1) ] . 5% of patients. 2% of patients. 7%) had a serious adverse reaction of hepatocellular injury.
In ALTA, AST elevations occurred in 38% of patients in the 90 mg group and 65% of patients in the 90→180 mg group. ALT elevations occurred in 34% of patients in the 90 mg group and 40% of patients in the 90→180 mg group. 9% of patients in the 90 mg group and did not occur in any patients in the 90→180 mg group.
7% of patients in the 90→180 mg group. Monitor AST, ALT and total bilirubin during treatment with ALUNBRIG, especially during first 3 months. Withhold ALUNBRIG for Grade 3 or 4 hepatic enzyme elevation with bilirubin less than or equal to 2 × ULN.
Upon resolution or recovery to Grade 1 or less (less than or equal to 3 × ULN) or to baseline, resume ALUNBRIG at a next lower dose as described in Table 2. 1) ] . 8 Hyperglycemia In ALTA 1L, 56% of patients who received ALUNBRIG experienced new or worsening hyperglycemia.
5% of patients. In ALTA, 43% of patients who received ALUNBRIG experienced new or worsening hyperglycemia. 7% of patients. Two of 20 (10%) patients with diabetes or glucose intolerance at baseline required initiation of insulin while receiving ALUNBRIG.
Assess fasting serum glucose prior to initiation of ALUNBRIG and monitor periodically thereafter. Initiate or optimize antihyperglycemic medications as needed. 1) ] . 7% Grade 3 to 4. 9% of patients in the 90 mg→180 mg group. Grade 3 to 4 photosensitivity was not reported in patients in the 90 mg group or in the 90→180 mg group.
Advise patients to limit sun exposure while taking brigatinib, and for at least 5 days after discontinuation of treatment. Advise patients, when outdoors to wear a hat and protective clothing, and use a broad-spectrum Ultraviolet A (UVA)/ Ultraviolet B (UVB) sunscreen and lip balm (SPF ≥30) to help protect against sunburn.
1) ] . 10 Embryo-Fetal Toxicity Based on its mechanism of action and findings in animals, ALUNBRIG can cause fetal harm when administered to pregnant women. There are no clinical data on the use of ALUNBRIG in pregnant women. 26 times the human exposure at 180 mg once daily) or higher.
Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 4 months following the final dose. 1) ] .