IMPORTANT SAFETY INFORMATION, INDICATION, AND USAGE
Expand+WARNINGS AND PRECAUTIONS
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 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 the ALTA study, at the approved dose (90→180 mg), ILD/pneumonitis occurred in 9.1% of patients. Monitor for new or worsening respiratory symptoms (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 dose reduce or permanently discontinue ALUNBRIG. Permanently discontinue ALUNBRIG for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis.
Hypertension
In ALTA 1L, hypertension was reported in 32% of patients receiving ALUNBRIG; 13% of patients experienced Grade 3 hypertension. Control blood pressure prior to treatment with ALUNBRIG. Monitor blood pressure and withhold ALUNBRIG for Grade 3 hypertension despite optimal antihypertensive therapy. Consider permanent discontinuation of treatment with ALUNBRIG for Grade 4 hypertension or recurrence of Grade 3 hypertension. Use caution when administering ALUNBRIG in combination with antihypertensive agents that cause bradycardia.
Bradycardia
In ALTA 1L, heart rates less than 50 beats per minute (bpm) occurred in 8.1% of patients receiving ALUNBRIG; one patient (0.7%) experienced Grade 3 bradycardia. Monitor heart rate and blood pressure during treatment with ALUNBRIG. For symptomatic bradycardia, withhold ALUNBRIG and review concomitant medications for those known to cause bradycardia; dose reduce concomitant medication or ALUNBRIG as appropriate. Discontinue ALUNBRIG for life-threatening bradycardia if no contributing concomitant medication is identified.
Visual Disturbance
In ALTA 1L, Grade 1 or 2 adverse reactions leading to visual disturbance, including blurred vision, photophobia, photopsia, and reduced visual acuity, were reported in 7.4% of patients receiving ALUNBRIG. In the ALTA study, at the approved dose (90→180 mg), Grade 3 macular edema and cataract occurred in one patient each. 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, dose reduce as appropriate. Permanently discontinue treatment with ALUNBRIG for Grade 4 visual disturbances.
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. 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. Upon resolution or recovery to Grade 1 CPK elevation or baseline, resume ALUNBRIG at the same dose or at a reduced dose.
Pancreatic Enzyme Elevation
In ALTA 1L, amylase elevation occurred in 52% of patients and Grade 3 or 4 amylase elevation occurred in 6.8% of patients who received ALUNBRIG. Lipase elevations occurred in 59% of patients and Grade 3 or 4 lipase elevation occurred in 17% of patients. Monitor lipase and amylase during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 or 4 pancreatic enzyme elevation. Upon resolution or recovery to Grade 1 or baseline, resume ALUNBRIG at the same dose or at a reduced dose.
Hepatotoxicity
In ALTA 1L, aspartate aminotransferase (AST) elevations occurred in 72% of patients and Grade 3 or 4 AST elevations occurred in 4.5% of patients who received ALUNBRIG. Alanine aminotransferase (ALT) elevations occurred in 52% of patients and Grade 3 or 4 ALT elevations occurred in 5.2% of patients. One patient (0.7%) had a serious adverse reaction of hepatocellular injury. Monitor AST, ALT and total bilirubin during treatment with ALUNBRIG, especially during the 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. Permanently discontinue ALUNBRIG for Grade 2 to 4 hepatic enzyme elevation with concurrent total bilirubin elevation greater than 2 times the ULN in the absence of cholestasis or hemolysis.
Hyperglycemia
In ALTA 1L, 56% of patients who received ALUNBRIG experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 7.5% of patients. In the ALTA study, 2 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 anti-hyperglycemic medications as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, withhold ALUNBRIG until adequate hyperglycemic control is achieved and consider reducing the dose of ALUNBRIG.
Photosensitivity
In ALTA 1L, 3.7% of patients who received ALUNBRIG experienced photosensitivity, with 0.7% of patients experiencing Grade 3 to 4 reactions. Advise patients to limit sun exposure while taking ALUNBRIG, and for at least 5 days after discontinuation of treatment. Advise patients, when outdoors, to wear protective clothing and use a broad-spectrum sunscreen (SPF ≥30) to help protect against sunburn. Based on the severity, withhold ALUNBRIG, then resume at the same dose, or reduce the dose, or permanently discontinue.
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. Advise women of the potential risk to a fetus.
ADVERSE REACTIONS
The most common adverse reactions (≥25%) with ALUNBRIG were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, and dyspnea.
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.
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.
USE IN SPECIFIC POPULATIONS
Females and Males of Reproductive Potential
Verify pregnancy status in females of reproductive potential prior to initiating ALUNBRIG. Advise females of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 4 months after the final dose. 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. ALUNBRIG may cause reduced fertility in males.
Lactation: Advise patients not to breastfeed.
Hepatic Impairment: Reduce the dose of ALUNBRIG for patients with severe hepatic impairment.
Renal Impairment: Reduce the dose of ALUNBRIG for patients with severe renal impairment.
To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1-844-217-6468 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see full Prescribing Information.
INDICATION
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.