Alunbrig Special Precautions

Pulmonary Adverse Reactions: Severe, life-threatening, and fatal pulmonary adverse reactions, including those with features consistent with ILD/pneumonitis, can occur in patients treated with brigatinib (see Adverse Reactions).
Most pulmonary adverse reactions were observed within the first 7 days of treatment. Grade 1-2 pulmonary adverse reactions resolved with interruption of treatment or dose modification. Increased age and shorter interval (less than 7 days) between the last dose of crizotinib and the first dose of brigatinib were independently associated with an increased rate of these pulmonary adverse reactions. These factors should be considered when initiating treatment with brigatinib.
Some patients experienced pneumonitis later in treatment with brigatinib.
Patients should be monitored for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), particularly in the first week of treatment. Evidence of pneumonitis in any patient with worsening respiratory symptoms should be promptly investigated. If pneumonitis is suspected, brigatinib should be withheld, and the patient evaluated for other causes of symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia) and dosing modified accordingly (see Dosage & Administration).
Hypertension: Hypertension has occurred in patients treated with brigatinib (see Adverse Reactions).
Blood pressure should be monitored regularly during treatment with brigatinib. Hypertension should be treated according to standard guidelines to control blood pressure. Heart rate should be monitored more frequently in patients if concomitant use of a medicinal product known to cause bradycardia cannot be avoided. For severe hypertension (≥Grade 3), brigatinib should be withheld until hypertension has recovered to Grade 1 or to baseline. The dose should be modified accordingly (see Dosage & Administration).
Bradycardia: Bradycardia has occurred in patients treated with brigatinib (see Adverse Reactions). Caution should be exercised when administering brigatinib in combination with other agents known to cause bradycardia. Heart rate and blood pressure should be monitored regularly.
If symptomatic bradycardia occurs, treatment with brigatinib should be withheld and concomitant medications known to cause bradycardia should be evaluated. Upon recovery, the dose should be modified accordingly (see Dosage & Administration). In case of life-threatening bradycardia, if no contributing concomitant medication is identified or in case of recurrence, treatment with brigatinib should be discontinued (see Dosage & Administration).
Visual Disturbance: Visual disturbance adverse reactions have occurred in patients treated with brigatinib (see Adverse Reactions). Patients should be advised to report any visual symptoms. For new or worsening severe visual symptoms, an ophthalmologic evaluation and dose reduction should be considered (see Dosage & Administration).
Creatine Phosphokinase Elevation: Elevations of CPK have occurred in patients treated with brigatinib (see Adverse Reactions). Patients should be advised to report any unexplained muscle pain, tenderness, or weakness. CPK levels should be monitored regularly during brigatinib treatment. Based on the severity of the CPK elevation, and if associated with muscle pain or weakness, treatment with brigatinib should be withheld, and the dose modified accordingly (see Dosage & Administration).
Pancreatic Enzyme Elevation: Elevations of amylase and lipase have occurred in patients treated with brigatinib (see Adverse Reactions). Lipase and amylase should be monitored regularly during treatment with brigatinib. Based on the severity of the laboratory abnormalities, treatment with brigatinib should be withheld, and the dose modified accordingly (see Dosage & Administration).
Hepatic Enzyme Elevation: Elevations of hepatic enzymes (aspartate aminotransferase, alanine aminotransferase) have occurred in patients treated with brigatinib (see Adverse Reactions). Liver function, including AST, ALT and total bilirubin should be monitored regularly during treatment with brigatinib, specially during the first 3 months. Based on the severity of the laboratory abnormalities, treatment should be withheld, and the dose modified accordingly (see Dosage & Administration).
Hyperglycemia: Elevations of serum glucose have occurred in patients treated with brigatinib (see Adverse Reactions). Fasting serum glucose should be assessed prior to initiation of brigatinib and monitored periodically thereafter. Antihyperglycemic medications should be initiated or optimized as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, brigatinib should be withheld until adequate hyperglycemic control is achieved; upon recovery reducing the dose of brigatinib may be considered or brigatinib may be permanently discontinued (see Dosage & Administration).
Photosensitivity: Photosensitivity to sunlight has occurred in patients treated with brigatinib (see Adverse Reactions). Patients should be advised to avoid prolonged sun exposure while taking brigatinib, and for at least 5 days after discontinuation of treatment. When outdoors, patients should be advised to wear a hat and protective clothing, and to use a broad-spectrum Ultraviolet A (UVA)/Ultraviolet B (UVB) sunscreen and lip balm (SPF ≥30) to help protect against potential sunburn. For severe photosensitivity reactions (≥Grade 3), brigatinib should be withheld until recovery to baseline. The dose should be modified accordingly (see Dosage & Administration).
Effects on Ability to Drive and Use Machines: There are no data on the effect of brigatinib on the ability to drive and use machines. Visual disturbance, dizziness, and fatigue have been observed in clinical trials. Patients should be advised not to drive or operate machines if they experience any of these symptoms while taking brigatinib.
Use in Pregnancy & Lactation: See Use in Pregnancy & Lactation section for further information.