Alunbrig® 30, 90 mg

/ Takeda

The recommended dosing regimen for Brigatinib is:
– 90 mg orally once daily for the first 7 days;
– If 90 mg is tolerated during the first 7 days, increase the dose to 180 mg orally once daily.
Administration of  Brigatinib will continue until disease progression or unacceptable toxicity.
If Brigatinib 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.
Brigatinib may be taken with or without food. Instruct patients to swallow tablets whole. Do not crush or chew tablets, as the tablets are film-coated.
If a dose of Brigatinib is missed or vomiting occurs after taking a dose, do not administer an additional dose and take the next dose of Brigatinib at the scheduled time.
For dose modifications for adverse reactions and strong CYP3A inhibitors: See prescribing information.

Treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

Hypersensitivity to the active substance or to any of the excipients.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with Brigatinib.
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 early (within 9 days of initiation of Brigatinib ; 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 Brigatinib. Withhold Brigatinib 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 Brigatinib with dose reduction according to prescribing information after recovery to baseline or permanently discontinue Brigatinib. Permanently discontinue Brigatinib for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis.
Hypertension: In ALTA, hypertension was reported in 11% of patients in the 90 mg group who received Brigatinib  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 Brigatinib. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with Brigatinib. Withhold Brigatinib for Grade 3 hypertension despite optimal antihypertensive therapy. Upon resolution or improvement to Grade 1 severity, resume Brigatinib at a reduced dose. Consider permanent discontinuation of treatment with Brigatinib for Grade 4 hypertension or recurrence of Grade 3 hypertension.
Use caution when administering Brigatinib in combination with antihypertensive agents that cause bradycardia.
Bradycardia: Bradycardia can occur with Brigatinib. 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 Brigatinib. Monitor patients more frequently if concomitant use of drug known to cause bradycardia cannot be avoided.
For symptomatic bradycardia, withhold Brigatinib 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 Brigatinib at the same dose following resolution of symptomatic bradycardia; otherwise, reduce the dose of Brigatinib following resolution of symptomatic bradycardia. Discontinue Brigatinib for life-threatening bradycardia if no contributing concomitant medication is identified.
Visual Disturbance: In ALTA, adverse reactions leading to visual disturbance including blurred vision, diplopia, and reduced visual acuity, were reported in 7.3% of patients receiving BRIGATINIB  in the 90 mg group and 10% of patients in the 90→180 mg group. Grade 3 macular edema and cataract occurred in one patient each in the 90→180 mg group.
Advise patients to report any visual symptoms. Withhold Brigatinib 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 Brigatinib at a reduced dose. Permanently discontinue treatment with Brigatinib for Grade 4 visual disturbances.
Creatine Phosphokinase (CPK) Elevation: In ALTA, creatine phosphokinase (CPK) elevation occurred in 27% of patients receiving  Brigatinib  in the 90 mg group and 48% of patients in the 90 mg→180 mg group. The incidence of Grade 3-4 CPK elevation was 2.8% in the 90 mg group and 12% in the 90→180 mg group.
Dose reduction for CPK elevation occurred in 1.8% of patients in the 90 mg group and 4.5% in the 90→180 mg group.
Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor CPK levels during Brigatinib treatment. Withhold Brigatinib for Grade 3 or 4 CPK elevation. Upon resolution or recovery to Grade 1 or baseline, resume Brigatinib at the same dose or at a reduced dose as described in prescribing information.
Pancreatic Enzyme Elevation: 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. Grade 3 or 4 amylase elevation occurred in 3.7% of patients in the 90 mg group and 2.7% of patients in the 90→180 mg group. Grade 3 or 4 lipase elevation occurred in 4.6% of patients in the 90 mg group and 5.5% of patients in the 90→180 mg group.
Monitor lipase and amylase during treatment with Brigatinib. Withhold Brigatinib for Grade 3 or 4 pancreatic enzyme elevation. Upon resolution or recovery to Grade 1 or baseline, resume Brigatinib at the same dose or at a reduced dose as described in prescribing information.
Hyperglycemia: In ALTA, 43% of patients who received Brigatinib  experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 3.7% of patients. Two of 20 (10%) patients with diabetes or glucose intolerance at baseline required initiation of insulin while receiving Brigatinib.
Assess fasting serum glucose prior to initiation of Brigatinib and monitor periodically thereafter. Initiate or optimize anti­ hyperglycemic medications as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, withhold Brigatinib until adequate hyperglycemic control is achieved and consider reducing the dose of Brigatinib as described in prescribing information or permanently discontinuing Brigatinib.
See prescribing information for full details.

Interstitial lung disease (ILD)/pneumonitis, hypertension, bradycardia visual disturbance, creatine phosphokinase (CPK) elevation, pancreatic enzyme elevation, hyperglycemia.
See prescribing information for full details

Drugs that may increase brigatinib plasma concentrations
Strong CYP3A Inhibitors: Co-administration of itraconazole, a strong CYP3A inhibitor, increased brigatinib plasma concentrations and may result in increased adverse reactions. Avoid the concomitant use of strong CYP3A inhibitors with brigatinib, including but not limited to certain antivirals (e.g., boceprevir, cobicistat, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir), macrolide antibiotics (e.g., clarithromycin), antifungals (e.g., itraconazole, ketoconazole, posaconazole, voriconazole), and conivaptan. Avoid grapefruit or grapefruit juice as it may also increase plasma concentrations of brigatinib. If concomitant use of a strong CYP3A inhibitor cannot be avoided, reduce the dose of brigatinib by approximately 50%.
Drugs that may decrease brigatinib plasma concentrations
Strong CYP3A Inducers: Co-administration of brigatinib with rifampin, a strong CYP3A inducer, decreased brigatinib plasma concentrations and may result in decreased efficacy.
Avoid the concomitant use of strong CYP3A inducers with brigatinib, including but not limited to rifampin, carbamazepine, phenytoin, and St. John’s Wort. Drugs that may have their plasma concentrations altered by brigatinib
CYP3A Substrates: Brigatinib induces CYP3A in vitro and may decrease concentrations of CYP3A substrates. Co-administration of brigatinib with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and loss of efficacy of CYP3A substrates.
See prescribing information for full details.

Pregnancy: There are no clinical data on the use of Brigatinib in pregnant women.
Lactation: 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 Brigatinib and for 1 week following the final dose.
See prescribing information for full details.

See prescribing information for full details.

Lactose: contains lactose.
Sodium: contains sodium.