Brigacent 90mg

Drugs that may Increase Brigacent Plasma Concentrations: Strong CYP3A Inhibitors: Coadministration of Itraconazole, a strong CYP3A inhibitor, increased Brigacent plasma concentrations and may result in increased adverse reactions. Concomitant use of strong CYP3A inhibitors with Brigacent, 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 should be avoided. Grapefruit or grapefruit juice should be avoided as it may also increase plasma concentrations of Brigacent. If concomitant use of a strong CYP3A inhibitor cannot be avoided, the dose of Brigacent should be reduced by approximately 50%.

Drugs that may Decrease Brigacent Plasma Concentrations: Strong CYP3A Inducers: Coadministration of Brigacent with Rifampin, a strong CYP3A inducer, decreased Brigacent plasma concentrations and may result in decreased efficacy. Concomitant use of strong CYP3A inducers with Brigacent should be avoided, including but not limited to Rifampin, Carbamazepine, Phenytoin, and St. John’s Wort.

Drugs that may have their Plasma Concentrations altered by Brigacent: CYP3A Substrates: Brigacent induces CYP3A in vitro and may decrease concentrations of CYP3A substrates. Coadministration of ALUNBRIG with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and loss of efficacy of CYP3A substrates.

It is contraindicated in patients with known hypersensitivity to Brigatinib or any other components of this product.

• Interstitial Lung Disease (ILD)/Pneumonitis
• Hypertension
• Bradycardia
• Visual Disturbance
• Creatine Phosphokinase (CPK) Elevation
• Pancreatic Enzyme Elevation
• Hyperglycemia

Pregnancy: There are no clinical data on the use of Brigatinib in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus.

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, lactating women should be advised not to breastfeed during treatment with Brigatinib and for 1 week following the final dose.

Females Reproductive Potential: Females of reproductive potential should be advised to use effective non-hormonal contraception during treatment with Brigatinib and for at least 4 months after the final dose. Patients should be counseled to use a non-hormonal method of contraception since Brigatinib can render some hormonal contraceptives ineffective.

Males Reproductive Potential: Because of the potential for genotoxicity, males with female partners of reproductive potential should be advised to use effective contraception during treatment with Brigatinib and for at least 3 months after the final dose.

Infertility: Based on findings in male reproductive organs in animals, Brigatinib may cause reduced fertility in males.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with Brigacent. It should be withheld 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). Brigacent should be discontinued permanently for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis.

Hypertension: Hypertension was reported in 11% of patients in the 90 mg group who received Brigacent and 21% of patients in the 90-180 mg group. Grade 3 hypertension occurred in 5.9% of patients overall. Blood pressure should be controlled prior to treatment with Brigacent. Blood pressure should be monitored after 2 weeks and at least monthly thereafter during treatment with Brigacent. It should be withheld for Grade 3 hypertension despite optimal antihypertensive therapy. Permanent discontinuation of treatment should be considered with Brigacent for Grade 4 hypertension or recurrence of Grade 3 hypertension. Caution should be used when administering Brigacent in combination with antihypertensive agents that cause bradycardia.

Bradycardia: Bradycardia can occur with Brigacent. Heart rate and blood pressure should be monitored during treatment with Brigacent. Patients should be monitored more frequently if concomitant use of drug known to cause bradycardia cannot be avoided.

Visual Disturbance: Adverse reactions leading to visual disturbance including blurred vision, diplopia, and reduced visual acuity, were reported in 7.3% of patients receiving Brigacent in the 90 mg group and 10% of patients in the 90-180 mg group. Patients should be advised to report any visual symptoms. Brigacent should be withheld and obtained 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, Brigacent should be resumed at a reduced dose. Treatment with Brigacent should be permanently discontinued for Grade 4 visual disturbances.

Creatine Phosphokinase (CPK) Elevation: Creatine phosphokinase (CPK) elevation occurred in 27% of patients receiving Brigacent in the 90 mg group and 48% of patients in the 90 mg-180 mg group. Patients should be advised to report any unexplained muscle pain, tenderness, or weakness. CPK levels should be monitored during Brigacent treatment. Brigacent should be withheld for Grade 3 or 4 CPK elevation.

Pancreatic Enzyme Elevation: 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. Lipase and amylase should be monitored during treatment with Brigacent. Brigacent should be withheld for Grade 3 or 4 pancreatic enzyme elevation.

Hyperglycemia: 43% of patients who received Brigacent 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 Brigacent or glucose intolerance at baseline required initiation of insulin while receiving Brigacent. Fasting serum glucose should be assessed prior to initiation of Brigacent and monitored periodically thereafter. Antihyperglycemic medications should be initiated or optimized as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, Brigacent should be withheld until adequate hyperglycemic control is achieved and considered reducing the dose of Brigacent.