Indications & Uses
Bigatab 30 is indicated for:
Pharmacology
Brigatinib is a tyrosine kinase inhibitor. In laboratory tests, at concentrations that can be reached in patients, it was active against several kinases, including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R) and FLT-3, as well as EGFR deletion and point mutations. In in-vitro and in vivo assays, it blocked autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2 and S6. It also blocked the in vitro proliferation of cell lines expressing EML4-ALK and NPM ALK fusion proteins, and in mice it slowed the growth of EML4-ALK-positive NSCLC xenografts in a dose-dependent way. The exposure-response relationships and the time course of the pharmacodynamic response are unknown.
Absorption: After single oral doses of 30 to 240 mg, the median time to peak concentration (Tmax) ranged from 1 to 4 hours.
Distribution: Brigatinib is 66% bound to human plasma proteins, and in vitro this binding does not depend on concentration. The blood to plasma concentration ratio is 0.69. With 180 mg taken once daily, the mean apparent volume of distribution (Vz/F) at steady-state was 153 L.
Elimination: With 180 mg taken once daily, the mean apparent oral clearance (CL/F) at steady-state is 12.7 L/h, and the mean plasma elimination half-life is 25 hours.
Metabolism: In vitro, Brigatinib is mainly metabolized by CYP2C8 and CYP3A4. Healthy subjects were given a single 180 mg oral dose of radiolabeled Brigatinib. In them, N-demethylation and cysteine conjugation were the two major metabolic pathways. The main circulating radioactive components were unchanged Brigatinib (92%) and its primary metabolite, AP26123 (3.5%). In patients, the steady-state AUC of AP26123 was less than 10% of the AUC of Brigatinib exposure. In vitro, AP26123 inhibited ALK with approximately 3-fold lower potency than Brigatinib.
Excretion: After healthy subjects took a single 180 mg oral dose of radiolabeled Brigatinib, 65% of the dose was recovered in feces and 25% in urine. Unchanged Brigatinib made up 41% of the total radioactivity in feces and 86% in urine.
Dosage Reference
Reference Information Only
Dosages shown are general references from official sources. Always consult your doctor or pharmacist for personalized dosing.
Adults:
The recommended dose of Brigatinib is 90 mg by mouth once daily for the first 7 days. If the patient tolerates 90 mg during those 7 days, the dose is raised to 180 mg once daily. Brigatinib should be given until the disease progresses or the toxicity becomes unacceptable.
If treatment is interrupted for 14 days or longer for reasons other than adverse reactions, it should be restarted at 90 mg once daily for 7 days. After that, the dose can be increased to the one the patient tolerated before.
Brigatinib may be taken with or without food. Patients should be told to swallow the tablets whole, and the tablets should not be crushed or chewed. If a dose is missed, or if vomiting occurs after a dose, no additional dose should be given. The next dose of Brigatinib should be taken at the scheduled time.
Pediatric Use: The safety and efficacy of Brigatinib in pediatric patients have not been established.
Side Effects
Brigatinib can cause interstitial lung disease (ILD) or pneumonitis, hypertension, bradycardia, visual disturbance, creatine phosphokinase (CPK) elevation, pancreatic enzyme elevation and hyperglycemia.
Cautions & Contraindications
Warnings & Precautions
Interstitial Lung Disease (ILD)/Pneumonitis Severe, life-threatening and fatal lung reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with Brigatinib. The medicine should be withheld in any patient with new or worsening breathing symptoms, and the patient should be checked promptly for ILD/pneumonitis or other causes of those symptoms (for example pulmonary embolism, tumor progression and infectious pneumonia). It should be stopped permanently for Grade 3 or 4 ILD/pneumonitis, or if Grade 1 or 2 ILD/pneumonitis comes back. Hypertension Hypertension was reported in 11% of patients in the 90 mg group and in 21% of patients in the 90 to 180 mg group. Grade 3 hypertension occurred in 5.9% of patients overall. Blood pressure should be controlled before treatment starts, then checked after 2 weeks and at least monthly after that for as long as the patient takes Brigatinib. The medicine should be withheld for Grade 3 hypertension that continues despite the best antihypertensive treatment. Permanent discontinuation should be considered for Grade 4 hypertension or if Grade 3 hypertension recurs. Take care when giving it together with antihypertensive agents that cause bradycardia. Bradycardia Bradycardia can occur with Brigatinib. Heart rate and blood pressure should be monitored during treatment. If a drug known to cause bradycardia cannot be avoided, the patient should be monitored more often. Visual Disturbance Visual reactions, including blurred vision, diplopia and reduced visual acuity, were reported in 7.3% of patients in the 90 mg group and 10% of patients in the 90 to 180 mg group. Patients should be told to report any visual symptoms. For new or worsening visual symptoms of Grade 2 or greater severity, the medicine should be withheld and an ophthalmologic evaluation obtained. Once Grade 2 or Grade 3 visual disturbances recover to Grade 1 severity or to baseline, Brigatinib should be restarted at a reduced dose. For Grade 4 visual disturbances, treatment should be stopped permanently. Creatine Phosphokinase (CPK) Elevation Creatine phosphokinase (CPK) elevation occurred in 27% of patients in the 90 mg group and 48% of patients in the 90 mg to 180 mg group. Patients should be told to report any unexplained muscle pain, tenderness or weakness. CPK levels should be monitored during treatment, and the medicine 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 elevation 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, and Brigatinib should be withheld for Grade 3 or 4 pancreatic enzyme elevation. Hyperglycemia New or worsening hyperglycemia was seen in 43% of patients who received Brigatinib. 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 needed to start insulin while on treatment. Fasting serum glucose should be checked before starting Brigatinib and then monitored from time to time. Antihyperglycemic medicines should be started or adjusted as needed. If good glucose control cannot be reached with the best medical management, the medicine should be withheld until control is achieved, and a lower dose should be considered.
Contraindications
Brigatinib must not be given to anyone who is known to be allergic to it, or to any other ingredient in the product.
Pregnancy & Breastfeeding
Pregnancy: There are no clinical data on the use of Brigatinib in pregnant women. If the medicine is used during pregnancy, or if the patient becomes pregnant while taking it, she should be told about the potential risk to the fetus.
Lactation: No data are available on whether Brigatinib passes into human milk, or on its effects on a breastfed infant or on milk production. Because breastfed infants could have adverse reactions, women who are breastfeeding should be advised not to breastfeed during treatment with Brigatinib and for 1 week after the final dose.
Females of reproductive potential: These women should be advised to use effective non-hormonal contraception during treatment and for at least 4 months after the final dose. They should be counselled to choose a non-hormonal method, since Brigatinib can make some hormonal contraceptives ineffective.
Males of reproductive potential: Brigatinib has the potential for genotoxicity, so males with female partners of reproductive potential should be advised to use effective contraception during treatment and for at least 3 months after the final dose.
Infertility: Animal findings in the male reproductive organs suggest that Brigatinib may reduce fertility in males.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Storage
Store Brigatinib below 30°C, and keep it away from light and moisture. Keep it out of the reach of children.
Drug Interactions
Common questions about Bigatab 30 30 mg
What is Bigatab 30 30 mg Tablet?
Bigatab 30 30 mg Tablet is a medicine that contains Brigatinib. It is made by Eskayef Pharmaceuticals Ltd., Narayanganj. It belongs to the Cytotoxic Chemotherapy group of medicines.
What is Bigatab 30 used for?
Bigatab 30 is used for: Cancer.
What are the side effects of Bigatab 30?
Brigatinib can cause interstitial lung disease (ILD) or pneumonitis, hypertension, bradycardia, visual disturbance, creatine phosphokinase (CPK) elevation, pancreatic enzyme elevation and hyperglycemia.
Can I take Bigatab 30 during pregnancy or while breastfeeding?
Pregnancy: There are no clinical data on the use of Brigatinib in pregnant women. If the medicine is used during pregnancy, or if the patient becomes pregnant while taking it, she should be told about the potential risk to the fetus. Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
How should I store Bigatab 30?
Store Brigatinib below 30°C, and keep it away from light and moisture. Keep it out of the reach of children.
Can I take other medicines with Bigatab 30?
Some medicines can interact with Brigatinib, for example: Carbamazepine, Clarithromycin, Nelfinavir, Saquinavir, Ritonavir, Posaconazole. Tell your doctor or pharmacist about every medicine you take.
Do I need a prescription for Bigatab 30?
Bigatab 30 is a prescription (Rx) medicine. Take it as your doctor advises.