Drug information of brigatinib
Brigatinib, is a reversible dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR). It presents selectivity against the mutant forms of EGFR compared to the wild-type. It also exhibits selectivity against 9 different Crizotinib-resistant mutants of the EML4-ALK fusion gene, which is a pivotal player in the transformation of susceptible lung parenchyma.
Mechanism of effect
Brigitanib acts as a tyrosine kinase inhibitor with activity against multiple kinases including ALK, ROS1, insulin-like growth factor 1 receptor and against EGFR deletions and point mutations. It acts by inhibiting ALK phosphorylation and the activation of downstream signaling proteins.
Brigitanib presents a dose-dependent inhibition of tumor growth, tumor burden and prolonged survival in mice EML4-ALK xenograft models.
Peak plasma time: 1-4 hr
Peak plasma concentration: 552 ng/mL (90 mg); 1452 ng/mL (180 mg)
AUC: 8165 ng·h/mL (90 mg); 20,276 ng·h/mL (180 mg)
Protein bound: 66%
Vd: 153 L (steady-state)
Primarily metabolized by CYP2C8 and CYP3A4
Active metabolite: AP26123 is ~3-fold less potent than brigatinib
Half-life: 25 hr
Oral clearance: 12.7 L/hr
Excretion: 65% feces; 25% urine (unchanged brigatinib represented 41% and 86% of the total radioactivity in feces and urine, respectively)
Non-Small Cell Lung Cancer
Indicated for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) in patients who have progressed on or are intolerant to crizotinib
90 mg PO qDay for the first 7 days; if 90 mg/day is tolerated, increase the dose to 180 mg PO qDay
Safety and efficacy not established
Side effectsanemia , Insomnia , High Blood Pressure , Diarrhea , Headache , nausea , vomiting , fever , myalgia , Increased ALT , Increased AST , peripheral nephropathy , pneumonia , tiredness , shortness of breath , Abdominal pain , Rash
InteractionsDisopyramide , Midazolam , fentanyl , nelfinavir , Ethosuximide , Everolimus , Oxecarbazepin , Itraconazole , Isoniazid , Ifosfamide , Eslicarbazepine acetate , stiripentol , Doravirine , Apalutamide , conivaptan , norethindrone , neratinib , nafcillin , Lumacaftor , Triazolam , Nicardipine , cobicistat , Delavirdine , Butabarbital , Quinine , Indinavir , Butalbital and Acetaminophen , Fosphenytoin , Idelalisib , Ivacaftor , mitotane , Fosamprenavir , Lopinavir , Sufentanil , Alfentanil , Palifermin , Amobarbital , Ethinyl Estradiol , Nefazodone , ritonavir , saquinavir , nevirapine , Rifabutin , Atazanavir , Darunavir , Quinidine , Grapefruit , Pentobarbital , Ketoconazole , Clarithromycin , Colchicine , Clonidine , Enzalutamide , ergotamine , Phenobarbital , Phenytoin , Levonorgestrol , Medroxyprogesterone , Voriconazole , Carbamazepine , Tinidazole , Dexamethasone , Dihydroergotamine , Rifampin , Sirolimus , Cyclosporine , Imatinib , Bosentan , Primidone , Posaconazole , Pimozide , Tacrolimus , Fosinopril , Felodipine , Ramipril , Efavirenz , Tipranavir , lumacaftor and Ivacaftor , Etravirine , Dabrafenib , Mibefradil , trametinib , pexidartinib , Entrectinib , Lopinavir and Ritonavir , Triphasic , oleandomycin , Gefitinib , Meningococcal conjugate vaccine , voxelotor , Fidaxomicin
Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with brigatinib; monitor for new or worsening respiratory symptoms (eg, dyspnea, cough), particularly during the first week of initiating
Dose-related hypertension reported; control BP prior to treatment; monitor BP after 2 weeks and at least monthly thereafter
Bradycardia (HR <50 bpm) reported; monitor HR and BP; monitor more frequently if concomitant use of drugs known to cause bradycardia cannot be avoided
May cause visual disturbances; advise patients to report any visual symptoms
Increased CPK reported; advise patients to report any unexplained muscle pain, tenderness, or weakness; monitor CPK during treatment
Serum pancreatic enzyme elevation reported; monitor lipase and amylase during treatment
May cause new or worsening hyperglycemia; assess fasting serum glucose before initiating drug and periodically thereafter; initiate or optimize antihyperglycemic medications as needed
May cause fetal harm
Drug interaction overview
- Brigatinib is a substrate and inducer of CYP3A
- Strong or moderate CYP3A inhibitors increase brigatinib plasma concentrations and may increase adverse effects; avoid coadministration
- Strong or moderate CYP3A inducers may decrease brigatinib plasma concentrations and result in decreased efficacy; avoid coadministration
- CYP3A substrates
- Brigatinib induces CYP3A in vitro and may decrease concentrations of CYP3A substrates
- Coadministration with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and loss of efficacy
Points of recommendation
Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.
Brigatinib is usually taken once per day, with or without food.
Do not crush, chew, or break a brigatinib tablet. Swallow it whole.
If you vomit shortly after taking brigatinib, do not take another dose. Stay on your regular schedule.
You should not stop using brigatinib unless your doctor tells you to.
Store at room temperature away from moisture and heat.
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
Pregnancy levelNot assigned
this drug may cause fetal harm based on findings in animals and the mechanism of action.
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