ALUNBRIG
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALUNBRIG (ALUNBRIG).
Alunbrig (brigatinib) is a tyrosine kinase inhibitor that targets ALK and ROS1. It inhibits autophosphorylation of ALK and ALK-mediated activation of downstream signaling proteins STAT3, AKT, ERK1/2, and PLCγ in ALK-dependent tumor cells.
| Metabolism | Primarily metabolized by CYP2C8 and CYP3A4. After oral administration, the major metabolic pathways include N-demethylation, oxidation, and N-glucuronidation. |
| Excretion | Primarily hepatic metabolism (CYP3A4); 65% fecal (unchanged and metabolites), 25% renal (1% unchanged). Biliary excretion contributes to fecal elimination. |
| Half-life | Terminal half-life approximately 25 hours. Supports once-daily dosing; steady state achieved in ~5 days. |
| Protein binding | >99% bound, primarily to albumin. High binding limits free drug fraction. |
| Volume of Distribution | 153 L (oral), indicating extensive extravascular distribution. Not normalized to body weight; suggests large tissue binding. |
| Bioavailability | Oral bioavailability not determined; absorption moderate with Tmax 4 hours. Coadministration with high-fat meal increases AUC and Cmax (31-51% higher). |
| Onset of Action | Oral: Clinical effects (e.g., tumor response) observed within weeks; median time to objective response 1.8 months in ALTA-1L trial. |
| Duration of Action | Duration depends on continued dosing; continuous inhibition of ALK. Median progression-free survival 24 months in first-line ALTA-1L study. |
90 mg orally once daily for first 7 days, then increase to 180 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥ 30 mL/min. For GFR < 30 mL/min not on dialysis, reduce dose to 90 mg once daily. |
| Liver impairment | Child-Pugh A: no dose adjustment. Child-Pugh B: reduce dose to 60 mg once daily for first 7 days, then increase to 90 mg once daily if tolerated. Child-Pugh C: reduce dose to 60 mg once daily. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment recommended, but monitor for adverse effects more frequently due to potential age-related physiological changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALUNBRIG (ALUNBRIG).
| Breastfeeding | There are no data on the presence of brigatinib in human milk, its effects on the breastfed infant, or its effects on milk production. Because of the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment with ALUNBRIG and for at least 1 week after the last dose. The milk-to-plasma (M/P) ratio is not known. |
| Teratogenic Risk | Based on animal studies and its mechanism of action (ALK inhibitor), ALUNBRIG (brigatinib) can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, oral administration of brigatinib to pregnant rats during organogenesis resulted in adverse developmental outcomes including embryo-fetal lethality, decreased fetal body weights, and malformations (external, visceral, and skeletal) at maternal exposures approximately 0.3 times the human exposure at the recommended dose. Therefore, it is advised to avoid pregnancy during treatment and for at least 4 months after the last dose. The risk of teratogenicity is present throughout all trimesters, with the highest risk during the first trimester when organogenesis occurs. |
■ FDA Black Box Warning
There are no FDA-issued black box warnings for Alunbrig.
| Serious Effects |
None
| Precautions | ["Interstitial lung disease/pneumonitis","Hypertension","Bradycardia","Visual disturbances","Creatine phosphokinase elevation","Pancreatic enzyme elevation","Hyperglycemia","Photosensitivity","Embryo-fetal toxicity"] |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided as they may increase brigatinib concentrations. No other specific dietary restrictions; can be taken with or without food. |
| Clinical Pearls |
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| Fetal Monitoring | Monitor pregnancy status in women of reproductive potential prior to starting treatment and periodically during therapy. Perform pregnancy testing before initiating ALUNBRIG and during treatment as clinically indicated. Monitor for fetal development via ultrasound if pregnancy is suspected or confirmed. Additionally, monitor maternal thyroid function, hepatic function, and pancreatic enzymes as per standard ALUNBRIG monitoring, as pregnancy may alter these parameters. Fetal echocardiography may be considered due to potential cardiac effects seen in animal studies. |
| Fertility Effects | Based on animal studies, ALUNBRIG may impair fertility in females and males. In female rats, ovarian changes including decreased corpora lutea and reduced fertility were observed. In male rats, testicular degeneration and reduced sperm motility were noted. The reversibility of these effects is unknown. Human data on fertility effects are lacking. Advise patients of the potential for impaired fertility. |
| ALUNBRIG (brigatinib) is a potent ALK inhibitor indicated for ALK-positive metastatic NSCLC. Monitor for pulmonary toxicity (ILD/pneumonitis), especially within the first week of therapy; if suspected, hold drug and evaluate. Also monitor for hypertension, bradycardia, hyperglycemia, and pancreatitis. Dose reduction required with strong CYP3A4 inhibitors; avoid strong CYP3A4 inducers. Administer once daily with or without food at the same time each day; do not crush or split tablets. |
| Patient Advice | Take exactly as prescribed at the same time each day with or without food. Swallow tablets whole; do not crush or split. · Report any new or worsening cough, fever, or shortness of breath immediately, especially in the first week of treatment. · Monitor blood pressure regularly; report high readings or symptoms like headache or dizziness. · Report any rapid or irregular heartbeats, fainting, or dizziness. · Report severe abdominal pain, nausea, vomiting, or signs of pancreatitis. · Avoid grapefruit or grapefruit juice during treatment. · Inform your doctor of all medications, including over-the-counter drugs and supplements, as many can interact with ALUNBRIG. |