brigatinib, Alunbrig Classification

 Indications

Metastatic non-small cell lung cancer (NSCLC) that is

positive for anaplastic lymphoma kinase (ALK) in patients

who have progressed on or intolerant to crizotinib.

Action

Inhibits receptor tyrosine kinases including anaplastic

lymphoma kinase (ALK), insulin-like growth factor—1

receptor (IGF-1R), ROS1, and FMS-like tyrosine kinase-

3 (FLT-3). Therapeutic Effects: Decreased

spread of lung cancer.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Bioavailability reduced by high fat meals.

Distribution: Extensively distributed to tissues.

Metabolism and Excretion: Mostly metabolized

by the liver (CYP2C8 and CYP3A4 isoenzymes); also induces

CYP3A. 27% excreted in feces unchanged, 22%

eliminated unchanged in urine.

Half-life: 25 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unknown 1–4 hr unknown

Contraindications/Precautions

Contraindicated in: Concurrent use of strong inhibitors/

inducers of the CYP3A enzyme system; OB: May

cause fetal harm; Lactation: Avoid breast feeding.

Use Cautiously in: Diabetes; Moderate or severe

hepatic impairment; Severe renal impairment; Rep:

Women of reproductive potential and men with female

sexual partners of reproductive potential; Pedi: Safety

and effectiveness not established.

Adverse Reactions/Side Effects

CNS: headache, insomnia. CV: BRADYCARDIA, HYPERTENSION.

Derm: rash. EENT: blurred vision,pvisual acuity, diplopia, cataracts, macular edema. Endo: hyperglycemia.

F and E: hypophosphatemia. GI: abdominal

pain, constipation,pappetite, diarrhea,qamylase,

qlipase,qliver enzymes, nausea, vomiting.

Hemat: anemia,qactivated partial thromboplastin

time, lymphopenia. MS: arthralgia, back pain,qcreatine

phosphokinase, muscle spasms, myalgia. Neuro:

peripheral neuropathy. Resp: INTERSTITIAL LUNG DISEASE/

PNEUMONITIS, cough, dyspnea, hypoxia, pneumonia.

Misc: fatigue, fever.

Interactions

Drug-Drug: Strong CYP3A inhibitors, including,

clarithromycin, cobicistat, conivaptan, indinavir,

itraconazole, ketoconazole, lopinavir, nefazodone,

nelfinavir, posaconazole, ritonavir, saquinavir,

and voriconazole mayqlevels; concurrent use

should be avoided. Strong CYP3A inducers, including

carbamazepine, phenytoin, and rifampin may

plevels and effectiveness; concurrent use should be

avoided. Mayplevels of CYP3A substrates, including

hormonal contraceptives. Beta-blockers, verapamil,

diltiazem, digoxin, and clonidine mayqrisk of

bradycardia; avoid concurrent use, if possible.

Drug-Natural Products: Concurrent use of St.

John’s wort mayplevels and effectiveness and should

be avoided.

Drug-Food: Grapefruit or grapefruit juice mayq

levels and should be avoided.

Route/Dosage

PO (Adults): 90 mg once daily for 7 days, then 180 mg

once daily. Continue until disease progression or unacceptable

toxicity. Concurrent use of strong CYP3A inhibitor—

pdose by 50%.

Availability

Film-coated tablets: 30 mg, 90 mg.