brigatinib

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Diabetes;
Severe renal impairment (↓ dose);
Severe hepatic impairment (↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, bradycardia

Derm: rash, photosensitivity

EENT: ↓visual acuity, blurred vision, diplopia, cataracts, macular edema, photophobia

Endo: hyperglycemia

F and E: hypophosphatemia

GI: ↑amylase, ↑lipase, ↑liver enzymes, abdominal pain, constipation, diarrhea, nausea, vomiting

Hemat: ↑activated partial thromboplastin time, anemia, lymphopenia

Metab: ↓appetite

MS: ↑CK, arthralgia, back pain, muscle spasms, myalgia

Neuro: fatigue, headache, insomnia, peripheral neuropathy

Resp: cough, dyspnea, hypoxia, INTERSTITIAL LUNG DISEASE (ILD)/PNEUMONITIS, pneumonia

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A inhibitors or moderate CYP3A inhibitors, including, clarithromycin, cobicistat, conivaptan, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir, posaconazole, ritonavir, and voriconazole may ↑ levels and risk of toxicity; avoid concurrent use; if concurrent use necessary, ↓ brigatinib dose.
Strong CYP3A inducers or moderate CYP3A inducers, including carbamazepine, phenytoin, and rifampin may ↓ levels and effectiveness; avoid concurrent use; if concurrent therapy needed with moderate CYP3A inducer, ↑ brigatinib dose.
Beta-blockers, verapamil, diltiazem, digoxin, and clonidine may ↑ risk of bradycardia; avoid concurrent use, if possible.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit or grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

Availability ⬆ ⬇

Film-coated tablets: 30 mg; 90 mg; 180 mg

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: If previously taking 180 mg once daily, ↓ to 90 mg once daily; if previously taking 90 mg once daily, ↓ to 60 mg once daily; Concurrent use of moderate CYP3A inhibitor: If previously taking 180 mg once daily, ↓ to 120 mg once daily; if previously taking 120 mg once daily, ↓ to 90 mg once daily; if previously taking 90 mg once daily, ↓ to 60 mg once daily; Concurrent use of moderate CYP3A inducer:↑ daily dose in 30-mg increments after 7 days of treatment with the dose used prior to initiation of moderate CYP3A inducer; may ↑ dose up to a max of twice the dose that was tolerated prior to initiating the moderate CYP3A inducer.

Renal Impairment

PO (Adults ): CCr 15–29 mL/min: If previously taking 180 mg once daily, ↓ to 90 mg once daily; if previously taking 90 mg once daily, ↓ to 60 mg once daily.

Hepatic Impairment

PO (Adults ): Severe hepatic impairment: If previously taking 180 mg once daily, ↓ to 120 mg once daily; if previously taking 120 mg once daily, ↓ to 90 mg once daily; if previously taking 90 mg once daily, ↓ to 60 mg once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits receptor tyrosine kinases including ALK, insulin-like growth factor-1 receptor, ROS1, and FMS-like tyrosine kinase-3.

Therapeutic effects:

Improved progression-free survival.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration. Bioavailability ↓ by high fat meals.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP2C8 and CYP3A4 isoenzymes; also induces CYP3A. 27% excreted in feces unchanged, 22% eliminated unchanged in urine.

Half-Life: 25 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–4 hr	unknown

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take brigatinib as directed. If patient vomits or misses a dose, omit dose and take next dose as scheduled. Do not double doses.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Advise patient to avoid eating grapefruit or drinking grapefruit juice during therapy.
Advise patient to notify health care professional if signs/symptoms of lung problems, hypertension (headaches, dizziness, blurred vision, chest pain, shortness of breath), bradycardia (dizziness, lightheadedness, feeling faint), visual changes, pancreatitis (upper abdominal pain, weight loss, nausea), myalgia (unexplained muscle pain, tenderness, or weakness), hepatotoxicity (fatigue, jaundice, upper right quadrant pain), or hyperglycemia (feeling very thirsty, needing to urinate more than usual, feeling very hungry, nausea, feeling weak or tired, feeling confused) occur, may require dose ↓ or discontinuation.
Advise patient to limit sun exposure while taking brigatinib, and for >5 days after stopping therapy. Wear a hat and protective clothing, and use a broad-spectrum Ultraviolet A/ Ultraviolet B sunscreen and lip balm (SPF ≥30) to help protect against sunburn. Sunburn may require interrupting or discontinuing therapy based on severity.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective non-hormonal contraception during and for >4 mo after final dose. Advise men with female partners of reproductive potential to use effective contraception during and for >3 mo after last dose of brigatinib. Advise patient to avoid breastfeeding during and for 1 wk after last dose. Inform men that brigatinib may impair fertility.

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Indications ⬇

Contraind./Precautions ⬆ ⬇