Genetic Implications:
Pronunciation:
too-ka-ti-nib
Trade Name(s)
Ther. Class.
Pharm. Class.
kinase inhibitors
Advanced unresectable or metastatic HER2-positive breast cancer in patients who previously received ≥1 anti-HER2-based regimens in the metastatic setting (in combination with trastuzumab and capecitabine).
Acts as tyrosine kinase inhibitor of HER2, thereby inhibiting the growth of HER2-expressing tumors.
Therapeutic Effect(s):
Improved survival and progression-free survival in metastatic breast cancer.
Absorption: High-fat foods increase extent of and delay absorption.
Distribution: Extensively distributed to extravascular tissues.
Metabolism and Excretion: Primarily metabolized by liver via CYP2C8 isoenzyme, and to a lesser extent by CYP3A4. Primarily excreted in feces (86%; 16% as unchanged drug), with 4% being excreted in urine.
Half-life: 8.5 hr.
TIME/ACTION PROFILE (plasma concentrations)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | unknown | 1–4 hr | 12 hr |
Contraindicated in:
Use Cautiously in:
CNS: headache
Derm: palmar-plantar erythrodysesthesia, rash
EENT: epistaxis
F and E: hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia
GI: DIARRHEA, HEPATOTOXICITY, abdominal pain, hyperbilirubinemia, nausea, stomatitis, vomiting
GU: ↑ serum creatinine, ↓ fertility
Hemat: anemia
Metabolic: ↓ appetite, ↓ weight
MS: arthralgia
Neuro: peripheral neuropathy
Misc: fatigue
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
PO (Adults): 300 mg twice daily; continue until disease progression or unacceptable toxicity. Concurrent use of strong CYP2C8 inhibitors– 100 mg twice daily; continue until disease progression or unacceptable toxicity.
Hepatic Impairment
PO (Adults): Severe hepatic impairment– 200 mg twice daily; continue until disease progression or unacceptable toxicity.
Tablets: 50 mg, 150 mg
Monitor for diarrhea. Usually occurs be 12 days and takes 8 days to resolve. Administer antidiarrheals and perform diagnostic tests to exclude other causes. If Grade 3 diarrhea occurs without antidiarrheal treatment: Begin or intensify medical therapy. Hold tucatinib until recovery to ≤ Grade 1, then resume at the same dose level. If Grade 3 diarrhea occurs with antidiarrheal treatment: Begin or intensify medical therapy. Hold tucatinib until recovery to ≤ Grade 1, then resume at next lower dose level. If Grade 4 diarrhea occurs: permanently discontinue tucatinib.
Lab Test Considerations:
Verify negative pregnancy test before starting therapy.
Monitor ALT, AST, and bilirubin before to starting tucatinib, every 3 wk during therapy, and as clinically indicated. If Grade 2 bilirubin (>1.5 to 3 × ULN) occurs: hold tucatinib until recovery to ≤ Grade 1, then resume at the same dose level. If Grade 3 ALT or AST (> 5–20 × ULN) OR Grade 3 bilirubin (> 3–10 × ULN) occurs: hold tucatinib until recovery to ≤ Grade 1, then resume at the next lower dose level. If Grade 4 ALT or AST (> 20 × ULN) OR Grade 4 bilirubin (> 10 × ULN) occurs: permanently discontinue tucatinib. If ALT or AST > 3 × ULN AND bilirubin > 2 × ULN: permanently discontinue tucatinib.
Inform patient of potential for severe diarrhea and to notify health care professional if a change in bowel movements or severe diarrhea occurs. May lead to loss of too much body fluids (dehydration), low blood pressure, kidney problems and death.
Advise patient to notify health care professional if signs and symptoms of liver problems (itching, yellowing of skin or eyes, dark or brown urine, pain in upper right side of abdomen, feel very tired, decreased appetite, bleeding or bruising more easily than normal) occur.
Improved survival and progression-free survival in metastatic breast cancer.