Tukysa
(Tucatinib)Dosage & Administration
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Tukysa Prescribing Information
Indications and Usage ( TUKYSA is indicated in combination with trastuzumab for the treatment of adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. | 1/2023 |
Patient Selection ( 2.1 Patient Selection Select patients for treatment of unresectable or metastatic colorectal cancer with TUKYSA based on the presence of:
| 1/2023 |
Warnings and Precautions ( TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death [see Adverse Reactions (6.1)] .If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA [see Dosage and Administration (2.2)] .TUKYSA with trastuzumab and capecitabine In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 0.5% with Grade 4 diarrhea and 12% with Grade 3 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB. TUKYSA with trastuzumab In MOUNTAINEER, diarrhea occurred in 64% of patients, including Grade 3 (3.5%), Grade 2 (10%), and Grade 1 (50%). TUKYSA can cause severe hepatotoxicity [see Adverse Reactions (6.1)] .Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA [see Dosage and Administration (2.2)] .TUKYSA with trastuzumab and capecitabine In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase > 5 × ULN, 6% had an AST increase > 5 × ULN, and 1.5% had a bilirubin increase > 3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients. TUKYSA with trastuzumab In MOUNTAINEER, 6% of patients had a bilirubin increase > 3 × ULN (Grade ≥3), 6% had an AST increase > 5 × ULN, and 4.7% had an ALT increase > 5 × ULN. Hepatotoxicity led to dose reduction of TUKYSA in 3.5% of patients and discontinuation of TUKYSA in 2.3% of patients. | 1/2023 |
• In patients with unresectable or metastatic colorectal cancer, confirm the presence of HER2 protein overexpression and RAS wild-type in tumor specimens prior to the initiation of TUKYSA ()2.1 Patient SelectionSelect patients for treatment of unresectable or metastatic colorectal cancer with TUKYSA based on the presence of:• HER2 overexpression or gene amplification[see Clinical Studies (14.2)].FDA-approved tests for the detection of HER2 overexpression and gene amplification in patients with unresectable or metastatic colorectal cancer are not currently available,and• RAS wild-type[see Clinical Studies (14.2)].Information on FDA-approved tests for the detection of RAS mutations in patients with unresectable or metastatic colorectal cancer is available at http://www.fda.gov/CompanionDiagnostics.
• Recommended dosage: 300 mg taken orally twice daily with or without food. ()2.1 Patient SelectionSelect patients for treatment of unresectable or metastatic colorectal cancer with TUKYSA based on the presence of:• HER2 overexpression or gene amplification[see Clinical Studies (14.2)].FDA-approved tests for the detection of HER2 overexpression and gene amplification in patients with unresectable or metastatic colorectal cancer are not currently available,and• RAS wild-type[see Clinical Studies (14.2)].Information on FDA-approved tests for the detection of RAS mutations in patients with unresectable or metastatic colorectal cancer is available at http://www.fda.gov/CompanionDiagnostics.
• For patients with severe hepatic impairment, the recommended dosage is 200 mg orally twice daily. (,2.3 Dosage Modifications for Adverse ReactionsThe recommended TUKYSA dose reductions and dosage modifications for adverse reactions are provided in Tables 1 and 2. Refer to the Full Prescribing Information for trastuzumab and capecitabine for information about dosage modifications for these drugs.
Table 1: Recommended TUKYSA Dose Reductions for Adverse Reactions Dose ReductionRecommended TUKYSA DosageFirst
250 mg orally twice daily
Second
200 mg orally twice daily
Third
150 mg orally twice daily
Permanently discontinue TUKYSA in patients unable to tolerate 150 mg orally twice daily.
Table 2: Recommended TUKYSA Dosage Modifications for Adverse Reactions Adverse ReactionGrades based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03SeverityTUKYSA Dosage ModificationDiarrhea
[see Warnings and Precautions (5.1)]Grade 3 without anti-diarrheal treatment
Initiate or intensify appropriate medical therapy. Hold TUKYSA until recovery to ≤ Grade 1, then resume TUKYSA at the same dose level.
Grade 3 with anti-diarrheal treatment
Initiate or intensify appropriate medical therapy. Hold TUKYSA until recovery to ≤ Grade 1, then resume TUKYSA at the next lower dose level.
Grade 4
Permanently discontinue TUKYSA.
HepatotoxicityAbbreviations: ULN = upper limit of normal; ALT = alanine aminotransferase; AST = aspartate aminotransferase
[see Warnings and Precautions (5.2)]Grade 2 bilirubin (>1.5 to 3 × ULN)
Hold TUKYSA until recovery to ≤ Grade 1, then resume TUKYSA at the same dose level.
Grade 3 ALT or AST (> 5 to 20 × ULN)
OR
Grade 3 bilirubin (> 3 to 10 × ULN)Hold TUKYSA until recovery to ≤ Grade 1, then resume TUKYSA at the next lower dose level.
Grade 4 ALT or AST (> 20 × ULN)
OR
Grade 4 bilirubin (> 10 × ULN)Permanently discontinue TUKYSA.
ALT or AST > 3 × ULN
AND
Bilirubin > 2 × ULNPermanently discontinue TUKYSA.
Other adverse reactions
[see Adverse Reactions (6.1)]Grade 3
Hold TUKYSA until recovery to ≤ Grade 1, then resume TUKYSA at the next lower dose level.
Grade 4
Permanently discontinue TUKYSA.
)8.7 Hepatic ImpairmentTucatinib exposure is increased in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment
[see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].No dose adjustment for TUKYSA is required for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.
Tablets:
• 50 mg: round, yellow, film-coated, debossed with “TUC” on one side and “50” on the other side.• 150 mg: oval-shaped, yellow, film-coated, debossed with “TUC” on one side and “150” on the other side.
None.