TUKYSA® Dosage and Administration

(tucatinib)

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Select 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.

2.2 Recommended Dosage

Metastatic Breast Cancer

The recommended dosage of TUKYSA is 300 mg taken orally twice daily in combination with trastuzumab and capecitabine until disease progression or unacceptable toxicity [see Clinical Studies (14.1)].

Unresectable or Metastatic Colorectal Cancer

The recommended dosage of TUKYSA is 300 mg taken orally twice daily in combination with trastuzumab until disease progression or unacceptable toxicity [see Clinical Studies (14.2)].

Advise patients to swallow TUKYSA tablets whole and not to chew, crush, or split prior to swallowing. Advise patients not to ingest tablet if it is broken, cracked, or not otherwise intact.

Advise patients to take TUKYSA approximately 12 hours apart and at the same time each day with or without a meal.

If the patient vomits or misses a dose of TUKYSA, instruct the patient to take the next dose at its usual scheduled time.

When given in combination with TUKYSA, the recommended dosage of capecitabine is 1000 mg/m2 orally twice daily taken within 30 minutes after a meal. TUKYSA and capecitabine can be taken at the same time. Refer to the Full Prescribing Information for trastuzumab and capecitabine for additional information.

2.3 Dosage Modifications for Adverse Reactions

The 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 Reduction

Recommended TUKYSA Dosage

First

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
*
Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
†
Abbreviations: ULN = upper limit of normal; ALT = alanine aminotransferase; AST = aspartate aminotransferase

Adverse Reaction*

Severity

TUKYSA Dosage Modification

Diarrhea [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.

Hepatotoxicity†[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 × ULN

Permanently 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.

2.4 Dosage Modifications for Severe Hepatic Impairment

For patients with severe hepatic impairment (Child-Pugh C), reduce the recommended dosage to 200 mg orally twice daily [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.5 Dosage Modifications for Concomitant Use with Strong CYP2C8 Inhibitors

Avoid concomitant use of strong CYP2C8 inhibitors with TUKYSA. If concomitant use with a strong CYP2C8 inhibitor cannot be avoided, reduce the recommended dosage to 100 mg orally twice daily. After discontinuation of the strong CYP2C8 inhibitor for 3 elimination half-lives, resume the TUKYSA dose that was taken prior to initiating the inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

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Health Professional Information

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection

Select 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.

2.2 Recommended Dosage

Metastatic Breast Cancer

The recommended dosage of TUKYSA is 300 mg taken orally twice daily in combination with trastuzumab and capecitabine until disease progression or unacceptable toxicity [see Clinical Studies (14.1)].

Unresectable or Metastatic Colorectal Cancer

The recommended dosage of TUKYSA is 300 mg taken orally twice daily in combination with trastuzumab until disease progression or unacceptable toxicity [see Clinical Studies (14.2)].

Advise patients to swallow TUKYSA tablets whole and not to chew, crush, or split prior to swallowing. Advise patients not to ingest tablet if it is broken, cracked, or not otherwise intact.

Advise patients to take TUKYSA approximately 12 hours apart and at the same time each day with or without a meal.

If the patient vomits or misses a dose of TUKYSA, instruct the patient to take the next dose at its usual scheduled time.

When given in combination with TUKYSA, the recommended dosage of capecitabine is 1000 mg/m2 orally twice daily taken within 30 minutes after a meal. TUKYSA and capecitabine can be taken at the same time. Refer to the Full Prescribing Information for trastuzumab and capecitabine for additional information.

2.3 Dosage Modifications for Adverse Reactions

The 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 Reduction

Recommended TUKYSA Dosage

First

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
*
Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
†
Abbreviations: ULN = upper limit of normal; ALT = alanine aminotransferase; AST = aspartate aminotransferase

Adverse Reaction*

Severity

TUKYSA Dosage Modification

Diarrhea [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.

Hepatotoxicity†[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 × ULN

Permanently 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.

2.4 Dosage Modifications for Severe Hepatic Impairment

For patients with severe hepatic impairment (Child-Pugh C), reduce the recommended dosage to 200 mg orally twice daily [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.5 Dosage Modifications for Concomitant Use with Strong CYP2C8 Inhibitors

Avoid concomitant use of strong CYP2C8 inhibitors with TUKYSA. If concomitant use with a strong CYP2C8 inhibitor cannot be avoided, reduce the recommended dosage to 100 mg orally twice daily. After discontinuation of the strong CYP2C8 inhibitor for 3 elimination half-lives, resume the TUKYSA dose that was taken prior to initiating the inhibitor [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].
Medication Guide

Health Professional Information

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