tucatinib (Rx)

Brand and Other Names:Tukysa
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 50mg
  • 150mg

Advanced or Metastatic Breast Cancer

Indicated in combination with trastuzumab and capecitabine for treatment of advanced unresectable or metastatic human epidermal growth factor (HER2)-positive breast cancer (including brain metastases) in patients who have received ≥1 anti-HER2-based regimens in the metastatic setting

300 mg PO BID in combination with trastuzumab and capecitabine

Continue until disease progression or unacceptable toxicity

Refer to the full prescribing information for trastuzumab and capecitabine for additional information

Dosage Modifications

Refer to the full prescribing information for trastuzumab and capecitabine for dosage modifications

Dose reductions for adverse reactions

  • First dose reduction: 250 mg PO BID
  • Second dose reduction: 200 mg PO BID
  • Third dose reduction: 150 PO BID
  • Patient unable to tolerate 150 mg PO BID: Permanently discontinue

Diarrhea

  • Grade 3 with antidiarrheal treatment: Initiate or intensify appropriate medical therapy; hold until recovery to Grade ≤1, then resume at the same dose level

  • Grade 3 without antidiarrheal therapy: Initiate or intensify appropriate medical therapy; hold until recovery to Grade ≤1, then resume at the same dose level or at next lower dose level

  • Grade 4: Permanently discontinue

Hepatotoxicity

  • Grade 2 bilirubin (>1.5 to 3x ULN): Hold until recovery to Grade ≤1, then resume at the same dose level
  • Grade 3 ALT or AST (>5 to 20x ULN) OR Grade 3 bilirubin (>3 to 10x ULN): Hold until recovery to Grade ≤1, then resume at the next lower dose level
  • Grade 4 ALT/AST (>20x ULN) OR Grade 4 bilirubin (>10x ULN): Permanently discontinue
  • ALT/AST >3x ULN AND bilirubin >2x ULN: Permanently discontinue

Other adverse reactions

  • Grade 3: Hold until recovery to Grade ≤1, then resume at the next lower dose level
  • Grade 4: Permanently discontinue

Coadministration with strong CYP2C8 inhibitors

  • Avoid coadministration; if unavoidable, reduce tucatinib to 100 mg PO BID
  • After discontinuing strong CYP2C8 inhibitor for 3 elimination half-lives, resume tucatinib dose taken before initiating the inhibitor

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl <30 mL/min): Use in combination with trastuzumab and capecitabine is not recommended; capecitabine is contraindicated in patients with severe renal impairment

Hepatic impairment

  • Mild-to-moderate (Child-Pugh A or B): No dosage adjustment necessary
  • Severe (Child-Pugh C): Reduce to 200 mg BID

Dosing Considerations

Verify pregnancy status of females of reproductive potential before initiating

Safety and efficacy not established

Next:

Adverse Effects

>10% (in combination with capecitabine and trastuzumab)

All grades

  • Diarrhea (81%)
  • Palmoplantar erythrodysesthesia syndrome (63%)
  • Decreased hemoglobin (59%)
  • Nausea (58%)
  • Decreased phosphate (57%)
  • Increased bilirubin (47%)
  • Increased ALT (46%)
  • Increased AST (43%)
  • Hepatotoxicity (42%)
  • Decreased magnesium (40%)
  • Vomiting (36%)
  • Decreased potassium (36%)
  • Increased creatinine (33%)
  • Stomatitis (32%)
  • Decreased sodium (28%)
  • Increased alkaline phosphatase (26%)
  • Decreased appetite (25%)
  • Anemia (21%)
  • Rash (20%)
  • Arthralgia (15%)
  • Increased creatinine (14%)
  • Decreased weight (13%)
  • Peripheral neuropathy (13%)
  • Epistaxis (12%)

Grade 3 to 4

  • Palmoplantar erythrodysesthesia syndrome (13%)
  • Diarrhea (0.5-12%)

1-10% (in combination with capecitabine and trastuzumab)

Grade 3 to 4

  • Hepatoxicity (0.2-9%)
  • Increased ALT (8%)
  • Decreased phosphate (8%)
  • Increased AST (6%)
  • Decreased potassium (6%)
  • Anemia (3.7%)
  • Nausea (3.7%)
  • Decreased hemoglobin (3.3%)
  • Vomiting (3%)
  • Stomatitis (2.5%)
  • Decreased sodium (2.5%)
  • Increased bilirubin (1.5%)
  • Decreased weight (1%)

<1% (in combination with capecitabine and trastuzumab)

Grade 3 to 4

  • Decreased magnesium (0.8%)
  • Rash (0.7%)
  • Arthralgia (0.5%)
  • Peripheral neuropathy (0.5%)
  • Increased alkaline phosphatase (0.5%)
  • Decreased appetite (0.5%)
Previous
Next:

Warnings

Contraindications

None

Cautions

Severe hepatotoxicity has been report; monitor ALT, AST, and bilirubin prior to initiation, q3Weeks during treatment, and as clinically indicated

May cause fetal harm

Diarrhea

  • Severe diarrhea, including dehydration, acute kidney injury, and death, has been reported
  • Administer antidiarrheal treatment as clinically indicated
  • Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea

Drug interaction overview

Tucatinib is a substrate of CYP3A4, CYP2C8, P-glycoprotein (P-gp), and BCRP

Also, reversible inhibitor of CYP3A4 and CYP2C8; time-dependent inhibitor of CYP3A4; P-gp inhibitor

  • Strong CYP3A or moderate CYP2C8 inducers
    • Avoid coadministration
    • Concomitant use of tucatinib with a strong CYP3A or moderate CYP2C8 inducer decreased tucatinib plasma concentrations, which may reduce the efficacy of tucatinib
  • CYP2C8 inhibitors
    • Avoid coadministration with strong CYP2C8 inhibitors; reduce tucatinib dose if concomitant use cannot be avoided
    • Concomitant use of tucatinib with a strong CYP2C8 inhibitor may increase tucatinib plasma concentrations, which may increase the risk of tucatinib toxicity
    • Coadministration with moderate CYP2C8 inhibitors: Increase monitoring for tucatinib toxicity
  • CYP3A substrates
    • Avoid coadministration with sensitive CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities
  • P-gp substrates
    • Consider reducing dose of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities
Previous
Next:

Pregnancy & Lactation

Refer to the full prescribing information of trastuzumab and capecitabine for pregnancy and lactation information

Pregnancy

Based on animal data and its mechanism of action, fetal harm may occur when administer to pregnant females

No data available on use in pregnant females to inform a drug-associated risk

Verify pregnancy status of females of reproductive potential before treatment

Contraception

  • Females of reproductive potential or males with female partners of reproductive potential: Use effective contraception during treatment and at least 1 week after final dose

Infertility

  • May impair male and female fertility

Animal data

  • Administration to pregnant rats and rabbits during organogenesis resulted in embryofetal mortality, reduced fetal weight, and fetal abnormalities at maternal exposure ≥1.3x the AUC at the recommended dose
  • Advise pregnant women and females of reproductive potential of potential risk to fetus

Lactation

No data available on the presence of tucatinib or its metabolites in human or animal milk or its effects on the breastfed child or on milk production

Advise females not to breastfeed during treatment and for at least 1 week after final dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Previous
Next:

Pharmacology

Mechanism of Action

Tyrosine kinase inhibitor for HER2

Inhibits HER2 and HER3 phosphorylation in vitro, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed antitumor activity in HER2 expressing tumor cells

In vivo, tucatinib inhibited growth of HER2 expressing tumors

Absorption

Peak plasma time: ~2 hr

Steady-state reached at ~4 days

Distribution

Vd: 1670 L

Protein bound: 97.1%

Metabolism

Metabolized primarily by CYP2C8 and to a lesser extent via CYP3A

Elimination

Half-life: ~8.5 hr

Clearance: 148 L/hr

Excretion

  • Feces: ~86% (16% unchanged)
  • Urine: 4.1%
  • Plasma: ~76% unchanged (19% metabolites)
Previous
Next:

Administration

Oral Administration

Take with or without meals

Note: Capecitabine is given PO BID and taken within 30 min after a meal

When given in combination, tucatinib and capecitabine can be taken at the same time

Swallow tablets whole; do not chew, crush, or split before swallowing

Do not ingest tablet if broken, cracked, or not otherwise intact

Take ~12 hr apart and at the same time each day

Missed or vomited dose: Take next dose at usual scheduled time

Storage

Store at room temperature, 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

Dispense and store in original container only to protect from moisture

Replace cap securely each time after opening

Do not discard desiccant

Once opened, use within 3 months; discard any unused tablets 3 months after opening

Previous
Next:

Images

Previous
Next:

Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
Additional Offers
Email to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Email Forms to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Previous
Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.