Tukysa (Tucatinib)

What is Tukysa and also, how to use it?

Experts use Tukysa, a prescription medicine with the medicines trastuzumab and capecitabine to treat adults with:

  • human epidermal growth factor receptor-2 (HER2) positive breast cancer that has spread to other parts of the body such as the brain (metastatic), or that cannot be removed by surgery, and
  • who have also received one or more anti-HER2 breast cancer treatments.

However, the question lies on Tukysa being safe and effective in children.

What are important side effects of Tukysa?

Tukysa may cause serious side effects, including:

  • Diarrhea. Diarrhea is common with Tukysa and can sometimes also be severe. In fact, tell your healthcare provider if you have a change in your bowel movements or severe diarrhea. Severe diarrhea can lead to loss of too much body fluids (dehydration), low blood pressure, kidney problems and also death. Your healthcare provider may prescribe medicines to treat your diarrhea during treatment with Tukysa.
  • Liver Problems. Tukysa can cause severe liver problems. Your healthcare provider will do blood tests to check your liver function before and every 3 weeks during treatment with Tukysa, or as needed. In fact, tell your healthcare provider right away if you have any signs and symptoms of liver problems including:
    • itching
    • yellowing of your skin or eyes
    • dark or brown urine (tea-colored)
    • pain in the upper right side of your stomach-area (abdomen)
    • feel very tired
    • decreased appetite
    • bleeding or bruising more easily than normal

The most common side effects of Tukysa:

  • diarrhea
  • rash, redness, pain, swelling or blisters on the palms of your hands or soles of your feet
  • mouth sores (stomatitis)
  • decreased appetite
  • stomach-area (abdomen) pain
  • nausea
  • tiredness
  • increased liver function blood tests
  • vomiting
  • headache
  • low red blood cell counts (anemia)
  • rash

Description

Tucatinib is a kinase inhibitor. The chemical name is (N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3methylphenyl)-N6-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine. The molecular formula is C26H24N8O2 and the molecular weight is 480.52 g/mol. The chemical structure is as follows:

TUKYSA (tucatinib) is supplied as 50 mg and 150 mg film-coated tablets for oral use and contain the following inactive ingredients:

Tablet core: copovidone, crospovidone, sodium chloride, potassium chloride, sodium bicarbonate, colloidal silicon dioxide, magnesium stearate, and also microcrystalline cellulose.

Coating: yellow film coat: polyvinyl alcohol, titanium dioxide, macrogol/polyethylene glycol, talc, and also yellow iron oxide non-irradiated.

Each TUKYSA 50 mg tablet contains 10.10 mg (0.258 mEq) potassium and also 9.21 mg (0.401 mEq) sodium.

Each TUKYSA 150 mg tablet contains 30.29 mg (0.775 mEq) potassium and also 27.64 mg (1.202 mEq) sodium.

Indications

In fact, TUKYSA is indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Dosage and Administration

However, 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].

Advise patients to swallow TUKYSA tablets whole and not to chew, crush, or split prior to swallowing. Experts advise patients not to ingest tablet if it broke, or had a crack, 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.

However, 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 experts recommend the dosage of capecitabine is 1000 mg/m² orally twice; and also to take it daily within 30 minutes after a meal. However, one can take TUKYSA and capecitabine at the same time. Refer to the Full Prescribing Information for trastuzumab and also capecitabine for additional information.

Dosage Modifications For Severe Hepatic Impairment

In fact, for patients with severe hepatic impairment (Child-Pugh C), reduce the recommended dosage to 200 mg orally twice daily; [see Use In Specific Populations, CLINICAL PHARMACOLOGY].

Dosage Modifications For Concomitant Use With Strong CYP2C8 Inhibitors

Avoid concomitant use of strong CYP2C8 inhibitors with TUKYSA. In fact, if concomitant’s use with a strong CYP2C8 inhibitor cannot be avoided, reduce the recommended dosage to 100 mg orally twice daily. However, 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, CLINICAL PHARMACOLOGY].

How Supplied

Dosage Forms And Strengths

Tablets
  • 50 mg: round, yellow, film-coated, debossed with “TUC” on one side and also “50” on the other side.
  • 150 mg: oval-shaped, yellow, film-coated, debossed with “TUC” on one side and also “150” on the other side.

Storage And Handling

TUKYSA 50 mg tablets are supplied as yellow, film-coated, round tablets containing 50 mg of tucatinib. In fact, each tablet is debossed with “TUC” on one side and “50” on the other side, and is packaged as follows:

50 mg tablets: 60 count in 75 cc bottle: NDC 51144-001-60

TUKYSA 150 mg tablets are supplied as yellow, film-coated, oval-shaped tablets containing 150 mg of tucatinib. In fact, each tablet is debossed with “TUC” on one side and “150” on the other side, and is packaged as follows:

150 mg tablets: 60 count in 75 cc bottle: NDC 51144-002-60

150 mg tablets: 120 count in 150 cc bottle: NDC 51144-002-12

However, store at controlled room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Dispense to patient in original container only. However, store in original container to protect from moisture. Replace cap securely each time after opening and also do not discard desiccant.

Once opened, use within 3 months. However, discard any unused tablets 3 months after opening the bottle.

Dosage Modifications For Adverse Reactions

The recommended dose reductions and also the dosage modifications for adverse reactions are provided in Tables 1 and 2. Refer to the Full Prescribing Information for trastuzumab and also capecitabine for information about dosage modifications for these drugs.

Permanently discontinue TUKYSA in patients unable to tolerate 150 mg orally twice daily.

Table 2: Recommended TUKYSA Dosage Modifications for Adverse Reactions

Hepatotoxicity2 [see WARNINGS AND PRECAUTIONS]Grade 2 bilirubin (>1.5 to 3 x ULN)Hold TUKYSA until recovery to ≤ Grade 1, then resume TUKYSA at the same dose level.
Grade 3 ALT or AST (> 5 to 20 x ULN) OR Grade 3 bilirubin (> 3 to 10 x ULN)Hold TUKYSA until recovery to ≤ Grade 1, then resume TUKYSA at the next lower dose level.
Grade 4 ALT or AST (> 20 x ULN) OR Grade 4 bilirubin (> 10 x ULN)Permanently discontinue TUKYSA.
ALT or AST > 3 x ULN AND Bilirubin > 2 x ULNPermanently discontinue TUKYSA.
Other adverse reactions [see ADVERSE REACTIONS]Grade 3Hold TUKYSA until recovery to ≤ Grade 1, then resume TUKYSA at the next lower dose level.
Grade 4Permanently discontinue TUKYSA.
1Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.032Abbreviations: ULN = upper limit of normal; ALT = alanine aminotransferase; AST = aspartate aminotransferase

Dosage Modifications For Severe Hepatic Impairment

However, for patients with severe hepatic impairment (Child-Pugh C); reduce the recommended dosage to 200 mg orally twice daily [see Use In Specific Populations, CLINICAL PHARMACOLOGY].

Dosage Modifications For Concomitant Use With Strong CYP2C8 Inhibitors

Avoid concomitant use of strong CYP2C8 inhibitors with TUKYSA. In fact, if you cannot avoid concomitant’s use with a strong CYP2C8 inhibitor, reduce the recommended dosage to 100 mg orally twice daily. However, 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, CLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

Tablets
  • 50 mg: round, yellow, film-coated, debossed with “TUC” on one side and also “50” on the other side.
  • 150 mg: oval-shaped, yellow, film-coated, debossed with “TUC” on one side and also “150” on the other side.

Storage And Handling

TUKYSA 50 mg tablets are supplied as yellow, film-coated, round tablets containing 50 mg of tucatinib. In fact, each tablet is debossed with “TUC” on one side and “50” on the other side, and is packaged as follows:

50 mg tablets: 60 count in 75 cc bottle: NDC 51144-001-60

TUKYSA 150 mg tablets are supplied as yellow, film-coated, oval-shaped tablets containing 150 mg of tucatinib. In fact, each tablet is debossed with “TUC” on one side and “150” on the other side, and is packaged as follows:

150 mg tablets: 60 count in 75 cc bottle: NDC 51144-002-60

150 mg tablets: 120 count in 150 cc bottle: NDC 51144-002-12

Also, store at controlled room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Dispense to patient in original container only. Store in original container 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 the bottle.

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Diarrhea [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

HER2-Positive Metastatic Breast Cancer

HER2CLIMB

The safety of TUKYSA in combination with trastuzumab and capecitabine was evaluated in HER2CLIMB [see Clinical Studies]. Patients received either TUKYSA 300 mg twice daily plus trastuzumab and capecitabine (n=404) or placebo plus trastuzumab and capecitabine (n=197). The median duration of treatment was 5.8 months (range: 3 days, 2.9 years) for the TUKYSA arm.

Serious adverse reactions occurred in 26% of patients who received it. Serious adverse reactions in ≥ 2% of patients who received this had were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

Adverse reactions leading to treatment discontinuation occurred in 6% of patients who received TUKYSA. Unfavorable reactions leading to treatment discontinuation of TUKYSA in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%).

Adverse reactions leading to dose reduction occurred in 21% of patients who received TUKYSA. Adverse reactions leading to dose reduction of TUKYSA in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%).

The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash