Medical Editor: John P. Cunha, DO, FACOEP
What Is Tukysa?
Tukysa (tucatinib) is a kinase inhibitor used in combination with trastuzumab and capecitabine to treat 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.
What Are Side Effects of Tukysa?
Side effects of Tukysa include:
- diarrhea,
- hand-foot syndrome (palmar-plantar erythrodysesthesia),
- nausea,
- fatigue,
- liver toxicity,
- inflammation of mouth and lips,
- vomiting,
- decreased appetite,
- abdominal pain,
- headache,
- anemia, and
- rash
Dosage for Tukysa
The recommended dosage of Tukysa is 300 mg taken orally twice daily with or without food.
Tukysa In Children
The safety and effectiveness of Tukysa in pediatric patients have not been established.
What Drugs, Substances, or Supplements Interact with Tukysa?
Tukysa may interact with other medicines such as:
- strong CYP3A inducers or moderate CYP2C8 inducers,
- strong or moderate CYP2C8 inhibitors,
- CYP3A substrates, and
- P-gp substrates
Tell your doctor all medications and supplements you use.
Tukysa During Pregnancy and Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant before using Tukysa; it may harm a fetus. Females of reproductive potential and males with female partners of reproductive potential are advised to use effective contraception during treatment with Tukysa and for at least 1 week after the last dose. There are no data on the presence of Tukysa or its metabolites in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, breastfeeding is not recommended during treatment with Tukysa and for at least 1 week after the last dose. Tukysa is used in combination with trastuzumab and capecitabine. Refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy and breastfeeding information.
Additional Information
Our Tukysa (tucatinib) Tablets, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
SLIDESHOW
Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See SlideshowGet emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have:
- severe or ongoing diarrhea;
- pain, blisters, bleeding, or severe rash in the palms of your hands or the soles of your feet;
- blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;
- a seizure;
- liver problems--loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
- low red blood cells (anemia)--pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet.
Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.
Common side effects may include:
- diarrhea;
- nausea, vomiting, stomach pain, loss of appetite;
- anemia;
- mouth sores;
- rash;
- headache, tiredness; or
- abnormal liver function tests.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Tukysa (Tucatinib Tablets)
QUESTION
A lump in the breast is almost always cancer. See AnswerSIDE 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 TUKYSA. Serious adverse reactions in ≥ 2% of patients who received TUKYSA 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. Adverse 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.
Table 3 summarizes the adverse reactions in HER2CLIMB.
Table 3: Adverse Reactions (≥10%) in Patients Who Received TUKYSA and with a Difference Between Arms of ≥ 5% Compared to Placebo in HER2CLIMB (All Grades)
| Adverse Reaction | TUKYSA + Trastuzumab + Capecitabine N = 404 | Placebo + Trastuzumab + Capecitabine N = 197 | ||||
| All Grades % | Grade 3 % | Grade 4 % | All Grades % | Grade 3 % | Grade 4 % | |
| Gastrointestinal disorders | ||||||
| Diarrhea | 81 | 12 | 0.5 | 53 | 9 | 0 |
| Nausea | 58 | 3.7 | 0 | 44 | 3 | 0 |
| Vomiting | 36 | 3 | 0 | 25 | 3.6 | 0 |
| Stomatitis1 | 32 | 2.5 | 0 | 21 | 0.5 | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Palmar-plantar erythrodysesthesia syndrome | 63 | 13 | 0 | 53 | 9 | 0 |
| Rash2 | 20 | 0.7 | 0 | 15 | 0.5 | 0 |
| Hepatobiliary disorders | ||||||
| Hepatotoxicity3 | 42 | 9 | 0.2 | 24 | 3.6 | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 25 | 0.5 | 0 | 20 | 0 | 0 |
| Blood and lymphatic system disorders | ||||||
| Anemia4 | 21 | 3.7 | 0 | 13 | 2.5 | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 15 | 0.5 | 0 | 4.6 | 0.5 | 0 |
| Investigations | ||||||
| Creatinine increased5 | 14 | 0 | 0 | 1.5 | 0 | 0 |
| Weight decreased | 13 | 1 | 0 | 6 | 0.5 | 0 |
| Nervous System Disorders | ||||||
| Peripheral neuropathy6 | 13 | 0.5 | 0 | 7 | 1 | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Epistaxis | 12 | 0 | 0 | 5 | 0 | 0 |
| 1Stomatitis includes stomatitis, oropharyngeal pain, oropharyngeal discomfort, mouth ulceration, oral pain, lip ulceration, glossodynia, tongue blistering, lip blister, oral dysesthesia, tongue ulceration, and aphthous ulcer 2Rash includes rash maculo-papular, rash, dermatitis acneiform, erythema, rash macular, rash papular, rash pustular, rash pruritic, rash erythematous, skin exfoliation, urticaria, dermatitis allergic, palmar erythema, plantar erythema, skin toxicity, and dermatitis 3Hepatotoxicity includes hyperbilirubinemia, blood bilirubin increased, bilirubin conjugated increased, alanine aminotransferase increased, transaminases increased, hepatotoxicity, aspartate aminotransferase increased, liver function test increased, liver injury, and hepatocellular injury 4Anemia includes anemia, hemoglobin decreased, and normocytic anemia Page 6 of 18 5Due to inhibition of renal tubular transport of creatinine without affecting glomerular function 6Peripheral neuropathy includes peripheral sensory neuropathy, neuropathy peripheral, peripheral motor neuropathy, and peripheral sensorimotor neuropathy | ||||||
Table 4: Laboratory Abnormalities (≥20%) Worsening from Baseline in Patients Who Received TUKYSA and with a Difference of ≥5% Compared to Placebo in HER2CLIMB
| TUKYSA + Trastuzumab +Capecitabine1 | Placebo + Trastuzumab +Capecitabine1 | |||
| All Grades % | Grades ≥3 % | All Grades % | Grades ≥3 % | |
| Hematology | ||||
| Decreased hemoglobin | 59 | 3.3 | 51 | 1.5 |
| Chemistry | ||||
| Decreased phosphate | 57 | 8 | 45 | 7 |
| Increased bilirubin | 47 | 1.5 | 30 | 3.1 |
| Increased ALT | 46 | 8 | 27 | 0.5 |
| Increased AST | 43 | 6 | 25 | 1 |
| Decreased magnesium | 40 | 0.8 | 25 | 0.5 |
| Decreased potassium 2 | 36 | 6 | 31 | 5 |
| Increased creatinine 3 | 33 | 0 | 6 | 0 |
| Decreased sodium 4 | 28 | 2.5 | 23 | 2 |
| Increased alkaline phosphatase | 26 | 0.5 | 17 | 0 |
| 1The denominator used to calculate the rate varied from 351 to 400 in the TUKYSA arm and 173 to 197 in the control arm based on the number of patients with a baseline value and at least one post-treatment value. Grading was based on NCI-CTCAE v.4.03 for laboratory abnormalities, except for increased creatinine which only includes patients with a creatinine increase based on the upper limit of normal definition for grade 1 events (NCI CTCAE v5.0). 2Laboratory criteria for Grade 1 is identical to laboratory criteria for Grade 2. 3Due to inhibition of renal tubular transport of creatinine without affecting glomerular function. 4There is no definition for Grade 2 in CTCAE v.4.03. | ||||
Increased Creatinine
The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed [see CLINICAL PHARMACOLOGY].
Read the entire FDA prescribing information for Tukysa (Tucatinib Tablets)
© Tukysa Patient Information is supplied by Cerner Multum, Inc. and Tukysa Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.