Tukysa Side Effects Center

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?

Tukysa may cause serious side effects including:

hives,
difficulty breathing,
swelling of your face, lips, tongue, or throat,
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,
seizure,
loss of appetite,
stomach pain (upper right side),
tiredness,
itching,
dark urine,
clay-colored stools,
yellowing of the skin or eyes (jaundice),
pale skin,
unusual tiredness,
lightheadedness,
shortness of breath, and
cold hands and feet

Get medical help right away, if you have any of the symptoms listed above.

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

Seek medical care or call 911 at once if you have the following serious side effects:

Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheadedness, or passing out;
Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

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.

SLIDESHOW

Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See Slideshow

Tukysa Consumer Information

Get 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.

QUESTION

A lump in the breast is almost always cancer. See Answer

Tukysa Professional Information

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 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
Adverse Reaction	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
^1. Stomatitis includes stomatitis, oropharyngeal pain, oropharyngeal discomfort, mouth ulceration, oral pain, lip ulceration, glossodynia, tongue blistering, lip blister, oral dysesthesia, tongue ulceration, and aphthous ulcer ^2. Rash 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 ^3. Hepatotoxicity 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 ^4. Anemia includes anemia, hemoglobin decreased, and normocytic anemia ^5. Due to inhibition of renal tubular transport of creatinine without affecting glomerular function ^6. Peripheral 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 magne	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
^1. The 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). ^2. Laboratory criteria for Grade 1 is identical to laboratory criteria for Grade 2. ^3. Due to inhibition of renal tubular transport of creatinine without affecting glomerular function. ^4. There 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].

DRUG INTERACTIONS

Effects Of Other Drugs On TUKYSA

Table 5 summarizes the effect of other drugs on TUKYSA.

Table 5: Drug Interactions that Affect TUKYSA

Strong CYP3A Inducers or Moderate CYP2C8 Inducers
Clinical Impact	Concomitant use of TUKYSA with a strong CYP3A or moderate CYP2C8 inducer decreased tucatinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may reduce TUKYSA activity.
Management	Avoid concomitant use of TUKYSA with a strong CYP3A inducer or a moderate CYP2C8 inducer.
Strong or Moderate CYP2C8 Inhibitors
Clinical Impact	Concomitant use of TUKYSA with a strong CYP2C8 inhibitor increased tucatinib plasma concentrations [see CLINICAL PHARMACOLOGY], which may increase the risk of TUKYSA toxicity.
Management	Avoid concomitant use of TUKYSA with a strong CYP2C8 inhibitor. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors.

Effects Of TUKYSA On Other Drugs

Table 6 summarizes the effect of TUKYSA on other drugs.

Table 6: TUKYSA Drug Interactions that Affect Other Drugs

CYP3A Substrates
Clinical Impact	Concomitant use of TUKYSA with a CYP3A substrate increased the plasma concentrations of CYP3A substrate [see CLINICAL PHARMACOLOGY], which may increase the toxicity associated with a CYP3A substrate.
Management	Avoid concomitant use of TUKYSA with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage in accordance with approved product labeling.
P-glycoprotein (P-gp) Substrates
Clinical Impact	Concomitant use of TUKYSA with a P-gp substrate increased the plasma concentrations of P-gp substrate [see CLINICAL PHARMACOLOGY], which may increase the toxicity associated with a P-gp substrate.
Management	Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

Read the entire FDA prescribing information for Tukysa (Tucatinib Tablets)