Tucatinib

Tucatinib Uses, Dosage, Side Effects, Food Interaction and all others data.

Tucatinbib is a kinase inhibitor drug used with trastuzumab and capecitabine in the treatment of unresectable or metastatic HER-2 positive breast cancer. It was developed by Seattle Genetics and approved by the FDA on April 17, 2020. Tucatinib is a promising new treatment for patients with metastatic breast cancer who have not responded adequately to other chemotherapy regimens.

By inhibiting tyrosine kinase, tucatinib exerts anti-tumor activity, reducing the size of HER-2 positive breast cancer tumors. In clinical trials, the regimen of tucatinib and trastuzumab showed enhanced activity both in vitro and in vivo when compared to either drug administered by itself.

Tucatinib
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Tucatinib
Availability	Prescription only
Generic	Tucatinib
Tucatinib Other Names	Tucatinib
Related Drugs	Arimidex, Ibrance, Femara, Xeloda, Herceptin, Lynparza
Weight	150mg, 50mg
Type	Oral tablet
Formula	C₂₆H₂₄N₈O₂
Weight	Average: 480.532 Monoisotopic: 480.202222045
Protein binding	Tucatinib is about 97% bound to plasma proteins.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Tucatinib is a kinase inhibitor used to treat certain types of unresectable/metastatic HER-2 positive breast cancer.

Tucatinib is indicated with trastuzumab and capecitabine for treatment of adults diagnosed with advanced unresectable or metastatic HER2-positive breast cancer. This includes patients with brain metastases and those who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Tucatinib is also used to associated treatment for these conditions: Breast Cancer, Unresectable Breast Cancer

How Tucatinib works

Mutations in the HER-2 gene are observed in some types of breast carcinoma. Tucatinib inhibits the tyrosine kinase enzyme of the HER-2 gene. Mutations of tyrosine kinase in the HER-2 gene lead to cascade effects of increased cell signaling and proliferation, resulting in malignancy. Results of in vitro studies show that tucatinib inhibits the phosphorylation of both HER-2 and HER-3, leading to downstream changes in MAPK and AKT signaling and cell proliferation. Anti-tumor activity occured in the cells that expressed HER-2. In vivo, tucatinib has been shown to inhibit HER-2 expressing tumors, likely by the same mechanism.

Toxicity

LD50 information and overdose information for tucatinib are not readily available in the literature. In the case of an overdose with this drug, increased adverse effects, such as diarrhea, nausea, abdominal pain, vomiting fatigue, hepatotoxicity, vomiting, decreased appetite, anemia, headache, and rash are expected.

Food Interaction

Take with or without food. There is no meaningful clinical effect of food on this drug.

Volume of Distribution

The volume of distribution of tucatinib is about 1670 L. This drug penetrates the blood-brain barrier.

Elimination Route

The Tmax for tucatinib ranges from 1 to 4 hours. One pharmacokinetic study revealed a Cmax of 1120 ng/mL after a dose of 350 mg twice daily with a Tmax ranging from 1 to 3 hours. The AUCtau was reported to be about 7120 hours×ng/mL.

Half Life

A pharmacokinetic study revealed a half-life of approximately 5.38 hours. Prescribing information mentions a geometric mean half-life of about 8.21 hours.

Clearance

The apparent clearance is 148 L/h.

Elimination Route

In a study of radiolabled tucatinib, about 86% of the total dose was excreted in the feces and 4.1% was found in the urine. About 16% of the tucatinib dose recovered in the feces was identified as unchanged tucatinib.