Generic
Tucatinib
2 brands available in the market
At a glance
Tucatinib 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.
Description
Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation. In vivo, tucatinib inhibited the growth of HER2 expressing tumors.
Indications
- HER2-positive metastatic breast cancer
- HER2-positive breast cancer with brain metastases
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
HER2 Tyrosine Kinase Inhibitor
Pharmacology
Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity compared to either drug alone.
Mechanism of action
Inhibits HER2 and HER3 phosphorylation, blocking MAPK and AKT signaling and cell proliferation.
Dosage
Adult Dose (Oral):
- 300 mg twice daily in combination with trastuzumab and capecitabine until disease progression or unacceptable toxicity
- Swallow tablets whole; do not chew, crush, or split
- Take approximately 12 hours apart at the same time each day with or without a meal
- If patient vomits or misses a dose, take the next dose at its usual scheduled time
- Severe hepatic impairment (Child-Pugh C): 200 mg twice daily
- Avoid concomitant use with strong CYP2C8 inhibitors; if unavoidable, reduce dose to 100 mg twice daily
Administration
- May be taken with or without food
- Swallow tablets whole
- Take at the same time each day
- Take capecitabine within 30 minutes after a meal
Missed dose
If patient vomits or misses a dose, take the next dose at its usual scheduled time; do not double the dose.
Side effects
Common Side Effects:
- Diarrhea
- Palmar-plantar erythrodysesthesia
- Nausea
- Fatigue
- Hepatotoxicity
- Vomiting
- Stomatitis
- Decreased appetite
- Abdominal pain
- Headache
- Anemia
- Rash
Precautions & warnings
- Can cause severe diarrhea; administer antidiarrheal treatment as clinically indicated
- Monitor ALT, AST, and bilirubin prior to starting, every 3 weeks during treatment, and as clinically indicated
- May cause fetal harm; use effective contraception during treatment and for at least 1 week after last dose
- Advise male patients with female partners of reproductive potential to use effective contraception
Contraindications
- History of serious hypersensitivity reactions to Tucatinib
Drug interactions
- Strong CYP2C8 inhibitors: avoid concomitant use; if unavoidable, reduce dose to 100 mg twice daily
Food interactions
Food interactions are not significant.
Use in pregnancy
Use in Pregnancy: Animal studies show embryo-fetal mortality, reduced fetal weight, and fetal abnormalities; advise pregnant women of potential risk.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Unknown if excreted in human milk; do not breastfeed during treatment and for at least 1 week after last dose.
Pediatric use
Safety and effectiveness not established in pediatric patients
Geriatric use
No overall differences in safety or effectiveness in elderly
Renal / hepatic impairment
Renal Impairment: Mild or moderate (ClCr 30-89 mL/min): no dose adjustment; severe (ClCr <30 mL/min): not recommended (due to capecitabine)
Hepatic Impairment: Mild or moderate (Child-Pugh A/B): no dose adjustment; severe (Child-Pugh C): 200 mg twice daily
Overdose effects
No specific antidote; benefit of hemodialysis unknown.
Treatment: Withhold tucatinib and apply general supportive measures.
Storage conditions
Store below 25°C in a cool and dry place. Keep away from light. Keep out of reach of children.