Tykerb

Instructions for Lapatinib (Tykerb)

Common name: Lapatinib

Trade name: Tykerb

All names: Lapatinib, Tykerb, Tykerb, lapatinib, Lapani x

1. Indications of lapatinib

It is used in combination with capecitabine to treat advanced or metastatic breast cancer with ErbB-2 overexpression and who have previously received treatment with anthracyclines, paclitaxel, and trastuzumab (Herceptin).

2. Lapatinib usage and dosage

The recommended dose is 1250 mg, once daily, taken on days 1 to 21, combined with capecitabine 2000 mg/d, taken in two divided doses on days 1 to 14.

Lapatinib should be taken once a day. Taking it in divided doses is not recommended. Take it 1 hour before a meal or 2 hours after a meal. If you miss a dose, you do not need to double the dose on the second day.

Pregnancy level D, contraindicated for pregnant women. It is not clear whether it is secreted through breast milk, and lactating women should stop breastfeeding.

No significant difference was found between the elderly and young patients.

No clinical trials have been conducted on patients with severe kidney damage or dialysis. Patients with moderate to severe liver damage should reduce the dose.

3. Adverse reactions of lapatinib

More than 10% of the adverse reactions observed in clinical trials were mainly gastrointestinal reactions, including nausea, diarrhea, stomatitis and indigestion, dry skin, rash, and others including back pain, dyspnea, and insomnia. When combined with capecitabine, adverse reactions include nausea, diarrhea and vomiting, and poor touch of the palmar and plantar muscles. Individual patients may experience decreased left ventricular ejection fraction and interstitial pneumonia. The most common side effects are side effects on the gastrointestinal system, such as nausea, vomiting, diarrhea and other symptoms. Others include skin redness, swelling, itching, pain, and fatigue. There are also rare but serious side effects, including heart and lung problems. When a patient experiences a decrease in the left ventricular stroke fraction of the heart at level 2 or above, use must be stopped to avoid heart failure. When the left ventricular stroke fraction returns to normal or the patient becomes asymptomatic, the drug can be restarted at a lower dose two weeks later. Compared with cranberry chemotherapy drugs, the cardiotoxicity of lapatinib is reversible. Unlike cranberries, which are irreversible and have a maximum lifetime dosage, lapatinib does not have a maximum lifetime dosage. Since lapatinib is a drug metabolized by the hepatic CYP enzyme system, attention must be paid to dose adjustment when using other drugs that induce or inhibit CYP enzymes. Pregnant women should generally not use lapatinib because its pregnancy toxicity classification is D. Therefore, if there is no absolute need or there is great benefit to the mother, it is not recommended for pregnant women or those who are pregnant.

4. Lapatinib is contraindicated

It is contraindicated in patients with telisa and similar allergies.

5. Pharmacology and Toxicology of Lapatinib

Lapatinib tosylate tablets are small molecule 4-anilinoquinazoline receptor tyrosine kinase inhibitors that inhibit epidermal growth factor receptor (ErbB1) and human epidermal factor receptor 2 (ErbB2). Among the four breast cancer cell lines, BT474 and SKBr3 were sensitive to lapatinib, with half inhibitory concentrations of 25 and 32 nmol/L. MDA-MB-468 and T47D cell lines were insensitive, with half inhibitory concentrations at the micromolar level. For two bladder cancer cell lines, RT112 (high expression of ErbB1 and ErbB2) and J82 (low expression of ErbB1 and ErbB2), the efficacy of cisplatin was enhanced. It can inhibit epidermal factor-driven tumor growth in a variety of animals. Lapatinib is effective against trastuzumab-resistant tumor cell lines.

6. Lapatinib pharmacokinetics

Oral absorption is incomplete, and individual differences are large. It reaches the maximum concentration (Cmax) after about 4 hours, has a half-life of 24 hours, and reaches steady state 6 to 7 days after daily administration. Daily administration of 1250 mg, Cmax is 2.43 μg/ml (1.57-3.77 μg/ml), and the area under the plasma concentration-time curve (AUC) is 36.2 μg.h/ml (23.4-56 μg.h/ml). Taking it separately will double the AUC compared to taking it once a day. Taking it with food will increase the AUC by 3 to 4 times [3]. Lapatinib has a high binding rate to albumin and α1-acid glycoprotein (>99%). In vitro studies [4] have confirmed that lapatinib is a substrate for breast cancer anti-cancer protein transport and P-glycoprotein. The terminal half-life of a single dose is 14.2 hours. After multiple doses, the effective half-life is extended to 24 hours. It is mainly metabolized in the liver by CYP3A4 and CYP3A5, and a small part is completed by CYP2C19 and CYP2C8. Renal excretion is minimal and recovery in feces is approximately 27% of the oral dose.

7. Precautions for lapatinib

(1) Decreased left ventricular ejection fraction

(2) Hepatotoxicity

(3) Patients with severe liver damage

(4) Diarrhea

(5) Interstitial Sexual lung disease/pneumonia

(6) QT prolongation

(7) Drug interactions

(8) Effects on the ability to drive and operate machines

8. Lapatinib storage

Seal and store in a cool and dry place.