Lapatinib

Lapatinib is an antineoplastic agent belonging to the pharmacological class of tyrosine kinase inhibitors.

The FDA approved Lapatinib for treating advanced or metastatic breast cancer, particularly in combination with other medications.

Lapatinib shows a variable absorption, i.e., three to fourfold enhancement by food. It strongly binds over 99% to plasma proteins and undergoes hepatic metabolism primarily via CYP3A4/A5 and, to a lesser extent, via CYP2C19/2C8. The drug is predominately excreted through the faecal route.

The most common side effects of Lapatinib include nausea, headache, back pain, and breathing difficulty.

Lapatinib is available as an oral tablet.

The molecule is available in India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.

Lapatinib is an antineoplastic agent belonging to the pharmacological class of tyrosine kinase inhibitors.

Lapatinib is a 4-anilinoquinazoline kinase inhibitor with a dissociation half-life of less than 300 minutes. It inhibits the intracellular tyrosine kinase domains of the human epidermal growth factor receptor (EGFR) type 2 (HER2/ERBB2) and the epidermal growth factor receptor receptor (HER1/EGFR/ERBB1). In vitro and in different animal models, Lapatinib inhibits the growth of tumour cells driven by ERBB. An in vitro study using a combination treatment of Lapatinib and 5-fluorouracil (capecitabine's active metabolite) in 4 tumour cell lines showed an additive effect. Trastuzumab-conditioned cell lines were used to assess Lapatinib's growth inhibitory effects. Lapatinib exhibited notable efficacy against breast cancer cell lines chosen for prolonged growth in an in vitro trastuzumab-containing medium. These in vitro results suggest the absence of cross-resistance between the two medications.

Lapatinib achieves peak plasma concentration at 4 hours.

Following a 1.25 g dose, Lapatinib attains a peak plasma concentration of 2.43 mcg/mL.

Lapatinib is available as an oral tablet.

Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.

The physician recommends taking this medication orally once daily, with or without food.

When combined with other medications or treatments, such as chemotherapy, Lapatinib can help treat breast cancer and increase its efficacy, particularly in cases where the disease is advanced or has spread to other areas of the body. Breast texture changes, nipple discharge, and breast lumps are the symptoms this medication relieves. Lapatinib actively prevents or stops the multiplication of cancer cells by blocking essential proteins involved in cancer cell growth. This focused strategy targets breast cancers that are HER2-positive in particular, improving patient outcomes overall and enhancing the quality of life for patients receiving the treatment. Its mechanism represents a breakthrough in the treatment of breast cancer, as it not only kills cancer cells but also stops them from growing.

Lapatinib is indicated in the following conditions:

Limitations of Use: Patients should be treated with Lapatinib plus capecitabine only after their disease progresses while on trastuzumab.

Orally: Patients take Lapatinib orally, using tablets swallowed with water once daily. The tablets should be ingested whole on an empty stomach, with or without a meal, but preferably taken at least 1 hour before or 1 hour after meals, following the prescribed dosage and timing to ensure effectiveness in treating conditions like breast cancer. Patients should refrain from crushing, chewing, or breaking the tablets unless instructed by their healthcare provider. Adherence to these instructions is crucial for the medication to work optimally in managing the specified conditions, emphasizing the importance of following the healthcare professional's guidance for proper administration.

The dosage and duration of treatment should be as per the treating physician's clinical judgment,

Lapatinib is available as an oral tablet.

Individuals who have previously undergone treatment with anthracycline, taxane, and trastuzumab should take 1,250 mg once daily on days 1–21 in addition to capecitabine, which should be taken in two divided doses separated approximately 12 hours apart on days 1–14 of the cycle.

Women going through post-menopause for whom hormonal therapy is appropriate: 1,500 mg given continuously once daily when combined with 2.5 mg of letrozole given once daily.

While using Lapatinib, refrain from consuming grapefruit or its juice to prevent potential drug metabolism issues. There are no specific dietary restrictions; maintain regular meals and emphasize adequate hydration. Quit smoking and alcohol consumption. Include green leafy vegetables, sweet potatoes, broccoli, tomatoes, carrots, mangoes, citrus fruits, berries, and cocoa. Consume lean proteins such as fish, meat, and poultry. Prioritize hydration by drinking plenty of water, herbal tea, and vegetable and fruit juices. Avoid processed and refined foods.

The dietary restriction should be individualized as per patient requirements.

The adverse reactions related to Lapatinib can be categorized as:

Anaphylaxis or hypersensitivity reactions

Nail disorders (paronychia)

Syndrome of Steven Johnson (SJS)

Toxic epidural necrolysis.

Torsades de Points (TdP) or ventricular arrhythmias

QT prolongation in the ECG

Skin fissures

The clinically relevant drug interactions of Lapatinib are briefly summarized here.

It could increase the levels of P-glycoprotein substrates, CYP2C8, and CYP3A4 in the serum. Increased exposure w/ CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, atazanavir, ritonavir). Inducers of CYP3A4 (such as carbamazepine and rifampicin) may lessen the exposure to Lapatinib. Drugs known to lengthen QT intervals, such as antiarrhythmic agents and cumulative high-dose anthracycline therapy, increase the risk of QT prolongation. It may raise digoxin levels in the blood.

Elevated exposure to Lapatinib with a meal. Grapefruit juice may cause an increase in plasma levels. St. John's wort may reduce systemic exposure to Lapatinib.

Pregnancy Category D (FDA): Use in cases where no safer medication is available, and life is in danger. Positive evidence of prenatal risk in humans.

When given to a pregnant woman, Lapatinib may harm the fetus due to its mechanism of action and results from studies conducted on animals. There is no human data available to discuss the risks associated with drugs.

The administration of Lapatinib to pregnant rats during organogenesis and lactation resulted in the death of offspring within the first four days of birth at maternal exposures that were ≥ 3.3 times the human clinical exposure based on AUC after 1,250 mg of Lapatinib plus capecitabine, according to an animal reproduction study. Lapatinib produced abortions in rabbits or fetal abnormalities in rats when given to pregnant animals during the organogenesis stage at doses that were toxic to the mother.

Advise pregnant women and females of reproductive potential and the potential risk to the fetus.

Female: Pregnant women may experience harm to their fetus if Lapatinib is given to them, according to results from animal studies. Advise women who are fertile to use effective contraception both during and for one week following their lapatinib treatment.

Men: Male patients who have female partners who may become pregnant should be advised to use effective contraception during Lapatinib treatment and for one week following the last dose, according to research on animal reproduction.

No information is available regarding Lapatinib's presence in human milk, how it affects breastfed children, or how much milk is produced. Breastfeeding mothers are advised not to breastfeed during Lapatinib treatment and for one week following the last dose due to the possibility of severe adverse reactions in a breastfed child.

As per the FDA, the safety and efficacy of Lapatinib have not been specifically studied in pediatric patients.

The pharmacokinetics of Lapatinib have yet to be mainly investigated in hemodialysis or patients with renal impairment. Concerning patients with severe renal impairment, there is no experience with Lapatinib.

The pharmacokinetics of Lapatinib, however, are unlikely to be impacted by renal impairment because the kidneys excrete less than 2% of an administered dose (Lapatinib and metabolites).

Lapatinib pharmacokinetics was investigated in 8 healthy control subjects and four subjects with preexisting moderate (n = 8) or severe (n = 4) hepatic impairment. For moderate and severe hepatic impairment, systemic exposure increased by about 14% and 63%, respectively, following a single oral 100 mg dose. Given the increased drug exposure associated with severe hepatic impairment, patients must exercise caution when starting Lapatinib. Consider dose reduction in these patients. Abruptly stop Lapatinib and avoid retreatment if severe hepatotoxicity develops while on therapy.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Lapatinib.

Overconsumption of Lapatinib could lead to severe diarrhoea, nausea, vomiting, rash, fatigue, and potential cardiac abnormalities.

In the event of a Lapatinib overdose, promptly discontinue the medication and initiate supportive care. Consider gastric lavage and activated charcoal if ingestion is recent. Administer symptomatic treatment such as antiemetics for nausea and vomiting and antidiarrheals for diarrhoea. Monitor vital signs and cardiovascular functions closely and administer symptomatic treatment for observed complications. Maintain adequate hydration and electrolyte balance, and consider ECG monitoring. Hemodialysis is unlikely to be beneficial due to Lapatinib's extensive protein binding.

Lapatinib is a small molecule belonging to the kinase inhibitor class 4-anilinoquinazoline. GlaxoSmithKline (GSK) created the anti-cancer medication lapatinib to treat solid tumours like breast and lung cancer. On March 13, 2007, the FDA approved its use in conjunction with capecitabine, a chemotherapy drug, for patients with advanced metastatic breast cancer.