Lefibenz

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

Lefibenz is a kinase inhibitor. The epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells and plays a role in the processes of cell growth and proliferation. Some EGFR activating mutations (exon 19 deletions or exon 21 point mutation L858R) within non-small cell lung cancer (NSCLC) cells have been identified as contributing to the promotion of tumor cell growth, blocking of apoptosis, increasing the production of angiogenic factors and facilitating the processes of metastasis.

Lefibenz reversibly inhibits the kinase activity of wild-type and certain activating mutations of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signalling and blocking EGFR-dependent proliferation.

Lefibenz binding affinity for EGFR exon 19 deletion or exon 21 point mutation L858R mutations is higher than its affinity for the wild-type EGFR. Lefibenz also inhibits IGF and PDGF-mediated signalling at clinically relevant concentrations; inhibition of other tyrosine kinase receptors has not been fully characterized.

Lefibenz inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells.

Lefibenz
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	Lefibenz
Availability	Prescription only
Generic	Gefitinib
Gefitinib Other Names	Gefitinib
Related Drugs	Opdivo, methotrexate, Keytruda, pembrolizumab, cisplatin, Tagrisso, Avastin
Type	Tablet
Formula	C₂₂H₂₄ClFN₄O₃
Weight	Average: 446.902 Monoisotopic: 446.152096566
Protein binding	90% primarily to serum albumin and alpha 1-acid glycoproteins (independent of drug concentrations).
Groups	Approved, Investigational
Therapeutic Class	Targeted Cancer Therapy
Manufacturer	Admac Formulations
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Lefibenz is a tyrosine kinase inhibitor used for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

Limitation of Use: Safety and efficacy of Lefibenz have not been established in patients whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution mutations.

Lefibenz is also used to associated treatment for these conditions: Metastatic Non-Small Cell Lung Cancer

How Lefibenz works

Lefibenz is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase that binds to the adenosine triphosphate (ATP)-binding site of the enzyme. EGFR is often shown to be overexpressed in certain human carcinoma cells, such as lung and breast cancer cells. Overexpression leads to enhanced activation of the anti-apoptotic Ras signal transduction cascades, subsequently resulting in increased survival of cancer cells and uncontrolled cell proliferation. Lefibenz is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. By inhibiting EGFR tyrosine kinase, the downstream signaling cascades are also inhibited, resulting in inhibited malignant cell proliferation.

Dosage

Lefibenz dosage

The recommended dose of Lefibenz is 250 mg orally once daily with or without food until disease progression or unacceptable toxicity. Do not take a missed dose within 12 hours of the next dose.

Side Effects

Common side effects are pruritus, rash, angioedema, urticaria, epistaxis, haematuria, alopecia, dry mouth and skin, nausea, vomiting, anorexia, stomatitis, diarrhoea, nail disorders, asthenia, pyrexia, proteinuria, eye pain, corneal erosion or ulcer, aberrant eyelash growth and elevations in blood creatinine. Rarely, pancreatitis, erythema multiforme, toxic epidermal necrolysis, corneal membrane sloughing, ocular ischemia, or ocular haemorrhage.

Toxicity

The acute toxicity of gefitinib up to 500 mg in clinical studies has been low. In non-clinical studies, a single dose of 12,000 mg/m² (about 80 times the recommended clinical dose on a mg/m² basis) was lethal to rats. Half this dose caused no mortality in mice. Symptoms of overdose include diarrhea and skin rash.

Precaution

Interstitial lung disease (ILD): ILD occurred in patients taking Lefibenz. Lefibenz should be withheld for worsening of respiratory symptoms. It should be discontinued if ILD is confirmed.

Hepatotoxicity: Periodic liver function testing should be performed. Lefibenz should be withheld for Grade 2 or higher for ALT and/or AST elevations. It should be discontinued for severe hepatic impairment.

Gastrointestinal perforation: Lefibenz should be discontinued for gastrointestinal perforation.

Diarrhea: Lefibenz should be withheld for Grade 3 or higher diarrhea.Ocular Disorders including Keratitis: Lefibenz should be withheld for signs and symptoms of severe or worsening ocular disorders including keratitis. It should be discontinued for persistent ulcerative keratitis.Bullous and Exfoliative Skin Disorders: Lefibenz should be withheld for Grade 3 or higher skin reactions or exfoliative conditions.

Embryo-fetal Toxicity: Lefibenz can cause fetal harm. Potential risk of Lefibenz to a fetus should be advised and effective contraception should be used.

Interaction

Concomitant use with CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, barbiturates) may reduce serum gefitinib levels. Plasma concentrations may be increased with potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole). Increased INR or bleeding events with warfarin. May increase plasma levels of metoprolol. May exacerbate vinorelbine-induced neutropenia. Decreased plasma levels and potential reduction in efficacy with drugs that affect gastric pH (e.g. PPIs, H2-receptor antagonists).

Food Interaction

Avoid grapefruit products.
Take with or without food. The absorption is unaffected by food.

Lefibenz Drug Interaction

Moderate: diltiazem, diltiazemUnknown: aspirin, aspirin, amoxicillin, amoxicillin, ubiquinone, ubiquinone, glucose, glucose, metoprolol, metoprolol, metoprolol, metoprolol, acetaminophen, acetaminophen, valproic acid, valproic acid, cyanocobalamin, cyanocobalamin

Lefibenz Disease Interaction

Major: dermatologic toxicities, GI disorders, ocular disorders, pulmonary toxicity, liver diseaseModerate: renal dysfunction

Volume of Distribution

1400 L [IV administration]

Elimination Route

Absorbed slowly after oral administration with a mean bioavailability of 60%. Peak plasma levels occurs 3-7 hours post-administration. Food does not affect the bioavailability of gefitinib.

Half Life

48 hours [IV administration]

Clearance

595 mL/min [IV administration]

Elimination Route

Elimination is by metabolism (primarily CYP3A4) and excretion in feces. Excretion is predominantly via the feces (86%), with renal elimination of drug and metabolites accounting for less than 4% of the administered dose.

Pregnancy & Breastfeeding use

Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Hypersensitivity. Lactation.

Special Warning

Pediatric Use: The safety and effectiveness of Lefibenz in pediatric patients have not been established.

Geriatric Use: No overall differences in safety were observed between patients 65 years and older and those younger than 65 years. There is insufficient information to assess for differences in efficacy between older and younger patients.

Administration to patients who have difficulty swallowing solids: Immerse Lefibenz tablets in 4 to 8 ounces of water by dropping the tablet in water, and stir for approximately 15 minutes. Immediately drink the liquid or administer through a naso-gastric tube. Rinse the container with 4 to 8 ounces of water and immediately drink or administer through the naso-gastric tube.