Erlotinib

What it is and how it works

Mechanism of Action Epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells. In some tumor cells signaling through this receptor plays a role in tumor cell survival and proliferation irrespective of EGFR mutation status. Erlotinib reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and thereby inhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild type receptor. Erlotinib inhibition of other tyrosine kinase receptors has not been fully characterized.

Indications

Erlotinib tablets are a kinase inhibitor indicated for: The 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 receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen. First-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer, in combination with gemcitabine. Limitations of Use: Safety and efficacy of erlotinib tablets have not been established in patients with NSCLC whose tumors have other EGFR mutations. Erlotinib tablets are not recommended for use in combination with platinum-based chemotherapy.

Dosage and administration (summary)

NSCLC: 150 mg orally, on an empty stomach, once daily Pancreatic cancer: 100 mg orally, on an empty stomach, once daily Selection of Patients with Metastatic NSCLC Select patients for the treatment of metastatic NSCLC with erlotinib tablets based on the presence of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations in tumor or plasma specimens . If these mutations are not detected in a plasma specimen, test tumor tissue if available. Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.

Contraindications

None. None

Warnings and precautions

Interstitial lung disease (ILD) : Occurs in 1.1% of patients. Withhold erlotinib for acute onset of new or progressive unexplained pulmonary symptoms, such as dyspnea, cough and fever. Discontinue erlotinib if ILD is diagnosed. Renal failure : Monitor renal function and electrolytes, particularly in patients at risk of dehydration. Withhold erlotinib for severe renal toxicity. Hepatotoxicity : Occurs with or without hepatic impairment, including hepatic failure and hepatorenal syndrome: Monitor periodic liver testing. Withhold or discontinue erlotinib for severe or worsening liver tests.

Pregnancy

Pregnancy Risk Summary Based on animal data and its mechanism of action, erlotinib can cause fetal harm when administered to a pregnant woman. Limited available data on use of erlotinib tablets in pregnant women are not sufficient to inform a risk of major birth defects or miscarriage.

Storage and supply

Erlotinib Tablets are available as follows: 25 mg: Round, biconvex, unscored, white film-coated tablets, debossed TEVA on one side and E2 on the other side; supplied in bottles of 30 (NDC 0093-7662-56). 100 mg: Round, biconvex, unscored, white film-coated tablets, debossed TEVA on one side and 7663 on the other side.

Source: Erlotinib (Erlotinib) — US FDA prescribing information, 2021-03-17, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.