Erlotinib (erlotinib HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Erlotinib hydrochloride, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is an antineoplastic agent.
Erlotinib, a reversible inhibitor of epidermal growth factor receptor (EGFR/human epidermal growth factor receptor type 1 (HER1)/ErbB1) and mutated EGFR (e.g., exon 19 deletion (del19), exon 21 substitution (L858R)) tyrosine kinases, is an antineoplastic agent. EGFR is expressed on the cell surface of many cancer cells, as well as many normal cells; activation of EGFR tyrosine kinase is thought to initiate a cascade of intracellular signaling events leading to cell proliferation and influencing processes critical to cell survival and tumor progression (e.g., angiogenesis, apoptosis, metastasis). Some EGFR-activating mutations, such as exon 19 deletion (del19) and exon 21 (L858R) substitution mutation, contribute to increased cell proliferation and survival in non-small cell lung cancer (NSCLC) cells harboring these mutations.
The drug binds to the kinase domains of EGFR and reversibly inhibits tyrosine kinase phosphorylation, resulting in downregulation of EGFR signaling. Erlotinib has demonstrated a greater affinity for cell lines expressing del19 or L858R mutations than for wild-type EGFR. Specificity with regard to other tyrosine kinase receptors has not been fully characterized.
Approximately 60% of an oral dose of erlotinib is absorbed from the GI tract; presence of food in the GI tract increases oral bioavailability to approximately 100%. Peak plasma concentrations of erlotinib occur at 4 hours following oral administration. Steady-state concentrations of erlotinib are achieved within 7-8 days.
Erlotinib is 93% bound to plasma proteins (mainly to albumin and alpha1-acid glycoprotein). Erlotinib is extensively metabolized via the cytochrome P-450 (CYP) enzyme system, mainly by CYP3A4 and, to a lesser extent, by CYP1A1 (principally an extrahepatic enzyme) and CYP1A2. The half-life of erlotinib is approximately 36 hours; the clearance is approximately 24% higher in smokers.
Following a 100-mg oral dose, erlotinib is excreted mainly as metabolites in feces (83%) and urine (8%).
Systemic exposure of erlotinib does not appear to be affected substantially by age, body weight, or gender in patients receiving the drug as a single agent for maintenance or second- or third-line therapy in NSCLC or in combination with gemcitabine for the treatment of pancreatic cancer.
USES: Erlotinib is used to treat lung and pancreatic cancer. It works by slowing or stopping the growth of cancer cells.
Generic name: erlotinib HCl
Pronunciation: (er-LOE-ti-nib)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Erlotinib
Indications
The following indications are listed for Erlotinib:
- Adenocarcinoma Of Pancreas
- Metastatic Non-Small Cell Lung Cancer With Egfr Exon 19 Deletion
- Metastatic Non-Small Cell Lung Cancer With Egfr Exon 21 L858r Substitution Mutation
Also known as: Egfr Exon 19 Deletion Mutation-Positive Metastatic Non-Small Cell Lung Cancer (Nsclc), Egfr L858r Substitution Mutation-Positive Metastatic Non-Small Cell Lung Cancer (Nsclc), Metastatic Non-Small Cell Lung Cancer With Egfr Exon 21 Leu858arg Substitution, Metastatic Nsclc With Egfr Ex19del, Pancreatic Adenocarcinoma.
Dosing
Dosage of erlotinib hydrochloride is expressed in terms of erlotinib.
Dosage interruption and/or reduction, or discontinuance of erlotinib therapy, may be necessary based on severity of adverse reactions. When dosage reduction is required, reduce the dose of erlotinib by 50-mg decrements.
Administer erlotinib orally once daily. The drug should be administered on an empty stomach (e.g., at least 1 hour before or 2 hours after ingestion of food).
Store erlotinib tablets at 25degreesC (excursions permitted between 15-30degreesC).
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Erlotinib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4 and, to a lesser extent, CYP1A1 and CYP1A2.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*The manufacturer states that there are no known contraindications to the use of erlotinib.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in >=20% of patients receiving erlotinib in a pooled analysis of data from patients with NSCLC across all approved lines of therapy, with and without EGFR mutations, and in patients with pancreatic cancer were rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, and vomiting.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of erlotinib have not been established in pediatric patients.
In a clinical trial, 25 patients 3-20 years of age with recurrent or refractory ependymoma received erlotinib (85 mg/m2 orally daily). No overall difference in safety relative to adults was observed.
Among patients 2-21 years of age, age did not appear to substantially affect erlotinib clearance normalized to body surface area in a population pharmacokinetic analysis.
Erlotinib may cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
It is not known whether erlotinib is distributed into human milk or if the drug or its metabolites have any effect on milk production or the nursing infant. Because of the potential for serious adverse reactions to erlotinib in nursing infants, women should be advised not to breast-feed while receiving the drug and for 2 weeks after the last dose of the drug.
The manufacturer currently makes no special dosage recommendations for geriatric patients.
In clinical studies in patients with NSCLC or pancreatic cancer, 40% of patients receiving erlotinib were >=65 years of age and 10% were >=75 years of age. No overall differences in safety and efficacy relative to younger adults were observed.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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