Pediatric Use: The safety and effectiveness of Erlotinib in children have not been established.

Geriatric Use: No significant differences in safety or efficacy have been observed between older patients (≥65 years) and younger adults.

Single oral doses of Erlotinib up to 1,000 mg in healthy individuals and weekly doses up to 1,600 mg in cancer patients have been tolerated. However, repeated twice-daily doses of 200 mg caused severe diarrhea, rash, and liver enzyme elevation. In the case of suspected overdose, Erlotinib should be discontinued immediately, and symptomatic treatment should be provided.

Store it at a temperature not exceeding 30°C in a dry place, away from light and moisture. Keep the medication out of reach of children to prevent accidental ingestion.

Erlotinib is primarily 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 substitution mutations, as detected through appropriate diagnostic testing. It is also used as a maintenance therapy for patients with locally advanced or metastatic NSCLC whose disease has not progressed following four cycles of platinum-based first-line chemotherapy. Additionally, it is prescribed for patients with locally advanced or metastatic NSCLC after the failure of at least one prior chemotherapy regimen. Moreover, Erlotinib is used in combination with gemcitabine as a first-line treatment for patients with locally advanced, unresectable, or metastatic pancreatic cancer.

Erlotinib, a kinase inhibitor, belongs to the quinazolinamine class of compounds and has the chemical name N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine. It works by reversibly inhibiting the kinase activity of the Epidermal Growth Factor Receptor (EGFR), preventing the autophosphorylation of tyrosine residues associated with the receptor. By doing so, Erlotinib effectively disrupts downstream signaling pathways, which are essential for tumor growth and survival. It exhibits a higher binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations compared to the wild-type receptor. However, its inhibitory effects on other tyrosine kinase receptors have not been fully characterized.

For Non-Small Cell Lung Cancer (NSCLC), the recommended daily dose of Erlotinib is 150 mg, taken on an empty stomach, meaning at least one hour before or two hours after food intake. The treatment should be continued until disease progression or until unacceptable toxicity occurs.

For Pancreatic Cancer, the recommended daily dose is 100 mg, administered in combination with gemcitabine. Similar to NSCLC, Erlotinib should be taken on an empty stomach to ensure optimal absorption. Treatment should be continued until disease progression or until severe side effects develop.

If severe reactions occur due to the concomitant use of strong CYP3A4 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, or grapefruit juice), the Erlotinib dose should be reduced by 50 mg increments.

If Erlotinib is taken with CYP3A4 inducers (e.g., rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, or St. John's Wort), the dose may be increased by 50 mg increments at two-week intervals, up to a maximum of 450 mg, if tolerated. However, avoiding co-administration is recommended.

In patients who smoke, Erlotinib dosage may need to be increased by 50 mg increments every two weeks, up to a maximum of 300 mg. Upon cessation of smoking, the dose should be immediately reduced to the recommended 150 mg (for NSCLC) or 100 mg (for pancreatic cancer) daily.

Erlotinib interacts with several drugs, which can alter its efficacy and safety profile:

Anticoagulants: When used with coumarin-derived anticoagulants like warfarin, Erlotinib may increase the International Normalized Ratio (INR), raising the risk of severe bleeding events.

CYP3A4 Inhibitors: As Erlotinib is primarily metabolized by CYP3A4, potent inhibitors like ketoconazole can increase its blood levels by 67%, leading to increased toxicity. Ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, increases Erlotinib’s AUC (exposure) by 39% and its Cmax (maximum concentration) by 17%.

CYP3A4 Inducers: Pre-treatment with strong CYP3A4 inducers like rifampicin significantly decreases Erlotinib exposure by 58% to 80%, which may reduce its effectiveness. Dose modifications are required when co-administered with CYP3A4 inducers.

Drugs Affecting Gastric pH: Medications like omeprazole and ranitidine lower Erlotinib absorption, reducing its AUC by 46% and 33%, respectively.

Erlotinib may cause several adverse reactions, some of which may be severe. The most commonly reported side effects (≥20% incidence) include rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, and vomiting. Serious but less common side effects, some of which can be fatal, include:

Interstitial Lung Disease (ILD)
Renal Failure
Hepatotoxicity with or without Hepatic Impairment
Gastrointestinal Perforation
Bullous and Exfoliative Skin Disorders
Myocardial Infarction (Heart Attack) / Ischemia
Cerebrovascular Accident (Stroke)
Microangiopathic Hemolytic Anemia with Thrombocytopenia
Ocular Disorders
Severe Hemorrhage in Patients Taking Warfarin

Patients experiencing severe side effects should discontinue the drug and seek immediate medical attention.

Erlotinib is classified as Pregnancy Category D, meaning it may cause fetal harm when administered to pregnant women. It is unknown whether Erlotinib is excreted in human breast milk. However, given the potential risk of serious adverse effects in nursing infants, a decision should be made to either discontinue the drug or discontinue breastfeeding, depending on the mother's medical needs.

Several precautions should be considered when prescribing Erlotinib:

Interstitial Lung Disease (ILD): Occurs in 1.1% of patients. If a patient experiences unexplained respiratory symptoms such as dyspnea, cough, or fever, Erlotinib should be discontinued.

Renal Failure: Regular monitoring of renal function and electrolytes is necessary, especially in patients at risk of dehydration. If severe renal toxicity occurs, the drug should be withheld.

Hepatotoxicity: Regular liver function tests should be conducted. Discontinue Erlotinib in cases of severe hepatic impairment.

Gastrointestinal Perforations: Immediate discontinuation is required if perforation occurs.

Skin Disorders: Discontinue the drug if severe bullous or exfoliative skin reactions develop.

Cardiac Risks: Patients with pancreatic cancer may have a higher risk of myocardial infarction or ischemia.