[Product Name] Erlotinib Tablets

[English Name] LuciErlo Erlotinib Tablets

[Active Ingredient] Erlotinib

[Specification] 150 mg × 30 tablets/box

[Manufacturer] Lucius Pharmaceutical (Laos) Co., Ltd.

[Laos National Drug Administration Registration No.] 09L1214/24

[Indications]

Erlotinib monotherapy is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This includes use as first-line therapy, maintenance therapy, or as second-line or later-line therapy following disease progression after at least one prior chemotherapy regimen.

Results from two multicenter, randomized, placebo-controlled Phase III trials demonstrated that Erlotinib in combination with platinum-based chemotherapy regimens (carboplatin + paclitaxel; or gemcitabine + cisplatin) as first-line therapy for patients with locally advanced or metastatic NSCLC did not provide additional clinical benefit compared to platinum-based chemotherapy alone; therefore, it is not recommended for use as first-line therapy in the aforementioned settings.

[Dosage and Administration]

Prior to initiating treatment with this product for patients with locally advanced or metastatic NSCLC, patients should undergo testing for EGFR mutation status.

The recommended dose of Erlotinib monotherapy for non-small cell lung cancer is 150 mg per day, taken at least 1 hour before or 2 hours after a meal. Treatment should be continued until disease progression or the occurrence of intolerable toxicity. Currently, there is no evidence to suggest that continuing treatment with this product after disease progression provides clinical benefit to the patient.

Dose Adjustment:

If a patient develops new-onset acute or progressive pulmonary symptoms—such as dyspnea, cough, and fever—Erlotinib therapy should be temporarily suspended to allow for diagnostic evaluation. If Interstitial Lung Disease (ILD) is confirmed, Erlotinib should be permanently discontinued, and appropriate treatment should be administered (see [Precautions] Warnings – Pulmonary Toxicity). Erlotinib should be permanently discontinued in patients who develop hepatic failure or gastrointestinal perforation. Patients who are dehydrated and at risk of renal failure, those suffering from severe bullous, blistering, or exfoliative skin disorders, and those with acute or worsening ocular disorders should interrupt or discontinue the use of erlotinib.

Diarrhea can usually be controlled with loperamide. Patients experiencing severe diarrhea that is unresponsive to loperamide, or who develop dehydration, require a dose reduction and temporary interruption of treatment. Patients experiencing severe skin reactions also require a dose reduction and temporary interruption of treatment.

If a dose reduction is necessary, the erlotinib dose should be decreased by 50 mg increments.

Dose reduction should be considered when erlotinib is co-administered with strong CYP3A4 inhibitors—such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, etc.—or with grapefruit or grapefruit juice; otherwise, severe adverse reactions may occur. Similarly, for patients co-administering dual CYP3A4 and CYP1A2 inhibitors (e.g., ciprofloxacin), the erlotinib dose should be reduced if severe adverse reactions develop.

Pre-treatment with the CYP3A4 inducer rifampin can reduce the AUC of erlotinib by two-thirds to four-fifths. The use of alternative medications that lack CYP3A4-inducing activity should be considered. If no alternative medications are available, an erlotinib dose higher than 150 mg may be considered, provided that safety is closely monitored. The maximum studied dose of erlotinib when co-administered with rifampin is 450 mg. If the erlotinib dose is increased, it should be promptly reduced back to the initial dose upon discontinuation of rifampin or other inducers. Other CYP3A4 inducers include, but are not limited to, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John’s Wort; the use of these agents should also be avoided whenever possible.

Erlotinib undergoes hepatic metabolism and biliary excretion. Although erlotinib exposure in patients with moderate hepatic impairment (Child-Pugh Class 7–9) is similar to that in patients with normal hepatic function, erlotinib should be used with caution in patients with hepatic impairment. Erlotinib should be used with caution in patients with total bilirubin > 3xULN. If baseline liver function tests are abnormal, and severe changes in liver function occur—such as a doubling of total bilirubin and/or a threefold increase in transaminases—erlotinib administration should be interrupted or discontinued. If liver function abnormalities are observed to be progressively worsening, interruption and/or dose reduction should be considered—along with increased frequency of liver function monitoring—before severe abnormalities are reached. If baseline liver function tests are normal, and total bilirubin > 3xULN and/or transaminases > 5xULN, erlotinib administration should be interrupted or discontinued.

Efficacy and safety studies have not been conducted in patients with renal impairment (serum creatinine concentration > 1.5xULN). Based on pharmacokinetic data, no dose adjustment is required for patients with mild or moderate renal impairment.

It has been established that smoking leads to a 50–60% reduction in erlotinib exposure. The maximum tolerated dose of erlotinib in current smokers with NSCLC is 300 mg. In patients who continue to smoke, the 300 mg dose—compared to the recommended 150 mg dose—did not demonstrate improved efficacy in the second-line treatment setting following chemotherapy failure.

[Adverse Reactions]

During the use of erlotinib, patients may experience certain uncomfortable symptoms; these constitute adverse reactions to the medication. All medications carry the potential for adverse reactions, though they do not occur in every patient. Some adverse reactions associated with erlotinib may resolve during the course of treatment; patients should promptly communicate with their attending physician if they encounter any adverse reactions during therapy.

The most common adverse reactions (≥ 20%) include: rash, diarrhea, anorexia, fatigue, dyspnea, cough, nausea, and vomiting.

[Use in Specific Populations]

Pregnancy

Based on animal data and its mechanism of action, administration of erlotinib to pregnant women may cause fetal harm. Limited available data regarding the use of erlotinib in pregnant women are insufficient to inform the risk of major birth defects or miscarriage. When administered during organogenesis, at exposures approximately 3 times the recommended human daily dose of 150 mg, erlotinib administration resulted in embryo-fetal lethality and abortion in rabbits.

**Lactating Patients**

There are no data regarding the presence of erlotinib in human milk, nor are there data regarding the effects of erlotinib on the breastfed infant or on milk production. Because serious adverse reactions—including interstitial lung disease, hepatotoxicity, bullous and exfoliative skin disorders, microangiopathic hemolytic anemia with thrombocytopenia, ocular disorders, and diarrhea—may occur in breastfed infants exposed to erlotinib, lactating women are advised not to breastfeed during treatment with erlotinib and for 2 weeks after the final dose.

**Pediatric Patients**

The safety and efficacy of erlotinib in pediatric patients have not been established.

**Manufacturer Information:**

**Company Profile**

Lucius Pharmaceutical (Laos) Co., Ltd. (hereinafter referred to as "Lucius Pharmaceutical") is a modern, multinational, high-tech biopharmaceutical enterprise. Currently, the company operates one global R&D center and collaborates with three top-tier R&D teams within the industry. Specializing in the research and development of complex chemical formulations and biologics, the company has achieved technological breakthroughs in key generic drugs. Today, Lucius Pharmaceutical has emerged as one of the global leaders in generic drug R&D capabilities, enjoying an excellent professional reputation and strong market standing within the industry.

In 2020, Lucius Pharmaceutical officially launched its Asia-Pacific strategy, investing heavily to construct the "Asia-Pacific No. 1 Smart Factory" in Vientiane, the capital of Laos. Built in strict compliance with GMP production standards, this facility incorporates state-of-the-art pharmaceutical equipment from countries such as China, the United States, and Germany. It houses an international-standard, high-end formulation workshop with an annual generic drug production capacity exceeding 1.5 billion tablets. The company's product portfolio currently encompasses over 200 categories—including oncology, cardiovascular, hematology, diabetes, dermatology, men's health, and anti-aging—and is exported to more than 50 countries and regions worldwide, including destinations across Europe, South America, Africa, the Middle East, India, Vietnam, and Nepal. Lucius has established a pharmaceutical manufacturing facility in Laos that currently sets the highest standards in the country. Since the completion and commencement of operations at the Lucius Laos plant, the company—in collaboration with the Association of Southeast Asian Nations (ASEAN)—will accelerate its internationalization process, strengthen intellectual cooperation in global pharmaceutical R&D, enrich its product portfolio, and enhance product quality, striving to become a leading global pharmaceutical enterprise.