Erlotinib Hydrochloride Tablets

Erlotinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor I (also known as HER1). Erlotinib effectively inhibits intracellular EGFR phosphorylation, which is normally expressed on the surface of normal cells and tumor cells. In non-clinical trial models, inhibition of EFGF phosphorylation can cause cell growth arrest and/or cell death.

The main ingredient of this product is erlotinib hydrochloride.

1. Erlotinib alone is indicated for locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one chemotherapy regimen. 2. In two multicenter, randomized, placebo-controlled Phase III trials, the results showed that erlotinib combined with platinum-containing chemotherapy (carboplatin-paclitaxel; or gemcitabine-cisplatin) as first-line treatment for patients with locally advanced or metastatic NSCLC did not increase clinical benefit compared with platinum-containing chemotherapy alone, so it is not recommended for first-line treatment in the above situation. 3. Erlotinib alone can be used for maintenance treatment of patients with locally advanced or metastatic non-small cell lung cancer whose disease is stable after 4 cycles of platinum-based first-line chemotherapy. This indication is based on the results of a randomized, double-blind, placebo-controlled study (B018192) [see [Clinical Trials]]. No clinical research data comparing the use of erlotinib for treatment without progression and after progression after first-line chemotherapy have been obtained. 4. Clinical research on this product for first-line treatment of EGFR mutation populations is ongoing. It is recommended that the treating physician consider appropriate treatment options based on the research progress of this product and similar drugs and the patient's own condition.

This product must be used under the guidance of a physician who has experience in using such drugs. The recommended dose of erlotinib monotherapy for non-small cell lung cancer is 150 mg/day, taken at least 1 hour before or 2 hours after meals. Continue medication until disease progression or intolerable toxicity occurs. There is no evidence that continued treatment after progression can benefit patients. Dose adjustment 1. Patients with new acute or progressive lung symptoms, such as dyspnea, cough and fever, should suspend erlotinib treatment for diagnostic evaluation. If ILD (interstitial lung disease) is confirmed, erlotinib should be discontinued and appropriate treatment should be given (see [Precautions] Warning - Pulmonary Toxicity). Erlotinib should be discontinued in patients with liver failure or gastrointestinal perforation. Patients who are dehydrated and at risk of renal failure, patients with severe bullous, blistering or exfoliative skin diseases, and patients with acute/worsening eye diseases should interrupt or stop using erlotinib [see [Precautions]]. 2. Diarrhea can usually be controlled with loperamide. Patients with severe diarrhea who are ineffective with loperamide or who develop dehydration need to have their dose reduced and treatment temporarily stopped. Patients with severe skin reactions also need to have their dose reduced and treatment temporarily stopped. 3. If a dose reduction is necessary, erlotinib should be reduced by 50 mg each time. 4. When using strong CYP3A4 inhibitors such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, or grapefruit or grapefruit juice, a dose reduction should be considered, otherwise serious adverse reactions may occur. Similarly, patients who are using co-inhibitors of CYP3A4 and CYPIA2 (such as ciprofloxacin) at the same time should reduce the dose of erlotinib if serious adverse reactions occur (see [Drug Interactions]). 5. The use of the CYP3A4 inducer rifampicin before treatment can reduce the AUC of erlotinib by 2/3-4/5. Other alternative drugs without CYP3A4 induction activity should be considered. If there is no alternative drug, the dose of erlotinib may be considered higher than 150 mg, but safety needs to be closely monitored. The maximum study dose of erlotinib when used in combination with rifampicin is 450 mg. If the dose of erlotinib is increased, erlotinib should be quickly reduced to the initial dose when rifampicin or other inducers are stopped. Other CYP3A4 inducers include but are not limited to rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital and St. John's Wort, and these drugs should also be avoided if possible (see [Precautions] and [Drug Interactions]). 6. Erlotinib is metabolized by the liver and secreted by the bile duct. Although the exposure of erlotinib in patients with moderate hepatic impairment (Child-Pugh grade 7-9) is similar to that in patients with normal hepatic function, erlotinib should be used with caution in patients with hepatic impairment. Patients with total bilirubin 3×ULN should use erlotinib with caution. In the case of abnormal pre-treatment tests, if there are severe changes in liver function, such as doubling of total bilirubin and/or tripling of transaminases, erlotinib should be interrupted or discontinued. When the examination finds that the liver function abnormalities continue to worsen, interruption and/or dose reduction should be considered before reaching severe abnormalities, and the frequency of liver function test monitoring should be increased. In the case of normal pre-treatment tests, if the total bilirubin is 3×ULN and/or the transaminase is 5×ULN, erlotinib should be interrupted or discontinued (see [Precautions] and [Adverse Reactions]). 7. Efficacy and safety studies in patients with renal impairment (serum creatinine concentration 1.5×ULN) have not been conducted. Based on pharmacokinetic data, no dose adjustment is required for patients with mild or moderate renal impairment. Erlotinib is not recommended for patients with severe renal impairment. 8. Smoking has been shown to reduce erlotinib exposure by 50-60%. The maximum tolerated dose of erlotinib for smoking NSCLC patients is 300 mg. The efficacy and long-term safety of giving patients who continue to smoke a dose of erlotinib higher than the recommended starting dose (14 days) have not been confirmed (see [Drug Interactions] Special Populations). If the dose of erlotinib has been increased, the patient should immediately reduce it to the approved starting dose after stopping smoking.

1. Erlotinib monotherapy: The most common adverse reactions of Tarceva tablets are rash (75%) and diarrhea (54%). The degree is mostly grade I or II and can be controlled without intervention. The incidence of grade III/IV rash and diarrhea in patients treated with erlotinib was 9% and 6%, respectively. The proportion of patients treated with erlotinib who terminated the trial due to rash or diarrhea was 1%. 6% and 1% of patients required dose reduction due to rash and diarrhea, respectively. The median time to rash in BR.21 was 8 days, and the median time to diarrhea was 12 days. 2. Erlotinib combined with chemotherapy: The most common adverse reactions in pancreatic cancer patients treated with 100 mg erlotinib gemcitabine were fatigue, rash, nausea, loss of appetite and diarrhea. In the erlotinib gemcitabine treatment group, the incidence of grade III/IV rash and diarrhea in treated patients was 5%, with a median time of 10 days and 15 days, respectively, each leading to dose reduction in 2% of patients and no more than 1% of patients stopping the drug. 3. Gastrointestinal abnormalities: Gastrointestinal perforation has been reported in the erlotinib treatment group, but it is uncommon, less than 1%. Gastrointestinal bleeding is common in NSCLC trials and combination trials for pancreatic cancer, some of which are related to the concomitant use of warfarin or nonsteroidal anti-inflammatory drugs. These reports include bleeding from peptic ulcers (gastritis, gastric and duodenal ulcers), hemoptysis, blood in the stool, melena, and possible bleeding from colitis. 4. Abnormal liver function: Abnormal liver function tests (including elevated ALT, AST, and bilirubin) are often observed in clinical trials of erlotinib, especially in the PA3 study. Most are mild to moderate, transient or related to liver metastases. Rare cases of liver failure (including death) have been reported during the use of erlotinib. Confounding factors include preexisting liver disease or concomitant use of hepatotoxic drugs. 5. Eye diseases: There are very rare reports of corneal ulcers or perforations in patients receiving erlotinib. Keratitis and conjunctivitis occur frequently during erlotinib treatment. Abnormal eyelash growth includes: ingrown eyelashes, excessive growth, and thickening of eyelashes. 6. Respiratory, chest and mediastinal abnormalities: When erlotinib is used to treat NSCLC and other progressive solid tumors, patients have been reported to have severe interstitial lung disease (ILD)-like events (including death) (see Precautions). Epistaxis has been reported in both NSCLC and pancreatic cancer trials. 7. Skin and subcutaneous tissue abnormalities: The most commonly reported adverse reaction in patients treated with erlotinib is rash, which generally manifests as mild to moderate erythema and pustular papules, and often occurs or worsens on sun-exposed parts of the body. For patients who are to be exposed to the sun, it is recommended to wear protective clothing and/or use sunscreen (e.g., mineral-containing). Other mild skin reactions such as pigmentation have also been observed, but they are uncommon (less than 1%). Bullous, blistering and exfoliative skin changes have been reported, including very rare Stevens-Johnson syndrome/toxic epidermal necrolysis, which in some cases is fatal. Other hair and nail changes, usually not serious, have been reported in clinical trials, such as paronychia, which is common, and eyelash/eyebrow changes, and brittle and loose nails, which are rare. 8. Post-marketing: Skin and subcutaneous tissue abnormalities - Hair and nail changes, usually not serious, have been reported rarely in post-marketing surveillance, such as hirsutism, eyelash/eyebrow changes, paronychia, and brittle and loose nails.

It is contraindicated for those who are allergic to this product or its ingredients.

Precautions for children: The efficacy and safety of erlotinib have not been studied in children. Erlotinib is not recommended for use in children. Precautions for pregnancy and lactation: 1. Pregnancy category D 2. No adequate, controlled studies of erlotinib have been conducted in pregnant women. During the organogenesis period, when the plasma drug concentration of erlotinib in rabbits reached 3 times the human plasma concentration when 150 mg was administered daily, maternal toxicity occurred, leading to embryonic death and abortion. Female rats receiving erlotinib at a dose equivalent to 0.3 or 0.7 times the clinical dose of 150 mg (calculated based on mg/m2) before mating to the first week of pregnancy can cause early absorption and lead to a decrease in the number of viable fetuses. The potential risk to humans is unknown. Women of childbearing age should avoid pregnancy while taking erlotinib. Adequate contraception should be used during treatment and for at least 2 weeks after completion of treatment. Pregnant women can only continue treatment if it is believed that the benefit to the mother outweighs the risk to the fetus. If erlotinib is used during pregnancy, patients should be aware of the potential harm to the fetus and the possibility of abortion. 3. It is unclear whether erlotinib is secreted in human milk. Because many drugs can be secreted into human milk and the effects of erlotinib on infants have not been studied, women are advised to avoid breastfeeding when using erlotinib. Elderly precautions: 1. NSCLC maintenance therapy Among all patients participating in randomized NSCLC maintenance therapy trials, approximately 66% of patients were younger than 65 years old, and 34% of patients were equal to or older than 65 years old. The hazard ratio for overall survival in patients under 65 years old was 0.78 (95% CI: 0.65, 0.95), and the hazard ratio for overall survival in patients 65 years old or older was 0.88 (95% CI: 0.68, 1.15). 2. Second/third-line treatment for NSCLC Among the total population participating in randomized NSCLC trials, 62% of patients were younger than 65 years old, while 38% were older than 65 years old. Survival benefits were obtained in both age groups (see [Clinical Trials]). 3. First-line treatment for pancreatic cancer In pancreatic cancer trials, 53% of patients were younger than 65 years old, while 47% were older than 65 years old. No meaningful safety and pharmacokinetic differences were observed between younger or older patients. Therefore, no dose adjustment is recommended for elderly patients.

1. Interaction studies have only been conducted in adults. 2. In vitro studies have found that erlotinib is a strong inhibitor of CYPIA1, a moderate inhibitor of CYP3A4 and CYP2C8, and a strong inhibitor of UGTIA1-induced glucuronidation. 3. Due to the very limited expression of CYPIA1 in human tissues, it is impossible to obtain the physiological relevance of strong CYPIA1 inhibitors. 4. The inhibition of glucuronidation may lead to interactions with some UGTIA1 substrate drugs that can only be cleared through this pathway. For patients with low UGTIA1 expression levels or genetic glucuronidation diseases (such as Gilbert's disease), their serum bilirubin concentration may be increased and must be used with caution. 5. Erlotinib is metabolized by the liver, mainly through CYP3A4, and a small amount through CYPIA2 and the lung isoenzyme CYPIA1. Any drug metabolized by these enzymes or inhibitors or inducers of the enzymes may interact with erlotinib. 6. Strong CYP3A4 inhibitors can reduce erlotinib metabolism and increase its blood concentration. Compared with erlotinib alone, ketoconazole (200 mg twice daily for 5 days) increased the AUC of erlotinib (mean AUC increased by 86%) and Cmax by 69% by inhibiting CYP3A4 metabolic activity. When erlotinib was co-administered with ciprofloxacin, an inhibitor of CYP3A4 and CYPIA2, the AUC and Cmax of erlotinib increased by 39% and 17%, respectively, and the AUC and Cmax of the active metabolite increased by approximately 60% and 48%, respectively. The clinical relevance of this increased exposure has not yet been determined. Erlotinib should be used with caution in combination with ciprofloxacin or strong CYPIA2 inhibitors (such as fluvoxamine). Therefore, care should be taken when erlotinib is co-administered with strong CYP3A4 inhibitors or combined CYP3A4/CYPIA2 inhibitors. Once toxic effects are found, the erlotinib dose should be reduced. 7. Strong CYP3A4 inducers can increase the metabolism of erlotinib and significantly reduce the blood concentration of erlotinib. Compared with erlotinib alone, after administration of 150 mg erlotinib, rifampicin (600 mg once daily for 7 days) caused a 69% decrease in the mean AUC of erlotinib by inducing CYP3A4 metabolic activity. 8. If rifampicin has been used before treatment or during treatment, the mean AUC of erlotinib after a single dose of 450 mg is 57.5% of that after a single dose of 150 mg erlotinib without rifampicin treatment. If possible, other drugs that do not have strong CYP3A4 induction should be selected for treatment. For patients who need to be treated with a strong CYP3A4 inducer (such as rifampicin) for erlotinib, the dose should be increased to 300 mg under close monitoring of drug safety (see [Precautions]). If it can be well tolerated for more than 2 weeks, the dose can be further increased to 450 mg, while closely monitoring drug safety. Higher doses have not been studied under this condition. When used in combination with other inducers, such as phenytoin, carbamazepine, barbiturates or St. Johns Wort, exposure may also be reduced. Special caution should be exercised when erlotinib is used in combination with these active drugs. If possible, other therapeutic drugs without strong CYP3A4 induction activity can be considered. 9. Erlotinib pretreatment or co-administration has no effect on the clearance of typical CYP3A4 substrates midazolam and erythromycin. Therefore, significant interactions with the clearance of other CYP3A4 substrates are unlikely to occur. The oral availability of midazolam appears to be reduced by 24%, but this is not due to the effect of CYP3A4 activity. In another clinical trial, erlotinib was co-administered with paclitaxel, a CYP3A4/2C8 substrate, and had no effect on its pharmacokinetics. Therefore, there may be no significant interaction with the clearance of other CYP3A4 substrates. 10. The solubility of erlotinib is related to pH. When the pH value increases, the solubility of erlotinib decreases. Drugs that alter the pH of the upper gastrointestinal tract may alter the solubility of erlotinib and, in turn, its bioavailability. When erlotinib was coadministered with the proton pump inhibitor omeprazole, the AUC and Cmax of erlotinib were reduced by 46% and 61%, respectively. There was no change in Tmax or half-life. When erlotinib was coadministered with 300 mg of the H2 receptor blocker ranitidine, the AUC and Cmax of erlotinib were reduced by 33% and 54%, respectively. Therefore, when possible, erlotinib should be avoided in combination with drugs that reduce gastric acid production. Increasing the dose of erlotinib when coadministered with these drugs is unlikely to compensate for the reduced exposure. However, when erlotinib was administered at intervals from ranitidine (ranitidine 150 mg twice daily, erlotinib was administered 2 hours before or 10 hours after administration), the AUC and Cmax of erlotinib were only reduced by 15% and 17%, respectively. If patients need to receive such drugs, H2 receptor blockers such as ranitidine should be considered and administered at intervals. Erlotinib must be administered 2 hours before or 10 hours after H2 receptor blockers. 11. Erlotinib is a substrate of the active substrate transporter of P-glycoprotein. Co-administration with Pgp inhibitors (such as cyclosporine and verapamil) may change the distribution and/or elimination of erlotinib. The effect of this interaction on toxicity (such as CNS) is not yet clear, so it should be used with caution in this case. 12. Erlotinib will increase platinum concentrations. In a clinical study, the combination of erlotinib with carboplatin and paclitaxel increased the total platinum AUC0-48 by 10.6%. Although the difference is statistically significant, the degree of difference is not considered clinically relevant. In clinical practice, there may be other common factors that lead to increased exposure to carboplatin, such as renal impairment. Carboplatin and paclitaxel have no significant effect on the pharmacokinetics of erlotinib. 13. Capecitabine may increase the concentration of erlotinib. When erlotinib is used in combination with capecitabine, the erlotinib AUC increases statistically significantly, and the Cmax value increases marginally compared to the data from another study of erlotinib alone. Erlotinib has no significant effect on the pharmacokinetics of capecitabine. 14. The combination of this product with statins may increase the incidence of statin-induced myopathy, including the rare rhabdomyolysis. 15. Smoking is known to induce CYPIA1 and CYPIA2, resulting in a 50-60% reduction in erlotinib exposure. Smokers are advised to quit smoking (see [Dosage and Administration]).

Store at 25℃. 15-30℃ is also acceptable. Keep the medicine out of reach of children.

100 mg

36 months