Erlotinib hydrochloride

The main ingredient of this product is erlotinib hydrochloride.

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]).

The main ingredient of this product is erlotinib hydrochloride.

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]).

The main ingredient of this product is erlotinib hydrochloride.

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]).