Tegadur 替吉奥胶囊

【 Function and Indication 】
The indications of S-1 capsule are gastric cancer, head and neck tumor, inoperable or resectable breast cancer, non-small cell cancer, colon cancer, pancreatic cancer and biliary tract cancer.

“Model and specification”
20mg, 14 capsules per box, 28 capsules per box and 42 capsules per box.

【 Usage and dosage 】
Usually, the reference dose (one dose) of the first dose for adults should be calculated according to the body surface area in the table below, twice a day, once after breakfast and once after dinner, for 28 days, and then the drug is stopped for 14 days. This is a cycle and can be repeated.

[Combined medication]
Oral S-1 capsule 80mg/m2/ day, twice a day, once after breakfast and once after dinner, for 14 days, and the drug was stopped for 7 days; Cisplatin: 75mg/m2, intravenous drip for three days (days 1, 2 and 3). Every 3 weeks is a cycle, and treatment should be carried out for at least 2 cycles.
It can be combined with some traditional Chinese medicine life preservers to improve the effect of S-1 and reduce the side effects of drugs. The combination of traditional Chinese medicine and western medicine complements each other.

[Clinical research]
(S-1) is an oral anticancer agent derived from fluorouracil, which includes tegafur (FT) and the following two kinds of regulators: gemmipramine (CDHP) and oteracil (Oxo). The functions of its three components are as follows: FT is a prodrug of 5-Fu, which has excellent oral bioavailability,

It can be converted into 5-Fu in vivo. CDHP can inhibit the catabolism of 5-Fu released from FT under the action of dihydropyrimidine dehydrogenase, which is helpful to neutralize the effective depth of 5-Fu in tumor tissue for a long time, thus achieving similar curative effect as continuous intravenous infusion of 5-Fu. Oxo can block the phosphorylation of 5-Fu. After oral administration, Oxo has a high distribution concentration in gastrointestinal tissues, thus affecting the distribution of 5-Fu in gastrointestinal tract and further reducing the toxicity of 5-Fu. Compared with 5-Fu, S-1 has the following advantages: ① It can maintain a high blood concentration and improve its anticancer activity; ② obviously reduce drug toxicity; ③ Convenient administration.
In Japan, S-1 was approved to treat advanced gastric cancer in 1999, head and neck cancer in 2001, colorectal cancer in 2003 and non-small cell lung cancer in 2004. Years of clinical application have proved that S-1 is a safe and effective anticancer drug. According to statistics, more than 80% cases of advanced gastric cancer in Japan are treated with S-1, and the effective rate (CR+PR) can reach 44.6%.

【 Precautions 】
1. The dose-limiting toxicity of this product is myelosuppression, which is different from the previous oral fluorouracil drugs. Special attention should be paid to frequent clinical examination when using it.
2. This product may occasionally cause serious liver damage such as severe hepatitis, so it is necessary to check the liver function regularly for early detection. We must pay attention to the precursor symptoms of liver damage such as loss of appetite and fatigue. If jaundice (yellow eyeball) occurs, we should stop taking the medicine immediately and give appropriate treatment.
3. Combined with other fluorouracil antineoplastic drugs, or with other drugs (such as folinic acid, tegafur, uracil combined chemotherapy, etc.), or with the antifungal drug flucytosine, it may lead to serious blood dysfunction, so it is not appropriate to combine with the above drugs.

Other considerations:
1. Matters needing attention related to usage and dosage
(1) In the course of treatment, if it is necessary to shorten the drug withdrawal period for treatment, it must be confirmed that there are no abnormal clinical examination values (hematological examination, liver and kidney function examination) and digestive tract symptoms related to this product, and there is no safety problem. The withdrawal period shall not be less than 7 days. The safety of shortening the withdrawal period for patients with inoperable or recurrent breast cancer has not been established (no experience).
(2) In order to avoid serious side effects such as bone marrow suppression and severe hepatitis, clinical examination (hematological examination, liver and kidney function examination, etc.) should be conducted at least once every two weeks before the start of each cycle and during the administration period, and the patient’s condition should be closely observed. In case of abnormal situation, appropriate measures should be taken, such as prolonging the withdrawal time, reducing the dosage and stopping the administration. Especially in the first cycle and when the dose is increased, clinical examination should be carried out frequently (refer to clinical trial items).
(3) Basic research shows that the bioavailability of potassium oteracil changes greatly when administered on an empty stomach in rats, which can inhibit the phosphorylation of 5-FU and weaken the anti-tumor effect, so this product should be taken after meals.
(4) For patients with non-small cell cancer, the effectiveness and safety beyond the usage and dosage used in the late phase II clinical study (oral administration of this product for 21 consecutive days and cisplatin 60mg/m2 on the eighth day) have not been established.
(5) The efficacy and safety of this product combined with chest and abdomen radiotherapy have not been established.

2. The following patients should be used with caution.
(1) Patients with myelosuppression.
(2) Patients with renal dysfunction.
(3) Patients with liver dysfunction.
(4) Patients with infection.
(5) Patients with abnormal glucose tolerance.
(6) Interstitial pneumonia or patients with previous history of interstitial pneumonia.
(7) Patients with heart disease or patients with previous heart disease history.
(8) Patients with peptic ulcer or bleeding.

3. Important considerations
(1) After stopping using this product, give other fluorouracil antineoplastic drugs or antifungal drugs flucytosine at least 7 days later.
(2) After stopping using fluorouracil antineoplastic drugs or antifungal drugs, it is necessary to give this product at an appropriate interval.
(3) It has been reported that severe infection (sepsis) caused by bone marrow suppression leads to septic shock or disseminated intravascular coagulation or even death, so attention should be paid to the appearance or deterioration of symptoms such as infection and bleeding tendency.
(4) When patients of childbearing age need to take medicine, the influence on gonads should be considered.
(5) It has been reported that this product can lead to the deterioration or even death of interstitial pneumonia. Therefore, when using this product, it is necessary to confirm whether there is interstitial pneumonia, closely observe the respiratory state, cough, fever and other clinical symptoms, and conduct chest X-ray examination. Pay attention to the appearance and deterioration of interstitial pneumonia. Stop taking drugs and take appropriate measures when abnormal conditions are found. [Especially in patients with non-small cell lung cancer, the possibility of lung function damage such as interstitial pneumonia is greater than that of other tumor patients.

[Adverse reactions and contraindications]
In the clinical trials of single drug administration (except for patients with breast cancer, pancreatic cancer and biliary tract cancer who have been treated), 578 cases can be evaluated for side effects, and the incidence of side effects is 87.2%(504 cases). The incidence of side effects in patients with breast cancer (including inoperable breast cancer or recurrent breast cancer (excluding breast cancer treated in the early stage), pancreatic cancer and biliary tract cancer were 96.4%, 98.3% and 94.9%, respectively, which was higher than other tumors. Among patients with pancreatic cancer, the incidence of severe side effects is high, especially gastrointestinal symptoms such as loss of appetite, nausea, vomiting and diarrhea.

[taboo]
1. Patients with severe allergic history to the ingredients of this product.
2. Patients with severe myelosuppression (which may worsen symptoms).
3. Patients with severe renal dysfunction.
4. Patients with severe liver dysfunction.
5 patients who are using other fluorouracil antineoplastic drugs (including combined chemotherapy with these drugs).
6. Patients who are using fluorocytosine.

[Medication for pregnant women]
1. Pregnant women and women of childbearing age are forbidden to use this product.
2. Lactating women should stop breastfeeding if they need medication.

[Drug for children]
The safety of this product for infants, newborns, infants and children with low birth weight has not been established.

[Drug Interaction]
(1) It shall not be combined with the following drugs
Drug name, clinical symptoms, treatment mechanism and risk factors
Fluorouracil antineoplastic agents
Fluorouracil (5-Fu, etc.)
Tegafur uracil compound preparation (UFT, etc.)
Tegafur (Futraful)
Furtulon (deoxyuridine)
Capecitabine (Xeloda)
In the early stage, carmofur combined with medication can lead to serious blood system disorders and digestive tract dysfunction such as diarrhea and stomatitis.
Use other drugs at least 7 days after stopping using this product. After other drugs are stopped, it is necessary to give this product at an appropriate interval. Gemmipramine in this product can inhibit the catabolism of 5-FU in the combined drugs, and significantly increase the concentration of 5-FU in blood (refer to the pharmacokinetic term).
Combined chemotherapy of folinic acid+tegafur+uracil
(folinic acid +UFT, etc.)
Calcium levofolinate+fluorouracil combined chemotherapy
(calcium levofolinate +5-FU)
Fluoropyrimidine antifungal agents
Flucytosine
(2) Care should be taken when it is combined with the following drugs.
Drug name, clinical symptoms, treatment mechanism and risk factors
Phenytoin sodium can cause phenytoin sodium poisoning (nausea, vomiting, nystagmus, dyskinesia, etc.). Observe the patient’s condition closely, stop using this product immediately and take appropriate measures if any abnormality is found. Tegafur can inhibit the metabolism of phenytoin sodium and increase its blood concentration.
Dicoumarin Potassium This product can enhance the effect of dicoumarin and lead to abnormal coagulation function. The mechanism is unknown
Other antineoplastic drugs
Radiation exposure can enhance the side effects of blood system and digestive system. Pay attention to the patient’s state, and take appropriate measures such as reducing the amount or stopping the drug when finding any abnormality. Side effects are mutually reinforcing.

[Drug overdose]
Once an overdose occurs, it should be closely monitored, supported and treated symptomatically.

[storage]
Sealed and stored away from light at room temperature.