TS-ONE

TS-ONE

tegafur + gimeracil + oteracil

Manufacturer:

Taiho

Distributor:

Pharmaforte
Full Prescribing Info
Contents
Tegafur, gimeracil, oteracil potassium.
Description
Each TS-ONE capsule 20 contains tegafur 20 mg, gimeracil 5.8 mg and oteracil potassium 19.6 mg.
Each TS-ONE capsule 25 contains tegafur 25 mg, gimeracil 7.25 mg and oteracil potassium 24.5 mg. TS-ONE contains the following inactive ingredients: Lactose hydrate, magnesium stearate, gelatin, sodium lauryl sulfate, titanium oxide and FD&C yellow No.6 (TS-ONE 25).
Size and Weight: Total Length: 14.5 mm; long diameter (cap): 5.2 mm; short diameter (body): 5 mm; weight: Approximately 179 mg (TS-ONE 20), 214 mg (TS-ONE 25).
Action
Pharmacology: Antitumor Activity: TS-ONE inhibits the growth of tumors eg, Yoshida sarcoma, AH-130 hepatoma, Sato lung carcinoma (in rats), Sarcoma-180, Lewis lung carcinoma and Colon-26 (in mice) transplanted SC. It also inhibits the growth of human cancers eg, gastric, colorectal, breast, lung, pancreatic and renal when transplanted SC to nude rats or mice.
TS-ONE has survival effects in the mouse Lewis lung carcinoma and L5178Y metastasis models and has effect to inhibit the growth of tumors in nude rat models, in which human gastric cancer and colorectal cancer cell lines were orthotopically implanted.
Mechanism of Action: TS-ONE contains tegafur (FT), gimeracil (CDHP) and oteracil potassium (Oxo) and its antitumor activity after oral administration is based on 5-fluorouracil (5-FU) that appears gradually in the body via the transformation of FT. CDHP increased the concentration of 5-FU, which is converted from FT, by selectively and reversibly inhibiting DPD, a catabolic enzyme of 5-FU, which is particularly distributed in the liver. 5-fluoronucleotides, phosphorylated metabolites of 5-FU, are highly maintained in tumor tissues, thereby enhancing the antitumor activity in proportion to the increase in the concentration of 5-FU in the body. Oxo selectively inhibits the production of 5-fluoronucleotides from 5-FU by distributing in the gastrointestinal tissue as a result of oral administration, and selectively and reversibly inhibiting orotate phosphoribosyltransferase.
The main mechanism of action of 5-FU is the inhibition of DNA synthesis resulting from the antagonistic effect of the active metabolite FdUMP, acting upon dUMP to form ternary complex with thymidylate synthase and the reduced folic acid. RNA function is also thought to be damaged by conversion of 5-FU to FUTP and its incorporation into RNA molecule.
Pharmacokinetics: Pharmacokinetic parameters obtained from the plasma concentrations of TS-ONE administered to 12 cancer patients in a single oral dose of 32-40 mg/m2 after a meal are shown in Table 1. The amount excreted in the urine within 72 hrs after administration accounted for 52.8% of the CDHP, 7.8% of the FT, 2.2% of the Oxo, 11.4% of the metabolite cyanuric acid (CA) and 7.4% of the 5-FU. (See Table 1.)

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When TS-ONE was orally administered at a dose of 25-200 mg/body, the area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax) of FT, CDHP, Oxo and 5-FU increased in a dose-dependent manner. When its plasma concentration was measured 1 day, 7 days, 14 days and 28 days after administration of 32-40 mg/m2 of TS-ONE twice daily for 28 consecutive days, it rapidly reached a constant level. Endogenous uracil (Ura) rapidly decreased even after consecutive administration of TS-ONE and the CDHP-induced DPD inhibition was reversible, and no enhancing effect was observed.
TS-ONE, alone or in combination with other fluoropyrimidine-group drugs, was orally administered to rats for 7 consecutive days and the plasma concentrations of 5-FU was measured 2 hrs after the final dose. It was found to be 4.1, 8.1, 2.8, 5.7, 6.9 and 2.3 times higher when combined with 5-FU, FT, FT·Ura, carmofur, doxifluridine and flucytosine, respectively, than when administered alone. This suggests that the combined use of TS-ONE and other fluoropyrimidine-group drugs may enhance adverse reactions.
When TS-ONE was administered to a renal dysfunction rabbit, CDHP renal clearance was found to be decreased and the blood concentration of 5-FU was markedly increased compared to control animal. These suggest that adverse reactions may be enhanced.
Creatinine clearance value (CrCl estimate) was calculated from serum creatinine value, gender, age and weight using the Cockcroft-Gault equation* for the clinical study patients for whom pharmacokinetics was examined in detail. The AUCs of 2 patient groups with normal and slightly impaired renal function were tabulated by range of creatinine clearance value (CrCl estimate).
Insufficient data are currently available to recommended dose modifications in patients with renal impairment. TS-ONE should be administered with caution in such patients.
Use of TS-ONE in patients with severe renal impairment has not been studied. Hence, TS-ONE is contraindicated in such patients (see Contraindications). See Table 2.

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Pharmacokinetics of TS-ONE in patients with hepatic impairment has not been evaluated. It should be used with caution in patients with mild or moderate hepatic impairment. TS-ONE is contraindicated in patients with severe hepatic impairment.
Protein-Binding: The rates of protein-binding of each component and 5-FU in human serum were 49-56% for FT, 32-33% for CDHP, 7-10% for Oxo and 17-20% for 5-FU (in vitro).
Metabolic Enzyme: It has been reported that CYP2A6 is the major cytochrome P-450 isoenzymes in human liver microsomes involved in the metabolic transformation of FT to 5-FU (in vitro).
Clinical Studies: Randomized Phase III Study of Postoperative Adjuvant Chemotherapy: The survival benefit of TS-ONE monotherapy (1 year after surgery, 529 patients) was compared with surgery alone (530 patients) in patients with stage II or III gastric cancer after curative gastrectomy (median postoperative follow-up period: 3 years). TS-ONE reduced the risk of death by 32% compared with surgery alone, with a hazard ratio for death of 0.675 (95% confidence interval: 0.523-0.871, p=0.0024 by the log-rank test). The 3-year survival rate after surgery was 80.5% in the TS-ONE group and 70.1% in the surgery alone group. (See Figure 1.)
TS-ONE reduced the risk of relapse by 38% compared with surgery alone, with a hazard ratio for relapse or death of 0.622 (95% confidence interval: 0.501-0.772, p<0.0001 by the log-rank test). The 3-year relapse-free survival rate was 72.2% in the TS-ONE group and 60.1% in the surgery alone group. (See Figure 2.)

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Time of Occurrence of Adverse Reactions and Period of Recovery: The time of occurrence of noteworthy adverse reactions following administration of TS-ONE was analyzed in 453 patients enrolled in late clinical phase II studies of TS-ONE for advanced or recurrent cancer in Japan. The results were as follows: Among abnormal laboratory test results below any of the criteria including a white blood cell (WBC) count of 3000/mm3, a hemoglobin level of 8 g/dL, and a platelet count of 7.5 x 104/mm3, the median time to nadir in the cycle, where the lowest level in a case was reached, was 27 days for WBC count, 25 days for hemoglobin level and 24 days for platelet count.
On the other hand, in patients who were confirmed to have recovered from the above criteria, the median between the nadir of these values and recovery from them in the course were 7 days, 5.5 days and 6 days, respectively. (See Table 3.)

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When the time of occurrence of adverse reactions after the start of the 1st dose of TS-ONE was examined to assess the causality between them, the median until the occurrence of diarrhea, rash and stomatitis, which were judged adverse reactions were 24.5 days, 21 days and 28 days, respectively.
On the other hand, the median between the highest grade of these adverse reactions and the improvement from them were 9 days for diarrhea, 14 days for rash and 13.5 days for stomatitis. (See Table 4.)

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Adverse Reactions in the Presence of Renal Disorder: In the analysis of the drug use investigation (survey of actual use on the market) conducted for one year after the initial marketing in Japan, frequency of adverse reactions was tabulated by the range of creatinine clearance value (CrCl estimate), calculated from serum creatinine value, gender, age and weight using Cockcroft-Gault equation. The results are presented in Table 5.
In the patients, as creatinine clearance value decreased, the incidence of adverse reactions increased and the severity of the adverse reactions also increased. Additionally, in the patients who were treated initially at the lower dose (mostly, 1 stage lower than the standard), the incidence of adverse reactions was low, compared with the patients who were treated initially at the standard dose. (See Table 5.)

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Indications/Uses
Postoperative adjuvant chemotherapy for locally-advanced [stage II (excluding T1), IIIA or IIIB] gastric cancer.
Dosage/Direction for Use
The standard doses stated as follows are the recommended initial dose for adults according to body surface area (BSA). TS-ONE should be administered twice daily after breakfast and after the evening meal, for 28 consecutive days, followed by a 14-day rest. This is regarded as 1 course of the regimen. BSA (m2) ≥1.5: Initial dose (tegafur equivalent): 60 mg; BSA (m2) 1.25 to <1.5: Initial dose (tegafur equivalent): 50 mg; BSA (m2) of <1.25: Initial dose (tegafur equivalent): 40 mg. All doses are to be taken twice daily.
The initial dose can be decreased according to the patient's tolerance to the medication. The reduction of dose may be done in 10-mg intervals, with a lower limit of 40 mg.
When the dose is decreased according to the patient's condition, the following standard doses should be referenced. For the initial dose of 40 mg twice daily, the decrease should be to drug rest. From 50 mg twice daily, the decrease should be to 40 mg twice daily, then to drug rest. From 60 mg twice daily, the decrease should be to 50 mg twice daily, then to 40 mg twice daily, up to drug rest.
If a drug rest period therapeutically needs to be shortened, it should be implemented after confirming that no drug-induced abnormalities in laboratory findings (hematological tests, liver and renal function tests) and no gastrointestinal symptoms occur, ie, the drug is not problematic in terms of safety. A minimum drug rest period of 7 days must be provided.
To avoid serious adverse reactions eg, bone marrow depression and fulminant hepatitis, the patient's condition should be monitored thoroughly by performing laboratory tests (hematological tests, liver and renal function tests) before the start of each course and at least once every 2 weeks during dosing. If any abnormal findings are observed, appropriate measures should be taken eg, prolongation of the drug rest period, dosage reduction according to the previously mentioned standard doses, or discontinuing administration of TS-ONE. Laboratory tests should be performed frequently, particularly when one course of the regimen is conducted and the dose is increased (see Clinical Studies under Actions).
Since basic investigations (rats) have revealed that the bioavailability of oteracil potassium changes when TS-ONE is administered in the fasting state, it is speculated that phosphorylation of fluorouracil is inhibited and that its antitumor effect is reduced, TS-ONE should be administered after meals.
The recommended treatment course for postoperative adjuvant chemotherapy for gastric cancer is 1 year after surgery. Treatment with TS-ONE >1 year after surgery has not been studied.
Contraindications
History of severe hypersensitivity to tegafur, gimeracil and/or oteracil potassium, or to any of the ingredients of TS-ONE.
Severe bone marrow depression (bone marrow may be aggravated); severe renal disorder [The urinary excretion of gimeracil, a catabolic enzyme inhibitor of fluorouracil (5-FU), is markedly decreased, thereby the blood concentration of 5-FU is increased. These suggest that adverse reactions eg, bone marrow depression may be enhanced (see Pharmacokinetics under Actions)].
Severe hepatic disorder (hepatic disorder may be aggravated); treatment with other fluoropyrimidine-group anticancer drugs including combination therapies with them (see Interactions); treatment with flucytosine (see Interactions).
Use in pregnancy & lactation: TS-ONE is contraindicated to patients who are or may be pregnant. It has been reported that pregnant women treated with tegafur/uracil have been delivered of neonates with malformation.
Teratogenicity is also reported in animal experiments. Consecutive oral administration of TS-ONE (corresponding to 7 mg/kg and 1.5 mg/kg as tegafur) to pregnant rats and rabbits has been observed to have fetal visceral and skeletal anomalies, and retarded ossification.
When TS-ONE is administered to nursing mothers, breastfeeding should be discontinued (there is no clinical data). Excretion to milk has been reported in animal (rats) experiments.
Warnings
Cancer chemotherapy with TS-ONE should be administered only to patients for whom treatment with TS-ONE has been judged appropriate, under the supervision of experienced physicians who are familiar with cancer chemotherapy and who are based in medical institutions with adequate emergency facilities. A patient who will receive chemotherapy that includes TS-ONE should be carefully selected with reference to the package insert of each concomitant drug. TS-ONE should only be administered after the effectiveness and risks have been explained, and informed consent has been given by the patient or by patient's guardian before chemotherapy is started.
Since the dose-limiting toxicity (DLT) of TS-ONE is bone marrow depression (see Adverse Reactions), in which it is different from conventional oral fluorouracil-group drugs, it is necessary to be alert for changes in the laboratory data. Laboratory tests should be performed frequently.
In as much as there may occur severe hepatic disorders eg, fulminant hepatitis, the patient's hepatic functions should be monitored closely by periodic hepatic function tests to detect hepatic disorder early. Close monitoring is necessary to detect possible malaise accompanied by anorexia, which is thought to be a sign or subjective symptom of hepatic disorder. If jaundice (yellow ocular coloring) appears, TS-ONE should be discontinued immediately, and appropriate measures should be taken.
TS-ONE should not be combined with other fluoropyrimidine-group anticancer drugs, combination therapies with them, or the antifungal agent flucytosine because there is a possibility that combination with these drugs may cause adverse reactions eg, serious blood dyscrasia (see Interactions).
In addition, TS-ONE should be administered in strict conformity with the Dosage & Administration.
Special Precautions
Patients with bone marrow depression (it may be aggravated), renal disorder [the urinary excretion of gimeracil, a catabolic enzyme inhibitor of fluorouracil (5-FU), is markedly decreased, thereby increasing the blood concentration of 5-FU. These suggest that adverse reactions eg, bone marrow depression may be enhanced (see Pharmacokinetics under Actions)], hepatic disorder (it may be aggravated). Also in patients having infectious disease (it may be aggravated as a result of bone marrow depression); abnormal glucose tolerance (it may be aggravated); with a current or previous history of interstitial pneumonia (it may be aggravated or may develop); with a current or previous history of heart disease (symptoms may be aggravated); with gastrointestinal ulcer or hemorrhage (symptoms may be aggravated) and with varicella (fatal systemic damage may occur).
Important Precautions: A minimum wash out period of 7 days must be provided when other fluoropyrimidine-group anticancer drugs or the antifungal agent flucytosine are used after withdrawal of TS-ONE (see Interactions).
If dehydration secondary to severe enteritis occurs, proper measures should be taken eg, fluid replacement (see Clinically Significant Adverse Reactions under Adverse Reactions).
An appropriate wash out period must be provided when TS-ONE is used after withdrawal of other fluoropyrimidine-group anticancer drugs or the antifungal agent flucytosine in consideration of the influence of these prior agents (see Interactions).
Since patients who have died of septic shock or disseminated intravascular coagulation due to serious infectious disease (septicemia) caused by bone marrow depression have been reported, care should be taken to avoid the appearance or aggravation of infection or bleeding tendency.
Administration to patients with reproductive potential should be performed with consideration of potential gonadic effects.
TS-ONE may cause or aggravate interstitial pneumonia with a possible fatal outcome. Therefore, patients must be examined for the presence of interstitial pneumonia before receiving TS-ONE, and be properly monitored for respiratory status and the onset of symptoms eg, cough and fever while receiving TS-ONE. Monitoring should include chest x-ray examination. If the onset or progression of interstitial pneumonia is observed, TS-ONE should be discontinued and appropriate measures should be taken.
Other Precautions: It has been reported that acute leukemia (in some cases accompanied with preleukemic phase) or myelodysplastic syndrome (MDS) have occurred in patients treated with TS-ONE.
It has been reported that deficiency of dihydropyrimidine dehydrogenase (DPD), a catabolic enzyme of fluorouracil, exists in an extremely rare patients and if fluorouracil-group drugs are administered to such patients, serious adverse reactions (eg, stomatitis, diarrhea, blood dyscrasia and neuropathy) may occur in the early stages of administration.
Although the causality of TS-ONE was unknown, it has been reported that cerebral infarction has occurred.
It has been reported that a remarkable decrease in gastric pH may induce diarrhea because oteracil potassium is labile to decompose in the gastric fluid under a hyperacid condition (in dogs) and its relief effect on the gastrointestinal toxicity is reduced when its composition ratio is decreased (in rats).
Repeated administration of TS-ONE to dogs has been reported to cause bulbar conjunctival and scleral pigmentation and nebula.
Use in children: The efficacy and safety of TS-ONE in children and adolescents have not been established. Therefore, use in this patient population is not recommended.
Use in the elderly: Since elderly patients often have decreased physiological functions, TS-ONE should be administered with care.
Use In Pregnancy & Lactation
TS-ONE is contraindicated to patients who are or may be pregnant. It has been reported that pregnant women treated with tegafur/uracil have been delivered of neonates with malformation.
Teratogenicity is also reported in animal experiments. Consecutive oral administration of TS-ONE (corresponding to 7 mg/kg and 1.5 mg/kg as tegafur) to pregnant rats and rabbits has been observed to have fetal visceral and skeletal anomalies, and retarded ossification.
When TS-ONE is administered to nursing mothers, breastfeeding should be discontinued (there is no clinical data). Excretion to milk has been reported in animal (rats) experiments.
Adverse Reactions
Table 6 shows frequency of the adverse events occurring in ≥5% of patients reported in the randomized study of postoperative adjuvant chemotherapy with TS-ONE for gastric cancer (see Table 6). The data are shown for 517 evaluable patients in the TS-ONE group and 526 evaluable patients in surgery alone group for adverse events. Frequency of all adverse events was 100% in the TS-ONE group and 93.3% in the surgery alone group, respectively. See Table 6.

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Clinically Significant Adverse Reactions: The overall safety profile of TS-ONE is based on data from 751 patients treated with TS-ONE monotherapy in clinical studies for advanced or recurrent cancer and from post-marketing experiences in multiple indications in Japan. The following adverse reaction frequencies were calculated from data for these clinical studies.
Bone Marrow Depression, Hemolytic Anemia: Since severe bone marrow depression eg, pancytopenia, agranulocytosis (symptoms: Fever, sore throat and malaise), leucopenia (46.7%), anemia (40.6%) and thrombocytopenia (15.7%) and hemolytic anemia (incidence unknown) may occur, the patient's condition should be monitored closely. If any abnormal findings are observed, appropriate measures should be taken eg, discontinuing administration of TS-ONE.
Disseminated Intravascular Coagulation (DIC): Since DIC (0.4%) may occur, the patient's condition should be monitored closely. If any abnormal findings are observed on blood test including those for platelet count, serum FDP level and plasma fibrinogen level, TS-ONE administration should be discontinued and appropriate measures should be taken.
Severe hepatic disorder eg, fulminant hepatitis (incidence unknown). (See Warnings.)
Dehydration: Since severe diarrhea may occur and may lead to dehydration (incidence unknown), the patient's condition should be monitored closely. If any such symptoms are observed, TS-ONE administration should be discontinued and appropriate measures should be taken eg, fluid replacement.
Severe Enteritis (0.5%): Since hemorrhagic enterocolitis, ischaemic enterocolitis and necrotizing enterocolitis may occur, the patient's condition should be monitored closely. If severe symptoms eg, abdominal pain and diarrhea occur, TS-ONE administration should be discontinued and appropriate measures should be taken.
Interstitial Pneumonia: Since interstitial pneumonia (0.3%) (early symptoms: Cough, shortness of breath, dyspnea and fever) may occur, the patient's condition should be monitored closely. If any abnormal findings are observed, TS-ONE administration should be discontinued and appropriate measures should be taken eg, chest x-ray examination and treatment with corticosteroids.
Myocardial Infarction, Angina Pectoris, Arrhythmia, Cardiac Failure: Since myocardial infarction, angina pectoris, arrhythmia (including ventricular tachycardia) and cardiac failure (the incidences of these adverse reactions are unknown) may occur, the patient's condition should be monitored closely. If chest pain, syncope, palpitation, abnormal ECG or breathlessness are observed, TS-ONE administration should be discontinued, and appropriate measures should be taken.
Severe Stomatitis, Gastrointestinal Ulcer, Gastrointestinal Hemorrhage and Gastrointestinal Perforation: Since severe stomatitis (incidence unknown), gastrointestinal ulcer (0.5%), gastrointestinal hemorrhage (0.3%) and gastrointestinal perforation (incidence unknown) may occur, the patient's condition should be monitored closely. If any abnormal findings are observed, TS-ONE administration should be discontinued and appropriate measures should be taken eg, examination by abdominal x-ray.
Acute Renal Failure: Since severe renal disorder eg, acute renal failure (incidence unknown) may occur, the patient's condition should be monitored closely. If any abnormal findings are observed, TS-ONE administration should be discontinued and appropriate measures should be taken.
Muco-Cutaneo-Ocular Syndrome (Stevens-Johnson Syndrome) and Toxic Epidermal Necrolysis (Lyell Syndrome): Since muco-cutaneo-ocular syndrome and toxic epidermal necrolysis (incidence unknown) may occur, the patient's condition should be monitored closely. If any abnormal findings are observed, TS-ONE administration should be discontinued and appropriate measures should be taken.
Psychoneurologic Disorders including Leukoencephalopathy or other Symptoms: Since leukoencephalopathy (major symptoms include consciousness disturbance, cerebellar ataxia and dementia-like symptoms), consciousness disturbance, disorientation, somnolence, hypomnesia, extrapyramidal symptoms, speech disorder, quadriplegia, gait disturbance, urinary incontinence or sensory disturbance (the incidences of these adverse reactions are unknown) may occur, the patient's condition should be monitored closely and if any such symptoms are observed, TS-ONE administration should be discontinued.
Acute Pancreatitis: Since acute pancreatitis (incidence unknown) may occur, the patient's condition should be monitored closely. If abdominal pain or increased serum amylase were observed, TS-ONE administration should be discontinued and appropriate measures should be taken.
Rhabdomyolysis: Since rhabdomyolysis (incidence unknown) marked by muscle pain feeling of weakness, increased CK (CPK) and increased myoglobin in the blood or urine may occur, TS-ONE administration should be discontinued and appropriate measures should be taken. Care should also be taken to avoid appearance of acute renal failure due to rhabdomyolysis.
Anosmia: Since dysosmia (0.1%) may occur and anosmia (incidence unknown) may develop, the patient's condition should be monitored closely. If any abnormal findings are observed, appropriate measures should be taken eg, discontinuing administration of TS-ONE.
Clinically Significant Adverse Reactions (similar drugs): Since the following adverse reactions have been reported to be caused by tegafur, if any abnormal findings are observed, appropriate measures should be taken eg, discontinuing administration of TS-ONE.
Hepatic Cirrhosis (prolonged prothrombin time, decreased albumin and decreased cholinesterase); angina pectoris, myocardial infarction, arrhythmia (including ventricular tachycardia) (chest pain, syncope, breathlessness, palpitation and abnormal ECG); and nephrotic syndrome.
Other Adverse Reactions: Since the following adverse reactions may occur (see Table 7), if any abnormal findings are observed, appropriate measures should be taken eg, dose reduction or discontinuing administration of TS-ONE. If hypersensitivity is observed, TS-ONE administration should be discontinued and appropriate measures should be taken. See Table 7.

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In patients who were administered TS-ONE in the randomized study of postoperative adjuvant chemotherapy for gastric cancer, frequency of lacrimation (7.2%) was higher than in the studies for treatment of advanced or recurrent cancer.
Other Adverse Reactions (Similar Drugs): Since the adverse reactions eg, fatty liver, difficulty in swallowing, tinnitus, excitement, increased serum uric acid and gynecomastia have been reported to be caused by tegafur, if any abnormal findings are observed, appropriate measures should be taken eg, dose reduction or discontinuing administration of TS-ONE.
Drug Interactions
TS-ONE Should Not be Co-Administered with the Following Drugs: Fluoropyrimidine-group anticancer drugs eg, fluorouracil, tegafur/uracil, tegafur, doxifluridine, capecitabine and carmofur; folinate plus tegafur-uracil combination therapy, levofolinate and fluorouracil combination therapy; flucytosine (fluoropyrimidine-group antifungal agent).
Signs, Symptoms and Treatment: Serious blood dyscrasia and gastrointestinal disorders eg, diarrhea and stomatitis may occur early when co-administered with these agents (therapies). These agents should not be administered during at least 7 days after withdrawal of TS-ONE. Additionally, when TS-ONE is used after withdrawal of these agents, an approximate wash out period must be provided in consideration of the influence of these agents.
Mechanism and Risk Factors: The gimeracil in TS-ONE inhibits the catabolism of the combined fluorouracil or the combined fluoropyrimidine-produced fluorouracil, thereby markedly increasing the blood concentration of fluorouracil (see Pharmacokinetics under Actions).
Care should be taken when co-administering TS-ONE with phenytoin, since phenytoin intoxication (nausea, vomiting, nystagmus and movement disorder) may develop. Thus, the patient's condition should be monitored closely. If any abnormal findings are observed, appropriate measures should be taken eg, discontinuation of treatment.
Phenytoin metabolism is inhibited by tegafur, thereby increasing the blood concentration of phenytoin.
When co-administering TS-ONE with warfarin potassium, warfarin's effect may be enhanced. Thus, caution should be exercised with respect to fluctuation of coagulating ability. Its mechanism is unknown.
Co-administration of TS-ONE with other anticancer drugs or radiation therapy should be taken with care, since adverse reactions eg, blood dyscrasias and gastrointestinal disorder may be aggravated, the patient's condition should be monitored closely. If any abnormal findings are observed, appropriate measures should be taken eg, dose reduction or discontinuation of treatment. Adverse reactions may be aggravated mutually.
Caution For Usage
Precautions Concerning Use: For drugs that are dispensed in a press-through package (PTP), patient should be instructed to remove the drug from the package prior to use. It has been reported that, if the PTP sheet is swallowed, the sharp corners of the sheet may puncture the esophageal mucosa, resulting in severe complications eg, mediastinitis.
Storage
Store below 25°C.
ATC Classification
L01BC53 - tegafur, combinations ; Belongs to the class of antimetabolites, pyrimidine analogues. Used in the treatment of cancer.
Presentation/Packing
Cap 20 (opaque, hard-shell, white cap and white body marked with "TC442") x 56's. 25 (opaque, hard-shell, orange cap and white body marked with "TC443") x 56's.
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