TS-ONE Special Precautions

Precautions on Dosage and Administration: When the dose is decreased according to the patient's condition, the following standard doses should be referenced. (See Table 7.)

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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, i.e., 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 such as 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, such as 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 Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Since basic investigations (rats) have revealed that the bioavailability of oteracil potassium changes when the drug is administered in the fasting state, it is speculated that phosphorylation of fluorouracil is inhibited and that its antitumor effect is reduced; therefore, TS-ONE should be administered after meals.
The recommended treatment course for post-operative adjuvant chemotherapy for gastric cancer is one year after surgery. Treatment with TS-ONE beyond one year after surgery has not been studied.
Efficacy and safety of combination therapy with TS-ONE and chest or abdominal radiation have not yet been established.
Careful Administration (TS-ONE should be administered with care in the following patients): Patients with bone marrow depression [Bone marrow depression may be aggravated].
Patients with 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 such as bone marrow depression may be enhanced (See Pharmacology: Pharmacokinetics under Actions)].
Patients with hepatic disorder [Hepatic disorder may be aggravated].
Patients having infectious disease [Infectious disease may be aggravated as a result of bone marrow depression].
Patients with abnormal glucose tolerance [Abnormal glucose tolerance may be aggravated].
Patients with a current or previous history of interstitial pneumonia [Interstitial pneumonia may be aggravated or may develop].
Patients with a current or previous history of heart disease [Symptoms may be aggravated].
Patients with gastrointestinal ulcer or hemorrhage [Symptoms may be aggravated].
Elderly patients (See Use in the Elderly under Dosage & Administration).
Patients with varicella [Fatal systemic damage may occur].
Important Precautions: A minimum washout period of 7 days must be provided when other fluoropyrimidine-group anti-cancer drugs or the antifungal agent flucytosine are used after withdrawal TS-ONE (See Interactions).
If dehydration secondary to severe enteritis occurs, take proper measure such as fluid replacement. (See Clinically significant adverse reactions under Adverse Reactions).
An appropriate washout period must be provided when TS-ONE is used after withdrawal of other fluoropyrimidine-group anti-cancer 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 such as 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. Pulmonary disorders including interstitial pneumonia are more likely to occur in patients with non-small cell lung cancer than in patients with other cancers (See Adverse Reactions).
Since administration of TS-ONE in hepatitis B virus carriers, HBs antigen negative and HBc antibody positive patients, or HBs antigen negative and HBs antibody positive patients may result in reactivation of hepatitis B, the status of previous exposure to hepatitis infection should be confirmed, and appropriate measures should be taken before administration. Following administration of TS-ONE, it is necessary to pay attention to signs or symptoms of the reactivation of Hepatitis B, and follow-up monitoring for hepatic function tests or viral markers are recommended.
Precautions concerning Use: Precaution in giving the drug to patients: For drugs that are dispensed in a press-through package (PTP), instruct the patient 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 such as mediastinitis.]
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 extremely rare patients, and if fluorouracil-group drugs are administered to such patients, serious adverse reactions (such as 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 condition (in dogs) and its relief effect on the gastrointestinal toxicity 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.
Effect on ability to drive and use machine: TS-ONE has a moderate influence on the ability to drive and use machines as fatigue, dizziness, blurred vision, and nausea are common adverse reactions of TS-ONE in combination with cisplatin.