Furtulon Docefloxacin Capsules 200 (100 capsules) - for stomach and colon cancer.

Furtulon Docefluurine Capsules 200mg contain docefluurine (a fluorouracil derivative), which exerts its anti-cancer effect by inhibiting DNA synthesis in tumor cells. It is suitable for treating gastrointestinal malignancies such as gastric cancer and colorectal cancer.

I. Basic Drug Information

1. Generic name : Doxifluridine
2. English name : FURTULON Capsules
3. Product Name : Fluorotelon Capsules 200
4. Dosage form : Hard capsules (size 2)
5. Indications : Gastric cancer, colorectal cancer, breast cancer, cervical cancer, bladder cancer
6. Element
   • Active ingredient : Each capsule contains 200mg of desoxyfluorouridine, a drug approved by the Japanese Pharmacopoeia.
   • Additives : The contents contain lactose syrup, hydroxypropyl methylcellulose, talc, and magnesium stearate; the capsule shell contains titanium dioxide, ferric oxide, sodium lauryl sulfate, and gelatin.
7. Properties
   • Color : Pale reddish-white (capsule shell), white (contents)
   • Appearance : Hard capsule (size 2), identification code "Flutzlon/ 200"
   • Average weight : Approximately 278mg

II. Usage and Dosage

III. Taboos

1. Patients with a history of severe allergies to any of the ingredients in this drug.
2. Patients currently using tegafur-gemeracil-oteracil potassium combination preparations, and patients within 7 days of discontinuing this combination preparation (may experience serious blood disorders and other side effects).

IV. Precautions

1. Special populations
   • Patients with myelosuppression: May worsen myelosuppression and require close monitoring (refer to [Adverse Reactions 11.1.3]).
   • Patients with concurrent infectious diseases: Bone marrow suppression may worsen the infectious diseases, requiring close monitoring (refer to [Adverse Reactions 11.1.3]).
   • Patients with heart disease or a history of it: may experience a worsening of symptoms.
   • Patients with gastrointestinal ulcers or bleeding: may experience worsening of symptoms.
   • Chickenpox patients: May develop life-threatening systemic disorders.
   • Patients with renal impairment: may experience increased intensity of side effects.
   • Patients with impaired liver function: may experience increased intensity of side effects.
   • For those who are capable of reproduction: the potential effects of the medication on the gonads need to be considered.
   • Pregnant women: It is recommended to avoid administration. Animal studies have shown that high doses (above 50 mg/kg/day) may lead to fetal skeletal abnormalities and delayed ossification.
   • For breastfeeding mothers: breastfeeding should be stopped, as animal studies have shown that the drug can be transferred into breast milk.
   • Children: No clinical studies have been conducted in children, and special attention should be paid to side effects when administering the medication.
   • Elderly individuals: Physiological functions usually decline, so medication should be administered with caution.
2. Medication guidance
   • Serious side effects such as bone marrow suppression, dehydration, and acute renal failure may occur. During the course of treatment, regular clinical examinations (blood tests, liver and kidney function tests, etc.) should be performed (especially frequently in the early stages of treatment) to closely monitor the patient's condition.
   • Be alert to the occurrence or worsening of infections, bleeding tendencies.
   • When taking medications packaged in PTP, patients should be instructed to remove the capsule from the PTP blister pack before taking the medication to avoid accidentally swallowing the PTP blister pack, which could cause esophageal mucosal puncture, perforation, and serious complications such as mediastinitis.
   • There are reports that the combined use of fluorouracil drugs with other anti-cancer drugs may induce acute leukemia (possibly accompanied by a pre-leukemic phase) and myelodysplastic syndrome (MDS).
   • A very small number of patients may have a deficiency of dihydropyrimidine dehydrogenase (DPD), a fluorouracil metabolizing enzyme. These patients may experience serious side effects (stomatitis, diarrhea, blood disorders, neurological disorders, etc.) in the early stages of using fluorouracil drugs.
3. Drug storage : Store at room temperature; shelf life is 3 years.

V. Adverse Reactions

1. Allergic reaction
   • Incidence rate less than 1%: Rash
   • Incidence unknown: eczema, urticaria, photosensitivity
2. Digestive system reaction
   • Incidence unknown: Severe enteritis (hemorrhagic enteritis, ischemic enteritis, necrotizing enteritis, etc., with initial symptoms of abdominal pain, frequent loose stools, and diarrhea), dehydration symptoms (caused by severe diarrhea, with initial symptoms of abdominal pain and frequent loose stools), and acute pancreatitis (which may present with elevated serum amylase and abdominal pain).
3. Other serious adverse reactions
   • Acute renal failure: Severe diarrhea and dehydration can lead to circulatory disorders, which may cause ischemic acute renal failure. In such cases, medication should be stopped immediately and intravenous fluids and other treatments should be administered.
   • Bone marrow suppression and hemolytic anemia: These may include pancytopenia, leukopenia, thrombocytopenia, and anemia, requiring regular blood tests.
   • Severe neuropsychiatric disorders (such as leukoencephalopathy): May present with amnesia, walking difficulties, perceptual disturbances, extrapyramidal symptoms, dysarthria, altered consciousness, paralysis, urinary incontinence (incidence unknown), or decreased attention and dysarthria (incidence <0.1%). Be alert to early symptoms of leukoencephalopathy.
   • Interstitial pneumonia: Initial symptoms include cough, shortness of breath, difficulty breathing, and fever. Medication should be discontinued immediately and symptomatic treatment should be given.
   • Heart failure: Incidence unknown, requires close monitoring of cardiac function.
   • Liver disorders and jaundice: Severe liver damage, such as severe hepatitis, may occur, requiring regular liver function tests.
   • Cirrhosis: May occur with long-term use (incidence unknown).
   • Quiet angina, myocardial infarction, and arrhythmias (including ventricular tachycardia): Incidence is unknown, and cardiovascular symptoms need to be monitored.
   • Neurological syndrome: Incidence unknown.
   • Shock, allergic reactions: The incidence is unknown, but symptoms such as decreased blood pressure and difficulty breathing should be noted.
4. Other common adverse reactions
   | System | Occurrence rate above 5% | Occurrence rate 1-5% | Occurrence rate below 1% | Occurrence rate unknown |
   | ---- | ---- | ---- | ---- | ---- |
   | Skin | - | Pigmentation | Itching, hair loss | Dermatitis, erythema, nail abnormalities |
   | Circulatory System | - | - | Chest tightness | Increased heart rate, abnormal ECG (ST segment elevation, QT interval prolongation, T wave inversion) |
   | Other | - | - | Fever, sore throat, eye strain | Gynecomastia, edema |

VI. Drug Interactions

1. Contraindicated for combined use (prohibited from use)
   | Drug Name | Clinical Symptoms and Treatment | Mechanism of Action and Risk Factors |
   | ---- | ---- | ---- |
   | Tegafur-Gemeracil-Oteeracil Potassium Combination (Tegafur) | May cause severe blood disorders, diarrhea, stomatitis, and other gastrointestinal disturbances in the early stages. This medication is contraindicated during treatment and for at least 7 days after discontinuation. | Gemeracil inhibits the catabolism of fluorouracil, leading to a significant increase in fluorouracil concentration. |
2. Caution should be exercised when using these products together (use with caution).
   | Drug Name | Clinical Symptoms and Treatment | Mechanism of Action and Risk Factors |
   | ---- | ---- | ---- |
   Other anti-tumor drugs may increase side effects such as blood disorders and gastrointestinal disturbances. Close monitoring of the patient's condition is necessary; dosage reduction or discontinuation is required if abnormalities occur. Side effects can be cumulative and exacerbated.
   | Fluorouracil | May cause symptoms of fluorouridine poisoning such as dizziness, nystagmus, and ataxia | Mechanism unknown, but may lead to elevated blood concentrations of fluorouridine |
   | Warfarin potassium | May enhance the effects of warfarin potassium, increase bleeding tendency, and require monitoring of coagulation function | Mechanism unknown |
   | Trifluorouridine-tipiracil hydrochloride combination preparation | May enhance side effects | May affect the metabolism of fluoropyrimidine anti-cancer drugs |

VII. Pharmacological effects

1. Mechanism of action : This drug is converted to 5-fluorouracil (5-FU) by highly active pyrimidine nucleoside phosphorylase (PyNPase) in tumor tissue, exerting its anti-tumor effect. 5-FU is further metabolized to fluorouridine monophosphate (FdUMP), which competes with uridine-derived deoxyuridine monophosphate (dUMP) to inhibit thymidylate synthase and block DNA synthesis. Simultaneously, 5-FU can be converted to fluorouridine triphosphate (FUTP), which is incorporated into RNA to form fluoroRNA (F-RNA), disrupting RNA function.
2. Antitumor effects : It showed antitumor activity against transplanted tumors in mice (sarcoma 180, Ehrlich ascites carcinoma, Lewis lung cancer, colon cancer 26, etc.) and transplanted human tumors in nude mice (gastric cancer, colorectal cancer, breast cancer, cervical cancer, bladder cancer).
3. Effects on immune function : Compared with other fluoropyrimidine derivatives, this drug has a weaker inhibitory effect on humoral immunity, cellular immunity and bone marrow function.

VIII. Pharmacokinetics

1. Absorption : In patients with malignant tumors, after a single oral administration of 800 mg of deoxyfluorouridine, the serum concentration of the unaltered form reached its peak (approximately 1 μg/mL) within 1–2 hours, and then rapidly decreased; the concentration of 5-FU reached its peak within 1 hour, with the peak value being approximately 1/10 of that of the unaltered form.
2. Distribution : In patients with gastric cancer, colon cancer, breast cancer, cervical cancer, and bladder cancer, 1200 mg of deoxyfluorouridine was administered orally three times daily for 3 to 7 days. The concentration of 5-FU in tumor tissue was significantly higher than that in adjacent normal tissue and blood.
3. Metabolism : Deoxyfluorouridine is broken down into 5-FU and 5-deoxy-D-ribose-1-phosphate by pyrimidine nucleoside phosphorylase in tumor tissue.
4. Excretion : In patients with malignant tumors, after a single oral administration of 800 mg of deoxyfluorouridine, the main excretion products in the urine within 12 hours of administration are unaltered form, 5-FU and its metabolites, and 5-deoxy-D-ribitol.

IX. Clinical Research

1. Domestic multicenter study on efficacy
   • Gastric cancer: Based on the criteria for determining the direct effect of chemotherapy on solid tumors, the effective rate was 14.3% (20/140 cases).
   • Colorectal cancer: The effective rate was 9.2% (7/76 cases).
   • Breast cancer: The response rate was 35.9% (37/103 cases).
   • Cervical cancer: A joint study by 26 domestic institutions, based on the criteria for judging the direct effect of chemotherapy in gynecological cancers, showed an effective rate of 20.6% (7/34 cases).
   • Bladder cancer: Two studies showed response rates of 31.7% (13/41 cases) and 23.1% (3/13 cases), respectively.

10. Packaging Specifications

• 100 tablets/box: PTP packaging (10 tablets/blister x 10 blister packs)
• 500 tablets/box: PTP packaging (10 tablets/blister x 50 blister packs)

XI. Production Information

1. Manufacturer : Taiyo Falma Co., Ltd.