Product Information
Registration Status: ActiveSIN13673P
TS-ONE CAPSULE 25 is approved to be sold in Singapore with effective from 2009-07-13. It is marketed by TAIHO PHARMA SINGAPORE PTE LTD, with the registration number of SIN13673P.
This product contains Gimeracil 7.25mg,Oteracil Potassium 24.5mg, and Tegafur 25mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by Taiho Pharmaceutical Co. in JAPAN.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
Gimeracil is an adjunct to antineoplastic therapy, used to increase the concentration and effect of the main active componets within chemotherapy regimens. Approved by the European Medicines Agency (EMA) in March 2011, Gimeracil is available in combination with [DB03209] and [DB09256] within the commercially available product "Teysuno". The main active ingredient in Teysuno is [DB09256], a pro-drug of [DB00544] (5-FU), which is a cytotoxic anti-metabolite drug that acts on rapidly dividing cancer cells. By mimicking a class of compounds called "pyrimidines" that are essential components of RNA and DNA, 5-FU is able to insert itself into strands of DNA and RNA, thereby halting the replication process necessary for continued cancer growth. Gimeracil's main role within Teysuno is to prevent the breakdown of [DB00544] (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells [L933]. It functions by reversibly and selectively blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU [A31408]. This allows higher concentrations of 5-FU to be achieved with a lower dose of tegafur, thereby also reducing toxic side effects.
Indication
Gimeracil is used as an adjunct to antineoplastic therapy. When used within the product Teysuno, gimeracil is indicated for the treatment of adults with advanced gastric (stomach) cancer when given in combination with cisplatin.
Mechanism of Action
Gimeracil's main role within Teysuno is to prevent the breakdown of [DB00544] (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells [L933]. It functions by reversibly blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU [A31408].
Pharmacokinetics
- Absorption
- Mean 5-FU maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) values were approximately 3-fold higher after Teysuno administration than after administration of tegafur alone, despite a 16-fold lower Teysuno dose (50 mg of tegafur) compared to tegafur alone (800 mg), and are attributed to inhibition of DPD by gimeracil. Maximum plasma uracil concentration was observed at 4 hours, with a return to baseline levels within approximately 48 hours after dosing, indicating the reversibility of the DPD inhibition by gimeracil. After administration of a single dose of 50 mg Teysuno (expressed as tegafur content), median Tmax for Teysuno components tegafur, gimeracil, and oteracil was 0.5, 1.0, and 2.0 hours, respectively [L933].
- Distribution
- Although no intravenous data are available for Teysuno in humans, the volume of distribution could be roughly estimated from the apparent volume of distribution and urinary excretion data as 16 l/m2, 17 l/m2, and 23 l/m2 for tegafur, gimeracil and oteracil, respectively [L933].
- Metabolism
- Elimination
Active Ingredient/Synonyms
5-Chloro-2,4-dihydroxypyridine | 5-Chloro-4-hydroxy-2-pyridone | gimestat | Teysuno | Ts-1 (TN) | Gimeracil |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.
Description
Tegafur (INN, BAN, USAN) is a prodrug of [DB00544] (5-FU), an antineoplastic agent used as the treatment of various cancers such as advanced gastric and colorectal cancers. It is a pyrimidine analogue used in combination therapies as an active chemotherapeutic agent in conjunction with [DB09257] and [DB03209], or along with [DB00544] as [DB09327]. Tegafur is usually given in combination with other drugs that enhance the bioavailability of the 5-FU by blocking the enzyme responsible for its degradation, or serves to limit the toxicity of 5-FU by ensuring high concentrations of 5-FU at a lower dose of tegafur [L933]. When converted and bioactivated to 5-FU, the drug mediates an anticancer activity by inhibiting thymidylate synthase (TS) during the pyrimidine pathway involved in DNA synthesis. 5-FU is listed on the World Health Organization's List of Essential Medicines.
Indication
Indicated for the treatment of cancer usually in combination with other biochemically modulating drugs. Indicated in adults for the treatment of advanced gastric cancer when given in combination with [DB00515] [L933]. Indicated for the first-line treatment of metastatic colorectal cancer with [DB03419] and calcium folinate [L934].
Mechanism of Action
The transformation of 2'-deoxyurindylate (dUMP) to 2'-deoxythymidylate (dTMP) is essential in driving the synthesis of DNA and purines in cells [T28]. Thymidylate synthase catalyzes the conversion of dUMP to dTMP, which is a precursor of thymidine triphosphate (TTP), one of the four deoxyribonucleotides required for DNA synthesis [A31546]. After administration into the body, tegafur is converted into the active antineoplastic metabolite, fluorouracil (5-FU). In tumour cells, 5-FU undergoes phosphorylation to form the active anabolites, including 5-fluorodeoxyuridine monophosphate (FdUMP) [L933]. FdUMP and reduced folate are bound to thymidylate synthase leading to formation of a ternary complex which inhibits DNA synthesis [L933]. In addition, 5-fluorouridine-triphosphate (FUTP) is incorporated into RNA causing disruption of RNA functions [L933].
Pharmacokinetics
- Absorption
- Tegafur displays a dose-proportional pharmacokinetic properties. Tegafur is rapidly and well absorbed into the systemic circulation, reaching the peak plasma concentration within 1 to 2 hours of administration [L934].
- Distribution
- The volume of distribution based on apparent volume of distribution and urinary excretion data of tegafur is 16 L/m^2 [L933].
- Metabolism
- Hepatic CYP2A6 is the predominant enzyme that mediates 5-hydroxylation of tegafur to generate 5'-hydroxytegafur. This metabolite is unstable and undergoes spontaneous degradation to form 5-FU, which is an active antineoplastic agent that exerts a pharmacological action on tumours. 5-FU is rapidly metabolised by the liver enzyme dihydropyrimidine dehydrogenase (DPD) [A31546].
- Elimination
Clearance
No pharmacokinetic data available.
Toxicity
Oral LD50 value in rat, mouse and dog are 930mg/kg, 775mg/kg, and 34mg/kg, respectively [MSDS]. Continuous exposure to tegafur may cause physical defects in the developing embryo (teratogenesis). Acute toxicity from the combination use of tegafur was associated with nausea, vomiting, diarrhoea, mucositis, gastrointestinal irritation, bleeding, bone marrow depression, and respiratory failure [L933]. Overdose may lead to fatal complications [L934]. In case of overdose, appropriate therapeutic and supportive medical interventions should be implemented.
Active Ingredient/Synonyms
1-(2-Tetrahydrofuryl)-5-fluorouracil | Tegafur |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.