Teysuno
Teysuno Uses, Dosage, Side Effects, Food Interaction and all others data.
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 Oteracil and Tegafur within the commercially available product "Teysuno". The main active ingredient in Teysuno is Tegafur, a pro-drug of Fluorouracil (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 Fluorouracil (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells . It functions by reversibly and selectively blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU . This allows higher concentrations of 5-FU to be achieved with a lower dose of tegafur, thereby also reducing toxic side effects.
Tegafur (INN, BAN, USAN) is a prodrug of Fluorouracil (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 Gimeracil and Oteracil, or along with Fluorouracil as Tegafur-uracil. 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 . 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.
Tegafur is an antineoplastic agent that belongs in the class of pyrimidine analogues. It interferes with the 2'-deoxythymidylate (DTMP) synthesis in the pyrimidine pathway, resulting in inhibition of DNA synthesis . In a phase III trial investigating the clinical efficacy of S-1 (tegafur/gimeracil/oteracil) in patients with advanced or recurrent gastric cancer, treatment resulted in a high response rate and was associated with a longer overall survival and longer progression-free survival rate when used in combination with cisplatin . In a meta analysis, triple combination therapy consisting of tegafur, gimeracil and oteracil showed longer survival times and well tolerance in patients with advanced gastric cancer . Tegafur and its active metabolites are potent myleosuppressive agents .
| Trade Name | Teysuno |
| Generic | tegafur + gimeracil + oteracil monopotassium |
| Type | Capsule |
| Therapeutic Class | |
| Manufacturer | Nordic Pharma Limited, Taiho Pharma Europe Ltd, Nordic Group Bv |
| Available Country | United Kingdom, France, Italy, Portugal, Spain, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Gimeracil is a DPD inhibitor used as an adjunct to antineoplastic therapy to increase the systemic concentrations and therapeutic effectiveness of other antineoplastic agents.
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.
Tegafur is an antineoplastic agent used in combination with other anticancer medications to treat advanced gastric and colorectal cancers.
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 Cisplatin .
Indicated for the first-line treatment of metastatic colorectal cancer with Uracil and calcium folinate .
Teysuno is also used to associated treatment for these conditions: Advanced Gastric CancerAdvanced Gastric Cancer
How Teysuno works
Gimeracil's main role within Teysuno is to prevent the breakdown of Fluorouracil (5-FU), which helps to maintin high enough concentrations for sustained effect against cancer cells . It functions by reversibly blocking the enzyme dihydropyrimidine dehydrogenase (DPD), which is involved in the degradation of 5-FU .
The transformation of 2'-deoxyurindylate (dUMP) to 2'-deoxythymidylate (dTMP) is essential in driving the synthesis of DNA and purines in cells . 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 . 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) . FdUMP and reduced folate are bound to thymidylate synthase leading to formation of a ternary complex which inhibits DNA synthesis . In addition, 5-fluorouridine-triphosphate (FUTP) is incorporated into RNA causing disruption of RNA functions .
Toxicity
Oral LD50 value in rat, mouse and dog are 930mg/kg, 775mg/kg, and 34mg/kg, respectively . 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 . Overdose may lead to fatal complications . In case of overdose, appropriate therapeutic and supportive medical interventions should be implemented.
Volume of 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 .
The volume of distribution based on apparent volume of distribution and urinary excretion data of tegafur is 16 L/m^2 .
Elimination Route
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 .
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 .
Half Life
Following a single dose of Teysuno, T1/2 values ranged from 6.7 to 11.3 hours for tegafur, from 3.1 to 4.1 hours for gimeracil, and from 1.8 to 9.5 hours for oteracil .
The elimination half life of tegafur is approximately 11 hours .
Clearance
No pharmacokinetic data available.
Elimination Route
Following a single dose of Teysuno, approximately 3.8% to 4.2% of administered tegafur, 65% to 72% of administered gimeracil, and 3.5% to 3.9% of administered oteracil were excreted unchanged in the urine .
Following oral administration, about less 20% of total tegafur is excreted unchanged in the urine .
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