Tegafur + Gimeracil + Oteracil


Generic Medicine Info
Indications and Dosage
Oral
Gastric cancer
Adult: Available preparations:
Tegafur 15 mg, gimeracil 4.35 mg and oteracil 11.8 mg
Tegafur 20 mg, gimeracil 5.8 mg and oteracil 15.8 mg
Patient w/ advanced cases: In combination w/ cisplatin: 25 mg/m2 (expressed as tegafur content) bid for 21 days followed by 7 days rest. Repeat treatment cycle every 4 wk. Dosage may reduce w/ each cycle or w/in a cycle based on toxicity.
Renal Impairment
CrCl (mL/min) Dosage
<30 Not recommended.
30-50 20 mg/m2 (expressed as tegafur content) bid.
Hepatic Impairment
Severe: Not recommended.
Contraindications
History of severe and unexpected reactions to fluoropyrimidine therapy. DPD deficiency, severe bone marrow suppression (e.g. neutropaenia, leukopaenia or thrombocytopaenia), ESRD requiring dialysis. Pregnancy and lactation. Concomitant use w/ other fluopyrimidines and use w/in 4 wk treatment of DPD inhibitors.
Special Precautions
Severe hepatic and renal impairment (CrCl <30 mL/min).
Adverse Reactions
Significant: Bone marrow suppression (e.g. neutropaenia, leukopaenia, thrombocytopaenia, anaemia and pancytopaenia), acute renal failure, diarrhoea, dehydration, electrolyte disturbance, lacrimal disorders (e.g. increased lacrimation, dry eye, dacryostenosis).
Nervous: Peripheral neuropathy, dizziness, headache, fatigue, asthenia, insomnia.
CV: Hypotension, DVT, HTN, peripheral oedema.
GI: Nausea, vomiting, anorexia, dysgeusia, stomatitis, dry mouth, flatulence, dyspepsia, abdominal discomfort/pain, dysphagia, GI inflammation, GI haemorrhage.
Resp: Dyspnoea, epistaxis, hiccups, cough.
Hepatic: Hyperbilirubinaemia, increased ALT and AST.
Genitourinary: Hyperuricaemia.
Endocrine: Wt loss.
Musculoskeletal: Musculoskeletal pain.
Otic: Hearing impairment, deafness.
Ophthalmologic: Vision disorders (e.g. blurred vision, diplopia, photopsia, decreased visual acuity, blindness), conjunctivitis.
Dermatologic: Palmar-plantar erythrodysaesthesia syndrome, rash, pruritus, hyperpigmentation, dry skin, alopecia.
Others: Mucosal inflammation, pyrexia, chills.
Patient Counseling Information
This drug may cause blurred vision, dizziness, fatigue and nausea, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor haematology, renal (e.g. serum creatinine, CrCl) function, hepatic function and serum electrolytes.
Overdosage
Symptoms: Nausea, vomiting, diarrhoea, mucositis, GI irritation, bleeding, bone marrow depression and resp failure. Management: Supportive treatment.
Drug Interactions
Increased risk of bleeding w/ coumarin-derivative anticoagulants. Increased myelotoxicity and haematologic toxicity w/ clozapine. Increased adverse effects and toxicities w/ cimetidine, folinic acid metabolites, methotrexate and nitroimidazoles. Decreased efficacy w/ CYP2A6 inhibitors and allopurinol. Increased plasma concentration and toxicity w/ phenytoin.
Potentially Fatal: Increased serum level concentration and toxicities w/ other fluoropyrimidines (e.g. capecitabine, flucytosine, 5-FU) and DPD inhibitors (e.g. sorivudine, brivudine).
Food Interaction
Decreased exposure of gimeracil and oteracil.
Action
Description: Tegafur: Tegafur, a fluoropyrimidine antimetabolite agent, is a prodrug of 5-fluorouracil which forms an active metabolite, 5-fluoro-deoxyuridine-monophosphate (FdUMP). FdUMP and reduced folate binds to thymidylate synthase forming a ternary complex leading to inhibition of DNA synthesis.
Gimeracil: Gimeracil inhibits dihydropyrimidine dehydrogenase (DPD), the main enzyme degrading 5-FU, thereby increasing 5-FU exposure and anti-tumour activity.
Oteracil: Oteracil inhibits orotate phosphoribosyltransferase (OPRT), an enzyme thought to play a role in the GI toxicity of 5-FU, thereby decreasing toxicity of 5-FU in GI mucosa.
Pharmacokinetics:
Absorption: Tegafur: Well absorbed from the GI tract. Time to peak plasma concentration: 0.5-0.8 hr; 2 hr (5-FU).
Gimeracil: Time to peak plasma concentration: 1 hr.
Oteracil: Time to peak plasma concentration: 2 hr.
Distribution: Tegafur: Crosses blood-brain barrier and distributed in the CSF. Volume of distribution: 16 L/m2. Plasma protein binding: 52.3%; 18.4% (5-FU).
Gimeracil: Volume of distribution: 17 L/m2. Plasma protein binding: 32.2%.
Oteracil: Distributed into GI tract tissues. Volume of distribution: 23 L/m2. Plasma protein binding: 8.4%.
Metabolism: Tegafur: Metabolised in the liver by CYP2A6 into 5-FU which is further metabolised via phosphorylation into FdUMP (active).
Excretion: Tegafur: Via urine (3.8-4.2% as unchanged drug, 9.5-9.7% as 5-FU). Elimination half-life: 6.7-11.3 hr; 1.6-1.9 hr (5-FU).
Gimeracil: Via urine (65-72% as unchanged drug). Elimination half-life: 3.1-4.1 hr.
Oteracil: Via urine (3.5-3.9% as unchanged drug). Elimination half-life: 1.8-9.5 hr.
Chemical Structure

Chemical Structure Image
Tegafur

Source: National Center for Biotechnology Information. PubChem Database. Tegafur, CID=5386, https://pubchem.ncbi.nlm.nih.gov/compound/Tegafur (accessed on Jan. 23, 2020)


Chemical Structure Image
Gimeracil

Source: National Center for Biotechnology Information. PubChem Database. Gimeracil, CID=54679224, https://pubchem.ncbi.nlm.nih.gov/compound/Gimeracil (accessed on Jan. 23, 2020)


Chemical Structure Image
Oteracil

Source: National Center for Biotechnology Information. PubChem Database. Oxonic Acid, CID=4604, https://pubchem.ncbi.nlm.nih.gov/compound/Oxonic-Acid (accessed on Jan. 23, 2020)

Storage
This is a cytotoxic drug. Any unused portions should be disposed of in accordance w/ local requirements.
References
Buckingham R (ed). Gimeracil. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/08/2017.

Buckingham R (ed). Oteracil. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/08/2017.

Buckingham R (ed). Tegafur. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/08/2017.

Joint Formulary Committee. Tegafur with Gimeracil and Oteracil. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 09/08/2017.

Teysuno 15 mg/4.35 mg/11.8 mg and 20 mg/5.8 mg/15.8 mg Hard Capsules (Nordic Group BV). European Medicines Agency [online]. Accessed 15/08/2017.

Disclaimer: This information is independently developed by MIMS based on Tegafur + Gimeracil + Oteracil from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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