Tegafur with gimeracil and oteracil oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations containing tegafur, gimeracil and oteracil.
Drugs List
Therapeutic Indications
Uses
Advanced gastric carcinoma in combination with platinum-based regimen
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
The recommended dose is 25mg/metre squared of body surface area (BSA) (expressed as tegafur content) twice daily, morning and evening, for 21 consecutive days followed by 7 days rest (1 treatment cycle). This treatment cycle is repeated every 4 weeks.
Patients with Renal Impairment
Creatinine clearance below 30ml/minute: Not recommended unless the potential benefits outweighs the risks
Creatinine clearance 30 to 50ml/minute: 20mg/metre squared BSA (expressed as tegafur content).
Additional Dosage Information
To manage toxicity the following reductions should be followed:
First dose reduction: 20mg/metre squared BSA (expressed as tegafur content).
Second dose reduction: 15mg/metre squared BSA (expressed as tegafur content).
Third dose reduction: Discontinue treatment.
Non-haematological toxicities (excluding renal toxicities)
CTC Grade 1: No dose adjustment.
CTC Grade 2: Suspend treatment until CTC returns to at least grade 1 and resume at original dose.
CTC Grade 3 first or second occurrence: Suspend treatment until CTC returns to at least grade 1 and reduce next dose by 1 dose level.
CTC Grade 3 third occurrence: Permanently discontinue treatment.
Renal toxicities - Creatinine clearance should be determined before the start of treatment for every cycle.
Creatinine clearance equal to or greater than 50ml/minute: No dose adjustment.
Creatinine clearance 30 to 49ml/minute: Start treatment at first reduced dose level.
Creatinine clearance less than 30ml/minute: Suspend treatment until creatinine clearance recovers to 30ml/minute or above then restart treatment at 1 reduced dose level.
Haematologic toxicities
Neutrophils less than 0.5 x 10 to the power of 9 per litre: Suspend treatment until recovery to 1.5 x 10 to the power of 9 per litre or above - next dose reduce by 1 dose level.
Platelets less than 25 x 10 to the power of 9 per litre: Suspend treatment until recovery to 100 x 10 to the power of 9 per litre or above - next dose reduce by 1 dose level.
Haemoglobin 6.5g/dl: Suspend treatment until recovery to 10g/dl and reduce next dose by 1 dose level.
Doses omitted due to toxicity should not be replaced.
Once the dose has been reduced it should not be increased again.
If a patients vomits after taking a dose, the dose must not be replaced.
Contraindications
Children under 18 years
Haemoglobin concentration below 10g/dL
Neutrophil count below 1.5 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Breastfeeding
Complete dihydropyrimidine dehydrogenase deficiency
Galactosaemia
Long QT syndrome
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Dehydration
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Hepatitis B
History of hepatitis B
History of torsade de pointes
Lactose intolerance
Partial dihydropyrimidine dehydrogenase deficiency
Renal impairment - creatinine clearance 30-50ml/minute
Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Anti-emetics may be required during therapy
Before initiating screen all patients for hepatitis B infection
DPD deficiency phenotype/genotype testing is recommended prior to treatment
Hepatitis B: Refer prior to initiation to liver disease specialist
Recalculate BSA and adjust dose if weight changes by 10% or more
Treatment to be prescribed under the supervision of a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Reduce dose if creatinine clearance is < 50ml/min at start of cycle
Consider monitoring ECG in patients at risk of QT prolongation
Consider the use of fluid and electrolyte replacement
If visual disturbances occur, perform ophthalmic evaluation
Monitor creatinine clearance before day 1 of each treatment cycle
Monitor haematological parameters regularly throughout treatment
Monitor hepatic function regularly
Monitor patients who develop severe diarrhoea
Monitor prothrombin times closely in patients on anticoagulant therapy
Monitor renal function regularly
Monitor serum electrolytes
Advise patient to report signs of neuropathy
Reactivation of hepatitis B may occur in chronic carriers
Discontinue if severe and persistent diarrhoea develops
If dehydration occurs, discontinue treatment until patient has recovered
Suspend therapy if haemoglobin levels fall below 6.5 g/dl
Suspend therapy if neutrophils fall below 0.5 x 10 to the power of 9 / L
Suspend therapy if platelets fall below 25 x10 to the power of 9 / L
Male & female: Contraception required during & for 6 months after treatment
Advise patient of possible side effects and the need to report them
Prophylactic anti-diarrhoeal or anti-emetic treatment should be provided. If CTC grade 2 or higher diarrhoea occurs dose suspension/adjustment should be implemented if symptoms persist despite adequate treatment. Patients with diarrhoea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated.
Dehydration and related electrolyte disturbances should be corrected prior to or during treatment. Dehydration should be treated aggressively with rehydration and other appropriate measures. If CTC grade 2 or higher dehydration occurs, treatment should be suspended until the dehydration and its underlying cause has been corrected or adequately controlled.
If persistent or vision-reducing ocular symptoms such as lacrimation or corneal symptoms occur, an ophthalmic consultation should be sought.
Carriers of Hepatitis B virus (HBV) should be closely monitored for signs of active disease. Ongoing monitoring of liver function and viral markers is recommended.
Pregnancy and Lactation
Pregnancy
Tegafur with gimeracil and oteracil is contraindicated in pregnancy.
There have been reports of foetal abnormalities in human pregnancy. Discontinue tegafur with gimeracil and oteracil if pregnancy occurs during treatment. Discuss the potential risk to the foetus and consider genetic counselling.
Animal studies have shown reproductive toxicity both embryolethality and teratogenicity.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Tegafur with gimeracil and oteracil is contraindicated in breastfeeding
It is not known if tegafur with gimeracil and oteracil or its metabolites are excreted in human milk. Animal studies have shown excretion into milk therefore a risk to infants cannot be excluded and breastfeeding should be discontinued during treatment.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Counselling
Advise patient if they vomit after taking a dose that they must not replace that dose.
Advise patients of both sexes to use adequate contraception during and for 6 months after treatment has ended.
Advise patient to report any symptoms of moderate to severe toxicity promptly.
Advise patient that their ability to drive or operate machinery may be affected by side effects such as fatigue, dizziness, blurred vision and nausea.
Side Effects
Abnormal INR
Adrenal haemorrhage
Altered consciousness
Altered prothrombin concentration
Altered serum creatinine values
Anaemia
Angina pectoris
Anorexia
Anxiety
Aphasia
Ataxia
Atrial fibrillation
Blood pressure changes
Blood urea increased
Cardiac disorders
Cardiac failure
Cerebellar dysfunction
Cerebrovascular accident
CNS disturbances
Confusion
Convulsions
Corneal disorders
Deep vein thrombosis (DVT)
Dehydration
Diarrhoea
Dizziness
Dyspnoea
Electrolyte disturbances
Eosinophilia
Epistaxis
Eye disorder
Fatigue
Febrile neutropenia
Flushing
Gamma glutamyl transferase (GGT) increased
Gastrointestinal disorder
Gout
Granulocytosis
Haemorrhage
Hallucinations
Headache
Hearing disturbances
Hemiparesis
Hepatic failure
Hyperbilirubinaemia
Hyperglycaemia
Hyperkalaemia
Hyperlipidaemia
Hypersensitivity reactions
Hypoalbuminaemia
Hypoproteinaemia
Impaired memory
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increase in serum ALT/AST
Infections
Insomnia
Interstitial lung disease
Intravascular coagulation (disseminated)
Leukocytosis
Leukoencephalopathy
Leukopenia
Loss of balance
Lymphocytosis
Lymphopenia
Multiorgan failure
Musculoskeletal disturbances
Myocardial infarction
Neuropathy
Neutropenia
Neutropenic sepsis
Oedema
Oral herpes
Pain
Palmar-Plantar Erythrodysaesthesia syndrome
Palpitations
Pancytopenia
Pericardial effusion
Personality disorder
Photosensitivity
Pulmonary embolism
Reactivation of hepatitis B
Reduced libido
Renal failure
Renal toxicity
Restlessness
Rhabdomyolysis
Sepsis
Septic shock
Skin disorder
Stevens-Johnson syndrome
Tachycardia
Thrombocythaemia
Thrombocytopenia
Thrombophlebitis
Thrombosis
Toxic epidermal necrolysis
Tumour haemorrhage
Tumour pain
Visual disturbances
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2015
Reference Sources
HPRA Safety Notice - 5-Fluorouracil (i.v.), capecitabine and tegafur containing products: Pre-treatment testing to identify DPD-deficient patients at increased risk of severe toxicity Available at: https://www.hpra.ie/homepage/medicines/safety-notices/item?t=/important-safety-information-from-marketing-authorisation-holders-of-products-containing-5-fluorouracil-(i.v.)-capecitabine-and-tegafur-as-approved-by-the-hpra&id=809e0d26-9782-6eee-9b55-ff00008c97d0
Last accessed: 26 October 2020
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 3 July 2015.
Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press. Accessed on 3 July 2015.
Summary of Product Characteristics: Teysuno 15mg/4.35mg/11.8mg hard capsules. Nordic Pharma Ltd. November 2017.
Summary of Product Characteristics: Teysuno 20mg/5.8mg/15.8mg hard capsules. Nordic Pharma Ltd. November 2017.
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