Trifluridine with tipiracil oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of trifluridine with tipiracil.
Drugs List
Therapeutic Indications
Uses
Metastatic colorectal cancer
Metastatic gastric cancer
Monotherapy treatment of adult patients with metastatic colorectal cancer (CRC) who have previously been treated with, or are unsuitable for available therapies including fluoropyrimidine, oxaliplatin, and irinotecan based chemotherapies, anti-VEGF and anti-EGFR agents.
Monotherapy treatment of adult patients with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction, who have previously been treated with at least two prior systemic treatment regimens for advanced disease.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.
Adults
The recommended starting dose of trifluridine with tipiracil is 35 mg per metre squared body surface area (BSA) twice daily on days 1 to 5 and days 8 to 12 of each 28 day cycle. Dose should be rounded to nearest 5 mg increment and should not exceed 80mg.
Patients with Renal Impairment
Severe renal impairment
The recommended starting dose of trifluridine with tipiracil is 20mg per metre squared BSA twice daily.
One dose reduction to 15mg per metre squared BSA is permitted.
Additional Dosage Information
Dose interruption for haematological toxicities
Withhold treatment if neutrophil count is less than 0.5 x 10 to the power of 9/L until recovery to greater than or equal to 1.5 x 10 to the power of 9/L.
Withhold treatment if platelet count is less than 50 x 10 to the power of 9/L until recovery to greater than or equal to 75 x 10 to the power of 9/L.
Dose modification for haematological and non-haematological toxicities
Febrile neutropenia - withhold treatment until recovery to grade 1 or baseline.
Grade 4 neutropenia or thrombocytopenia leading to more than 1 weeks delay in treatment - withhold treatment until recovery to grade 1 or baseline.
Grade 3 or 4 non-haematologic toxicity (excluding nausea and/or vomiting or diarrhoea) - withhold treatment until recovery to grade 1 or baseline.
Following interruption due to the above toxicities, dose should be reduced by 5 mg per metre squared from the previous dosing level.
A maximum of 3 dose reductions are recommended to a minimum of 20 mg per metre squared BSA twice daily and dose escalations are not permitted after dose reduction.
Contraindications
Children under 18 years
Neutrophil count below 1.5 x 10 to the power of 9 / L
Platelet count below 75 x 10 to the power of 9 / L
Breastfeeding
Galactosaemia
Long QT syndrome
Moderate hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below 15ml/minute
Torsade de pointes
Precautions and Warnings
Family history of long QT syndrome
Patients over 75 years
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Lactose intolerance
Renal impairment - creatinine clearance 15-29ml/minute
Correct electrolyte disorders before treatment
Start antimicrobial regime if infection suspected during neutropenia
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
Treatment to be initiated and supervised by a specialist
Contains lactose
Consult local policy on the safe use of oral anti-cancer drugs
Staff: Not to be handled by pregnant staff
Monitor for proteinuria before and periodically during treatment
Perform full blood count before each treatment cycle
Consider monitoring ECG in patients at risk of QT prolongation
Consider the use of fluid and electrolyte replacement
Monitor for gastrointestinal toxicity
Monitor for haematological toxicities more frequently in renal impairment
Monitor patients with renal impairment
Monitor serum electrolytes
Consider G-CSF in severe neutropenia / agranulocytosis
Oversuppression of immune system may increase susceptibility to infection
Interrupt treatment if febrile neutropenia occurs
Interrupt treatment if platelet count <50 x 10 to the power of 9/L
Suspend therapy if neutrophils fall below 0.5 x 10 to the power of 9 / L
Suspend treatment and/or reduce dose if grade 4 thrombocytopenia
Suspend treatment and/or reduce dose in grade 3 non-haematological toxicity
Male & female: Contraception required during & for 6 months after treatment
Male & female: Two methods of contraception required (including barrier)
Pregnancy and Lactation
Pregnancy
Trifluridine with tipiracil is contraindicated during pregnancy.
The manufacturer recommends not using trifluridine with tipiracil during pregnancy unless the clinical condition of the woman requires treatment. Animal studies have shown embryo-foetal lethality and toxicity.
Lactation
Trifluridine with tipiracil is contraindicated during breastfeeding.
Due to the potential for serious toxicity in the nursing infant the manufacturer recommends that breastfeeding is discontinued during treatment. It is not known whether this agent or its metabolites are excreted in human breast milk. Animal studies have shown trifluridine and tipiracil to be excreted in milk.
The effect of concurrent therapies must also be considered.
Side Effects
Abnormal INR
Acne
Alopecia
Anaemia
Angina pectoris
Anxiety
Arrhythmias
Ascites
Biliary dilatation
Blistering
Blood urea increased
Burning sensation
Colitis
Cystitis
Decrease in haematocrit
Decreased appetite
Decreased total serum protein
Dehydration
Disturbances of sensation
Dizziness
Dysgeusia
Dysphonia
Ear discomfort
Electrolyte disturbances
Embolism
Enterocolitis
Epistaxis
Erythrocytopenia
Eye disorder
Febrile neutropenia
Flushing
Gastritis
Gastro-intestinal haemorrhage
Gastroesophageal reflux disease
Gastrointestinal disorder
Gingival bleeding
Glossitis
Gout
Granulocytopenia
Haematuria
Hepatotoxicity
Hyperbilirubinaemia
Hyperglycaemia
Hyperhidrosis
Hypertension
Hypoalbuminaemia
Hypotension
Ileus
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increased partial thromboplastin time
Increases in hepatic enzymes
Infections
Insomnia
Lethargy
Leukocytosis
Leukocyturia
Leukopenia
Lymphopenia
Menstrual disturbances
Micturition disorders
Monocytopenia
Monocytosis
Mouth ulcers
Musculoskeletal disturbances
Nail disorders
Neurotoxicity
Neutropenia
Neutropenic sepsis
Oesophagitis
Oral disorder
Oropharyngeal pain
Painful extremities
Palmar-Plantar Erythrodysaesthesia syndrome
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Photosensitivity
Pleural effusion
Proctalgia
Prolongation of QT interval
Proteinuria
Pulmonary embolism
Raised C-reactive protein
Renal failure
Respiratory disorders
Retching
Septic shock
Serum creatinine increased
Skin disorder
Stomatitis
Sub-ileus
Syncope
Thrombocytopenia
Tooth disorder
Unpleasant breath
Vertigo
Weight loss
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: November 2020
Reference Sources
Summary of Product Characteristics: Lonsurf 15mg/6.14mg and 20mg/8.19mg tablets. Servier Laboratories Ltd. Revised April 2020.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.