Trifluridine/Tipiracil Servier^® (trifluridine/ tipiracil)

Prescribing Information
Refer to Summary of Product Characteristics (SPC) before prescribing.

Presentation: Film-coated tablets, 15 mg trifluridine/6.14 mg tipiracil, 20 mg trifluridine /8.19 mg tipiracil.

Indication: Treatment (in combination) with bevacizumab for the treatment of adult patients with metastatic colorectal cancer (CRC) who have received two prior anticancer treatment regimens including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and/or anti-EGFR agents. Treatment (monotherapy) of adults with metastatic CRC previously treated with, or not considered candidates for, other available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti EGFR agents. Treatment (monotherapy) of adults with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction previously treated with at least two prior systemic treatment regimens for advanced disease.

Dosage and Administration: Posology: Recommended starting dose as monotherapy or in combination with bevacizumab is 35 mg/m²/dose administered orally twice daily on Days 1 to 5 and 8 to 12 of each 28-day cycle until disease progression or unacceptable toxicity. When trifluridine/tipiracil is used in combination with bevacizumab for the treatment of metastatic CRC, the dose of bevacizumab is 5 mg/kg of body weight given once every 2 weeks. Please refer to the full product information for bevacizumab. Dose calculated according to body surface area. Maximum dose 80 mg/dose. Dose adjustments: Maximum of 3 dose reductions to a minimum of 20 mg/m²/dose twice daily (or 15 mg/m²/dose twice daily in severe renal impairment), based on safety and tolerability. Dose escalation not permitted after dose reduction. Consult SPC for dose interruption/resumption and reduction criteria. Administration: Tablets taken with water within 1 hour after morning and evening meals. Renal impairment: No adjustment of starting dose required in mild (CrCl 60 to 89 mL/min) or moderate (CrCl 30 to 59 mL/min) renal impairment. In severe renal impairment (CrCl 15 to 29 mL/min) a starting dose of 20 mg/m² twice daily is recommended and 1 dose reduction to a minimum of 15 mg/m²/dose twice daily is permitted. Not recommended in end stage renal disease (CrCl below 15mL/min or requiring dialysis). Hepatic impairment: No adjustment of starting dose required in mild hepatic impairment. Not recommended in baseline moderate or severe hepatic impairment. Elderly: ≥ 65 years – No adjustment of starting dose. >75 years – Limited data.

Contraindications: Hypersensitivity to trifluridine/tipiracil or any excipients.

Warnings and Precautions: Bone marrow suppression: Increased incidence of myelosuppression including anaemia, neutropenia, leucopenia and thrombocytopenia. Perform complete blood cell counts prior to initiation of therapy/each treatment cycle and as needed to monitor toxicity. Do not start treatment if absolute neutrophil count < 1.5 x 10⁹/L, if platelet count < 75 x 10⁹/L or in unresolved Grade 3 or 4 non-haematological toxicity from prior therapies. Serious infections have been reported with trifluridine/tipiracil (mostly in context of bone marrow suppression). Monitor closely and use appropriate clinical measures if necessary. Gastrointestinal toxicity: Increased with trifluridine/tipiracil Monitor carefully patients with nausea, vomiting, diarrhoea or other gastrointestinal toxicities; administer treatment as clinically indicated and dose modifications if necessary (see section 4.2 of SPC). Renal impairment: Monitor patients with moderate or severe renal impairment more frequently for haematological toxicities. Not recommended for use in patients with end-stage renal disease. Proteinuria: Monitor by dipstick urinalysis before and during therapy. Lactose intolerance: Trifluridine/tipiracil contains lactose patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Contraception: Women of child-bearing potential / men with partner of child-bearing potential must use effective contraceptive measures during treatment and for up to 6 months after discontinuation of treatment. Pregnancy and lactation: Should not be used during pregnancy unless clinical condition requires treatment; breast-feeding should be discontinued during treatment. Fertility: Patients who wish to conceive a child should be advised to seek reproductive counselling and cryo-conservation of either the ovum or sperm prior to starting treatment.

Interactions: Caution when using medicines that interact with nucleoside transporters CNT1, ENT1 and ENT2 or with inhibitors of OCT2 and MATE1. Caution with concomitant use of antiviral medicines that are human thymidine kinase substrates e.g. zidovudine. Monitor for possible decreased efficacy of antiviral medicine and consider switching to an alternative that is not a human thymidine kinase substrate e.g. lamivudine, didanosine, abacavir. It is unknown whether trifluridine/tipiracil may reduce the effectiveness of hormonal contraception. Therefore, women using hormonal contraceptive must also use a barrier contraceptive method.

Side Effects: Very common: Neutropenia, leukopenia, anaemia, thrombocytopenia, decreased appetite, diarrhoea, nausea, vomiting, fatigue, stomatitis. Common: Lower respiratory tract infection, infection, febrile neutropenia, lymphopenia, hypoalbuminaemia, dysgeusia, dizziness, headache, hypertension, dyspnoea, abdominal pain, constipation, mouth ulceration, oral disorder, hyperbilirubinaemia, rash, arthralgia, myalgia, alopecia, pruritus, dry skin, proteinuria, pyrexia, oedema, mucosal inflammation, malaise, hepatic enzyme increased, blood alkaline phosphatase increased, weight decreased. Consult to the SPC for additional information on adverse reactions. Post-marketing experience: interstitial lung disease reported in patients with unresectable advanced or recurrent colorectal cancer.

NHS Price: Trifluridine/Tipiracil Servier 15mg/6.14 mg 20 pack: £500.00 and 60 pack: £1,500.00; Trifluridine/Tipiracil Servier 20mg/ 8.19mg 20 pack: £666.67 and 60 pack: £2,000.00. Legal Category: POM. Product Licence Numbers: Trifluridine/Tipiracil Servier 15mg/6.14mg PLGB 05815/0112; Trifluridine/Tipiracil Servier 20mg/8.19mg PLGB 05815/0113. Further Information: Servier Laboratories Ltd., Sefton Park, Stoke Poges, SL2 4JS. Tel 01753 666409. Date of Revision: June 2026.