Abbreviated Prescribing Information:
Please refer to the Summary of Product Characteristics before prescribing.
COMPOSITION* Lonsurf 15 mg/6.14 mg: film-coated tablet containing 15 mg trifluridine and 6.14 mg tipiracil (as hydrochloride). Lonsurf 20 mg/8.19 mg: film-coated tablet containing 20 mg trifluridine and 8.19 mg tipiracil (as hydrochloride).
INDICATIONS* :In combination with bevacizumab for the treatment of adult patients with metastatic colorectal cancer who have received two prior anticancer treatment regimens including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and/or anti-EGFR agents. As monotherapy for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents. As monotherapy for the treatment of adult patients with metastatic gastric cancer including adenocarcinoma of the gastroesophageal junction, who have been previously treated with at least two prior systemic treatment regimens for advanced disease.
DOSAGE AND ADMINISTRATION*: Recommended starting dose: 35 mg/m2/dose taken orally twice daily on Days 1 to 5 and Days 8 to 12 of each 28-day cycle, within 1 hour after completion of the morning and evening meals (20mg/m2/dose for patients with severe renal impairment). Dosage calculated according to body surface area, not exceeding 80 mg/dose. Possible dosing adjustments based on individual safety and tolerability: permitted dose reductions to a minimum dose of 20 mg/m2 twice daily (15mg/m2/dose for patients with severe renal impairment), dose escalation not permitted after a dose reduction. When Lonsurf 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.
CONTRAINDICATIONS*: Hypersensitivity to the active substances or to any of the excipients.
WARNINGS*: Bone marrow suppression: Complete blood cell counts must be obtained prior to initiation of therapy, prior to each cycle and as needed. Treatment must not be started if absolute neutrophil count < 1.5 x 109/L, if platelet counts < 75 x 109/L, or if unresolved Grade 3 or 4 non-haematological clinically relevant toxicity. Patient should be monitored closely for infections, appropriate measures should be administered as clinically indicated. Gastrointestinal toxicity: anti-emetic, anti-diarrhoeal and other measures should be administered as clinically indicated, dose modifications should be applied as necessary. Renal impairment: not recommended if end-stage renal disease. Patients with renal impairment should be monitored closely; patients with moderate or severe renal impairment should be more frequently monitored for haematological toxicities. Hepatic impairment: not recommended if baseline moderate or severe hepatic impairment. Proteinuria: monitoring by dipstick urinalysis recommended prior to starting and during therapy. Excipients: contain lactose.
INTERACTION(S)*:Precautions: medicinal products that interact with nucleoside transporters CNT1, ENT1 and ENT2, inhibitors of OCT2 or MATE1, human thymidine kinase substrates (e.g. zidovudine), hormonal contraceptives.
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 Lonsurf treatment.
PREGNANCY AND BREASTFEEDING*: Not recommended.
CONTRACEPTION*: For women and men, highly effective contraceptive measures must be used during treatment and for 6 months after stopping treatment.
DRIVE & USE MACHINES* : Fatigue, dizziness or malaise may occur.
UNDESIRABLE 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. Uncommon: biliary tract infection, influenza, urinary tract infection, gingivitis, herpes zoster, candida infection, bacterial infection, neutropenic sepsis, upper respiratory tract infection, conjunctivitis, cancer pain, pancytopenia, monocytopenia, erythropenia, leukocytosis, monocytosis, dehydration, hyperglycaemia, hyperkalaemia, hypokalaemia, hypophosphataemia, hyponatraemia, hypocalcaemia, anxiety, insomnia, neuropathy peripheral, neurotoxicity, paraesthesia, lethargy, vertigo, angina pectoris, arrhythmia, palpitations, hypotension, flushing, pulmonary embolism, dysphonia, epistaxis, rhinorrhoea, cough, gastrointestinal haemorrhage, ileus, colitis, gastritis, impaired gastric emptying, abdominal distension, anal inflammation, dyspepsia, gastrooesophageal reflux disease, glossitis, tooth disorder, retching, flatulence, hepatotoxicity, palmar-plantar erythrodysaesthesia syndrome, urticaria, acne, hyperhidrosis, nail disorder, bone pain, muscular weakness, muscle spasms, pain in extremity, renal failure, micturition disorder, haematuria, menstrual disorder, general physical health deterioration, pain, feeling of body temperature change, limb discomfort, blood creatinine increased, international normalised ratio increased, blood urea increased, blood lactate dehydrogenase increased, C-reactive protein increased, haematocrit decreased. Rare: enteritis infectious, tinea pedis, septic shock, granulocytopenia, gout, hypernatraemia, burning sensation, dysaesthesia, hyperaesthesia, hypoaesthesia, syncope, cataract, dry eye, vision blurred, diplopia, visual acuity reduced, ear discomfort, embolism, oropharyngeal pain, pleural effusion, ascites, pancreatitis acute, subileus, breath odour, buccal polyp, enterocolitis haemorrhagic, gingival bleeding, oesophagitis, periodontal disease, proctalgia, reflux gastritis, biliary dilatation, blister, erythema, photosensitivity reaction, skin exfoliation, joint swelling, cystitis noninfective, leukocyturia, xerosis, activated partial thromboplastin time prolonged, electrocardiogram QT prolonged, protein total decreased. Post-marketing experience: interstitial lung disease.
OVERDOSE* PROPERTIES* Trifluridine is an antineoplastic thymidine-based nucleoside analogue and tipiracil hydrochloride is a thymidine phosphorylase (TPase) inhibitor. Following uptake into cancer cells, trifluridine, is phosphorylated by thymidine kinase, further metabolised in cells to a deoxyribonucleic acid DNA substrate, and incorporated directly into DNA, preventing cell proliferation. However, trifluridine is rapidly degraded by TPase and readily metabolised by a first-pass effect following oral administration, hence the inclusion of the TPase inhibitor, tipiracil hydrochloride.
PRESENTATION* Pack of 20 or 60 film-coated tablets.
MARKETING AUTHORISATION HOLDER LES LABORATOIRES SERVIER, 50 rue Carnot, 92284 Suresnes cedex France. www.servier.com.
Marketing Authorisation: EU/1/16/1096/001-006.
Legal Classification for Supply: POM. Further information available from: Servier Laboratories (Ireland) Ltd.1st Floor, Building Two, The Green Dublin Airport Central. Dublin Airport, Swords Co. Dublin K67 E2H3. Ireland. Tel (01) 6638110, www.servier.ie.
*For complete information, please refer to the Summary of Product Characteristics available on medicines.ie
Date of last revision of text: October 2024
Adverse events should be reported. Reporting forms and further information can be found on the Health Products Regulatory Agency (HPRA) website: https://www.hpra.ie/report-an-issue. Adverse events should also be reported to Servier Laboratories (Ireland) Ltd: pharmacovigilance-dublin@servier.com.