Tegafur with gimeracil and oteracil (Specialist drug)

Source: UK SPC for Teysuno 15 mg/4.35 mg/11.8 mg hard capsules via MHRA Products. SPC §2: each hard capsule contains 15 mg tegafur, 4.35 mg gimeracil and 11.8 mg oteracil (as monopotassium) and 70.2 mg lactose monohydrate. §4.1: 'Teysuno is indicated in adults: - for the treatment of advanced gastric cancer when given in combination with cisplatin. - as monotherapy or in combination with oxaliplatin or irinotecan, with or without bevacizumab, for the treatment of patients with metastatic colorectal cancer for whom it is not possible to continue treatment with another fluoropyrimidine due to hand-foot syndrome or cardiovascular toxicity that developed in the adjuvant or metastatic setting.' The page's pearl is advanced gastric cancer with cisplatin, so that regimen is the dose above; the colorectal regimens are recorded below. SPECIALIST USE (§4.2): 'Teysuno should only be prescribed by a qualified physician experienced in treating cancer patients with anti-neoplastic medicinal products. Patients should be provided with outpatient prescriptions for anti-emetic and anti-diarrhoeal medicinal products.' BSA must be recalculated and the dose adjusted if body weight increases or decreases by >= 10% from the one used for the previous BSA calculation and the change is clearly not related to fluid retention; calculate BSA to 2 decimal places. GASTRIC REGIMEN (§4.2): 'The recommended standard dose of Teysuno when administered in combination with cisplatin is 25 mg/m2 (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... The recommended dose of cisplatin with this regimen is 75 mg/m2 by intravenous infusion administered once every 4 weeks. Cisplatin should be discontinued after 6 cycles without withdrawal of Teysuno. If cisplatin is discontinued before 6 cycles, Teysuno treatment alone can be resumed when the criteria for restarting it are met.' Refer to the cisplatin SmPC for pretreatment hyperhydration. Treatment should be discontinued if progressive disease or intolerable toxicity is observed. Dose levels (Table 1, expressed as tegafur content): Teysuno 25 -> 20 -> 15 mg/m2 and/or cisplatin 75 -> 60 -> 45 mg/m2. Table 2 dose per dosing by BSA (twice daily; number of 15 mg capsules / 20 mg capsules per dose; the retrieved §2 gives the composition of the 15 mg capsule only): STANDARD 25 mg/m2: BSA >= 2.30 m2 60 mg (0/3); 2.10-2.29 55 mg (1/2); 1.90-2.09 50 mg (2/1); 1.70-1.89 45 mg (3/0); 1.50-1.69 40 mg (0/2); 1.30-1.49 35 mg (1/1); <= 1.29 30 mg (2/0). FIRST REDUCTION to 20 mg/m2: >= 2.13 45 mg (3/0); 1.88-2.12 40 mg (0/2); 1.63-1.87 35 mg (1/1); 1.30-1.62 30 mg (2/0); <= 1.29 20 mg (0/1). SECOND REDUCTION to 15 mg/m2: >= 2.17 35 mg (1/1); 1.67-2.16 30 mg (2/0); 1.30-1.66 20 mg (0/1); <= 1.29 15 mg (1/0). METASTATIC COLORECTAL CANCER (second licensed indication): 'The proposed dose in mCRC for monotherapy is 30 mg/m2 b.i.d. days 1-14 with a one-week pause (+/- bevacizumab 7.5 mg/kg on day 1). For combination therapy (with oxaliplatin or irinotecan), 25 mg/m2 b.i.d. d1-14 followed by one-week pause is recommended.' Dose levels: monotherapy 30 -> 25 -> 20 mg/m2; combination Teysuno 25 -> 20 mg/m2 with oxaliplatin 130 -> 100 mg/m2 and irinotecan 150-225 mg/m2 (the SPC states the best irinotecan dose is not known). Elderly, more vulnerable patients with mCRC: 20 mg/m2 twice daily for 14 consecutive days followed by 7 days rest, with a reduced oxaliplatin dose of 100 mg/m2 on day 1 of a 3-week cycle. The colorectal BSA capsule table (Table 4) is not reproduced here. DOSE MODIFICATION (§4.2): doses omitted for toxicity are not replaced; a dose vomited is not replaced; once reduced the dose should not be increased again; a maximum of two consecutive dose reductions per medicinal product; with cisplatin, Teysuno is given only on Days 1 to 21 of each 4-week cycle and if either product is delayed both are delayed until restarting criteria for both are met. General toxicity (Table 5): Grade 1 maintain dose; Grade 2 suspend until Grade 0 or 1 (for Grade 2 nausea/vomiting optimise anti-emetic therapy first); Grade 3 or higher: first and second occurrence suspend until Grade 0 or 1 then reduce by one dose level, third occurrence discontinue. Renal function at the start of each cycle (Table 6): CrCl >= 50 ml/min no modification; 30 to 49 ml/min Teysuno at one reduced dose level and cisplatin at a 50% dose reduction from the previous cycle; < 30 ml/min suspend both until CrCl >= 30 ml/min, then Teysuno at one reduced dose level and cisplatin at a 50% reduction. Haematologic toxicity (Table 7): suspend Teysuno at neutrophils < 0.5 x 10^9/l or platelets < 25 x 10^9/l (the haemoglobin cell of Table 7 is garbled in the PDF extraction and is not stated), then resume at one reduced dose level once the Table 8 criteria are met: platelets >= 100 x 10^9/l, neutrophils >= 1.5 x 10^9/l, haemoglobin >= 6.2 mmol/l, calculated CrCl >= 30 ml/min, non-haematologic toxicity at baseline or Grade 1. Method of administration: 'The capsules should be taken by mouth with water at least 1 hour before or 1 hour after a meal.' Elderly: no adjustment of the standard dose in patients > 70 years. Ethnicity: no adjustment for patients of Asian ethnicity. Paediatric: 'Teysuno should not be administered to children or adolescents under 18 years of age.' The SPC prints no maximum dose. Some sections of the product information we used were incomplete — check the full SPC.