Lonsurf

Lonsurf should be prescribed by physicians experienced in the administration of anticancer therapy. 4). 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.

Please refer to the full product information for bevacizumab. The dose is calculated according to body surface area (BSA) (see Table 1). The dose must not exceed 80 mg/dose. If doses were missed or held, the patient must not make up for missed doses.

30 80 0 4 160 Recommended dose adjustments Dosing adjustments may be required based on individual safety and tolerability. A maximum of 3 dose reductions are permitted to a minimum dose of 20 mg/m2 twice daily. Dose escalation is not permitted after it has been reduced.

In the event of haematological and/or non-haematological toxicities patients should follow the dose interruption, resumption and reduction criteria stated in Table 2, Table 3 and Table 4. 5  109/L Platelets < 50  109/L  75  109/L a Resumption criteria applied to the start of the next cycle for all patients regardless of whether or not the interruption criteria were met.

5 x 109/L) or thrombocytopenia (< 25  109/L) that results in more than 1 week’s delay in start of next cycle • CTCAE* non-haematologic Grade 3 or Grade 4 adverse reaction; except for Grade 3 nausea and/or vomiting controlled by antiemetic therapy or diarrhoea responsive to antidiarrhoeal medicinal products • Interrupt dosing until toxicity resolves to Grade 1 or baseline.

• When resuming dosing, decrease the dose level by 5 mg/m2/dose from the previous dose level (Table 4). • Dose reductions are permitted to a minimum dose of 20 mg/m2/dose twice daily (or 15 mg/m2/dose twice daily in severe renal impairment).

• Do not increase dose after it has been reduced. 14 mg tablets in the evening. 2). 2). One dose reduction to a minimum dose of 15 mg/m2 twice daily is permitted 6 based on individual safety and tolerability (see Table 5). Dose escalation is not permitted after it has been reduced.

In the event of haematological and/or non-haematological toxicities patients should follow the dose interruption, resumption and reduction criteria stated in Table 2, Table 3 and Table 5. 14 mg tablets in the evening. 4). 2). • Moderate or severe hepatic impairment Administration is not recommended in patients with baseline moderate or severe […]

4). Lonsurf as monotherapy The safety profile of Lonsurf as monotherapy is based on the pooled data from 1114 patients with metastatic colorectal or gastric cancer in controlled phase III clinical studies. The most common adverse reactions (≥ 2%) that resulted in treatment discontinuation, dose reduction, dose delay, or dose interruption were neutropenia, anaemia, fatigue, leukopenia, thrombocytopenia, diarrhoea, and nausea.

Lonsurf in combination with bevacizumab The safety profile of Lonsurf in combination with bevacizumab is based on the data from 246 patients with metastatic colorectal cancer in the controlled phase III clinical study (SUNLIGHT). 10 The most common adverse reactions (≥ 30%) are neutropenia (69% [48% ≥ Grade 3]), fatigue (35% [3% ≥ Grade 3]), and nausea (33% [1% ≥ Grade 3]).

The most common adverse reactions (≥ 2%) that resulted in treatment discontinuation, dose reduction, dose delay, or dose interruption of Lonsurf when used in combination with bevacizumab were neutropenia, fatigue, thrombocytopenia, nausea and anaemia.

When Lonsurf is used in combination with bevacizumab, the frequency of the following adverse reactions was increased compared to Lonsurf as monotherapy: neutropenia (69% vs 53%), severe neutropenia (48% vs 34%), thrombocytopenia (24% vs 16%), stomatitis (11% vs 6%).

Tabulated list of adverse reactions The adverse reactions observed from the 533 treated patients with metastatic colorectal cancer in the placebo-controlled Phase III (RECOURSE) clinical study, the 335 treated patients with metastatic gastric cancer in the placebo-controlled Phase III (TAGS) clinical study, the 246 patients treated with Lonsurf in monotherapy and the 246 patients treated with Lonsurf in combination with bevacizumab for metastatic colorectal cancer in the controlled Phase III (SUNLIGHT) clinical study are shown in Table 6.

Bone marrow suppression Lonsurf caused an increase in the incidence of myelosuppression including anaemia, neutropenia, leukopenia, and thrombocytopenia. Complete blood cell counts must be obtained prior to initiation of therapy and as needed to monitor toxicity, but at a minimum, prior to each treatment cycle.

5 109/L, if the platelet counts are < 75  109/L, or if the patient has an unresolved Grade 3 or 4 non-haematological clinically relevant toxicity from prior therapies. 8). Given that the majority were reported in the context of bone marrow suppression, the patient’s condition should be monitored closely, and appropriate measures, such as antimicrobial agents and granulocyte-colony stimulating factor (G-CSF), should be administered as clinically indicated.

5% of patients in the Lonsurf group respectively received G- CSF mainly for therapeutic use. 3% for therapeutic use. Gastrointestinal toxicity Lonsurf caused an increase in the incidence of gastrointestinal toxicities including nausea, vomiting and diarrhoea.

Patients with nausea, vomiting, diarrhoea and other gastrointestinal toxicities should be carefully monitored, and anti-emetic, anti-diarrhoeal and other measures, such as fluid/electrolyte replacement therapy, should be administered as clinically indicated.

2). 2). 8 The global incidence of adverse events (AEs) is similar in normal renal function (CrCl ≥ 90 mL/min), mild (CrCl = 60 to 89 mL/min) or moderate (CrCl = 30 to 59 mL/min) renal impairment subgroups. However, the incidence of serious, severe AEs and AEs leading to dose modification tends to increase with advancing levels of renal impairment.

2). Patients with severe renal impairment (CrCl = 15 to 29 mL/min) and adjusted starting dose of 20 mg/m2 twice daily had a safety profile consistent with the safety profile of Lonsurf in patients with normal renal function or mild renal impairment.

1.