Raltitrexed (Specialist drug)

Dose is calculated on the basis of body surface area. Must only be given by or under the supervision of a physician experienced in cancer chemotherapy and in the management of chemotherapy-related toxicity. PRE-TREATMENT CHECKS: prior to initiation and before each subsequent treatment, perform a full blood count (including differential count and platelets), liver transaminases, serum bilirubin and serum creatinine. The total white cell count should be greater than 4,000/mm³, the neutrophil count greater than 2,000/mm³ and the platelet count greater than 100,000/mm³ prior to treatment. TOXICITY: in the event of toxicity the next scheduled dose should be withheld until signs of toxic effects regress; in particular, gastrointestinal toxicity (diarrhoea or mucositis) and haematological toxicity (neutropenia or thrombocytopenia) should have completely resolved before subsequent treatment. Patients who develop signs of gastrointestinal toxicity should have full blood counts monitored at least weekly. DOSE REDUCTIONS (based on the worst grade observed on the previous treatment, and only once that toxicity has completely resolved): 25% dose reduction for WHO grade 3 haematological toxicity or WHO grade 2 gastrointestinal toxicity; 50% dose reduction for WHO grade 4 haematological toxicity or WHO grade 3 gastrointestinal toxicity. Once a dose reduction has been made, all subsequent doses should be given at the reduced dose. DISCONTINUE in the event of any WHO grade 4 gastrointestinal toxicity, or WHO grade 3 gastrointestinal toxicity associated with WHO grade 4 haematological toxicity; manage promptly with standard supportive care including i.v. hydration and bone marrow support, and further use of raltitrexed is then not recommended. §4.2 adds that preclinical data suggest consideration should be given to administering leucovorin (folinic acid) in that setting, and that from clinical experience with other antifolates leucovorin may be given at a dose of 25 mg/m² i.v. every 6 hours until resolution of symptoms — note this is a rescue measure for established severe toxicity and is a dose of leucovorin, not of raltitrexed; routine concurrent administration of leucovorin, folic acid or vitamin preparations containing them is contraindicated (§4.3). §4.2 verbatim: 'It is essential that the dose reduction scheme should be adhered to since the potential for life threatening and fatal toxicity increases if the dose is not reduced or treatment not stopped as appropriate.' ELDERLY: dosage and administration as for adults, but use with caution — elderly patients are more vulnerable to the toxic effects and renal function tends to decline with age, so there is potential for accumulation. Raltitrexed is a cytotoxic agent and should be handled according to normal procedures for such agents.

§4.2 Paediatric population, verbatim: 'Raltitrexed is not recommended for use in children as safety and efficacy have not been established in this group of patients.' No paediatric figure is published here; the adult 3 mg/m² regimen has NOT been carried across and nothing has been scaled. Verify any under-18 use against a children's formulary and specialist oncology advice.