Cisplatin (Specialist drug)

SPC PREAMBLE: the dosage depends on the primary disease, the expected reaction, and on whether cisplatin is used for monotherapy or as a component of combination chemotherapy. COMBINATION THERAPY: if cisplatin is used in combination therapy the dose of cisplatin must be reduced — a typical dose is 20 mg/m2 or more once every 3 to 4 weeks. CERVICAL CANCER: cisplatin is used in combination with radiotherapy or other chemotherapeutics; a typical dose is 40 mg/m2 weekly for 6 weeks. HYDRATION (mandatory): adequate hydration must be maintained from 2 to 12 hours prior to administration until a minimum of 6 hours after administration, using sodium chloride 0.9% or a 1:1 mixture of sodium chloride 0.9% and glucose 5%. Pre-treatment: IV infusion of 100 to 200 ml/hour for 6 to 12 hours, total at least 1 litre. Post-treatment: a further 2 litres at 100 to 200 ml/hour over 6 to 12 hours. The patient must drink large quantities of liquid for 24 hours after the infusion. FORCED DIURESIS: may be required if urine secretion is less than 100 to 200 ml/hour after hydration — 37.5 g mannitol as a 10% solution (375 ml of mannitol 10%) intravenously, or a diuretic if renal function is normal. Mannitol or a diuretic is also required whenever the administered cisplatin dose is higher than 60 mg/m2 BSA. A urine output of 100 ml/hour or greater will tend to minimise nephrotoxicity. PRE-CYCLE PARAMETERS (SPC section 4.4): repeated administration should be postponed until serum creatinine is 130 micromol/l or less (1.5 mg/100 ml), urea is less than 25 mg/dl, white cells are above 4000/microlitre (4.0 x 10^9/l), platelets are above 100000/microlitre (100 x 10^9/l) and the audiogram is within the normal range. Renal function, hepatic function, haematopoietic function and serum electrolytes (calcium, sodium, potassium, magnesium) should be checked before, during and after administration and repeated weekly throughout treatment. PAEDIATRIC: the SPC states 'Adults and paediatric population... The dosage directions are applicable for both adults and children' — no separate numeric paediatric regimen is given, and doses are body-surface-area based rather than per kg, so no structured paediatric dose can be recorded. Ototoxicity may be more severe in children; the US label additionally states that all children should have audiometric monitoring before therapy, before each subsequent dose, and for several years post therapy. OTHER ROUTE: the SPC notes that although cisplatin is usually given intravenously, it has also been given by intraperitoneal instillation to patients with intraperitoneal malignancies (e.g. ovarian tumours) — no dose is stated for that route. SPECIALIST USE ONLY: to be administered under the direction of oncologists in specialist units with facilities for adequate monitoring and for control of anaphylactic reactions. SOURCE CAVEAT: the fetched UK SPC sections 4.4 and 4.8 were truncated at the source-fetch limit and section 4.5 (interactions) was not retrieved — the interaction list below is drawn from what was retrieved plus the US label, and must be checked against the full SPC.