Oxol Dosage/Direction for Use

For adults only.
The recommended dose for oxaliplatin in adjuvant setting is 85 mg/m² intravenously repeated every two weeks for 12 cycles (6 months).
The recommended dose for oxaliplatin in treatment of metastatic colorectal cancer is 85 mg/m² intravenously repeated every 2 weeks.
Dosage given should be adjusted according to tolerability (see Dose Modification Recommendations as follows).
The recommended dosed for oxaliplatin in the treatment of unresectable advanced or metastatic gastric cancer are: 100 mg/m² intravenously repeated every two weeks in combination with infusional 5-FU and folinic acid.
85 mg/m² intravenously (FLO regimen every 2 weeks in combination with fluorouracil 2,600 mg/m² and leucovorin 200 mg/m².
85 mg/m² intravenously (Modified FOLFOX regimen) every 2 weeks in combination with fluorouracil 1,000 mg/m² and leucovorin 200 mg/m².
130 mg/m² intravenously (EOX or EOF regimen) every 3 weeks cycle in combination with Epirubicin 50 mg/m² and Capecitabine 625 mg/m² or fluorouracil 200 mg/m².
The recommended dose for oxaliplatin in combination with 5-fluorouracil and folinic acid (FOLFOX) in the treatment of unresectable hepatocellular carcinoma is 85 mg/m² intravenously, repeated ever two weeks until disease progression or unacceptable toxicity.
Oxaliplatin should always be administered before fluoropyrimidines (5-FU).
Oxaliplatin is administered as a 2- to 6-hour intravenous infusion in 250 to 500 ml of 5% glucose solution to give a concentrate not less than 0.2 mg/ml.
Oxaliplatin was mainly used in combination with continuous infusion 5-fluorouracil based regimens. For the two-weekly treatment schedule 5-fluorouracil regimens combining bolus and continuous infusion were used.
Special Populations: Renal impairment: In gastrointestinal cancer patients with varying degrees of renal impairment, treated with oxaliplatin (2 hour IV infusion every two weeks for a maximum of 12 cycles) in combination with 5FU/FA (FOLFOX4), oxaliplatin showed minimal clinical impact on renal function as assessed by mean creatinine clearance.
The safety results were similar between the patient groups. However, the duration of exposure was shorter in patients with renal impairment. The median exposure was 4, 6 and 3 cycles for mild, moderate and severe renal impairment patients, respectively. In patients with normal renal function, the median exposure was 9 cycles. More patients discontinued treatment due to adverse events in renal impairment groups.
The oxaliplatin initial dose was already reduced to 65 mg/m² severe renal impairment patients.
In patients with normal renal function or mild to moderate renal impairment, the recommended close of oxaliplatin is 85 mg/m². In patients with severe renal impairment, the initial recommended dose should be reduced to 65 mg/m².
Hepatic insufficiency: Oxaliplatin has not been studied in patients with severe hepatic impairment. No increase in oxaliplatin acute toxicities was observed in the subset of patients with abnormal liver function tests at baseline. No specific dose adjustment for patients with abnormal liver function tests was performed during clinical development.
Elderly patients: No increase in severe toxicities was observed when oxaliplatin was used as a single agent or in combination with 5-flurouracil in patients over the age of 65. In consequence no specific dose adaptation is required for elderly patients.
Method of administration: Oxaliplatin is administered by intravenous infusion.
The administration of oxaliplatin does not require hyperhydration.
Oxaliplatin diluted in 250 to 500 ml of 5% glucose solution to give a concentration not less than 0.2 mg/ml must be infused via a central venous line or peripheral vein over 2 to 6 hours.
Oxaliplatin infusion should always precede that of 5-fluorouracil.
In the event of extravasation, administration must be discontinued immediately.
Instructions for use: Oxaliplatin must be diluted before use. Only the recommended diluent should be used to dilute the concentrate for solution for in fusion product.
Premedication with antiemetics, including 5-HT 3 blockers with or without dexamethasone, is recommended.
For information on 5-fluorouracil and leucovorin, see the respective package inserts.
Dose Modification Recommendations: Prolongation of infusion time for OXOL from 2 hours to 6 hours decreases the C_max by an estimated 32% and may mitigate acute toxicity. The infusion time for infusional 5-FU and leucovorin do not need to be changed.
For patients who experience persistent Grade 2 neurosensory events that do not 2 resolve, a dose reduction of OXOL to 65 mg/m² should be considered. For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered.
The infusional 5-FU/LV regimen need not be altered.
A dose reduction of OXOL to 65 mg/m² and infusional 5-FU by 20% (300 mg/m² bolus and 500 mg/m² 22 hour infusion) is recommended for patients after recovery from Grade 3/4 gastrointestinal (despite prophylactic treatment) or Grade 3/4 hematologic toxicity (neutrophils <1.5 x 10⁹/L, platelets <100 x 10⁹/L). The next dose should be delayed until neutrophils are >1.5 x 10⁹/L and platelets are >75 x 10⁹/L.
Neurotoxicity scale: The grading scale for paresthesias/dysesthesias was: Grade 1, resolved and did not interfere with functioning; Grade 2, interfered with function but not daily activities; Grade 3, pain or functional impairment that interfered with daily activities; Grade 4, persistent impairment that is disabling or life-threatening.