5-Fluorouracil dosage

Patients with poorly controlled diabetes are at risk of greater or more severe fluorouracil toxicity, causing hyperglycemia, which has been fatal. This effect seems to be independent of previous diabetic control and or fluorouracil dosage schedules (414)... 

Gamelin E, Boisdron-Celle M, Guer-in-Meyer V et al. Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer a potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. J Clin Oncol 1999 17 1105-1110. 

Katsumata K, Tomioka H, Sumi T et al. Correlation between clinicopathologic factors and kinetics of metabolic enzymes for 5-fluorouracil given to patients with colon carcinoma by two different dosage regimens. Cancer Chemother Pharmacol 2003 51 155-160. 

Hepatic and renal function. Patients with advanced cancer may have impaired liver function due to the presence of liver metastases. In this case drug doses may need to be adjusted. In the case of the FOLFOX regimen, 5-fluorouracil dose may need to be reduced if the impairment is moderate or severe. Mrs KT s baseline liver function tests indicate a normal liver function, but these parameters should be monitored carefully throughout treatment. Reduced renal function may also necessitate a decrease in drug dosage. In the case of the FOLFOX regimen, oxaliplatin is contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min). 

Cases of deliberate overdosage are unknown, but excessive duration or dosage of therapy will produce life-threatening toxicity because of the hematological effects and other symptoms and signs that are qualitatively similar to the adverse effects. There is no specific antidote to fluorouracil toxicity treatment consists of supportive care, including G-CSF and antidiarrheal agents. 

Based on the results of these trials, irinotecan shonld be considered standard second-line therapy for patients who have failed prior treatment with fluorouracil-based regimens. Either dosage regimen (irinotecan 125 mg/m IV weekly for 4 weeks followed by a 2-week rest period or 300 to 350 mg/m IV every 3 weeks) is acceptable. For the every 3-week regimen, initial administration of irinotecan at the lower dose should be considered for patients who have received significant prior pelvic or abdominal irradiation. Protracted continnons-infusion fluorouracil could be considered for those individuals with disease that no longer responds to bolus IV fluorouracil plus leucovorin or irinotecan. 

Davis DA, Fugate SE, Increasing warfarin dosage reductions associated widi concurrent warfarin and repeated cycles of 5-fluorouracil therapy. Pharmaco erapy (2005) 25, 442-7. 

In a study in 8 patients, cimetidine 400 mg twice daily increased the AUC of epirubicin by 50%. At the same time the AUCs of two metabolites of epirubicin, epirubicinol and 7-deoxydoxorubicinol aglycone, increased by 41% and 357%, respectively. Liver blood flow also increased by 17%. The mechanism is unknown. More study of this interaction is needed but be aware of the possibility of cimetidine inereasing the exposure to epirubicin monitor the patient closely and adjust epirubicin dosage if needed. Cimetidine is available without a preseription in some countries so that patients may unwittingly increase the toxicity of epirubicin. Cimetidine has also increased the levels or toxicity of some other antineoplastics, see Nitrosoureas + Cimetidine , p.655, Cyclophosphamide + H2-receptor antagonists , p.626 and Fluorouracil + H2-reeeptor antagonists , p.633. 

Fluorouracil (5-FU) 5-Fluo-rouracil (5-FU) is frequently used in the treatment of a wide variety of carcinomas. It is well known that many anticancer drugs are toxic to the treated organism and that the actual dosage must be carefully controlled. It was demonstrated that 5-FU reacts with the mercury electrode... 

Skin Cutaneous reactions to fluorouracil include photosensitivity, erythema, maculo-pamlar rashes, and hyperpigmentation [8 ]. Alopecia is uncommon. Hand-foot syndrome affects about 50% of patients but it is usually mild. It occurs after a median of nine cycles of treatment and necessitates dosage reduction or delay in 15% of patients [90 ]. It is less frequent with bolus doses than infusions [83 ]. 

Gastrointestinal Stomatitis, diarrhea, and nausea are significantly less common with capecitabine than fluorouracil and affect 24%, 48% and 38% of patients respectively (all grades). Grade 3/4 diarrhea affects 23% of patients and may require dosage modification [102 ] the median time to occurrence is 34 days. Severe mucositis is uncommon and is reported in 2% of patients. 

Skin Hand-foot syndrome is significantly more common with capecitabine than fluorouracil-I-leucovorin, perhaps because of more prolonged drug exposure [104 ]. It is characterized by painless or painful swelling, erythema, and desquamation of the palms and soles. It affects 54% of patients (any grade) and is severe in 17% [102 ]. Dosage modification may be required. 

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