Ifosfamide + Mesna

Indications

Ifosfamide + Mesna is used for: Germ Cell Testicular Cancer

Adult Dose

Germ Cell Testicular Cancer Indicated in combination with other antineoplastic agents for third-line germ cell testicular cancer 1.2 g/m²/day IV infusion over 30 minutes on days 1-5 q3-4wk or after recovering from hematologic toxicity (>100,000 cells/mm³ plateletes or >4,000 cells/mm³ WBC) Use concomitant mesna (240 mg/m² IV at 0, 4, 8 hr) to prevent hemorrhagic cystitis Hepatic Impairment Dose adjustments not described in package insert; some clinicians have used the following guidelines Bilirubin >3 mg/dL: 25% of regular dose

Child Dose

Renal Dose

Renal Impairment Dose adjustments not described in package insert; some clinicians have used the following guidelines CrCl >60 mL/min: 100% of regular dose CrCl 30-60 mL/min: 75% of regular dose CrCl 10-30 mL/min: 50% of regular dose CrCl <10 mL/min: Not recommended

Administration

Maintain oral or IV hydration >2 L fluid/day IV Preparation Reconstitute w/ D5W, NS, dextrose/saline or LR to a final concentration of 20 mg/mL IV Administration IVP: bolus 15 min before ifosfamide Intermittent infusion over 15-30 min Continuous Infusion: may be added to ifosfamide/cyclophosphamide in infusion bag Additive compatibility w/ cyclophosphamide shown only in D5W & LR

Contra Indications

Hypersensitivity, Severe myelosuppression

Precautions

Avoid pregnancy May interfere with wound healing Use caution in renal impairment Heart Failure risk Lactation: excreted in breast milk, do not nurse

Pregnancy-Lactation

Interactions

Causes enhanced toxicity with allopurinol, cisplatin. Ifosfamide enhances the anticoagulant effect of warfarin. CYP2A6 inducers (e.g. amobarbital, pentobarbital, phenobarbital, rifampin and secobarbital) may reduce serum levels of ifosfamide while the inhibitors (e.g. isoniazid, methoxsalen and miconazole) may increase its serum levels. CYP3A4 inducers (e.g. aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins) may reduce serum levels of ifosfamide while the inhibitors (e.g. azole antifungals, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid) may increase its serum levels.

Adverse Effects

Side effects of Ifosfamide + Mesna : >10% Alopecia (83%) Nausea (58%) Vomiting (58%) Leukopenia (50%) Hematuria (46%) Metabolic acidosis (31%) Thrombocytopenia (20%) CNS toxicity (12%) Neurotoxicity (10-20%) 1-10% Infection (8%) Nephrotoxicity (6%)

Mechanism of Action

Synthetic analog of cyclophosphamide; cross-links DNA strands; inhibits DNA synthesis and protein synthesis Oxidized to dimesna in the blood, and is in turn reduced back to mesna in the kidney; synthetic sulfhydryl (thiol) compound binds & detoxifies ifosfamide metabolite acrolein in bladder/kidney