Dosing and uses of Ifex (ifosfamide)
Adult dosage forms and strengths
kit: powder with mesna solution
- 1g/vial
- 3g/vial
solution
- 1g/20mL
- 3g/60mL
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)
Off-label: 2 g/m²/day IV infusion on days 1-3 (MAID regimen, for total dose of 6 g/m²); doses as high as 5 g/m² over 24hr via continuous IV infusion in combination with other antineoplastic agents used
Administration
Use concomitant mesna (240 mg/m² IV at 0, 4, 8 hr) to prevent hemorrhagic cystitis
Maintain oral or IV hydration >2 L fluid/day
Monitor: CBCs
Bone Sarcomas (Orphan)
Orphan indication sponsor
- Bristol-Myers Squibb Company; P.O. Box 4000, Mail Stop D12-02; Princeton, NJ 08543-4000
Soft Tissue Sarcomas (Orphan)
Orphan indication sponsor
- Bristol-Myers Squibb Company; P.O. Box 4000, Mail Stop D12-02; Princeton, NJ 08543-4000
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
Hepatic Impairment
Dose adjustments not described in package insert; some clinicians have used the following guidelines
Bilirubin >3 mg/dL: 25% of regular dose
Other Indications & Uses
Off-label: Cancer of lung, breast, ovary, cervix, pancreas, bladder, and stomach; NHL; sarcomas
Pediatric dosage forms and strengths
Safety and efficacy not established
Ifex (ifosfamide) adverse (side) effects
>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%)
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
Bone marrow suppression may occur
Hemorrhagic cystitis reported
Confusion and coma due to CNS toxicity have been associated with therapy. Discontinue therapy if it occurs.
Dose-related severe myelosuppression reported
Contraindications
Hypersensitivity
Severe myelosuppression
Cautions
Avoid pregnancy
May interfere with wound healing
Use caution in renal impairment
Heart Failure risk
- Acute heart failure, often occurring within 1 to 10 days of treatment, has been reported with induction therapy at doses greater than 12.5 mg/m2
- The onset of HF can be reversible, usually resolving over 3 to 4 weeks
Pregnancy and lactation
Pregnancy category: d
Lactation: excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ifex (ifosfamide)
Mechanism of action
Synthetic analog of cyclophosphamide; cross-links DNA strands; inhibits DNA synthesis and protein synthesis
Absorption
Bioavailability: 90-100%
Peak plasma time: 20-30 minutes
Distribution
Vd: 33 L
Metabolism
Extensively metabolized
Metabolites: 3-dechloroethylifosfamide, 2-dechloroethylifosfamide, and carboxyifosfamide
Elimination
Half-life elimination: 15 hr (high dose of 3800-5000 mg/m²); 7 hr (low dose of 1800-2400 mg/m²)
Excretion: Urine 70-86% (high dose of 5000 mg/m²); 12-16% (low dose of 1600-2400)
Administration
IV Incompatibilities
Syringe: mesna with epirubicin
Y-site: cefepime, methotrexate
IV Compatibilities
Solution: D5/Ringer's, D5/NS, D5W, LR, ½NS, NS, Na-Lactate (1/6 M)
Additive: carboplatin, carboplatin w/ etoposide, cisplatin, cisplatin w/etoposide, epirubicin, etoposide, fluorouracil, mesna
Syringe: epirubicin, mesna
Y-site (partial list): allopurinal, amphotericin B cholesteryl sulfate, etoposide phosphate, filgrastim, fludarabine, gemcitabine, granisetron, linezolid, melphalan, ondansetron, paclitaxel, propofol, NaHCO3, teniposide, thiotepa
IV Preparation
Reconstitute with SWI or NS to a concentration of 50 mg/mL
Standard dilution
- IV push: dose/syringe (concentration: 50 mg/mL)
- IVPB: dose/100-1000 mL D5W or NS
IV Administration
Slow IV infusion over 30 min, or continuous infusion over 5 d
Mesna should be administered concomitantly (20% of the ifosfamide dose 15 min before, 4 hr after, & 8 hr after ifosfamide administration)
Adequate hydration (at least 2 L/day) before & for 72 hr after therapy is recommended to minimize risk of hemorrhagic cystitis
Storage
Store intact vials at room temp or under refrigeration
Syringe & IVPB are stable for 7 days at room temp& 6 wk under refrigeration
