Parenteral Manual

Ifosfamide

Disclaimer: Official controlled document is the CHEO online copy. It is the responsibility of user to ensure that any paper copy version is the same as the online version before use.

Alternate Name(s): 
IFEX
Classification: 
Antineoplastic, alkylating agent - CYTOTOXIC
Original Date: 
August 2005
Revised Date: 
August 2023
Indications: 
  • Sarcomas           - Neuroblastoma           - Wilm's tumor
  • Brain tumors      - Relapsed and high risk leukemias

THIS MEDICATION IS TO BE ADMINISTERED BY A CHEMO-TRAINED NURSE. IF THE NURSE IS NOT CHEMO-TRAINED, THEY ARE TO CONTACT THE UNIT NURSE EDUCATOR OR ADVANCED PRACTICE NURSE.

Reconstitution and Stability: 
  • Reconstitute 3 g vial of powder with 60 mL SWI and 1 g vial of powder with 20 mL SWI
  • Reconstituted vial is 50 mg/mL clear & colourless solution.
  • Further diluted solutions are stable for 24 hours room temperature or 72 hours fridge
Compatibility: 

- Solutions Compatible:  D5W, NS, and combinations

- Additives/buretrol Compatible: mesna

- Y-site Compatible: allopurinol, amphotericin B, ondansetron, KCl, sodium bicarbonate (diluted)

- Incompatible: methotrexate

Administration: 

(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)

SC NO
IM NO
IV Direct NO
IV Intermittent Infusion YES
Usual dilution: dilute in 100-250 mL of compatible solution
Infusion time: 30-120 min, depends on dosage (30 min for each g/m2)
IV Continuous Infusion YES
Usual dilution: < 20 mg/mL
Dosage: 

(For neonatal dosages, refer to Neonatal IV Drug Manual.)

  • Usual dose is 1.8-2.4 g/m2/day x 5 days Q 3-4 weeks
  • High dose is 3.5 g/m2/day x 3-5 days
  • Dosages for children <0.5 m2 should be based on body weight (ie. mg/kg).  To convert mg/m2 to mg/kg, divide m2 dose by 30 (1m2 = 30 kg)

Must be given concomitantly with mesna to prevent hemorrhagic cystitis.  Total mesna dosage is usually 60-100% of ifosfamide dose. Mesna is given for 9-24 hours after ifosfamide, because of the shorter half-life

** Dosage may vary according to protocol

 Dosage adjustment in renal impairment:                                                                                \

  • Consult protocol for details. Do not give ifosfamide if CrCl < 60 mL/in/1.73 m2
Potential hazards of parenteral administration: 

Immediate:

  • Nausea and vomiting (moderately high emetogenic potential)
  • Hematuria, dysuria, frequency, hemorrhagic cystitis
  • SIADH (hyponatremia, water intoxication)
  • Neurotoxicity: somnolence, confusion, hallucinations, rarely seizures, tremor-usually reversible within several days.  Sedating antiemetics and other CNS active drugs (dimenhydrinate, diphenhydramine, droperidol, nabilone, prochlorperazine, metoclopramide) may potentiate neurotoxicity
  • If extravasation occurs, see Treatment of Infiltrated Vesicant or Irritant Drugs Guidelines on CHEOnet.

Delayed:

  • Myelosuppression (nadir 10-14 days)
  • Alopecia (common)
  • Sterile hemorrhagic cystitis (see below)
  • SIADH-like syndrome with inappropriately concentrated urine.
  • Sterility (dose and age related)

Late:

  • Renal Fanconi Syndrome- (proximal tubular damage): decreased phosphate, potassium and bicarbonate with acidosis, glycosuria with serum glucose <8 mmol/L and proteinuria).  GFR <50 mL/min/1.73 m2 (especially if patient has previously received nephrotoxic agents, ie. cisplatinum)

- Treatment for unusual side effects are available through the study chair identified on the front page of the protocol and/or pharmacy

Notes: 
  • Monitor hematologic status, serum electrolytes, liver & renal function, ins & outs
  • Frequent urination (q2h) necessary, check for macro and micro hematuria (dipstick urine for blood q2h). Monitor urine specific gravity, weigh daily. Consult pre-printed orders for urine output parameters
  • Urinary tract toxicity may be severe despite mesna.  Hydrate with 2.5-3 L/m2/24 hr of fluid, starting 3 hours before treatment and continuing 24 hours after
  • Mesna doesn't appear to protect against proximal tubular abnormalities
  • Monitor renal function carefully when it's absolutely necessary to administer nephrotoxic agents (ie. furosemide, cisplatinum and aminoglycosides) concomitantly
  • Hepatic enzyme inducers, ie. phenytoin, phenobarbital, rifampin etc, can increase activation of ifosfamide to its toxic metabolite
  • Ifosfamide-induced encephalopathy and/or seizures are thought to be due to the build up of CNS toxic metabolites.  Risk factors include decreased renal function, administration of other CNS active agents, and low serum albumin.  Dialysis and methylene blue (50 mg IV q6-8h) have both been used to speed recovery which usually eventually occurs as the metabolites are excreted.

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