IFEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for IFEX (IFEX).

How it works

IFEX (ifosfamide) is an alkylating agent that crosslinks DNA strands, inhibiting DNA synthesis and transcription. It requires hepatic activation via CYP3A4 to form active metabolites (ifosfamide mustard and acrolein).

What the body does with it

Metabolism	Hepatic via CYP3A4 to active metabolite ifosfamide mustard; also undergoes ring oxidation and side-chain cleavage. Acrolein is a toxic byproduct.
Excretion	Renal: approximately 50-70% of the administered dose is excreted in urine as unchanged drug; biliary/fecal excretion is minimal, accounting for less than 5%.
Half-life	Terminal elimination half-life is approximately 15 hours in adults with normal renal function; prolonged in renal impairment.
Protein binding	Negligible protein binding (<5%).
Volume of Distribution	Volume of distribution is approximately 30 L/kg, indicating extensive tissue distribution.
Bioavailability	Intravenous: 100% (only route available).
Onset of Action	Intravenous: clinical effects begin within 30-60 minutes after administration.
Duration of Action	Antineoplastic effect persists for 3-4 days after a single intravenous dose; myelosuppression nadir occurs at 10-14 days.

Classification & Brands

Dosing & administration

1.2 g/m2 intravenously daily for 5 consecutive days every 3 weeks, or 5 g/m2 as a 24-hour continuous infusion every 3 weeks.

Dosage form	INJECTABLE
Renal impairment	For CrCl 30-60 mL/min: reduce dose by 25-50%; for CrCl 10-29 mL/min: reduce dose by 50-75%; for CrCl <10 mL/min: not recommended or use with extreme caution. Hemodialysis: administer after dialysis and reduce dose by 75%.
Liver impairment	No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh C) and consider dose reduction based on bilirubin and transaminase levels.
Pediatric use	1.2 g/m2 intravenously daily for 5 consecutive days every 3 weeks; or 5 g/m2 as continuous infusion over 24 hours every 3 weeks. Adjust based on renal function and toxicity.
Geriatric use	Start at lower end of dosing range; monitor renal function closely as elderly patients are more prone to nephrotoxicity. No specific dose adjustment beyond renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for IFEX (IFEX).

Breastfeeding	Ifosfamide is excreted into human milk. M/P ratio is not established. Due to potential for serious adverse reactions (e.g., myelosuppression, mutagenicity) in the breastfed infant, breastfeeding is contraindicated during therapy and for at least 1 week after the last dose.
Teratogenic Risk	Ifosfamide (IFEX) is teratogenic. First trimester exposure is associated with major congenital malformations, including CNS, skeletal, and genitourinary defects. Second and third trimester exposure may cause intrauterine growth restriction, preterm birth, and myelosuppression in the neonate. Use is contraindicated in pregnancy unless no alternative.

Warnings & precautions

■ FDA Black Box Warning

IFEX can cause severe myelosuppression, nephrotoxicity (including hemorrhagic cystitis and renal failure), neurotoxicity (including coma and death), and secondary malignancies. Mesna and hydration are required to prevent hemorrhagic cystitis.

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe bone marrow suppression; hypersensitivity to ifosfamide; severe renal impairment; urinary outflow obstruction; active infection; pregnancy (FDA Category D); breastfeeding.

Clinical Precautions

Precautions

Myelosuppression (dose-limiting); hemorrhagic cystitis (requires mesna and hydration); nephrotoxicity (monitor renal function); neurotoxicity (CNS depression, confusion, seizures); cardiotoxicity; pulmonary toxicity; secondary malignancies; impaired fertility; veno-occlusive liver disease.

Clinical Tips & Counseling

Drug interactions

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IFEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for IFEX (IFEX).

How it works

What the body does with it

Metabolism	Hepatic via CYP3A4 to active metabolite ifosfamide mustard; also undergoes ring oxidation and side-chain cleavage. Acrolein is a toxic byproduct.
Excretion	Renal: approximately 50-70% of the administered dose is excreted in urine as unchanged drug; biliary/fecal excretion is minimal, accounting for less than 5%.
Half-life	Terminal elimination half-life is approximately 15 hours in adults with normal renal function; prolonged in renal impairment.
Protein binding	Negligible protein binding (<5%).
Volume of Distribution	Volume of distribution is approximately 30 L/kg, indicating extensive tissue distribution.
Bioavailability	Intravenous: 100% (only route available).
Onset of Action	Intravenous: clinical effects begin within 30-60 minutes after administration.
Duration of Action	Antineoplastic effect persists for 3-4 days after a single intravenous dose; myelosuppression nadir occurs at 10-14 days.

Classification & Brands

Dosing & administration

1.2 g/m2 intravenously daily for 5 consecutive days every 3 weeks, or 5 g/m2 as a 24-hour continuous infusion every 3 weeks.

Dosage form	INJECTABLE
Renal impairment	For CrCl 30-60 mL/min: reduce dose by 25-50%; for CrCl 10-29 mL/min: reduce dose by 50-75%; for CrCl <10 mL/min: not recommended or use with extreme caution. Hemodialysis: administer after dialysis and reduce dose by 75%.
Liver impairment	No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh C) and consider dose reduction based on bilirubin and transaminase levels.
Pediatric use	1.2 g/m2 intravenously daily for 5 consecutive days every 3 weeks; or 5 g/m2 as continuous infusion over 24 hours every 3 weeks. Adjust based on renal function and toxicity.
Geriatric use	Start at lower end of dosing range; monitor renal function closely as elderly patients are more prone to nephrotoxicity. No specific dose adjustment beyond renal function.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for IFEX (IFEX).

Breastfeeding	Ifosfamide is excreted into human milk. M/P ratio is not established. Due to potential for serious adverse reactions (e.g., myelosuppression, mutagenicity) in the breastfed infant, breastfeeding is contraindicated during therapy and for at least 1 week after the last dose.
Teratogenic Risk	Ifosfamide (IFEX) is teratogenic. First trimester exposure is associated with major congenital malformations, including CNS, skeletal, and genitourinary defects. Second and third trimester exposure may cause intrauterine growth restriction, preterm birth, and myelosuppression in the neonate. Use is contraindicated in pregnancy unless no alternative.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe bone marrow suppression; hypersensitivity to ifosfamide; severe renal impairment; urinary outflow obstruction; active infection; pregnancy (FDA Category D); breastfeeding.