IFEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IFEX (IFEX).
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).
| 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. |
| Molecular Weight | 261.26 |
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. |
| 1st trimester | Contraindicated due to teratogenicity; can cause fetal malformations. |
| 2nd trimester | Contraindicated; may cause fetal harm; consider risks vs benefits if no alternative. |
| 3rd trimester | Contraindicated; may cause adverse effects such as neonatal leukopenia, thrombocytopenia, and immunosuppression. |
Clinical note
Comprehensive clinical and safety monograph for IFEX (IFEX).
| Placental transfer | Ifosfamide crosses the placenta; documented in human studies. |
| Breastfeeding | Ifosfamide is excreted in breast milk; advise against breastfeeding due to potential serious adverse reactions in nursing infants. |
| Lactation Rating |
■ 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.
| Serious Effects |
Severe bone marrow suppressionKnown hypersensitivity to ifosfamide or other alkylating agentsActive infectionSevere renal impairment (CrCl <30 mL/min)Pregnancy
| 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. |
| Food/Dietary | No specific food interactions. Maintain adequate hydration with water and clear fluids. Avoid grapefruit juice due to potential CYP3A4 interaction. Follow a bland diet if nauseated. |
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| L5 |
| 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. |
| Fetal Monitoring | Monitor CBC with differential, renal function (serum creatinine, BUN, urinalysis for hematuria), and liver function tests prior to each cycle. Assess for neurotoxicity (confusion, hallucinations). During pregnancy, perform serial fetal ultrasounds for growth and anatomy, and consider non-stress testing in third trimester. Monitor maternal urine output and mesna coadministration. |
| Fertility Effects | Ifosfamide is gonadotoxic. In males, it may cause oligospermia, azoospermia, and testicular atrophy; in females, amenorrhea, premature ovarian failure, and reduced fertility. Effects may be permanent. Pre-treatment fertility preservation counseling is recommended. |
| Clinical Pearls | IFEX (ifosfamide) requires co-administration with mesna to prevent hemorrhagic cystitis. Hydration with at least 2 liters of fluid daily is essential. Monitor renal function and electrolytes, particularly potassium and phosphate, as ifosfamide can cause Fanconi syndrome. Administer antiemetics prophylactically due to high emetogenic potential. Observe for neurotoxicity (encephalopathy), which may require dose adjustment or discontinuation. Consider CYP3A4 drug interactions; avoid concurrent use with aprepitant. |
| Patient Advice | Take IFEX exactly as prescribed, usually intravenously in a clinic setting. · Drink plenty of fluids (at least 2 liters per day) to protect your bladder. · Report any blood in urine, confusion, drowsiness, or unusual weakness immediately. · You will receive a medication (mesna) to prevent bladder damage. · Avoid pregnancy; IFEX can harm unborn babies. Use effective contraception. · Do not take any other medications or herbal supplements without consulting your doctor. |