Ifosfamide

Ifosfamide is a prodrug that requires metabolic activation by hepatic cytochrome P450 isoenzymes to exert its cytotoxic activity. Activation occurs by hydroxylation at the ring carbon atom forming the unstable intermediate 4‑hydroxyifosfamide and its ring-opened aldo tautomer, which decomposes to yield the cytotoxic and urotoxic compound acrolein and an alkylating isophosphoramide mustard isophosphoramide mustard.

• Ifosfamide for Injection is indicated for use in adults in combination with certain other approved antineoplastic agents for third-line chemotherapy of germ cell testicular cancer. Ifosfamide for Injection is an alkylating drug indicated for use in adults in combination with certain other approved antineoplastic agents for third-line chemotherapy of germ cell testicular cancer.

• Ifosfamide for Injection is contraindicated in patients with: • Known hypersensitivity to administration of ifosfamide. • Urinary outflow obstruction.contraindicated

• Administer Ifosfamide for Injection with extensive hydration consisting of at least 2 liters of oral or intravenous fluid per day to reduce the incidence or severity of bladder toxicity. ( 2.1 , 5.3 ) • Administer mesna with Ifosfamide for Injection to reduce the incidence or severity of hemorrhagic cystitis. ( 2.1 , 5.3 ) • Administer Ifosfamide for Injection as a slow intravenous infusion (at least 30 minutes) at a dose of 1.2 grams per m 2 per day for 5 consecutive days. Repeat every 3 weeks or after recovery from hematologic toxicity. ( 2.2 ) • Individualize the dose and dosing schedule of Ifosfamide for Injection based on patient risk factors and adverse reactions. ( 2.2 ) • See Full Prescribing Information for instructions on preparation and administration. ( 2.3 ) 2.1 Important Administration Instructions Administer Ifosfamide for Injection with extensive hydration consisting of at least 2 liters of oral or intravenous fluid per day to reduce the incidence or severity of bladder toxicity. Administer Ifosfamide for Injection with mesna to reduce the incidence or severity of hemorrhagic cystitis [see Warnings and Precautions (5.3) ]. 2.2 Recommended Dosage The recommended dosage of Ifosfamide for Injection is 1.2 grams per m2 per day administered as a slow intravenous infusion (lasting at least 30 minutes) for 5 consecutive days. Treatment is repeated every 3 weeks or after recovery from hematologic toxicity. Individualize the dose and dosing schedule of Ifosfamide for Injection based on patient risk factors and adverse reactions.

• Myelosuppression: Monitor blood counts prior to treatment, during treatment, and as clinically indicated. ( 5.1 ) • Encephalopathy: Monitor for signs and symptoms of CNS toxicity during and after Ifosfamide for Injection treatment. Dose interruption or permanent discontinuation may be required based on individual safety and tolerability. ( 5.2 ) • Nephrotoxicity and Urotoxicity: Monitor signs and symptoms. Monitor serum and urine chemistries. (2.1, 5.3 ) • Cardiotoxicity: Arrhythmias, other ECG changes, and cardiomyopathy can occur and result in death. Cardiotoxicity is dose dependent and the risk is increased in patients with preexisting cardiac, treatment with other cardiotoxic agents, radiation, and renal impairment. ( 5.4 ) • Pulmonary toxicity: Interstitial pneumonitis, pulmonary fibrosis, and pulmonary toxicity with fatal outcomes can occur. Monitor for signs and symptoms of pulmonary toxicity and treat as clinically indicated. ( 5.5 ) • Secondary malignancies can occur. ( 5.6 ) • Veno-occlusive Liver Disease can occur. ( 5.7 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. ( 5.8 , 8.1 , 8.3 ) • Infertility: Can impair male and female reproductive function. ( 5.9 ) • Anaphylactic/anaphylactoid reactions have been reported. ( 5.10 ) 5.1 Myelosuppression Ifosfamide for Injection can cause myelosuppression that results in severe or fatal infections including sepsis or septic shock.

The most common (≥ 10%) adverse reactions were alopecia, nausea/vomiting, hematuria, leukopenia, anemia, CNS toxicity, infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at phone: 1 866 888 2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted from widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The adverse reactions in Table 2 below are based on 30 publications describing clinical experience with fractionated administration of ifosfamide as a single agent with a total dose of 4 to 12 g/m 2 per course. Table 2: Adverse Reactions in Patients Treated with Single Agent Ifosfamide for Injection Adverse Reaction Single Agent Ifosfamide for Injection % (number of patients) Skin and Subcutaneous Tissue Disorders Alopecia 90% (540/603) Dermatitis 0.08% (1/1317) Papular rash 0.08% (1/1317) Gastrointestinal Disorders Nausea/Vomiting 47% (443/964) Diarrhea 0.7% (9/1317) Stomatitis 0.3% (4/1317) Renal and Urinary Disorders Hemorrhagic cystitis Includes dysuria and pollakiuria Hematuria - without mesna 44% (282/640) - with mesna 21% (33/155) Macrohematuria - without mesna 11% (66/594) - with mesna 5% (5/97) Renal dysfunction Includes acute renal failure, irreversible renal failure (fatal outcomes) serum creatinine increased, BUN increased, creatinine clearance decreased, metabolic acidosis, anuria, oliguria…

• Lactation: Advise not to breastfeed. ( 8.2 ) • Renal impairment: Closely monitor for adverse reactions and consider dosage modifications. ( 8.6 ) 8.1 Pregnancy Risk Summary Based on mechanism of action [see Clinical Pharmacology (12.1) ] , and human and animal data (see Data) , Ifosfamide for Injection can cause fetal harm when administered to a pregnant woman. Fetal growth retardation and neonatal anemia have been reported following exposure to ifosfamide‑containing chemotherapy regimens during pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Animal studies indicate that ifosfamide is capable of causing gene mutations and chromosomal damage in vivo . In pregnant mice, resorptions increased and anomalies were present at day 19 after a 30 mg/m 2 dose of ifosfamide was administered on day 11 of gestation. Embryo-lethal effects were observed in rats following the administration of 54 mg/m 2 doses of ifosfamide from the 6th through the 15th day of gestation and embryotoxic effects were apparent after dams received 18 mg/m 2 doses over the same dosing period. Ifosfamide is embryotoxic to rabbits receiving 88 mg/m 2 /day doses from the 6th through the 18th day after mating.

Metabolism

Ifosfamide exhibits dose-dependent pharmacokinetics in humans. At single doses of 3.8 to 5.0 g/m 2 , the plasma concentrations decay biphasically and the mean terminal elimination half-life is about 15 hours.

No specific antidote for Ifosfamide for Injection is known. Patients who receive an overdose should be closely monitored for the development of toxicities. Serious consequences of overdosage include manifestations of dose-dependent toxicities such as CNS toxicity, nephrotoxicity, myelosuppression, and mucositis [see Warnings and Precautions (5) ]. Management of overdosage would include general supportive measures to sustain the patient through any period of toxicity that might occur, including appropriate state-of-the-art treatment for any concurrent infection, myelosuppression, or other toxicity. Ifosfamide as well as ifosfamide metabolites are dialyzable. Cystitis prophylaxis with mesna may be helpful in preventing or limiting urotoxic effects with overdose.

• Aug 14, 1987NDANDA019763Baxter Hlthcare
• May 28, 2002ANDAANDA076078Fresenius Kabi Usa
• Jun 29, 2011ANDAANDA076619Hikma

1. 1Off Label Use2,74613%
2. 2Febrile Neutropenia2,63913%
3. 3Disease Progression2,08910%
4. 4Neutropenia1,8829.0%
5. 5Drug Ineffective1,5577.5%
6. 6Thrombocytopenia1,5137.2%
7. 7Anaemia1,2295.9%
8. 8Pyrexia9784.7%
9. 9Product Use In Unapproved Indication9394.5%
10. 10Sepsis8674.2%
11. 11Infection7953.8%
12. 12Pancytopenia7633.7%
13. 13Vomiting7473.6%
14. 14Nausea7353.5%
15. 15Malignant Neoplasm Progression7173.4%

Recent PubMed references pinned to Ifosfamide as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Ifosfamide-Induced Encephalopathy in a Very Young Child With Rhabdomyosarcoma: Case Report and Literature Review.
  Journal of pediatric hematology/oncology · 2026 · Koronica R, De Leonardis F, Servedio M, et al.
  PMID 41818182DOI 10.1097/MPH.0000000000003183
• A natural nephroprotective adjuvant for cancer chemotherapy: Rosmarinic acid disrupts IL-17 A-Ferroptosis coupling in Ifosfamide-induced renal injury.
  Medical oncology (Northwood, London, England) · 2026 · Süzen Celbek B, Şimşek H, Akaras N, et al.
  PMID 41795721DOI 10.1007/s12032-026-03280-z
• [Persistent electrolyte deficiency in an oncology patient].
  Praxis · 2026 · Maurer N, Ledergerber K, Denecke B, et al.
  PMID 41725340DOI 10.23785/PRAXIS.2026.01.005
• High-Dose Continuous Infusion Ifosfamide as Effective Palliation in a Patient With Relapsed Ewing Sarcoma With Bone Marrow Infiltration and Severe Thrombocytopenia: A Case Report.
  Cancer reports (Hoboken, N.J.) · 2026 · Murtas F, Chiusole B, Tortorelli I, et al.
  PMID 41704154DOI 10.1002/cnr2.70468
• Real-World Experience of Efficacy and Tolerability of Continuous Infusion Ifosfamide for Advanced Soft Tissue and Bone Sarcoma Patients: A Single Centre Retrospective Cohort.
  Cancer medicine · 2026 · Mascagni I, Laffi A, Grimaudo MS, et al.
  PMID 41692427DOI 10.1002/cam4.71614
• Long-term benefit from high-dose ifosfamide in sarcoma depends on sustained prior control and timely intervention: a machine learning analysis.
  Journal of cancer research and clinical oncology · 2026 · Hoberger M, Zuber RL, Burkhard-Meier A, et al.
  PMID 41504936DOI 10.1007/s00432-025-06410-8
• Apatinib plus ifosfamide and etoposide versus ifosfamide and etoposide in patients with advanced osteosarcomas (OAIE/PKUPH-sarcoma 11): a randomized phase II study.
  Nature communications · 2025 · Xie L, Xu J, Sun X, et al.
  PMID 41290609DOI 10.1038/s41467-025-65467-8
• Chronotolerance of ifosfamide in mice: Evidence for a circadian rhythm.
  Chronobiology international · 2026 · Chennoufi MM, Boughattas NA
  PMID 41208488DOI 10.1080/07420528.2025.2581095

The 10 most recently updated of 544 ClinicalTrials.gov registrations naming Ifosfamide as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Eflornithine (DFMO) for Ewing Sarcoma and Osteosarcoma
  Recruiting · Phase 2 · Interventional · 406 enrolled · Milton S. Hershey Medical Center
  NCT07321912updated 2026-06-12
• Polatuzumab Vedotin Plus Rituximab, Ifosfamide, Carboplatin and Etoposide (Pola-R-ICE) Versus R-ICE Alone in Second Line Treatment of Diffuse Large B-cell Lymphoma (DLBCL)
  Completed · Phase 3 · Interventional · 306 enrolled · GWT-TUD GmbH
  NCT04833114updated 2026-06-10
• NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
  Recruiting · Phase 1 · Phase 2 · Interventional · 139 enrolled · St. Jude Children's Research Hospital
  NCT06239272updated 2026-06-10
• Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma
  Active not recruiting · Phase 3 · Interventional · 312 enrolled · National Cancer Institute (NCI)
  NCT02306161updated 2026-06-03
• A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
  Recruiting · Phase 1 · Phase 2 · Interventional · 65 enrolled · Hoffmann-La Roche
  NCT05533775updated 2026-06-03
• Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma
  Active not recruiting · Phase 3 · Interventional · 847 enrolled · National Cancer Institute (NCI)
  NCT02112916updated 2026-06-03
• TCRαβ-depleted Progenitor Cell Graft With Additional Memory T-cell DLI, Plus Selected Use of Blinatumomab, in Naive T-cell Depleted Haploidentical Donor Hematopoietc Cell Transplantation for Hematologic Malignancies
  Active not recruiting · Phase 2 · Interventional · 69 enrolled · St. Jude Children's Research Hospital
  NCT03849651updated 2026-06-03
• Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 543 enrolled · Genmab
  NCT04663347updated 2026-06-02
• Nivolumab, Ifosfamide, Carboplatin, and Etoposide as Second-Line Therapy in Treating Patients With Refractory or Relapsed HL
  Active not recruiting · Phase 2 · Interventional · 78 enrolled · City of Hope Medical Center
  NCT03016871updated 2026-05-28
• Study of CD19 Allogeneic Memory T-cell Therapy for Relapsed/Refractory CD19+ Leukemia
  Recruiting · Phase 1 · Interventional · 60 enrolled · St. Jude Children's Research Hospital
  NCT04881240updated 2026-05-26

Frequently asked questions

How does Ifosfamide work?

Ifosfamide is a prodrug that requires metabolic activation by hepatic cytochrome P450 isoenzymes to exert its cytotoxic activity. Activation occurs by hydroxylation at the ring carbon atom forming the unstable intermediate 4‑hydroxyifosfamide and its ring-opened aldo tautomer, which decomposes to yield the cytotoxic and urotoxic compound acrolein and an alkylating isophosphoramide mustard isophosphoramide mustard.

What is Ifosfamide used for?

According to FDA labeling, Ifosfamide carries indications including: Ifosfamide for Injection is indicated for use in adults in combination with certain other approved antineoplastic agents for third-line chemotherapy of germ cell testicular cancer. Ifosfamide for Injection is an alkylating drug indicated for use in adults in combination with certain other approved antineoplastic agents for third-line chemotherapy of germ cell testicular cancer.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ifosfamide?

Ifosfamide is classified as Nitrogen mustard analogues, Alkylating Drug, Alkylating Activity, Decreased DNA Integrity, Decreased DNA Replication.

What are the brand names for Ifosfamide?

Ifosfamide is marketed under brand names including Ifex.

What are the contraindications for Ifosfamide?

Ifosfamide labeling lists contraindications including: Ifosfamide for Injection is contraindicated in patients with: • Known hypersensitivity to administration of ifosfamide. • Urinary outflow obstruction.. Always consult the full prescribing information and a clinician.