Version July 2025
Myelosuppression can be severe and lead to fatal infections. Monitor blood counts prior to and at intervals after each treatment cycle.
Encephalopathy can be severe and may result in death. Monitor for CNS toxicity and discontinue treatment for encephalopathy.
Hemorrhagic cystitis can be severe and can be reduced by the prophylactic use of mesna.
Nephrotoxicity can be severe and result in renal failure.
Dosage guidance:
Safety: To prevent bladder toxicity, ifosfamide should be administered with mesna and hydration (at least 2 L of oral or IV fluid per day). Exclude or correct urinary tract obstructions prior to treatment. Avoid administration of ifosfamide for WBC <2,000/mm3 and/or platelets <50,000/mm3 (unless clinically necessary) or in patients with signs/symptoms of active infection (including active urinary tract infection) or severe immunosuppression.
Clinical considerations: Ifosfamide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Bladder cancer, advanced (off-label use): IV: 1,500 mg/m2/day for 5 days every 3 weeks (with mesna) until disease progression (Ref).
Cervical cancer, recurrent or metastatic (off-label use): IV: 1,500 mg/m2/day for 5 days every 3 weeks (with mesna) (Ref).
Ewing sarcoma (off-label use):
VAC/IE regimen: Adults ≤30 years: IE: IV: 1,800 mg/m2/day for 5 days (in combination with mesna and etoposide) alternate with VAC (vincristine, doxorubicin, and cyclophosphamide) every 3 weeks for a total of 17 courses (Ref).
VAIA regimen: IV: 3,000 mg/m2 day on days 1, 2, 22, 23, 43, and 44 for 4 courses (in combination with vincristine, doxorubicin, dactinomycin, and mesna) (Ref) or Adults ≤35 years: 2,000 mg/m2/day for 3 days every 3 weeks for 14 courses (in combination with vincristine, doxorubicin, dactinomycin, and mesna) (Ref).
VIDE regimen: Adults ≤50 years: IV: 3,000 mg/m2/day over 1 to 3 hours for 3 days every 3 weeks for 6 courses (in combination with vincristine, doxorubicin, etoposide, and mesna) (Ref).
IE regimen: IV: 1,800 mg/m2/day over 1 hour for 5 days every 3 weeks for 12 cycles (in combination with etoposide and mesna) (Ref).
ICE regimen: Adults ≤22 years: IV: 1,800 mg/m2/day for 5 days every 3 weeks for up to 12 cycles (in combination with carboplatin and etoposide [and mesna]) (Ref).
Extranodal NK/T-cell lymphoma, nasal type (off-label use):
DeVIC regimen: IV: 1,000 mg/m2/day on days 1, 2, and 3 every 3 weeks (in combination with dexamethasone, etoposide, carboplatin, filgrastim, and radiation therapy) for 3 cycles (Ref). Refer to protocol for dosage adjustment details.
m-SMILE regimen: IV: 1,500 mg/m2/day on days 2, 3, and 4 every 3 weeks (in combination with dexamethasone, methotrexate, leucovorin, etoposide, pegaspargase, mesna, and radiation therapy) for 2 to 6 cycles (Ref). Refer to protocol for further information.
SMILE regimen: IV: 1,500 mg/m2/day on days 2, 3, and 4 every 4 weeks (in combination with dexamethasone, methotrexate, leucovorin, etoposide, L-asparaginase, mesna, and filgrastim) for 2 cycles; therapy could continue beyond 2 cycles based on clinical condition and prescriber discretion; the median number of cycles administered was 3 (range: 1 to 6) (Ref). Refer to protocol for further information.
VIDL regimen: IV: 1,200 mg/m2/day on days 1, 2, and 3 every 4 weeks (in combination with etoposide, dexamethasone, and L-asparaginase) for 2 cycles (Ref). Note: Chemoradiotherapy was administered prior to VIDL; refer to protocol for further information.
VIPD regimen: IV: 1,200 mg/m2/day on days 1, 2, and 3 every 3 weeks (in combination with etoposide, cisplatin, dexamethasone, and mesna) for 3 cycles (Ref) or 1,200 mg/m2/day on days 1, 2, 3, and 4 every 4 weeks (in combination with etoposide, cisplatin, dexamethasone, and mesna) for 2 cycles (Ref). Note: Chemoradiotherapy was administered prior to VIPD; refer to protocols for further information.
Gestational trophoblastic neoplasia, high risk, refractory (off-label use): ICE regimen: IV: 1,200 mg/m2/day on days 1, 2, and 3 every 3 weeks (in combination with mesna, carboplatin, etoposide, and filgrastim) for at least 2 treatment cycles after a normal hCG level (Ref).
Hodgkin lymphoma, relapsed or refractory (off-label use):
ICE regimen: IV: 5,000 mg/m2 (over 24 hours) beginning on day 2 every 2 weeks for 2 cycles (in combination with mesna, carboplatin, and etoposide) (Ref).
Fractionated ICE regimen: IV: 1,667 mg/m2/day (infused over 2 to 3 hours each day) for 3 consecutive days every 21 days (in combination with mesna, carboplatin, etoposide, and filgrastim) for at least 2 cycles (Ref).
IGEV regimen: IV: 2,000 mg/m2/day for 4 days every 3 weeks for 4 cycles (in combination with mesna, gemcitabine, vinorelbine, and prednisolone) (Ref).
Non-Hodgkin lymphomas (off-label use):
Burkitt lymphoma (CODOX-M/IVAC regimen):
Adults ≤65 years of age: Cycles 2 and 4 (IVAC): IV: 1,500 mg/m2/day for 5 days (IVAC is combination with cytarabine, mesna, and etoposide; IVAC alternates with CODOX-M) (Ref).
Adults >65 years of age: Cycles 2 and 4 (IVAC): IV: 1,000 mg/m2/day for 5 days (IVAC is combination with cytarabine, mesna, and etoposide; IVAC alternates with CODOX-M) (Ref).
Diffuse large B-cell lymphoma (RICE regimen): IV: 5,000 mg/m2 (over 24 hours) beginning on day 4 every 2 weeks for 3 cycles (in combination with mesna, carboplatin, etoposide, and rituximab) (Ref).
Osteosarcoma (off-label use):
Ifosfamide/cisplatin/doxorubicin/HDMT regimen: Adults <40 years of age: IV: 3,000 mg/m2/day continuous infusion for 5 days during weeks 4 and 10 (preop) and during weeks 16, 25, and 34 (postop) (in combination with cisplatin, doxorubicin, methotrexate [high-dose], and mesna) (Ref).
ICE regimen (adults ≤22 years of age): IV: 1,800 mg/m2/day for 5 days every 3 weeks for up to 12 cycles (in combination with carboplatin and etoposide [and mesna]) (Ref).
Ovarian cancer, advanced, platinum resistant (off-label use): IV: 1,000 to 1,200 mg/m2/day for 5 days (with mesna) every 28 days for up to 6 cycles (Ref).
Penile cancer, metastatic, squamous cell; neoadjuvant therapy (off-label use): TIP regimen: IV: 1,200 mg/m2/day on days 1, 2, and 3 every 3 to 4 weeks (in combination with paclitaxel, cisplatin, and mesna ± filgrastim) for 4 cycles (Ref).
Soft tissue sarcoma (off-label use):
Single-agent ifosfamide: IV: 3,000 mg/m2/day over 4 hours for 3 days every 3 weeks for at least 2 cycles or until disease progression (Ref).
EIA regimen: IV: 1,500 mg/m2/day for 4 days every 3 weeks until disease progression or unacceptable toxicity (in combination with etoposide, doxorubicin, and regional hyperthermia) (Ref).
MAID regimen: IV: 2,000 mg/m2/day continuous infusion for 3 days every 3 weeks (in combination with mesna, doxorubicin, and dacarbazine) (Ref) or 2,500 mg/m2/day continuous infusion for 3 days every 3 weeks (in combination with mesna, doxorubicin, and dacarbazine); reduce ifosfamide to 1,500 mg/m2/day if prior pelvic irradiation (Ref).
Ifosfamide/epirubicin: IV: 1,800 mg/m2/day over 1 hour for 5 days every 3 weeks for 5 cycles (in combination with mesna and epirubicin) (Ref).
AIM regimens: IV: 1,500 mg/m2/day over 2 hours for 4 days every 3 weeks for 4 to 6 cycles (in combination with mesna and doxorubicin) (Ref) or 2,000 to 3,000 mg/m2/day over 3 hours for 3 days (in combination with mesna and doxorubicin) (Ref).
Testicular cancer:
VIP regimen: IV: 1,200 mg/m2/day for 5 days every 3 weeks for 4 cycles (in combination with etoposide, mesna, and cisplatin) (Ref).
VeIP regimen: IV: 1,200 mg/m2/day for 5 days every 3 weeks for 4 cycles (in combination with vinblastine, mesna, and cisplatin) (Ref).
Manufacturer's labeling (previously treated disease): IV: 1,200 mg/m2/day for 5 consecutive days every 3 weeks or after hematologic recovery (in combination with other chemotherapy agents and concurrent mesna).
Off-label dosing/combinations:
TIP regimen (off-label dosing): IV: 1,500 mg/m2/day for 4 days (days 2 to 5) every 3 weeks for 4 cycles (in combination with paclitaxel, mesna, and cisplatin) (Ref).
TICE regimen (off-label dosing): IV: 2,000 mg/m2/day over 4 hours for 3 days (days 2 to 4) every 2 weeks for 2 cycles (in combination with paclitaxel and mesna; followed by carboplatin and etoposide) (Ref).
Thymoma or thymic carcinoma, advanced or metastatic (initial therapy) (off-label use):
VIP regimen: IV: 1,200 mg/m2/day for 4 days every 3 weeks for 4 cycles (in combination with etoposide, cisplatin, and mesna) (Ref).
Thymoma or thymic carcinoma, advanced or metastatic, relapsed or refractory (later-line therapy) (off-label use): IV: 1,500 mg/m2/day for 5 days (with mesna) every 3 weeks for up to 9 cycles (Ref).
Uterine carcinosarcoma (off- label use):
Adjuvant therapy for stage 1 to 4 disease: IV: 1,500 mg/m2/day for 4 days (in combination with cisplatin and mesna) every 3 weeks for 3 cycles (Ref).
Persistent or refractory advanced disease: IV: 1,600 mg/m2/day for 3 days (in combination with mesna, paclitaxel, and filgrastim) every 3 weeks for up to 8 cycles; reduce ifosfamide dose to 1,200 mg/m2/day for 3 days every 3 weeks in patients who received prior radiation (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Consider dosage modification in patients with kidney impairment; however, there are no dosage adjustments provided in the manufacturer's labeling and specific recommendations for kidney dose adjustment have not been established; ifosfamide (and metabolites) are excreted renally and may accumulate in patients with kidney dysfunction. Ifosfamide and metabolites are dialyzable. Closely monitor patients with kidney impairment for adverse reactions.
General dosage adjustment recommendations for altered kidney function:
Kintzel 1995:
CrCl 46 to 60 mL/minute: Administer 80% of dose.
CrCl 31 to 45 mL/minute: Administer 75% of dose.
CrCl <30 mL/minute: Administer 70% of dose.
Krens 2019:
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Use is not recommended.
Hemodialysis: Use is not recommended.
There are no dosage adjustments provided in the manufacturer's labeling; however, ifosfamide is extensively hepatically metabolized to both active and inactive metabolites; use with caution. Closely monitor patients with liver impairment for adverse reactions.
Floyd 2006: Bilirubin >3 mg/dL: Administer 25% of dose.
Krens 2019:
Mild or moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended.
American Society of Clinical Oncology guidelines for appropriate chemotherapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Hematologic toxicity: May require dosage delays.
WBC <2,000/mm3 and/or platelets <50,000/mm3: Avoid administering ifosfamide (unless clinically necessary).
Encephalopathy: Dose interruption or permanent discontinuation may be required based on individual safety and tolerability. Consider methylene blue for treatment of encephalopathy.
Microscopic hematuria (>10 RBCs per high power field, detected via urinalysis): Withhold ifosfamide until complete resolution.
Hemorrhagic cystitis: May require treatment interruption or permanent discontinuation.
Pulmonary toxicity: Manage as clinically indicated.
Refer to adult dosing.
(For additional information see "Ifosfamide: Pediatric drug information")
Dosage guidance:
Safety: Dosing may be based on either BSA (mg/m2) or weight (mg/kg); use extra precautions to verify dosing parameters during calculations. Protocol-specific details concerning age, dosing, frequency, and combination regimens should be consulted. To prevent bladder toxicity, combination therapy with mesna (bladder protectant or chemoprotectant) and hydration in adults and pediatric patients is necessary; in adults, at least 2 L/day of oral or IV fluid. In pediatric patients, specific protocols should be consulted for hydration recommendation; for example, some centers have used 2 times maintenance or 3 L/m2/day.
Clinical considerations: Ifosfamide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Anaplastic large cell lymphoma: Limited data available:
ALCL99 regimen: Children and Adolescents: IV: 800 mg/m2 once daily for 5 days in cycles 1, 3, and 5 in combination with crizotinib or brentuximab, high-dose methotrexate, dexamethasone, etoposide, and cytarabine; alternating with cycles 2, 4, and 6 that include crizotinib or brentuximab, high-dose methotrexate, dexamethasone, cyclophosphamide, and doxorubicin (Ref).
Ewing sarcoma: Limited data available; dosing regimens and combinations variable; refer to specific protocol:
IE regimen:
Infants: IV: Initial cycle: 900 mg/m2 over 1 hour once daily for 5 days in combination with mesna and etoposide; alternating with VDC (vincristine, doxorubicin, and cyclophosphamide) or VC (vincristine and cyclophosphamide) every 2 or 3 weeks; refer to protocol for combinations and number of cycles. For next ifosfamide-containing cycle, if patient tolerates (no delays and counts are recovered), increase dose to 1,350 mg/m2 over 1 hour for 5 days; for third cycle, if patient tolerates, increase to 1,800 mg/m2 over 1 hour for 5 days for remainder of protocol (Ref).
Children and Adolescents: IV: 1,800 mg/m2 over 1 hour once daily for 5 days in combination with mesna and etoposide every 3 weeks for 12 cycles; or may alternate with VDC (vincristine, doxorubicin, and cyclophosphamide), VAC (vincristine, dactinomycin, and cyclophosphamide), or VC (vincristine and cyclophosphamide) every 2 or 3 weeks; refer to protocol for combinations and total number of cycles (Ref).
ICE regimen: Children and Adolescents: IV: 1,800 mg/m2 once daily for 5 days in combination with carboplatin, etoposide, and mesna every 3 to 4 weeks for up to 12 cycles or for 2 cycles followed by 2 courses of CAV (cyclophosphamide, doxorubicin, and vincristine) (Ref).
VAIA regimen: Reported dosing variable: Children and Adolescents: IV: 3,000 mg/m2 on days 1, 2, 22, 23, 43, and 44 for 4 courses in combination with vincristine, doxorubicin, dactinomycin, and mesna (Paulussen 2001) or 2,000 mg/m2 once daily for 3 days every 3 weeks for 14 courses in combination with vincristine, doxorubicin, and dactinomycin (Ref).
VIDE regimen: Children and Adolescents: IV: 3,000 mg/m2 over 1 to 3 hours once daily for 3 days every 3 weeks for 6 courses in combination with vincristine, doxorubicin, etoposide, and mesna (Ref).
Ewing sarcoma, metastatic: Limited data available:
VDC/IE regimen:
Induction:
Infants: IV: 60 mg/kg over 1 hour once daily on days 1 to 5 in weeks 3, 7, and 11 in combination with mesna and etoposide alternating every 2 weeks with VDC (vincristine, doxorubicin, and cyclophosphamide) for a 12-week cycle (Ref).
Children and Adolescents: IV: 1,800 mg/m2 over 1 hour once daily on days 1 to 5 in weeks 3, 7, and 11 in combination with mesna and etoposide alternating every 2 weeks with VDC (vincristine, doxorubicin, and cyclophosphamide) for a 12-week cycle (Ref).
Consolidation:
Infants: IV: 60 mg/kg over 1 hour once daily in days 1 to 5 in weeks 3, 5, 11, and 15 in combination with mesna and etoposide alternating with VDC (vincristine, doxorubicin, and cyclophosphamide) for a 16-week cycle (Ref).
Children and Adolescents: IV: 1,800 mg/m2 over 1 hour once daily on days 1 to 5 in weeks 3, 5, 11, and 15 in combination with mesna and etoposide alternating weeks with VDC (vincristine, doxorubicin, and cyclophosphamide) for a 16-week cycle (Ref).
Germ cell tumor, refractory:
TIC regimen: Children and Adolescents: IV: 1,800 mg/m2 once daily for 5 days in combination with mesna, paclitaxel, and carboplatin (Ref).
Lymphoma, Hodgkin (HL) and non-Hodgkin (NHL), recurrent/refractory: Limited data available; dosing regimens and combinations variable; refer to specific protocol:
ICE regimen:
Intermittent infusion: Children and Adolescents: IV: 1,800 mg/m2 once daily for 5 days every 3 weeks for 6 courses in combination with etoposide, carboplatin, and mesna; in the trial, although the minimum age for inclusion was 1 year of age, the reported patient age range was 8 months to 26 years (median: 10.5 years) (Ref).
Continuous infusion: Children ≥12 years and Adolescents: IV: 5,000 mg/m2/day continuous infusion over 24 hours beginning on day 2 every 2 weeks for 2 cycles in combination with mesna, carboplatin, and etoposide (Ref).
MIED regimen:
Children and Adolescents: IV: 2,000 mg/m2 over 2 hours on days 2 to 4 in combination with high-dose methotrexate, etoposide, and dexamethasone (and mesna); patients with NHL also received intrathecal methotrexate, hydrocortisone, and cytarabine (Ref).
MIED with rituximab regimen:
Children and Adolescents: IV: 3,000 mg/m2 over 2 hours on days 3 to 5 in combination with rituximab and ICE (carboplatin, etoposide, and mensa) every 23 days for up to 3 courses has been used in NHL patients (Ref).
Osteosarcoma: Limited data available; dosing regimens and combinations variable; refer to specific protocol:
IE regimen: Children and Adolescents: IV: 1,800 to 3,000 mg/m2 for 4 to 5 days; frequency and duration protocol specific with etoposide and mesna (Ref).
ICE regimen: Children and Adolescents: IV: 1,800 mg/m2 once daily for 5 days every 3 weeks for up to 12 cycles in combination with carboplatin, etoposide, and mesna (Ref).
Newly diagnosed high-grade osteosarcoma of the extremity with metastases: Multiple regimens reported; refer to specific protocols:
Bacci 2003: Children and Adolescents: IV: 3,000 mg/m2/day continuous infusion for 5 days (total dose: 15 g/m2) during weeks 4 and 10 (preop) and during weeks 16, 25, and 34 (postop) in combination with cisplatin, doxorubicin, methotrexate (high-dose), and mesna.
Basaran 2007: Adolescents: IV: 2,000 mg/m2 over 4 hours for 3 days (days 2, 3, and 4) every 3 weeks for 3 cycles (preop) and every 4 weeks for 3 cycles (postop) in combination with cisplatin, epirubicin, and mesna.
Le Deley 2007: Children and Adolescents: IV: 3,000 mg/m2 over 3 hours for 4 days during weeks 4 and 9 (three additional postop courses were administered in good responders) in combination with methotrexate (high-dose), etoposide, and mesna.
Neuroblastoma, relapsed or refractory: Limited data available: HD-ICE regimen: Children and Adolescents IV: 2,000 mg/m2 over 2 hours once daily for 5 days in combination with mesna, carboplatin, and etoposide with or without peripheral blood stem cell support (depending on hematologic reserve (Ref).
Rhabdomyosarcoma: Limited data available:
Interval-compressed I/E regimen:
Infants: IV: 900 mg/m2 once daily for 5 days in combination with mesna and etoposide on weeks 9, 13, 17, 26, and 30 (2 weeks after vincristine, doxorubicin, and cyclophosphamide therapy). Note: Infant dose is 50% of full dose in children; if infant tolerates dose (ie, no delayed count recovery or delayed resolution of other toxicities which delays administration), may consider increasing to 75% and then to 100% calculated full dose (Ref).
Children and Adolescents: IV: 1,800 mg/m2 once daily for 5 days in combination with mesna and etoposide on weeks 9, 13, 17, and 30 (2 weeks after vincristine, doxorubicin, and cyclophosphamide therapy) (Ref).
VAI (IRS-IV) regimen:
Infants: IV: 900 mg/m2 once daily for 5 days in combination with mesna, vincristine, and dactinomycin for a 21-day cycle for 8 cycles (omitting dactinomycin during radiation). Note: Infant dose is 50% of full dose in children; if infant tolerates dose (ie, no delayed count recovery or delayed resolution of other toxicities which delays administration), may consider increasing to 75% and then to 100% calculated full dose (Ref).
Children and Adolescents: IV: 1,800 mg/m2 once daily for 5 days in combination with mesna, vincristine, and dactinomycin for a 21-day cycle for 8 cycles (omitting dactinomycin during radiation) (Ref).
VIE (IRS-IV) regimen:
Infants: IV: 900 mg/m2 once daily for 5 days in combination with mesna, vincristine, and etoposide for a 21-day cycle for 8 cycles (omitting etoposide during radiation). Note: Infant dose is 50% of full dose in children; if infant tolerates dose (ie, no delayed count recovery or delayed resolution of other toxicities which delays administration), may consider increasing to 75% and then to 100% calculated full dose (Ref).
Children and Adolescents: IV: 1,800 mg/m2 once daily for 5 days in combination with mesna, vincristine, and etoposide for a 21-day cycle for 8 cycles (omitting etoposide during radiation) (Ref).
Sarcomas; soft tissue, non-Rhabdomyosarcoma: Limited data available: Children and Adolescents: IV: 3,000 mg/m2 once daily for 3 days every 21 days for 4 cycles in combination with mesna and doxorubicin (Ref)
Wilms tumor, relapsed: Limited data available: ICE regimen: Children and Adolescents: IV: 1,800 mg/m2 once daily for 5 days every 21 days for at least 2 cycles (median of 4 cycles reported) in combination with mesna, carboplatin, and etoposide (Ref)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: The following adjustments have been recommended (Ref)
GFR ≥10 mL/minute/1.73 m2: No dosage adjustment necessary
GFR <10 mL/minute/1.73 m2: Administer 75% of dose
Hemodialysis: 1,000 mg/m2 followed by hemodialysis 6 to 8 hours later
Continuous renal replacement therapy (CRRT): No dosage adjustment necessary
There are no pediatric specific recommendations; refer to protocol. Ifosfamide is extensively metabolized in the liver to both active and inactive metabolites; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions include ifosfamide monotherapy or combination therapy with other chemotherapeutic agents.
>10%:
Dermatologic: Alopecia (90%)
Gastrointestinal: Nausea and vomiting (47%)
Genitourinary: Gross hematuria (11%; with mesna: 5%), hematuria (44%; with mesna: 21%)
Hematologic & oncologic: Bone marrow depression (including anemia [38%], granulocytopenia, leukopenia [grade 4: 44%], lymphocytopenia, neutropenia, pancytopenia, thrombocytopenia [5%])
Nervous system: Central nervous system toxicity (15%; including abnormal electroencephalogram, aggressive behavior, agitation, anxiety, aphasia, asthenia, ataxia, behavioral changes, cerebellar syndrome, cerebral function deficiency, cognitive dysfunction, coma, confusion, cranial nerve disorder, depression, disorientation, dizziness, drowsiness, emotional lability, encephalopathy, flat affect, hallucination, headache, ideation, impaired consciousness, lethargy, memory impairment, mood changes, motor dysfunction, muscle spasm, myoclonus, peripheral neuropathy [<1%], progressive loss of brainstem reflexes, psychotic reaction, restlessness, seizure, tremor)
1% to 10%:
Gastrointestinal: Anorexia (1%)
Hematologic & oncologic: Febrile neutropenia (1%)
Hepatic: Hepatotoxicity (2%; including increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase)
Infection: Infection (10%; including fungal infection, infection due to an organism in genus Pneumocystis, parasitic infection [Strongyloides infection], pneumonia, progressive multifocal leukoencephalopathy, reactivation of disease [latent infections], sepsis, septic shock, viral hepatitis, viral infection [herpes zoster infection])
Local: Localized phlebitis (3%)
<1%:
Cardiovascular: Cardiotoxicity (including heart failure, pulmonary edema, tachycardia), hypotension (including shock)
Dermatologic: Dermatitis, papular rash
Gastrointestinal: Diarrhea, stomatitis
Nervous system: Fatigue
Frequency not defined: Nervous system: Malaise
Postmarketing:
Cardiovascular: Acute myocardial infarction, angina pectoris, atrial fibrillation, atrial flutter, bradycardia, capillary leak syndrome, cardiac insufficiency, cardiogenic shock, cardiomyopathy, chest pain, congestive cardiomyopathy, deep vein thrombosis, ECG abnormality (QR complex abnormal), edema (Banh 2022), flushing, hypertension, inversion T wave on ECG, left bundle branch block, left ventricular failure, myocarditis, palpitations, pericardial effusion, pericarditis, portal vein thrombosis, premature atrial contractions, premature ventricular contractions, pulmonary embolism, reduced ejection fraction, right bundle branch block, ST segment changes on ECG, supraventricular extrasystole, vasculitis, ventricular fibrillation, ventricular tachycardia
Dermatologic: Erythema of skin, hyperhidrosis, hyperpigmentation, macular eruption, nail disease, palmar-plantar erythrodysesthesia, pruritus, skin abnormalities related to radiation recall, skin necrosis, skin rash (Banh 2022), Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Amenorrhea, decreased plasma estrogen concentration, growth suppression (Stohr 2007), hyperglycemia, hypocalcemia, hypokalemia (Skinner 1989), hyponatremia (Cantwell 1990), hypophosphatemia (Skinner 1989), increased gonadal hormones, menopause (premature), metabolic acidosis, nephrogenic diabetes insipidus (Skinner 1989), phosphaturia, polydipsia, rickets (Stohr 2007), SIADH (Cantwell 1990), thyroid neoplasm
Gastrointestinal: Abdominal pain (Banh 2022), cholestasis, colitis, constipation, enterocolitis, fecal incontinence, gastrointestinal hemorrhage, intestinal obstruction, mucosal swelling, mucous membrane ulceration, neutropenic typhlitis, pancreatitis (Hung 2007), sialorrhea
Genitourinary: Azoospermia (Williams 2008), increased post-void residual urine volume (sensation of), infertility, inhibition of spermatogenesis, oligospermia, ovarian disease, ovarian failure, ovulatory cycle (disorder), polyuria, proteinuria (aminoaciduria), sterility, urinary incontinence (Alici-Evcimen 2007), urotoxicity (including hemorrhagic cystitis) (Mashhasi 2011)
Hematologic & oncologic: Agranulocytosis, bone marrow aplasia (febrile), bone marrow failure, disseminated intravascular coagulation, hemolytic anemia, hemolytic-uremic syndrome, hemorrhage (including myocardial) (Banh 2022), leukemia (including acute lymphocytic leukemia, acute myelocytic leukemia, acute promyelocytic leukemia), methemoglobinemia, myelodysplastic syndrome, non-Hodgkin lymphoma, petechia, sarcoma, tumor lysis syndrome (Luminais 2022)
Hepatic: Fulminant hepatitis, hepatic cytolysis, hepatic failure, hepatic sinusoidal obstruction syndrome
Hypersensitivity: Anaphylaxis, angioedema, facial swelling, hypersensitivity reaction, nonimmune anaphylaxis
Immunologic: Immunosuppression
Infection: Reactivation of HBV (Chhibar 2016)
Local: Erythema at injection site, inflammation at injection site, injection-site pruritus, pain at injection site, swelling at injection site, tenderness at injection site
Nervous system: Abnormal gait, amnesia, asterixis (Ataseven 2021), bradyphrenia, catatonia, chills, delirium (Szabatura 2015), delusion (Alici-Evcimen 2007), dysarthria, dysesthesia, extrapyramidal reaction, Guillain-Barré syndrome (Muzaffar 2018), hypoesthesia, leukoencephalopathy, mania (Ataseven 2021), mental status changes (Yeager 2020), movement disorder (Ames 2010), mutism (Ataseven 2021), neuralgia, pain (Banh 2022), panic attack, paranoid ideation, paresthesia, polyneuropathy, posterior reversible encephalopathy syndrome, psychological disorder (perseveration), speech disturbance (echolalia), status epilepticus (convulsive and nonconvulsive) (Ataseven 2021), talkativeness, vertigo
Neuromuscular & skeletal: Arthralgia, limb pain, muscle twitching, myalgia, osteomalacia, rhabdomyolysis
Ophthalmic: Blurred vision, conjunctivitis, eye irritation, visual impairment
Otic: Deafness, hypoacusis, tinnitus
Renal: Interstitial nephritis, nephrotoxicity (including acute kidney injury, chronic renal failure, Fanconi syndrome, renal parenchymal necrosis, renal tubular acidosis, renal tubular disease, renal tubular necrosis) (Boskabadi 2022, Leem 2014, Mashhasi 2011, Morrison 1997, Skinner 1989, Stohr 2007, Yeager 2020), renal cell carcinoma
Respiratory: Acute respiratory distress syndrome, bronchospasm, cough, dyspnea, hypoxia, interstitial lung disease, pleural effusion, pneumonitis, pulmonary alveolitis (allergic), pulmonary fibrosis, pulmonary hypertension, respiratory failure
Miscellaneous: Fever, multi-organ failure
Known hypersensitivity to ifosfamide or any component of the formulation; urinary outflow obstruction.
Canadian labeling: Additional contraindications (not in the US labeling): Severe myelosuppression; severe renal and/or hepatic impairment; urinary tract disease (cystitis); active infection (bacterial, fungal, viral); severe immunosuppression; advanced cerebral arteriosclerosis.
Concerns related to adverse effects:
• Bone marrow suppression: Bone marrow suppression may occur (may be severe and lead to fatal infections). Leukopenia, neutropenia, thrombocytopenia, and anemia are associated with ifosfamide. Myelosuppression is dose dependent and increased with decreased kidney function, bone marrow metastases, and prior radiation or exposure to cytotoxic agents. Severe myelosuppression may occur when administered in combination with other chemotherapy agents or radiation therapy. Bleeding events due to thrombocytopenia may occur.
• Cardiotoxicity: Ifosfamide-induced cardiotoxicity has been reported; may be severe or fatal. Supraventricular or ventricular arrhythmias (eg, atrial/supraventricular tachycardia, atrial fibrillation, pulseless ventricular tachycardia), decreased QRS voltage, ST-segment or T-wave changes, cardiomyopathy (leading to heart failure with congestion and hypotension), pericardial effusion, fibrinous pericarditis, and epicardial fibrosis may occur. The risk for cardiotoxicity is dose-dependent; concomitant cardiotoxic agents (eg, anthracyclines), irradiation of the cardiac region, and kidney impairment may also increase the risk. In a scientific statement from the American Heart Association, ifosfamide has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate/major) (AHA [Page 2016]).
• CNS toxicity: Ifosfamide may cause encephalopathy, which may be fatal. Signs and symptoms of encephalopathy include somnolence, confusion, hallucinations, psychotic behavior, extrapyramidal symptoms, seizures, coma, blurred vision, and/or urinary incontinence, and have been observed within hours to days after ifosfamide administration and generally resolve within 2 to 3 days of treatment discontinuation (although symptoms may persist longer); maintain supportive care until complete resolution of CNS signs/symptoms. Ifosfamide-induced encephalopathy may be due to the accumulation of the metabolite chloroacetaldehyde (Shin 2011). Risk factors for encephalopathy may include high ifosfamide dose, hypoalbuminemia, kidney dysfunction, poor performance status, bulky abdominal-pelvic disease, concomitant nephrotoxic treatments (eg, cisplatin), or alcohol use. Concomitant centrally acting medications may result in additive CNS effects.
• Hemorrhagic cystitis: Hemorrhagic cystitis may occur (may be severe and/or require blood transfusion); concomitant mesna reduces the risk of hemorrhagic cystitis. Acrolein (an ifosfamide metabolite) causes urotoxicity. Hydration (at least 2 L/day in adults), dose fractionation, and/or mesna administration will reduce the incidence of hematuria and protect against hemorrhagic cystitis. Hemorrhagic cystitis is dose dependent; past or concomitant bladder radiation or busulfan treatment may increase the risk for hemorrhagic cystitis.
• Hepatic effects: Hepatic sinusoidal obstruction syndrome (SOS), formerly called veno-occlusive disease (VOD), has been reported with ifosfamide-containing regimens.
• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions have been associated with ifosfamide. Cross sensitivity with similar agents may occur.
• Infection: May cause significant suppression of the immune responses; may lead to serious infection, sepsis or septic shock. Reported infections have included bacterial, viral, fungal, and parasitic; latent viral infections may be reactivated.
• Kidney toxicity: Ifosfamide may cause severe or fatal nephrotoxicity and urotoxicity, including glomerular or tubular dysfunction, tubular necrosis, renal parenchymal necrosis, acute kidney failure, and chronic kidney failure. Tubular damage may be delayed (months to years after cessation of ifosfamide). Risk for kidney toxicity is increased in patients with kidney impairment or reduced nephron reserve. Manifestations of kidney toxicity include decreased GFR, increased SCr, proteinuria, enzymuria, cylindruria, tubular acidosis, aminoaciduria, phosphaturia, glycosuria, and osteomalacia. Syndrome of inappropriate antidiuretic hormone (SIADH) and Fanconi syndrome have been reported.
• Pulmonary toxicity: Ifosfamide may cause severe or fatal pulmonary toxicities, including interstitial pneumonitis, pulmonary fibrosis, and respiratory failure.
• Secondary malignancy: Secondary malignancies may occur (onset may be delayed up to several years). Cases of myelodysplastic syndrome, acute leukemias, lymphomas, thyroid cancers, and sarcomas have been reported.
• Wound healing: Ifosfamide may interfere with normal wound healing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Generic: 1 g/20 mL (20 mL); 3 g/60 mL (60 mL)
Solution Reconstituted, Intravenous:
Ifex: 1 g (1 ea); 3 g (1 ea)
Generic: 1 g (1 ea); 3 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 1 g (1 ea); 3 g (1 ea)
Yes
Solution (Ifosfamide Intravenous)
1 g/20 mL (per mL): $2.20
3 g/60 mL (per mL): $2.15
Solution (reconstituted) (Ifex Intravenous)
1 g (per each): $44.09
3 g (per each): $125.56
Solution (reconstituted) (Ifosfamide Intravenous)
1 g (per each): $42.28 - $69.66
3 g (per each): $129.05
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous:
Ifex: 1 g (20 mL); 3 g (60 mL)
Generic: 3 g ([DSC])
IV: Ifosfamide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Administer IV over at least 30 minutes (infusion times may vary by protocol; refer to specific protocol for infusion duration). To prevent bladder toxicity, ifosfamide should be administered with mesna and hydration.
Ifosfamide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
IV: Administer as a slow IV intermittent infusion or continuous infusion; infusion times may vary; in pediatric trials, infusion time varied; doses usually infused over 1 to 6 hours or administered as a 24-hour infusion; refer to specific protocols.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Testicular cancer: Treatment (third-line; in combination with other chemotherapy agents) of germ cell testicular cancer in adults.
Bladder cancer, advanced; Cervical cancer (recurrent or metastatic); Ewing sarcoma; Extranodal NK/T-cell lymphoma, nasal type; Gestational trophoblastic neoplasia, high-risk, refractory; Hodgkin lymphoma, relapsed or refractory; Non-Hodgkin lymphomas; Osteosarcoma; Ovarian cancer, advanced (platinum-resistant); Penile cancer, metastatic, squamous cell; Soft tissue sarcoma; Thymoma or thymic carcinoma, advanced or metastatic; Uterine carcinosarcoma
Ifosfamide may be confused with cycloPHOSphamide, fostamatinib
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP2B6 (Minor), CYP2C19 (Minor), CYP2C8 (Minor), CYP2C9 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Aprepitant: May increase adverse/toxic effects of Ifosfamide. Specifically, the risk for ifosfamide induced encephalopathy may be increased. Aprepitant may increase active metabolite exposure of Ifosfamide. Specifically, concentrations of the active and toxic metabolites of ifosfamide may increase. Risk C: Monitor
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
BUPivacaine: Ifosfamide may increase adverse/toxic effects of BUPivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor
Busulfan: May increase adverse/toxic effects of Ifosfamide. Specifically, the risk of hemorrhagic cystitis may be increased. Risk C: Monitor
Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Moderate) may increase active metabolite exposure of Ifosfamide. Risk C: Monitor
CYP3A4 Inducers (Strong): May increase active metabolite exposure of Ifosfamide. CYP3A4 Inducers (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Moderate) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase adverse/toxic effects of Ifosfamide. CYP3A4 Inhibitors (Strong) may decrease active metabolite exposure of Ifosfamide. Risk C: Monitor
Dapsone (Topical): May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Fosaprepitant: May increase adverse/toxic effects of Ifosfamide. Specifically, the risk for ifosfamide induced encephalopathy may be increased. Fosaprepitant may increase active metabolite exposure of Ifosfamide. Specifically, concentrations of the active and toxic metabolites of ifosfamide may increase. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification
Local Anesthetics: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Nitric Oxide: May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Prilocaine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor
Primaquine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Primaquine. Specifically, the risk for methemoglobinemia may be increased. Management: Avoid concomitant use of primaquine and other drugs that are associated with methemoglobinemia when possible. If combined, monitor methemoglobin levels closely. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sodium Nitrite: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Vasopressin: Drugs Suspected of Causing SIADH may increase therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor
Vitamin K Antagonists: Ifosfamide may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Verify pregnancy status prior to treatment in patients who could become pregnant. Patients who could become pregnant should use effective contraception during treatment and for 12 months after the last ifosfamide dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 6 months after the last dose of ifosfamide.
Ifosfamide is associated with a high risk of infertility (ESMO [Lambertini 2020]). Amenorrhea has been reported; the risk of permanent amenorrhea induced by chemotherapy increases with age. Oligospermia or azoospermia may develop; azoospermia may be reversible in some patients, although it may take several years after treatment to reverse. Testicular atrophy may also occur.
Recommendations are available for fertility preservation of patients to be treated with anticancer agents (ASCO [Oktay 2018]; Klipstein 2020).
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to ifosfamide may cause fetal harm. Outcome data following maternal use of ifosfamide during pregnancy are limited (Harris 2014; Miller 2022; NTP 2013; Sipe 2021). Fetal growth retardation and neonatal anemia have been reported with exposure to ifosfamide-containing regimens during pregnancy.
The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach. In general, if chemotherapy is indicated, it should be avoided in the first trimester, there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
Ifosfamide is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 week after the last ifosfamide dose.
CBC with differential (prior to and at appropriated intervals after each cycle, and as clinically appropriate). Evaluate glomerular and tubular kidney function before treatment, during treatment, and as clinically indicated. Monitor serum and urine chemistries (including phosphorus and potassium), and urinalysis (for erythrocytes prior to each dose). Monitor liver function and for signs/symptoms of veno-occlusive liver disease. Verify pregnancy status prior to treatment in patients who could become pregnant. Monitor for signs/symptoms of cardiac toxicity, encephalopathy, hypersensitivity, pulmonary toxicity, urotoxicity/hemorrhagic cystitis, and secondary malignancies. Monitor closely for adverse reactions in patients with altered kidney or liver function.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Ifosfamide causes cross-linking of strands of DNA by binding with nucleic acids and other intracellular structures, resulting in cell death; inhibits protein synthesis and DNA synthesis.
Pharmacokinetics are dose dependent.
Distribution: Vd: Approximates total body water; median Vd 0.64 L/kg (day 1), 0.72 L/kg (day 5); penetrates CNS, but not in therapeutic levels.
Protein binding: Negligible.
Metabolism: Hepatic to active metabolites isofosforamide mustard, 4-hydroxy-ifosfamide, acrolein (implicated in the development of hemorrhagic cystitis), and inactive dichloroethylated and carboxy metabolites with liberation of the toxic metabolite, chloroacetaldehyde (implicated in the development of encephalopathy).
Half-life elimination (increased in the elderly):
High dose (3,800 to 5,000 mg/m2): ~15 hours.
Lower dose (1,600 to 2,400 mg/m2): ~7 hours.
Excretion:
High dose (5,000 mg/m2): Urine (70% to 86%; 61% as unchanged drug).
Lower dose (1,600 to 2,400 mg/m2): Urine (12% to 18% as unchanged drug).
