Ifex Prescribing Information
• Myelosuppression can be severe and lead to fatal infections. Monitor blood counts prior to and at intervals after each treatment cycle[see.]5.1 MyelosuppressionIFEX can cause myelosuppression that results in severe or fatal infections including sepsis or septic shock. Ifosfamide‑induced myelosuppression includes leukopenia, neutropenia, thrombocytopenia (with bleeding events), and anemia. The nadir of the leukocyte count usually occurs during the second week after administration of IFEX. The risk of myelosuppression is dose‑dependent and increased in patients with reduced renal function, bone marrow metastases, prior radiation, and concomitant or prior therapy with other cytotoxic agents.
Monitor complete blood counts, including leukocytes, neutrophils, platelets, and hemoglobin prior to each administration of IFEX, at appropriate intervals during treatment, and as clinically indicated.
Myelosuppression may require dosage delays. Avoid administration of IFEX to patients with a WBC count below 2000/µL, a platelet count below 50,000/µL, or when signs or symptoms of active infection or severe immunosuppression are present.
• Encephalopathy can be severe and may result in death. Monitor for CNS toxicity and discontinue treatment for encephalopathy[see.]5.2 EncephalopathyIFEX can cause encephalopathy which may be fatal. Signs and symptoms may include confusion, somnolence, coma, hallucination, blurred vision, psychotic behavior, extrapyramidal symptoms, urinary incontinence, and seizures.
Risk factors include high ifosfamide dosage, hypoalbuminemia, impaired renal function, poor performance status, bulky abdominal-pelvic disease, nephrotoxic treatments including cisplatin, CNS active drugs, or alcohol use.
Signs and symptoms may occur or recur within hours to days after administration of IFEX. Continue supportive care until complete resolution of CNS signs and symptoms.
Monitor for signs and symptoms of encephalopathy during and after IFEX treatment. Dose interruption or permanent discontinuation may be required based on individual safety and tolerability. Consider methylene blue for treatment of encephalopathy.
• Nephrotoxicity can be severe and result in renal failure. Hemorrhagic cystitis can be severe and can be reduced by the prophylactic use of mesna[see.]5.3 Nephrotoxicity and UrotoxicityIFEX can cause severe or fatal nephrotoxicity and urotoxicity including glomerular or tubular dysfunction, tubular necrosis, renal parenchymal necrosis, acute renal failure, chronic renal failure, and hemorrhagic cystitis (requiring blood transfusion).
Tubular damage may occur up to years after cessation of IFEX treatment. The risk of nephrotoxicity is increased in patients with renal impairment or reduced nephron reserve. Hemorrhagic cystitis is dose‑dependent and the risk is increased with past or concomitant radiation of the bladder or busulfan treatment.
Evaluate glomerular and tubular kidney function before treatment with IFEX, during IFEX treatment, and as clinically indicated. Monitor serum and urine chemistries (including phosphorus and potassium) and urinary sediment for the presence of erythrocytes or other signs of nephrotoxicity. Signs and symptoms may include a decrease in glomerular filtration rate, increased serum creatinine, proteinuria, enzymuria, cylindruria, aminoaciduria, phosphaturia, glycosuria, osteomalacia, tubular acidosis, Fanconi syndrome, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Before starting treatment, exclude or correct any urinary tract obstructions
[see Contraindications (4)]. During or immediately after administration, provide oral or intravenous fluid to force dieresis to reduce the risk of urinary tract toxicity. Administer mesna with IFEX to reduce the incidence and severity of urotoxicity[seeDosage and Administration (2.1)].Obtain a urinalysis prior to each dose of IFEX. Avoid administration of IFEX in patients with active urinary tract infections. If microscopic hematuria (greater than 10 RBCs per high power field) is present, then withhold administration of IFEX until complete resolution. Further administration of IFEX should be given with vigorous oral or parenteral hydration. Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability.
Boxed Warning 12/2024
Dosage and Administration (
Administer IFEX 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 IFEX with mesna to reduce the incidence or severity of hemorrhagic cystitis
The recommended dosage of IFEX is 1.2 grams per m2per 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 IFEX based on patient risk factors and adverse reactions.
IFEX is a hazardous drug. Follow applicable special handling and disposal procedures.1
Skin reactions associated with accidental exposure to IFEX may occur. To minimize the risk of dermal exposure, always wear impervious gloves when handling vials and solutions containing IFEX. If IFEX solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious amounts of water.
Prepare IFEX for intravenous use by adding
Dosage Strength | Quantity of Diluent | Final Concentration |
1 gram | 20 mL | 50 mg per mL |
3 grams | 60 mL | 50 mg per mL |
Solutions of ifosfamide may be diluted further to achieve concentrations of 0.6 to 20 mg/mL in the following fluids:
• 5% Dextrose Injection, USP• 0.9% Sodium Chloride Injection, USP• Lactated Ringer’s Injections, USP• Sterile Water for Injection, USP
Because essentially identical stability results were obtained for Sterile Water admixtures as for the other admixtures (5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer’s Injection), the use of large volume parenteral glass bottles, VIAFLEX bags or PAB bags that contain intermediate concentrations or mixtures of excipients (e.g., 2.5% Dextrose Injection, 0.45% Sodium Chloride Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection) is also acceptable.
Refrigerate constituted or constituted and further diluted solutions of IFEX and use within 24 hours. Benzyl-alcohol-containing solutions can reduce the stability of ifosfamide.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Warnings and Precautions (
• Myelosuppression: Monitor blood counts prior to treatment, during treatment, and as clinically indicated.• Encephalopathy: Monitor for signs and symptoms of CNS toxicity during and after IFEX treatment. Dose interruption or permanent discontinuation may be required based on individual safety and tolerability.• Nephrotoxicity and Urotoxicity: Monitor signs and symptoms. Monitor serum and urine chemistries.• 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.• 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.• Secondary malignancies can occur.• Veno-occlusive Liver Disease can occur.• Embryo-Fetal Toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception.• Infertility: Can impair male and female reproductive function.• Anaphylactic/anaphylactoid reactions have been reported.
IFEX can cause myelosuppression that results in severe or fatal infections including sepsis or septic shock. Ifosfamide‑induced myelosuppression includes leukopenia, neutropenia, thrombocytopenia (with bleeding events), and anemia. The nadir of the leukocyte count usually occurs during the second week after administration of IFEX. The risk of myelosuppression is dose‑dependent and increased in patients with reduced renal function, bone marrow metastases, prior radiation, and concomitant or prior therapy with other cytotoxic agents.
Monitor complete blood counts, including leukocytes, neutrophils, platelets, and hemoglobin prior to each administration of IFEX, at appropriate intervals during treatment, and as clinically indicated.
Myelosuppression may require dosage delays. Avoid administration of IFEX to patients with a WBC count below 2000/µL, a platelet count below 50,000/µL, or when signs or symptoms of active infection or severe immunosuppression are present.
IFEX can cause encephalopathy which may be fatal. Signs and symptoms may include confusion, somnolence, coma, hallucination, blurred vision, psychotic behavior, extrapyramidal symptoms, urinary incontinence, and seizures.
Risk factors include high ifosfamide dosage, hypoalbuminemia, impaired renal function, poor performance status, bulky abdominal-pelvic disease, nephrotoxic treatments including cisplatin, CNS active drugs, or alcohol use.
Signs and symptoms may occur or recur within hours to days after administration of IFEX. Continue supportive care until complete resolution of CNS signs and symptoms.
Monitor for signs and symptoms of encephalopathy during and after IFEX treatment. Dose interruption or permanent discontinuation may be required based on individual safety and tolerability. Consider methylene blue for treatment of encephalopathy.
IFEX can cause severe or fatal nephrotoxicity and urotoxicity including glomerular or tubular dysfunction, tubular necrosis, renal parenchymal necrosis, acute renal failure, chronic renal failure, and hemorrhagic cystitis (requiring blood transfusion).
Tubular damage may occur up to years after cessation of IFEX treatment. The risk of nephrotoxicity is increased in patients with renal impairment or reduced nephron reserve. Hemorrhagic cystitis is dose‑dependent and the risk is increased with past or concomitant radiation of the bladder or busulfan treatment.
Evaluate glomerular and tubular kidney function before treatment with IFEX, during IFEX treatment, and as clinically indicated. Monitor serum and urine chemistries (including phosphorus and potassium) and urinary sediment for the presence of erythrocytes or other signs of nephrotoxicity. Signs and symptoms may include a decrease in glomerular filtration rate, increased serum creatinine, proteinuria, enzymuria, cylindruria, aminoaciduria, phosphaturia, glycosuria, osteomalacia, tubular acidosis, Fanconi syndrome, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Before starting treatment, exclude or correct any urinary tract obstructions
Obtain a urinalysis prior to each dose of IFEX. Avoid administration of IFEX in patients with active urinary tract infections. If microscopic hematuria (greater than 10 RBCs per high power field) is present, then withhold administration of IFEX until complete resolution. Further administration of IFEX should be given with vigorous oral or parenteral hydration. Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability.
IFEX can cause severe or fatal cardiotoxicity including any of the following:
• Supraventricular or ventricular arrhythmias, including atrial/supraventricular tachycardia, atrial fibrillation, pulseless ventricular tachycardia• Decreased QRS voltage and ST-segment or T-wave changes• Toxic cardiomyopathy leading to heart failure with congestion and hypotension• Pericardial effusion, fibrinous pericarditis, and epicardial fibrosis
Cardiotoxic effects are dose‑dependent and the risk is increased in patients with cardiac disease, prior or concomitant treatment with other cardiotoxic agents, radiation of the cardiac region, and renal impairment.
IFEX can cause severe or fatal pulmonary toxicities including interstitial pneumonitis, pulmonary fibrosis, and respiratory failure. Monitor for signs and symptoms of pulmonary toxicity and treat as clinically indicated.
The incidence of secondary malignancies is increased in patients treated with IFEX-containing regimens. Cases of myelodysplastic syndrome, acute leukemias, lymphomas, thyroid cancers, and sarcomas have occurred and may develop several years after chemotherapy has been discontinued.
Veno-occlusive liver disease has been reported with chemotherapy that included ifosfamide.
Based on mechanism of action and human and animal data, IFEX can cause fetal harm when administered to a pregnant woman
Advise pregnant women and females of reproductive potential of the potential risk to the fetus
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with IFEX and for 6 months after completion of therapy
Male and female reproductive function and fertility may be impaired in patients treated with IFEX. Ifosfamide interferes with oogenesis and spermatogenesis. Amenorrhea, azoospermia; and sterility in both sexes have been reported. Development of sterility appears to depend on the dose of ifosfamide, duration of therapy, and state of gonadal function at the time of treatment. Sterility may be irreversible in some patients. Advise patients on the potential risks for infertility
Anaphylactic/anaphylactoid reactions have been reported in association with ifosfamide.
Cross-sensitivity between oxazaphosphorine cytotoxic agents has been reported.
Ifosfamide may interfere with normal wound healing.
IFEX is indicated for use in adults in combination with certain other approved antineoplastic agents for third-line chemotherapy of germ cell testicular cancer.
• Administer IFEX 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 Important Administration InstructionsAdminister IFEX 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 IFEX with mesna to reduce the incidence or severity of hemorrhagic cystitis
[see Warnings and Precautions (5.3)].)5.3 Nephrotoxicity and UrotoxicityIFEX can cause severe or fatal nephrotoxicity and urotoxicity including glomerular or tubular dysfunction, tubular necrosis, renal parenchymal necrosis, acute renal failure, chronic renal failure, and hemorrhagic cystitis (requiring blood transfusion).
Tubular damage may occur up to years after cessation of IFEX treatment. The risk of nephrotoxicity is increased in patients with renal impairment or reduced nephron reserve. Hemorrhagic cystitis is dose‑dependent and the risk is increased with past or concomitant radiation of the bladder or busulfan treatment.
Evaluate glomerular and tubular kidney function before treatment with IFEX, during IFEX treatment, and as clinically indicated. Monitor serum and urine chemistries (including phosphorus and potassium) and urinary sediment for the presence of erythrocytes or other signs of nephrotoxicity. Signs and symptoms may include a decrease in glomerular filtration rate, increased serum creatinine, proteinuria, enzymuria, cylindruria, aminoaciduria, phosphaturia, glycosuria, osteomalacia, tubular acidosis, Fanconi syndrome, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Before starting treatment, exclude or correct any urinary tract obstructions
[see Contraindications (4)]. During or immediately after administration, provide oral or intravenous fluid to force dieresis to reduce the risk of urinary tract toxicity. Administer mesna with IFEX to reduce the incidence and severity of urotoxicity[seeDosage and Administration (2.1)].Obtain a urinalysis prior to each dose of IFEX. Avoid administration of IFEX in patients with active urinary tract infections. If microscopic hematuria (greater than 10 RBCs per high power field) is present, then withhold administration of IFEX until complete resolution. Further administration of IFEX should be given with vigorous oral or parenteral hydration. Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability.
• Administer mesna with IFEX to reduce the incidence or severity of hemorrhagic cystitis. (,2.1 Important Administration InstructionsAdminister IFEX 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 IFEX with mesna to reduce the incidence or severity of hemorrhagic cystitis
[see Warnings and Precautions (5.3)].)5.3 Nephrotoxicity and UrotoxicityIFEX can cause severe or fatal nephrotoxicity and urotoxicity including glomerular or tubular dysfunction, tubular necrosis, renal parenchymal necrosis, acute renal failure, chronic renal failure, and hemorrhagic cystitis (requiring blood transfusion).
Tubular damage may occur up to years after cessation of IFEX treatment. The risk of nephrotoxicity is increased in patients with renal impairment or reduced nephron reserve. Hemorrhagic cystitis is dose‑dependent and the risk is increased with past or concomitant radiation of the bladder or busulfan treatment.
Evaluate glomerular and tubular kidney function before treatment with IFEX, during IFEX treatment, and as clinically indicated. Monitor serum and urine chemistries (including phosphorus and potassium) and urinary sediment for the presence of erythrocytes or other signs of nephrotoxicity. Signs and symptoms may include a decrease in glomerular filtration rate, increased serum creatinine, proteinuria, enzymuria, cylindruria, aminoaciduria, phosphaturia, glycosuria, osteomalacia, tubular acidosis, Fanconi syndrome, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Before starting treatment, exclude or correct any urinary tract obstructions
[see Contraindications (4)]. During or immediately after administration, provide oral or intravenous fluid to force dieresis to reduce the risk of urinary tract toxicity. Administer mesna with IFEX to reduce the incidence and severity of urotoxicity[seeDosage and Administration (2.1)].Obtain a urinalysis prior to each dose of IFEX. Avoid administration of IFEX in patients with active urinary tract infections. If microscopic hematuria (greater than 10 RBCs per high power field) is present, then withhold administration of IFEX until complete resolution. Further administration of IFEX should be given with vigorous oral or parenteral hydration. Dosage interruption or permanent discontinuation may be required based on individual safety and tolerability.
• Administer IFEX as a slow intravenous infusion (at least 30 minutes) at a dose of 1.2 grams per m2 per day for 5 consecutive days. Repeat every 3 weeks or after recovery from hematologic toxicity. ()2.2 Recommended DosageThe recommended dosage of IFEX is 1.2 grams per m2per 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 IFEX based on patient risk factors and adverse reactions.
• Individualize the dose and dosing schedule of IFEX based on patient risk factors and adverse reactions. ()2.2 Recommended DosageThe recommended dosage of IFEX is 1.2 grams per m2per 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 IFEX based on patient risk factors and adverse reactions.
• See Full Prescribing Information for instructions on preparation and administration. ()2.3 Preparation and AdministrationIFEX is a hazardous drug. Follow applicable special handling and disposal procedures.1
Skin reactions associated with accidental exposure to IFEX may occur. To minimize the risk of dermal exposure, always wear impervious gloves when handling vials and solutions containing IFEX. If IFEX solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious amounts of water.
Prepare IFEX for intravenous use by adding
Sterile Water for Injection, USPorBacteriostatic Water for Injection, USP(benzyl alcohol or parabens preserved) to the vial and shaking to dissolve. Before administration, the substance must be completely dissolved. Use the quantity of diluents shown in Table 1below to reconstitute the product:Table 1: IFEX Quantities for Dilution and Final Concentrations Dosage StrengthQuantity of DiluentFinal Concentration1 gram
20 mL
50 mg per mL
3 grams
60 mL
50 mg per mL
Solutions of ifosfamide may be diluted further to achieve concentrations of 0.6 to 20 mg/mL in the following fluids:
• 5% Dextrose Injection, USP• 0.9% Sodium Chloride Injection, USP• Lactated Ringer’s Injections, USP• Sterile Water for Injection, USP
Because essentially identical stability results were obtained for Sterile Water admixtures as for the other admixtures (5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer’s Injection), the use of large volume parenteral glass bottles, VIAFLEX bags or PAB bags that contain intermediate concentrations or mixtures of excipients (e.g., 2.5% Dextrose Injection, 0.45% Sodium Chloride Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection) is also acceptable.
Refrigerate constituted or constituted and further diluted solutions of IFEX and use within 24 hours. Benzyl-alcohol-containing solutions can reduce the stability of ifosfamide.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
For injection: white, crystalline powder available in:
• 1 gram single-dose vial for reconstitution• 3 gram single-dose vial for reconstitution
• Lactation: Advise not to breastfeed. ()8.2 LactationRisk SummaryIfosfamide is excreted in breast milk. Because of the potential for serious adverse events, and the tumorigenicity shown for ifosfamide in animal studies, advise women not to breastfeed during treatment with IFEX and for one week after the last dose.
• Renal impairment: Closely monitor for adverse reactions and consider dosage modifications.