Ifosfamide 1 g Injection, Powder, Lyophilized, For Solution, 1 vial
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Alkylating Drug class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Ifosfamide is used to treat certain types of cancer of the testicles. Ifosfamide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of cancer cells in your body.
Read the full MedlinePlus article ↗- Ifosfamide is a chemotherapy drug used to treat germ cell testicular cancer — specifically when at least two earlier treatment regimens haven't worked. It's always given as part of...
- Mesna is a protective drug that is always given alongside ifosfamide. One of ifosfamide's byproducts, acrolein, can irritate and damage your bladder, causing a serious condition ca...
- Why do I also have to take mesna, and what does it do?
- The most urgent things to call your care team about are: fever or signs of infection (your white blood cell count can drop dangerously low), blood in your urine, or any sudden conf...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Ifosfamide — tap one for details:
Ifosfamide may be associated with lower levels of 4 nutrients — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9208 | $27.613 / J9208 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Ifex 1 g/20mL 00338-3991-01 | Baxter | 1 vial | — | AP | FDA listed | — |
| Ifosfamide 1 g/20mL 10019-0925-01 | Baxter | 1 vial | — | AP | FDA listed | — |
| Ifosfamide 1 g/20mL 10019-0927-01 | Baxter | 1 vial | — | AP | FDA listed | — |
| Ifosfamide 1 gthis 63323-0142-10 | Fresenius | 1 vial | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 63323-0142-12 | 1 VIAL, SINGLE-DOSE in 1 BOX (63323-142-12) / 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL, SINGLE-DOSE | 2003-01-28 | Discontinued by firm |
| 63323-0142-10 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 BOX (63323-142-10) / 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 VIAL, SINGLE-DOSE | 2003-01-28 | Active |
Pack size FAQ
What quantity is in NDC 63323-0142-10?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: MYELOSUPPRESSION, NEUROTOXICITY, and UROTOXICITY Myelosuppression can be severe and lead to fatal infections. Monitor blood counts prior to and at intervals after each treatment cycle. CNS toxicities can be severe and result in encephalopathy and death.
Monitor for CNS toxicity and discontinue treatment for 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 Warnings and Precautions ( 5.1 - 5.3 )] WARNING: MYELOSUPPRESSION, NEUROTOXICITY, and UROTOXICITY See full prescribing information for complete boxed warning. • Myelosuppression can be severe and lead to fatal infections ( 5.1 ) • CNS toxicities can be severe and result in encephalopathy and death ( 5.2 ) • Nephrotoxicity can be severe and result in renal failure.
Hemorrhagic cystitis can be severe. ( 5.3 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Ifosfamide for Injection is indicated for use in combination with certain other approved antineoplastic agents for third-line chemotherapy of germ cell testicular cancer. It should be used in combination with mesna for prophylaxis of hemorrhagic cystitis. Ifosfamide for Injection is an alkylating drug indicated for use in combination with certain other approved antineoplastic agents for third-line chemotherapy of germ cell testicular cancer.
It should be used in combination with mesna for prophylaxis of hemorrhagic cystitis. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Ifosfamide for Injection should be administered intravenously at a dose of 1.2 grams per m 2 per day for 5 consecutive days. Treatment is repeated every 3 weeks or after recovery from hematologic toxicity. In order to prevent bladder toxicity, Ifosfamide for Injection should be given with extensive hydration consisting of at least 2 liters of oral or intravenous fluid per day.
Mesna should be used to reduce the incidence of hemorrhagic cystitis. Ifosfamide for Injection should be administered as a slow intravenous infusion lasting a minimum of 30 minutes. Studies of Ifosfamide for Injection in patients with hepatic or renal impairment have not been conducted [see Use in Specific Populations ( 8.6 , 8.7 )] .
Injections are prepared for parenteral use by adding Sterile Water for Injection, USP or Bacteriostatic Water for Injection, USP (benzyl alcohol or parabens preserved), to the vial and shaking to dissolve. Before parenteral administration, the substance must be completely dissolved. Use the quantity of diluents shown below to constitute the product: 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 Injection, 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.
Constituted or constituted and further diluted solutions of Ifosfamide for Injection should be refrigerated and used 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.
Dosage and duration of treatment and/or treatment intervals depend on the scheme of combination therapy, the patient’s general state of health and organ function, and the results of laboratory monitoring. ( 2 ) • Ifosfamide for Injection should be administered as a slow intravenous infusion lasting a minimum of 30 minutes at a dose of 1.2 grams per m 2 per day for 5 consecutive days. ( 2 ) • Treatment is repeated every 3 weeks or after recovery from hematologic toxicity.
( 2 ) • To prevent bladder toxicity, Ifosfamide for Injection should be given with extensive hydration consisting of at least 2 liters of oral or intravenous fluid per day. ( 2 , 5.3 ) • Mesna should be used to reduce the incidence of hemorrhagic cystitis. ( 2 )
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 1 gram single-dose vial 3 gram single-dose vial • Single dose vials: 1 gram, 3 grams ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Ifosfamide for Injection is contraindicated in patients with: • Known hypersensitivity to administration of ifosfamide. • Urinary outflow obstruction. • Known hypersensitivity to administration of ifosfamide. ( 4 ) • Urinary outflow obstruction. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Myelosuppression: Can be severe and lead to fatal infections. Monitor blood counts prior to and at intervals after treatment. ( 5.1 ) • Neurotoxicity: Severe and fatal neurotoxicity can occur.
Carefully monitor the patient for CNS toxicity and other neurotoxic effects. Discontinue therapy should encephalopathy develop. ( 5.2 ) • Urotoxicity: Severe nephrotoxicity with renal failure and death can occur.
Monitor for nephrotoxicity with serum and urine chemistries. Mesna should be used to reduce hemorrhagic cystitis. ( 5.3 ) • Cardiotoxicity: Arrhythmias, other ECG changes, and cardiomyopathy can occur and result in death.
Use with caution in patients with cardiac risk factors and in patients with preexisting cardiac disease. The risk of cardiotoxicity is dose dependent. ( 5.4 ) • Pulmonary toxicity: Interstitial pneumonitis, pulmonary fibrosis, and other forms of pulmonary toxicity with fatal outcomes can occur.
Monitor for signs and symptoms of pulmonary toxicity and treat as clinically indicated ( 5.5 ) • Secondary malignancies as late sequelae have occurred. ( 5.6 ) • Pregnancy: Can cause fetal harm. Women should not become pregnant and men should not father a child during therapy.
( 5.8 ) • Anaphylactic/anaphylactoid reactions have been reported. ( 5.10 )
5.1Myelosuppression, Immunosuppression, and Infections Treatment with ifosfamide may cause myelosuppression and significant suppression of immune responses, which can lead to severe infections. Fatal outcomes of ifosfamide-associated myelosuppression have been reported. Ifosfamide-induced myelosuppression can cause leukopenia, neutropenia, thrombocytopenia (associated with a higher risk of bleeding events), and anemia.
The nadir of the leukocyte count tends to be reached approximately during the second week after administration. When Ifosfamide for Injection is given in combination with other chemotherapeutic/hematotoxic agents and/or radiation therapy, severe myelosuppression is frequently observed. The risk of myelosuppression is dose-dependent and is increased with administration of a single high dose compared with fractionated administration.
The risk of myelosuppression is also increased in patients with reduced renal function. Severe immunosuppression has led to serious, sometimes fatal, infections. Sepsis and septic shock also have been reported.
Infections reported with ifosfamide include pneumonias, as well as other bacterial, fungal, viral, and parasitic infections. Latent infections can be reactivated. In patients treated with ifosfamide, reactivation has been reported for various viral infections.
Infections must be treated appropriately. Antimicrobial prophylaxis may be indicated in certain cases of neutropenia at the discretion of the managing physician. In case of neutropenic fever, antibiotics and/or antimycotics must be given.
Close hematologic monitoring is recommended. White blood cell (WBC) count, platelet count and hemoglobin should be obtained prior to each administration and at appropriate intervals after administration. Unless clinically essential, Ifosfamide for Injection should not be given to patients with a WBC count below 2,000/µL and/or a platelet count below 50,000/µL.
Ifosfamide for Injection should be given cautiously, if at all, to patients with presence of an infection, severe immunosuppression or compromised bone marrow reserve, as indicated by leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.
5.2Central Nervous System Toxicity, Neurotoxicity Administration of ifosfamide can cause CNS toxicity and other neurotoxic effects. The risk of CNS toxicity and other neurotoxic effects necessitates careful monitoring of the patient. Neurologic manifestations consisting of somnolence, confusion, hallucinations, blurred vision, psychotic behavior, extrapyramidal symptoms, urinary incontinence, seizures, and in some instances, coma, have…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS In clinical trials of ifosfamide monotherapy, the most common (≥ 10%) adverse reactions were alopecia, nausea/vomiting, leukopenia, anemia, CNS toxicity, hematuria, and infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Adverse Reactions from Clinical Trials Because clinical trials are conducted under 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 and frequencies below are based on 30 publications describing clinical experience with fractionated administration of ifosfamide as monotherapy with a total dose of 4 to 12 g/m 2 per course.
System Organ Class (SOC) Adverse Reaction Percentage (Ratio) INFECTIONS AND INFESTATIONS Infection 9.9% (112/1128) BLOOD AND LYMPHATIC SYSTEM DISORDERS Leukopenia 1 (any) - 1a Leukopenia <1 x 10 3 /µL 43.5% (267/614) Thrombocytopenia 2 (any) - 2a Thrombocytopenia, 50 x 10 3 /µL 4.8% (35/729) Anemia 3 37.9% (202/533) METABOLISM AND NUTRITION DISORDERS Anorexia 1.1% (15/1317) NERVOUS SYSTEM DISORDERS Central nervous system toxicity 4,5 15.4% (154/1001) Peripheral neuropathy 0.4% (5/1317) CARDIAC DISORDERS Cardiotoxicity 6 0.5% (7/1317) VASCULAR DISORDERS Hypotension 7 0.3% (4/1317) GASTROINTESTINAL DISORDERS Nausea/Vomiting 46.8% (443/964) Diarrhea 0.7% (9/1317) Stomatitis 0.3% (4/1317) HEPATOBILIARY DISORDERS Hepatotoxicity 8 1.8% (22/1190) SKIN AND SUBCUTANEOUS TISSUES DISORDERS Alopecia 89.6% (540/603) Dermatitis 0.08% (1/1317) Papular rash 0.08% (1/1317) RENAL AND URINARY DISORDERS Hemorrhagic cystitis - 9 Hematuria - without mesna 44.1% (282/640) - with mesna 21.3% (33/155) Macrohematuria - without mesna 11.1% (66/594) - with mesna 5.2% (5/97) Renal dysfunction 10 - Renal structural damage - GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS Phlebitis 11 2.8% (37/1317) Neutropenic fever 12 1.0% (13/1317) Fatigue 0.3% (4/1317) Malaise Unable to calculate 1 The following adverse reaction terms have been reported for leukopenia: neutropenia, granulocytopenia, lymphopenia, and pancytopenia.
For neutropenic fever, see below. 1a The frequency category of leukopenia is based on the frequency of leukopenia <3 x 10 3 /µL [42.5% (150/353) not shown in table] and <1 x 10 3 /µL; a relevant percentage ratio cannot be calculated for the pooled data and thus the conservative frequency category of “Very common” was included in the table. 2 Thrombocytopenia may also be complicated by bleeding.
Bleeding with fatal outcome has been reported. 2a Frequency of thrombocytopenia is based on the frequency of thrombocytopenia <100 x 10 3 /µL [12.2% (24/196) not shown in table] and <50 x 10 3 /µL; a relevant percentage ratio cannot be calculated from the pooled data and thus the conservative frequency of “Very common” was included in the table. 3 Includes cases reported as anemia and decrease in hemoglobin/hematocrit.
4 Encephalopathy with coma and death has been reported. 5 Central nervous system toxicity was reported to be manifested by the following signs and symptoms: Abnormal behavior, Affect lability Aggression, Agitation, Anxiety, Aphasia, Asthenia, Ataxia, Cerebellar syndrome, Cerebral function deficiency, Cognitive disorder, Coma, Confusional state, Convulsions, Cranial nerve dysfunction, Depressed state of consciousness, Depression, Disorientation, Dizziness, Electroencephalogram abnormal, Encephalopathy, Flat affect. Hallucinations, Headache, Ideation, Lethargy, Memory impairment, Mood change, Motor dysfunction, Muscle spasms, Myoclonus, Progressive loss of brainstem reflexes, Psychotic reaction, Restlessness, Somnolence, Tremor, Urinary incontinence.
6 Cardiotoxicity was reported as congestive heart failure, tachycardia, pulmonary edema. Fatal outcome has been reported. 7 Hypo…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Ifosfamide is a substrate for both CYP3A4 and CYP2B6. • CYP3A4 Inducers: monitor for increased toxicity when used in combination with CYP3A4 inducers. ( 7.1 ) • CYP3A4 Inhibitors: use in combination with CYP3A4 inhibitors could decrease the effectiveness of ifosfamide. ( 7.2 )
7.1Inducers of CYP3A4 CYP3A4 inducers (e.g., carbamazepine, phenytoin, fosphenytoin, phenobarbital, rifampin, St. John Wort) may increase the metabolism of ifosfamide to its active alkylating metabolites. CYP3A4 inducers may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde. Closely monitor patients taking ifosfamide with CYP3A4 inducers for toxicities and consider dose adjustment.
7.2Inhibitors of CYP3A4 CYP3A4 inhibitors (e.g., ketoconazole, fluconazole, itraconazole, sorafenib, aprepitant, fosaprepitant, grapefruit, grapefruit juice) may decrease the metabolism of ifosfamide to its active alkylating metabolites, perhaps decreasing the effectiveness of ifosfamide treatment.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Pregnancy: fetal growth retardation and neonatal anemia. ( 8.1 ) • Geriatric use: dose selection should be cautious. ( 8.5 ) • Patients with renal impairment: monitor for toxicity and consider dose reduction as needed ( 8.6 )
8.1Pregnancy Pregnancy Category D [see Warnings and Precautions ( 5.8 )] . 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.
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. The number of anomalies was also significantly increased over the control group. Women should not become pregnant and men should not father a child during therapy with ifosfamide.
Further, men should not father a child for up to 6 months after the end of therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug or after treatment, the patient should be apprised of the potential hazard to a fetus.
8.3Nursing Mothers Ifosfamide is excreted in breast milk. Because of the potential for serious adverse events and the tumorigenicity shown for ifosfamide in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Women must not breastfeed during treatment with ifosfamide.
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients.
8.5Geriatric Use In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. A study of patients 40 to 71 years of age indicated that elimination half-life appears to increase with advancing age [see Pharmacokinetics ( 12.3 )] . This apparent increase in half-life appeared to be related to increases in volume of distribution of ifosfamide with age.
No significant changes in total plasma clearance or renal or non-renal clearance with age were reported. Ifosfamide and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
8.6Use in Patients with Renal Impairment No formal studies were conducted in patients with renal impairment. Ifosfamide and its metabolites are known to be excreted by the kidneys and may accumulate in plasma with decreased renal function. Patients with renal impairment should be closely monitored for toxicity and dose reduction may be considered. Ifosfamide and its metabolites are dialyzable.
8.7Use in Patients with Hepatic Impairment No formal studies were conducted in patients with hepatic impairment. Ifosfamide is extensively metabolized in the liver and forms both efficacious and toxic metabolites. Ifosfamide for Injection should be given cautiously to patients with impaired hepatic function.
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category D [see Warnings and Precautions ( 5.8 )] . 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.
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. The number of anomalies was also significantly increased over the control group. Women should not become pregnant and men should not father a child during therapy with ifosfamide.
Further, men should not father a child for up to 6 months after the end of therapy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug or after treatment, the patient should be apprised of the potential hazard to a fetus.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. A study of patients 40 to 71 years of age indicated that elimination half-life appears to increase with advancing age [see Pharmacokinetics ( 12.3 )] . This apparent increase in half-life appeared to be related to increases in volume of distribution of ifosfamide with age.
No significant changes in total plasma clearance or renal or non-renal clearance with age were reported. Ifosfamide and its metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
🆘 Overdosage ▾
10 OVERDOSAGE 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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 as well as multiple other nontoxic products. The exact mechanism of action of ifosfamide has not been determined, but its cytotoxic action is primarily through DNA crosslinks caused by alkylation by the isophosphoramide mustard at guanine N-7 positions.
The formation of inter- and intra-strand cross-links in the DNA results in cell death.
12.3Pharmacokinetics 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. At doses of 1.6 to 2.4 g/m 2 /day, the plasma decay is monoexponential and the terminal elimination half-life is about 7 hours.
Ifosfamide exhibits time-dependent pharmacokinetics in humans. Following intravenous administration of 1.5 g/m 2 over 0.5 hour once daily for 5 days to 15 patients with neoplastic disease, a decrease in the median elimination half-life from 7.2 hour on Day 1 to 4.6 hours on Day 5 occurred with a concomitant increase in the median clearance from 66 mL/min on Day 1 to 115 mL/min on Day 5. There was no significant change in the volume of distribution on Day 5 compared with Day 1.
Distribution Ifosfamide volume of distribution (Vd) approximates the total body water volume, suggesting that distribution takes place with minimal tissue binding. Following intravenous administration of 1.5 g/m 2 over 0.5 hour once daily for 5 days to 15 patients with neoplastic disease, the median Vd of ifosfamide was
0.64 L/kg on Day 1 and
0.72L/kg on Day 5. Ifosfamide shows little plasma protein binding. Ifosfamide and its active metabolites are extensively bound by red blood cells.
Ifosfamide is not a substrate for P-glycoprotein. Metabolism Ifosfamide is extensively metabolized in humans through two metabolic pathways: ring oxidation (“activation”) to form the active metabolite, 4-hydroxy-ifosfamide and side-chain oxidation to form the inactive metabolites, 3-dechloro-ethylifosfamide or 2-dechloroethylifosfamide with liberation of the toxic metabolite, chloroacetaldehyde. Small quantities (nmol/mL) of ifosfamide mustard and 4-hydroxyifosfamide are detectable in human plasma.
Metabolism of ifosfamide is required for the generation of the biologically active species and while metabolism is extensive, it is also quite variable among patients. Excretion After administration of doses of 5 g/m 2 of 14 C-labeled ifosfamide, from 70% to 86% of the dosed radioactivity was recovered in urine as metabolites, with about 61% of the dose excreted as parent compound. At doses of 1.6 to 2.4 g/m 2 only 12% to 18% of the dose was excreted in the urine as unchanged drug within 72 hours.
Two different dechloroethylated derivatives of ifosfamide, 4-carboxyifosfamide, thiodiacetic acid and cysteine conjugates of chloroacetic acid have been identified as the major urinary metabolites of ifosfamide in humans and only small amounts of 4-hydroxyifosfamide and acrolein are present. Pediatrics Population PK analysis was performed on plasma data from 32 pediatric patients various malignant diseases aged between 1 and 18 years. Patients received a total of 45 courses of ifosfamide at doses of 1.2, 2.0 and 3.0 g/m 2 given intravenously over 1 or 3 hours on 1, 2, or 3 days.
The mean±standard error population estimates for the initial clearance and volume of distribution of ifosfamide were 2.4±0.33 L/h/m 2 and 21±1.6 L/m 2 with an interindividual variability of 43% and 32%, respectively. Effect of Age A study of 20 patients between 40 to 71 years of age receiv…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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 as well as multiple other nontoxic products. The exact mechanism of action of ifosfamide has not been determined, but its cytotoxic action is primarily through DNA crosslinks caused by alkylation by the isophosphoramide mustard at guanine N-7 positions.
The formation of inter- and intra-strand cross-links in the DNA results in cell death.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Ifosfamide for Injection, USP, is available in single-dose vials as follows: Product No. NDC No. 104210 63323-142-10 1 gram single dose vial, packaged individually.
104300 63323-143-00 3 grams single dose vial, packaged individually. The container closure is not made with natural rubber latex. Store at controlled room temperature 20°C to 25°C (68°F to 77°F).
Protect from temperatures above 30°C (86°F). Exercise caution when handling Ifosfamide for Injection. The handling and preparation of ifosfamide should always be in accordance with current guidelines on safe handling of cytotoxic agents.
Several guidelines on this subject have been published. 1-4 Skin reactions associated with accidental exposure to Ifosfamide for Injection may occur. To minimize the risk of dermal exposure, always wear impervious gloves when handling vials and solutions containing Ifosfamide for Injection.
If Ifosfamide for Injection solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious amounts of water.
📋 Description ▾
11 DESCRIPTION Ifosfamide for Injection, USP single-dose vials for constitution and administration by intravenous infusion each contain 1 gram or 3 grams of sterile ifosfamide. Ifosfamide is a chemotherapeutic agent chemically related to the nitrogen mustards and a synthetic analog of cyclophosphamide. Ifosfamide is 3-(2-chloroethyl)-2-[(2-chloroethyl)amino]tetrahydro-2H-1,3,2‑ oxazaphosphorine 2-oxide.
The molecular formula is C 7 H 15 Cl 2 N 2 O 2 P and its molecular weight is 261.1. Ifosfamide is a white crystalline powder soluble in water. There are no excipients in the formulation.
Each vial contains 1 gram or 3 grams of sterile ifosfamide alone. Its structural formula is: ifosfamide-structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Inform patients of the risks associated with the use of Ifosfamide for Injection as well as the plan for regular blood monitoring during therapy. Specifically inform patients of the following: • Treatment with ifosfamide may cause myelosuppression which can be severe and lead to fatal outcome. Significant suppression of immune responses can also occur which can lead to severe infections.
Latent infections can be reactivated. Patients should report fever or other symptoms of an infection. • The risk of bleeding and anemia. • The risk of CNS toxicity and other neurotoxic effects with fatal outcome. • The risk of bladder and kidney toxicity. Patients should be aware of the need to increase fluid intake and frequent voiding to prevent accumulation in the bladder. • The risk of cardiotoxicity and fatal outcome.
Patients should report preexisting cardiac disease. • The risk of pulmonary toxicity leading to respiratory failure with fatal outcome. • The risk of secondary malignancies due to therapy. • The risk of veno-occlusive liver disease. • The potential hazard to a fetus if a patient becomes pregnant or fathers a child during therapy and for up to 6 months after therapy. Effective methods of contraception should be used during therapy and for up to 6 months after therapy. • The potential for serious adverse reactions and tumorigenicity when children are breastfed during therapy. • The risk of amenorrhea, premature menopause, and sterility. • The risk of alopecia, wound healing, and other serious skin and subcutaneous tissue disorders. • Therapy may cause gastrointestinal disorders and alcohol may increase nausea and vomiting. • The risk of stomatitis and the importance of proper oral hygiene. • The risk of eye disorders such as visual impairment, blurred vision, and eye irritation. • The risk of ear and labyrinth disorders such as deafness, vertigo, and tinnitus.
The brand names mentioned in this document are the trademarks of their respective owners. www.fresenius-kabi.com/us 45929D Revised: December 2017 address