Professional Drug Information > IFEX

Ifosfamide (Systemic)

VA CLASSIFICATION
Primary: AN100

Commonly used brand name(s): IFEX.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Tumors, germ cell, testicular (treatment)¹—Ifosfamide is indicated, in combination with other antineoplastic agents and a prophylactic agent against hemorrhagic cystitis (such as mesna), for treatment of germ cell testicular tumors ^{{01} {03} {19}}.

[Carcinoma, head and neck (treatment) ]¹—Ifosfamide is indicated as reasonable medical therapy for treatment of head and neck carcinoma ^{{35} {36} {37} {38} {39} {40} {41} {42} {43} {44} {45}}. (Evidence rating: IIID )

[Sarcomas, soft-tissue (treatment)]
[Ewing's sarcoma (treatment)]¹
[Lymphomas, Hodgkin's (treatment) ]¹ or
[Lymphatics, non-Hodgkin's (treatment) ]¹—Ifosfamide is used for treatment of soft-tissue sarcomas ^{19}, Ewing's sarcoma ^{19}, and Hodgkin's ^{{19} {25} {26} {32}} and non-Hodgkin's lymphomas ^{{16} {19} {33}}.

[Carcinoma, breast (treatment)]¹
[Carcinoma, cervical (treatment)]
[Carcinoma, lung, small cell (treatment) ]¹
[Carcinoma, lung, non–small cell (treatment)]¹
[Carcinoma, ovarian epithelial (treatment) ]¹
[Leukemia, acute lymphocytic (treatment) ]¹
[Neuroblastoma (treatment)]¹or
[Osteosarcoma (treatment)]¹—Ifosfamide is indicated for treatment of breast carcinoma ^{{19} {25} {26} {29}}, cervical carcinoma ^{{19} {23} {25}}, small cell lung carcinoma ^{{19} {24} {25} {27}}, non–small cell lung carcinoma ^{19}, ovarian epithelial carcinoma ^{{19} {25} {26} {28}}, acute lymphocytic leukemia ^{{19} {25}}, neuroblastoma ^{{19} {30}}, and osteosarcoma ^{{19} {25} {31}}.

[Tumors, germ cell, ovarian (treatment) ]¹—Ifosfamide, in combination therapy, is considered reasonable medical therapy at some point in the management of germ cell ovarian tumors ^{{46} {47} {48} {50}} (Evidence rating: IIID).

[Carcinoma, bladder (treatment)]¹ or
[Carcinoma, endometrial (treatment) ]¹—Ifosfamide, alone and in combination with other chemotherapeutic agents, is considered reasonable medical therapy at some point in the management of bladder carcinoma ^{{59} {60} {61} {62} {63} {64} {65} {66} {67} {68} {69}} (Evidence rating: IIID) and endometrial carcinoma ^{{70} {71} {72} {73} {74}} (Evidence rating: IIIA).

[Carcinoma, thymic (treatment)]¹ or
[Thymoma (treatment)]¹—Ifosfamide is indicated for the treatment of relapsed or refractory thymoma and thymic carcinoma.^{{75}{76}{77}{78}{79}{80}{81}{82}{83}}

[Wilms' tumor (treatment)]¹—Ifosfamide is indicated, alone or in combination with other chemotherapeutic agents, as second-line therapy for the treatment of Wilms' tumor in patients who have not responded to or whose disease has progressed during previous treatment ^{{51} {52} {53} {54} {55} {56} {57} {58}}(Evidence rating: IIID).

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    261.09 ^{34}

Mechanism of action/Effect:

Ifosfamide is classified as an alkylating agent of the nitrogen mustard type. After metabolic activation, active metabolites of ifosfamide alkylate or bind with many intracellular molecular structures, including nucleic acids. The cytotoxic action is primarily due to cross-linking of strands of DNA ^{01} and RNA, as well as inhibition of protein synthesis ^{04}.

Distribution:

Active metabolites cross the blood-brain barrier to only a limited extent ^{02}.

Biotransformation:

Hepatic (including initial activation and subsequent degradation) ^{01}. Metabolic pathways appear to be saturated at high doses ^{{01} {02}}.

Half-life:

At single doses of 3.8 to 5 grams per square meter of body surface area—Biphasic: Terminal—15 hours ^{{01} {02}}.

At doses of 1.6 to 2.4 grams per square meter of body surface area per day—Monophasic: 7 hours ^{{01} {02}}.

Elimination:
        Renal, 70 to 86%; 61% unchanged at single doses of 5 grams per square meter of body surface area ^{01}. 12 to 18% unchanged at doses of 1.2 to 2.4 grams per square meter of body surface area ^{01}.



Precautions to Consider

Carcinogenicity

Secondary malignancies are potential delayed effects of many antineoplastic agents, although it is not clear whether the effect is related to their mutagenic or immunosuppressive action. The effects of dose and duration of therapy are also unknown, although risk seems to increase with long-term use. Although information is limited, available data seem to indicate that the carcinogenic risk is greatest with the alkylating agents.

Studies in rats have found ifosfamide to be carcinogenic, with female rats showing a significant incidence of leiomyosarcomas and mammary fibroadenomas ^{01}.

Mutagenicity

Ifosfamide has been shown to be mutagenic in bacterial studies in vitro and mammalian cells in vivo . In vivo , ifosfamide has induced mutagenic effects in mice and Drosophila melanogaster germ cells, and has induced a significant increase in dominant lethal mutations in male mice as well as recessive sex-linked lethal mutations in Drosophila . ^{01}

Pregnancy/Reproduction
Fertility—
Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients taking antineoplastic therapy, especially with the alkylating agents. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian function impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents.

Pregnancy—
First trimester: It is usually recommended that use of antineoplastics, especially combination chemotherapy, be avoided whenever possible, especially during the first trimester. Although information is limited because of the relatively few instances of antineoplastic administration during pregnancy, the mutagenic, teratogenic, and carcinogenic potential of these medications must be considered.

Other hazards to the fetus include adverse reactions seen in adults.

In general, use of a contraceptive is recommended during cytotoxic drug therapy.

Studies in animals have shown that ifosfamide is teratogenic in mice, rats, and rabbits given 0.05 to 0.075 times the human dose ^{01}.

FDA Pregnancy Category D.

Breast-feeding

Ifosfamide is distributed into breast milk ^{01}. Breast-feeding is not recommended during chemotherapy because of the risks to the infant (adverse effects, mutagenicity, carcinogenicity).

Pediatrics

Appropriate studies on the relationship of age to the effects of ifosfamide have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date. ^{15}


Geriatrics


No information is available on the relationship of age to the effects of ifosfamide in geriatric patients. However, elderly patients are more likely to have age-related renal function impairment, which may require caution ^{14}.


Dental

The bone marrow depressant effects of ifosfamide may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene during treatment, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Ifosfamide may also rarely cause stomatitis associated with considerable discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Blood dyscrasia–causing medications (see Appendix II )    (leukopenic and/or thrombocytopenic effects of ifosfamide may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of ifosfamide, if necessary, should be based on blood counts )


» Bone marrow depressants, other (see Appendix II ) or
» Radiation therapy    (additive bone marrow depression may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)


Hepatic enzyme inducers (see Appendix II )    (these agents may induce microsomal metabolism to increase formation of alkylating metabolites of ifosfamide; although it is unknown whether activity of ifosfamide is increased, neurotoxicity may be increased; caution is recommended )

^{17}
Nephrotoxic medications    (prior or concurrent use with ifosfamide may increase ifosfamide's nephrotoxic effects ^{02})

    (previous use of large cumulative doses of cisplatin may increase the risk of central nervous system (CNS) toxicity with ifosfamide ^{20})


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by ifosfamide therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)


» Vaccines, live virus    (because normal defense mechanisms may be suppressed by ifosfamide therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the ifosfamide therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Aspartate aminotransferase (AST [SGOT]) and
Lactate dehydrogenase (LDH)    (serum values may be increased as a sign of hepatotoxicity ^{{01} {02}})


Bilirubin    (serum concentrations may be increased as a sign of hepatotoxicity)


Blood urea nitrogen (BUN) ^{{01} {02}} or
Creatinine, serum ^{{01} {02}}    (concentrations may be increased transiently as a sign of renal toxicity )


Creatinine clearance ^{01}    (may be decreased transiently as a sign of renal toxicity)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Bone marrow depression ^{01}
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease)


» Hepatic function impairment    (effect of ifosfamide may be reduced or enhanced because of its dependence on hepatic microsomal enzyme activation and degradation ^{{05} {15}})


» Infection
» Renal function impairment    (reduced elimination; incidence of CNS toxicity and renal toxicity may be increased ^{{01} {02}}; dosage reduction may be necessary ^{06})


Sensitivity to ifosfamide ^{01}
Tumor cell infiltration of bone marrow ^{07}    (bone marrow depression)


» Caution should be used also in patients who have had previous cytotoxic drug therapy or radiation therapy.

Patient monitoring
The following are especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Alanine aminotransferase (ALT [SGPT]) values, serum and
Alkaline phosphatase values, serum ^{01} and
Aspartate aminotransferase (AST [SGOT]) values, serum and
Lactate dehydrogenase (LDH) values, serum    (recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


Bilirubin, concentrations, serum and
Blood urea nitrogen (BUN) concentrations and
Creatinine concentrations, serum    (recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


» Examination of urine for microscopic hematuria    (recommended prior to each dose ^{01})


» Hematocrit or hemoglobin and
» Leukocyte count, total and, if appropriate, differential and
» Platelet count    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)

^{01}
Phosphate concentrations, serum ^{01} and
Potassium concentrations, serum ^{01}    (recommended at periodic intervals during therapy)






Side/Adverse Effects

Note: Many “side effects” of antineoplastic therapy are unavoidable and represent the medication's pharmacologic action. Some of these (for example, leukopenia and thrombocytopenia) are actually used as parameters to aid in individual dosage titration.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
—dose-related     
CNS effects or encephalopathy ^{{01} {02}} (agitation ^{20}; confusion ^{{01} {02}}; hallucinations ^{{01} {02}}; unusual tiredness ^{{01} {02}}; less frequently, dizziness ^{01}; rarely, seizures ^{{01} {02}}; coma ^{{01} {02}})
    
leukopenia ^{{01} {02}}
    
thrombocytopenia ^{{01} {02}} (rarely associated with unusual bleeding or bruising; black, tarry stools ; blood in urine or stools; pinpoint red spots on skin)
    
urotoxicity, including hemorrhagic cystitis
dysuria
urinary frequency ^{01}{02}(blood in urine; frequent urination; painful urination)

Note: CNS effects and encephalopathy do not appear to be dose-related ^{20}. They may be associated with electroencephalogram (EEG) changes ^{20}. Signs and symptoms usually resolve within 3 days after withdrawal of ifosfamide, but may persist longer ^{20}. Fatalities have been reported ^{20}.
Leukopenia is usually mild to moderate ^{01}. Nadir of leukocyte count occurs within 7 to 14 days and counts usually recover by 21 days after a course ^{08}.
With thrombocytopenia, nadir of platelet count occurs within 7 to 14 days and counts usually recover by 21 days after a course ^{09}.
Urotoxicity may occur within a few hours or be delayed by several weeks; it is thought to be caused by a metabolite of ifosfamide (acrolein) ^{{02} {10}}. Urotoxicity usually resolves a few days after withdrawal of ifosfamide, but may persist ^{10} and may be fatal ^{10}. Incidence is reduced by fractionation of dosage, adequate hydration, and administration of mesna ^{{01} {02}}.


Incidence less frequent
    
Hepatotoxicity ^{{01} {02}}
    
infection, resulting from leukopenia ^{01} (fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination )
    
nephrotoxicity ^{{01} {02}}
    
phlebitis ^{01} (redness, swelling, or pain at site of injection)

Note: Hepatotoxicity is usually asymptomatic and detected on laboratory tests.
Nephrotoxicity is usually asymptomatic with signs of tubular damage detected on laboratory tests. Metabolic acidosis as a manifestation of nephrotoxicity has been reported to occur frequently in patients receiving high doses of ifosfamide ^{{01} {02}}. Renal tubular acidosis, Fanconi syndrome, and renal rickets have been reported ^{01}.


Incidence rare
    
Cardiotoxicity ^{01}
    
polyneuropathy ^{01}
    
pulmonary toxicity ^{01} (cough or shortness of breath)
    
stomatitis ^{01} (sores in mouth and on lips)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Nausea and vomiting ^{{01} {02}}

Note: Nausea and vomiting are usually controlled by antiemetics ^{01}.




Those not indicating need for medical attention
Incidence more frequent
    
Loss of hair ^{{01} {02}}



Those indicating the need for medical attention if they occur after medication is discontinued
    
Hemorrhagic cystitis (blood in urine)




Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ifosfamide (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to ifosfamide

Pregnancy—Use not recommended because of mutagenic, teratogenic, and carcinogenic potential; advisability of using contraception; telling physician immediately if pregnancy is suspected





Breast-feeding—Not recommended because of risk of serious side effects
Other medications, especially other bone marrow depressants, previous cytotoxic drug therapy or radiation therapy
Other medical problems, especially chickenpox, herpes zoster, hepatic function impairment, infection, renal function impairment

Proper use of this medication
Caution in taking combination therapy; taking each medication at the right time

Importance of ample fluid intake and subsequent increase in urine output, as well as frequent voiding ^{{02} {11}} (including at least once during night), to prevent hemorrhagic cystitis and aid in excretion of uric acid; following physician instructions for recommended fluid intake; some patients may require up to 3000 mL (3 quarts) per day

Probability of nausea and vomiting; importance of continuing medication despite stomach upset

» Proper dosing

Precautions while using this medication
» Importance of close monitoring by physician

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding other persons who have taken oral poliovirus vaccine within the past several months or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury might occur


Side/adverse effects
May cause adverse effects such as blood problems; loss of hair; toxicity to lungs, heart, liver, or bladder; and cancer; importance of discussing possible effects with physician

Signs of potential side effects, especially CNS effects, leukopenia, thrombocytopenia, urotoxicity, hepatotoxicity, infection, nephrotoxicity, phlebitis, cardiotoxicity, polyneuropathy, pulmonary toxicity, and stomatitis

Physician or nurse can help in dealing with side effects

Possibility of hair loss; normal hair growth should return after treatment has ended


General Dosing Information
Patients receiving ifosfamide should be under supervision of a physician experienced in cancer chemotherapy.

A variety of dosage schedules and regimens of ifosfamide, alone or in combination with other antitumor agents, are used. The prescriber may consult the medical literature as well as the manufacturer's literature in choosing a specific dosage.

Dosage must be adjusted to meet the individual requirements of each patient, based on clinical response and appearance or severity of toxicity.

To reduce the risk of hemorrhagic cystitis, adequate hydration is recommended prior to ifosfamide treatment and for at least 72 hours following treatment to ensure ample urine output. Concurrent use of an agent to prevent hemorrhagic cystitis (such as mesna) is recommended ^{01}. In addition, the patient should be encouraged to void frequently to prevent prolonged contact of irritating metabolites with bladder mucosa.

Development of mild bladder irritation (microscopic hematuria) may require adjustment of mesna dosage ^{18}. Although concurrent use of mesna greatly reduces the risk, ifosfamide should be discontinued at the first sign of hemorrhagic cystitis. In severe cases, blood replacement may be necessary. Electrocautery diversion of urine flow, cryosurgery, and formaldehyde bladder instillations have been used. Resumption of therapy should be undertaken with caution since recurrence is common. ^{12}

Each subsequent dose should be given only after microscopic hematuria, if present (defined as greater than 10 red blood cells per high power field), has resolved ^{{01} {03}}.

Ifosfamide therapy should be discontinued if severe CNS symptoms occur ^{{01} {02} {20}}.

Special precautions are recommended in patients who develop thrombocytopenia as a result of administration of ifosfamide. These may include extreme care in performing invasive procedures; regular inspection of intravenous sites, skin (including perirectal area), and mucous membrane surfaces for signs of bleeding or bruising; limiting frequency of venipuncture and avoiding intramuscular injections; testing urine, emesis, stool, and secretions for occult blood; care in use of regular toothbrushes, dental floss, toothpicks, safety razors, and fingernail and toenail cutters; avoiding constipation; and using caution to prevent falls and other injuries. Such patients should avoid alcohol and any aspirin intake because of the risk of gastrointestinal bleeding. Platelet transfusions may be required.

Patients who develop leukopenia should be observed carefully for signs of infection. Antibiotic support may be required. In neutropenic patients who develop fever, broad-spectrum antibiotic coverage should be initiated empirically, pending bacterial cultures and appropriate diagnostic tests.

If marked leukopenia (particularly granulocytopenia) or thrombocytopenia occurs, ifosfamide therapy should be withdrawn until leukocyte and platelet counts return to satisfactory levels ^{01}. Then therapy may be reinstituted, possibly at a lower dose ^{03}.

Safety considerations for handling this medication
There is limited but increasing evidence and concern that personnel involved in preparation and administration of parenteral antineoplastics may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of antineoplastic agents. Precautions that have been suggested include:    • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks.
   • Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
   • Cautious and proper disposal of needles, syringes, vials, ampuls, and unused medication.
A number of medical centers have developed detailed guidelines for handling of antineoplastic agents.


Combination chemotherapy
Ifosfamide may be used in combination with other agents in various regimens. As a result, incidence and/or severity of side effects may be altered and different dosages (usually reduced) may be used. For example, ifosfamide is part of the following chemotherapeutic combinations (some commonly used acronyms are in parentheses):    —etoposide, ifosfamide, and cisplatin (VIP) ^{{02} {03}}.
   —vinblastine, ifosfamide, and cisplatin (VeIP) ^{{02} {03}}.
For specific dosages and schedules, consult the literature. For information regarding each agent, consult the individual monograph.


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.


STERILE IFOSFAMIDE USP

Usual adult and adolescent dose
Germ cell testicular tumors ¹
Intravenous infusion (over at least thirty minutes), 1.2 grams per square meter of body surface area per day for five consecutive days, the course being repeated every three weeks or after hematologic recovery ^{{01} {13}}.

Note: Mesna is also administered during ifosfamide therapy to reduce hemorrhagic cystitis ^{01}.


[Carcinoma, breast]¹ or
[Carcinoma, cervical] or
[Carcinoma, head and neck]¹ or
[Carcinoma, lung, non–small cell]¹or
[Carcinoma, lung, small cell ]¹ or
[Carcinoma, ovarian epithelial]¹ or
[Ewing's sarcoma]¹or
[Leukemia, acute lymphocytic]¹ or
[Lymphomas, Hodgkin's]¹or
[Lymphomas, non-Hodgkin's]¹ or
[Neuroblastoma ]¹or
[ Osteosarcoma]¹ or
[Sarcomas, soft-tissue] or
[Tumors, germ cell, ovarian ]¹ or
[Carcinoma, bladder]¹or
[Carcinoma, endometrial]¹ or
[Wilms' tumor]¹
Consult medical literature or manufacturer's literature for information on appropriate dosage.

[Carcinoma, thymic]¹ or
[ Thymoma]¹
Because several doses and regimens using ifosfamide are showing activity, no individual dose/regimen is listed here. Consult medical literature and/or experts in the field of oncology for information on dosage.^{75}


Usual pediatric dose
Dosage has not been established.

Size(s) usually available:
U.S.—


1 gram (Rx) [IFEX (plus 1 gram vial of mesna)]^{01}


3 grams (Rx) [IFEX (plus 1 gram vial of mesna)]

Canada—


1 gram (Rx) [IFEX]


2 grams (Rx) [IFEX]


3 grams (Rx) [IFEX]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
May be prepared for parenteral use by adding 20, 40, or 60 mL of sterile water for injection or bacteriostatic water for injection (benzyl alcohol– or paraben-preserved) to the 1-gram, 2-gram, or 3-gram vial, respectively, and shaking to dissolve, to provide a solution containing 50 mg of ifosfamide per mL ^{01}. The resulting solution may be added to 5% dextrose injection, 0.9% sodium chloride injection, lactated Ringer's injection, or sterile water for injection for administration by intravenous infusion ^{01}. Use of intermediate concentrations or mixtures of excipients (e.g., 2.5% dextrose injection, 0.45% sodium chloride injection, 5% dextrose and 0.9% sodium chloride injection) is also acceptable ^{01}.

Caution: Use of diluents containing benzyl alcohol is not recommended for preparation of medications for use in neonates. A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with this use.

Stability:
Reconstituted or diluted solutions of ifosfamide are stable for up to 24 hours in a refrigerator (2 to 8 °C [36 to 46 °F]).

Note: Because ifosfamide for injection contains no preservative, caution in preparing and storing solutions is required to ensure sterility.
Ifosfamide and mesna may be mixed in the same infusion ^{02}.

Revised: 04/24/2002

References

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7. Reviewers' responses to Hematologic and Oncologic Disease Advisory Panel memo #10 of 1990.
   

8. Reviewers' responses to Hematologic and Oncologic Disease Advisory Panel memo #11 of 1990.
   

9. Reviewers' responses to Hematologic and Oncologic Disease Advisory Panel memo #12 of 1990.
   

10. Reviewers' responses to Hematologic and Oncologic Disease Advisory Panel memo #13 of 1990.
    

11. Reviewers' responses to Hematologic and Oncologic Disease Advisory Panel memo #14 of 1990.
    

12. Reviewers' responses to Hematologic and Oncologic Disease Advisory Panel memo #15 of 1990.
    

13. Reviewers' consensus on monograph revision of 1990.
    

14. Reviewers' responses to Geriatric Advisory Panel of 1990.
    

15. Panel comment, 5/17/89.
    

16. Reviewers' consensus on monograph revision of 1990.
    

17. Reviewers' consensus on monograph revision of 1990.
    

18. Panel comment, 1990.
    

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31. Osteosarcoma. National Cancer Institute. Available from: URL: http://cancernet.nci.nih.gov
    

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33. Devita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 2209.
    

34. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 370.
    

35. Pai VR, Mazumdar AT, Parikh DM, et al. Recent experience with ifosfamide in head and neck cancer. XVI International Cancer Congress, 1994; Oct 30-Nov 5 New Delhi, India: Abstract Book Number 3 (Satellite) Ed. PB Desai: 16-21.
    

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