ifosfamide
Ifex

Pharmacologic classification: alkylating agent (not specific to cell cycle phase)
Therapeutic classification: antineoplastic
Pregnancy risk category D


Available forms
Available by prescription only
Injection: 1-g, 3-g vials

Indications and dosages
Dosages and indications may vary. Check current literature for recommended protocol.
 Germ cell testicular cancer in combination with other antineoplastic agents as a third line chemotherapeutic agent. Adults: 1.2 g/m2 I.V. daily for 5 days. Regimen is usually repeated q 3 weeks. Drug may be given by slow I.V. push, by intermittent infusion over at least 30 minutes, or by continuous infusion.
 Lung cancer ◇, Hodgkin’s and malignant lymphoma ◇, breast cancer ◇, acute and chronic lymphocytic leukemia ◇, ovarian cancer ◇, gastric cancer ◇, pancreatic cancer ◇, sarcomas ◇. Adults: 1.2 g/m2 I.V. daily for 5 days. Regimen is usually repeated q 3 weeks. Drug may be given by slow I.V. push, by intermittent infusion over at least 30 minutes, or by continuous infusion.

Pharmacodynamics
Antineoplastic action: Ifosfamide requires activation by hepatic microsomal enzymes to exert its cytotoxic activity. The active compound cross-links strands of DNA and also breaks the DNA chain.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Crosses the blood-brain barrier along with its metabolites.
Metabolism: About 50% of a dose is metabolized in the liver.
Excretion: Excreted primarily in the urine. The terminal half-life is about 7 hours at doses of 1.6 to 2.4 g/m2 daily and about 15 hours at a single dose of 3.8 to 5 g/m2.

Route Onset Peak Duration
I.V. Unknown Unknown Unknown


Contraindications and precautions
Contraindicated in patients with severe bone marrow suppression or hypersensitivity to drug. Contraindicated in pregnancy because of possible embryotoxic and teratogenic effects on the fetus.
  Use cautiously in patients with renal or hepatic impairment, compromised bone marrow reserve as indicated by granulocytopenia, bone marrow metastases, prior radiation therapy, or therapy with cytotoxic agents.

Interactions
Drug-drug. Chloral hydrate, phenobarbital, phenytoin: May increase activity of ifosfamide by induction of hepatic microsomal enzymes, increasing the conversion of ifosfamide to its active form. Be alert for possible combined drug actions, desirable or undesirable, involving ifosfamide, even though it has been used successfully with other drugs, including other cytotoxic drugs.

Adverse reactions
CNS: somnolence, confusion,coma, seizures, ataxia, hallucinations, depressive psychosis, dizziness, disorientation, cranial nerve dysfunction.
CV: phlebitis.
GI: nausea, vomiting.
GU: hemorrhagic cystitis, hematuria,nephrotoxicity, dysuria, urinary frequency.
Hematologic: leukopenia, thrombocytopenia, myelosuppression.
Hepatic: liver dysfunction.
Metabolic: metabolic acidosis.
Skin: alopecia.
Other: infection.

Effects on lab test results
• May increase liver enzyme, bilirubin, BUN, and creatinine levels.
• May decrease hemoglobin, hematocrit, and WBC and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include myelosuppression, nausea, vomiting, alopecia, and hemorrhagic cystitis.
 Treatment is usually supportive and includes antiemetics, transfusion of blood components, and bladder irrigation.

Special considerations
• Follow all established procedures for the safe handling, administration, and disposal of chemotherapeutic agents.
• Push fluids (3 L daily) and administer with mesna (Mesnex) to prevent hemorrhagic cystitis. Avoid giving drug at bedtime, because infrequent voiding during the night increases the possibility of cystitis. Bladder irrigation with normal saline solution decreases the possibility of cystitis.
• Drug can be further diluted with D5W or normal saline solution for I.V. infusion. This solution is stable for 7 days at room temperature and for 6 weeks at 41° F (5° C).
• Drug may be given by I.V. push injection in a minimum of 75 ml normal saline solution over 30 minutes.
• Infusing each dose over 2 hours or longer decreases the possibility of cystitis.
• Obtain urinalysis before each dose and if microscopic hematuria is present, withhold subsequent administration until complete resolution.
• Assess patient for changes in mental status and cerebellar dysfunction. Dose may have to be decreased.
• Sterile phlebitis may occur at the injection site; apply warm compresses.
Pregnant patients
• Patient who becomes pregnant while taking drug should be informed of the risk to fetus.
Breast-feeding patients
• Drug appears in breast milk. Because of the potential for serious adverse reactions, mutagenicity, and carcinogenicity in the infant, breast-feeding isn’t recommended.
Pediatric patients
• Safety and efficacy in children haven’t been established.

Patient education
• Tell patient to ensure adequate fluid intake to prevent bladder toxicity and to facilitate excretion of uric acid.
• Warn patient to avoid exposure to infections and to report signs of infection or unusual bleeding immediately.
• Reassure patient that hair should grow back after treatment has ended.
• Tell patient to call immediately if blood appears in the urine.
• Advise both men and women to use contraceptive measures during therapy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use