ifosfamide

ifosfamide /ifos·fa·mide/ (i-fos´fah-mīd) a cytotoxic alkylating agent of the nitrogen mustard group, in structure and actions similar to cyclophosphamide; used in the treatment of solid tumors of the testis, ovary, and lung as well as sarcomas.

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ifosfamide,

an antineoplastic alkylating agent.

indications This drug is used to treat testicular cancer, soft tissue sarcoma, Ewing's sarcoma, non-Hodgkin's lymphoma, lung sarcoma, and pancreatic sarcoma.

contraindications Pregnancy, bone marrow suppression, and known hypersensitivity to this drug prohibit its use.

adverse effects Adverse effects of this drug include facial paresthesia, fever, malaise, somnolence, confusion, depression, hallucinations, dizziness, disorientation, cranial nerve dysfunction, nausea, vomiting, anorexia, stomatitis, constipation, diarrhea, dysuria, urinary frequency, dermatitis, alopecia, and pain at the injection site. Life-threatening side effects include seizures, coma, hepatoxicity, hematuria, nephrotoxicity, hemorrhagic cystitis, thrombocytopenia, leukopenia, and anemia.

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ifosfamide Warning - Hazardous drug!

Iflex, Mitoxana (UK)

Pharmacologic class: Alkylating agent, nitrogen mustard

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Boxed Warning

• Give under supervision of physician experienced in using cancer chemotherapy, in facility with adequate diagnostic and treatment resources. Adverse urotoxic effects (especially hemorrhagic cystitis) and CNS toxicities (such as confusion and coma) have occurred; these effects may warrant drug discontinuation.
• Severe myelosuppression may occur.

Action

Alkylates DNA, interfering with replication and synthesis of susceptible cells and ultimately causing cell death

Availability

Injection: 1 g or 3 g in single-dose vials

⊘Indications and dosages

➣ Germ-cell testicular cancer

Adults: 1.2 g/m²/day by I.V. infusion over 30 minutes for 5 days. May repeat q 3 weeks or after recovery from hematologic toxicity.

Off-label uses

• Acute leukemia
• Breast, lung, ovarian, and pancreatic cancer
• Malignant lymphomas
• Sarcomas

Contraindications

• Hypersensitivity to drug
• Severe bone marrow depression
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• impaired renal or hepatic function, mild to moderate bone marrow depression.

Administration

• Follow facility policy for handling antineoplastic agents.
• Know that drug is usually given with other antineoplastics and hemorrhagic cystitis agent.
• To reconstitute, add sterile water or bacteriostatic water to vial, and shake gently.
• Mix 20 ml of diluent with 1-g vial or 60 ml of diluent with 3-g vial, to yield a concentration of 50 mg/ml. For smaller concentrations, dilute solution further with normal saline solution, dextrose 5% in water, lactated Ringer's solution, or sterile water.
• Administer I.V. slowly over at least 30 minutes.

Route	Onset	Peak	Duration
I.V.	Immediate	Unknown	Unknown

Adverse reactions

CNS: drowsiness, confusion, ataxia, hallucinations, depressive psychosis, dizziness, disorientation, cranial nerve dysfunction, coma, seizures

CV: phlebitis

GI: nausea, vomiting, diarrhea, anorexia, stomatitis

GU: hematuria, bladder fibrosis, gonadal suppression, nephrotoxicity, hemorrhagic cystitis

Hematologic: anemia, leukopenia, thrombocytopenia , bone marrow depression

Metabolic: metabolic acidosis

Skin: alopecia

Other: infection, secondary neoplasms

Interactions

Drug-drug. Anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs: increased risk of bleeding

Barbiturates, chloral hydrate, fosphenytoin, phenytoin: increased risk of toxicity

Corticosteroids: decreased ifosfamide effects

Cyclophosphamide: increased risk of cardiac tamponade

Myelosuppressants: increased hematologic toxicity

Drug-diagnostic tests. Hepatic enzymes, uric acid: increased levels

Platelets, white blood cells: decreased counts

Patient monitoring

• Monitor hematopoietic function tests (such as CBC with white cell differential) before therapy and weekly during therapy.
• Assess fluid intake and output. Ensure fluid intake of at least 2 L daily to prevent bladder toxicity.
☞ Monitor urine output for hematuria and hemorrhagic cystitis. Administer mesna (protective drug), as indicated and prescribed.

Patient teaching

☞ Tell patient to immediately report jaundice, unusual bleeding or bruising, bloody urine, pain on urination, fever, chills, sore throat, cough, difficulty breathing, unusual lumps or masses, mouth sores, or pain in flank, stomach, or joints.
• Instruct patient to maintain adequate hydration and nutrition. Advise him to drink 10 to 12 glasses of fluid each day.
• Inform patient that drug may cause hair loss.
• Advise both male and female patients to use reliable contraception during and immediately after therapy, because drug may cause severe birth defects.
• Urge patient to keep regular follow-up appointments for blood tests and monitoring of drug effects.
• As appropriate, review other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

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ifosfamide

Oncology An alkylating antineoplastic agent approved under an IND protocol as a 3^rd-line therapy for germ-cell testicular malignancy; it is also used for cervical CA, soft tissue sarcomas Side effects Myelosuppression, encephalopathy, confusion, coma, hemorrhagic cystitis Treatment Hemorrhagic cystitis may respond to mesna, encephalopathy may respond to methylene blue