ifosfamide

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Metabolized by the liver to active antineoplastic compounds.

Half-Life: 15 hr.

Time/Action Profile ⬆ ⬇

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	7–14 days	21 days

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Active infections;
↓bone marrow reserve;
Renal impairment;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: Drug may accumulate in older adults due to age-related renal impairment.

Adv. Reactions/Side Effects ⬆ ⬇

CV: cardiotoxicity

Derm: alopecia

GI: nausea, vomiting, anorexia, constipation, diarrhea, hepatotoxicity

GU: hemorrhagic cystitis, dysuria, renal impairment, sterility

Hemat: ANEMIA, LEUKOPENIA, THROMBOCYTOPENIA

Local: phlebitis

Neuro: confusion, sedation, disorientation, dizziness

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

CYP3A4 inhibitors, including ketoconazole, fluconazole, itraconazole, sorafenib, and aprepitant may ↓ its effectiveness.
CYP3A4 inducers, including carbamazepine, phenytoin, phenobarbital, and rifampin may ↑ the formation of a toxic metabolite and may ↑ risk of toxicity.
↑myelosuppression with other antineoplastics or radiation therapy.
Toxicity may be ↑ by allopurinol or phenobarbital.
May ↓ antibody response to and ↑ risk of adverse reactions from live-virus vaccines.

Grapefruit juice may ↑ levels; avoid concurrent use.

Route/Dosage ⬆ ⬇

IV (Adults ): 1.2 g/m²/day for 5 days; coadminister with mesna. May repeat cycle every 3 wk.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 1 g/vial; 3 g/vial
Solution for injection: 50 mg/mL

Assessment ⬆ ⬇

Monitor BP, pulse, respiratory rate, and temperature frequently during administration. Report significant changes.
Monitor urinary output frequently during therapy. Notify health care professional if hematuria occurs. To reduce the risk of hemorrhagic cystitis, fluid intake should be at least 3000 mL/day for adults and 1000–2000 mL/day for children. Mesna is given concurrently to prevent hemorrhagic cystitis.
Monitor neurologic status. Ifosfamide should be discontinued if severe CNS symptoms (agitation, confusion, hallucinations, unusual tiredness) occur. Symptoms usually abate within 3 days of discontinuation of ifosfamide but may persist for longer; fatalities have been reported.
Assess nausea, vomiting, and appetite. Weigh weekly. Premedication with an antiemetic may be used to minimize GI effects. Adjust diet as tolerated.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.

Lab Test Considerations:

Monitor CBC, differential, and platelet count prior to and periodically during therapy. Withhold dose if WBC <2000/mm³ or platelet count is <50,000/mm³. Nadir of leukopenia and thrombocytopenia occurs within 7–14 days and usually recovers within 21 days of therapy.
- Urinalysis should be evaluated before each dose. Withhold dose until recovery if urinalysis shows >10 RBCs per high-power field.
- May cause ↑ in liver enzymes and serum bilirubin.
- Monitor AST, ALT, serum alkaline phosphatase, bilirubin, and LDH prior to and periodically during therapy. May cause ↑ in liver enzymes and serum bilirubin.
- Monitor BUN, serum creatinine, phosphate, and potassium periodically during therapy. May cause hypokalemia.

Implementation ⬆ ⬇

Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.

IV Administration:

IV: Prepare solution by diluting each 1-g vial with 20 mL of sterile water or bacteriostatic water for injection containing parabens. Use solution prepared without bacteriostatic water within 6 hr. Solution prepared with bacteriostatic water is stable for 1 wk at 30°C or 6 wk at 5°C.
Intermittent Infusion: Diluent: May be further diluted in D5W, 0.9% NaCl, LR, or sterile water for injection.Concentration: 0.6 to 20 mg/mL (maximum 40 mg/mL). Dilute solution is stable for 7 days at room temperature or 6 wk if refrigerated.
Rate: Administer over at least 30 min.
Has also been administered as a continuous infusion over 72 hr.

Patient/Family Teaching ⬆ ⬇

Emphasize need for adequate fluid intake throughout therapy. Patient should void frequently to decrease bladder irritation from metabolites excreted by the kidneys. Notify health care professional immediately if hematuria is noted.
Instruct patient to drink at least 8 glasses of water/day during and for 3 days after completion of therapy.
Advise patient to avoid grapefruit and grapefruit juice during therapy.
Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; or confusion occurs.
Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should also be cautioned not to drink alcoholic beverages or to take products containing aspirin or NSAIDs, as these may precipitate GI hemorrhage.
Discuss with patient the possibility of hair loss. Explore methods of coping.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Instruct patient not to receive any vaccinations without advice of health care professional; ifosfamide may decrease antibody response to and increase risk of adverse reactions from live-virus vaccines.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Review with patient the need for contraception during therapy and for at least 6 mo after therapy. Women should avoid pregnancy and breastfeeding, and men should avoid fathering a child during and for at least 6 mo after end of therapy. Caution patient about the potential for amenorrhea, premature menopause, and sterility from this medication.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇