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ifosfamide (Ifex, Friedman acid)

Tradename: Ifex. Indications: - Hodgkin's disease & non-Hodgkin's lymphoma - acute leukemia - testicular carcinoma - lung cancer - Ewing's sarcoma - breast cancer - osteogenic sarcoma - head & neck cancer [4] - bladder cancer [4] Contraindications: - severe bone marrow depression Dosage: - 1 to 1.2 g/m2/day IV over 5 consecutive days every 3-4 weeks a) adequate hydration is necessary b) mesna is used in combination (60% of ifosfamide dose) 1] 20% before 20% 4 hours after 20% 8 hours after ifosfamide dose, or 2] equal to ifosfamide dose, delivered continuously Powder for injection: 1 g with 200 mg of mesna per ampule. Pharmacokinetics: 1) activated by liver enzymes 2) metabolized by liver by cyt P450 3A4 3) eliminated in urine 4) 1/2life 6-15 hours 5) more efficacious when given as daily dose over 5 days than given as single dose Adverse effects: 1) common (> 10%) a) alopecia - 50-83% within 2-4 weeks - up to 100% with combination chemotherapy b) gastrointestinal - nausea/vomiting - mild to moderate, but may be severe - dose & schedule related; more common with higher doses & after boluses - anorexia - diarrhea - constipation - transient increases in liver function tests - stomatitis c) genitourinary - hemorrhagic cystitis - NEVER use without uroprotective agent (i.e. MESNA) - hematuria - renal tubular damage - proximal renal tubular nephrotoxicity [5] - renal insufficiency - may resemble Fanconi syndrome: glycosuria, amino aciduria, phosphaturia, uricosuria - metabolic acidosis (up to 30%) - renal tuberular acidosis type 2 2) less common (1-10%) a) myelosuppression - leukopenia is mild to moderate - thrombocytopenia (rare) - anemia (rare) - onset 7 days - nadir 10-14 days - recovery 21 days b) neurologic (due to chloroacetaldehyde metabolite) - somnolence, confusion, hallucinations (12%) - coma (generally with higher doses) - depressive psychoses c) phlebitis, nasal stuffiness, SIADH, immunosuppression, sterility, hyperpigmentation of the skin, pulmonary fibrosis, cardiotoxicity, dermatitis, nail ridging, possible secondary malignancy, impaired wound healing, allergic reactions 3) uncommon (< 1%) - cardiotoxicity - pulmonary toxicity Drug interactions: 1) any drug that inhibits cyt P450 3A4 may increase levels of ifosfamide 2) any drug that induces cyt P450 3A4 may diminish levels of ifosfamide 3) allopurinol, cimetidine, phenobarbital, phenytoin & chloral hydrate may increase ifosfamide toxicity [1] Test interactions: increase in serum K+ Mechanism of action: 1) alkylating agent 2) interferes with DNA template

Interactions

drug adverse effects of alkylating agents

Related

cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) mesna; 2-mercaptoethane sulfonate; 2-sulfanylethanesulfonic acid (Mesnex, Uromitexan, Mistabronco)

General

alkylating agent nitrogen mustard

Properties

MISC-INFO: elimination route LIVER URINE pregnancy-category D 1/2life 6-15 HOURS

Database Correlations

PUBCHEM correlations

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary
  2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998
  3. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  4. Deprecated Reference
  5. Medical Knowledge Self Assessment Program (MKSAP) 19. American College of Physicians, Philadelphia 2021

Component-of

ifosfamide/mesna