ifosfamide (Ifex, Friedman acid)
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Introduction
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
Powder for injection: 1 g with 200 mg of mesna per ampule.
Pharmacokinetics
- activated by liver enzymes
- metabolized by liver by cyt P450 3A4
- eliminated in urine
- 1/2life 6-15 hours
- more efficacious when given as daily dose over 5 days than given as single dose
elimination via liver
elimination via urine
1/2life = 6-15 hours
Adverse effects
- common (> 10%)
- alopecia
- 50-83% within 2-4 weeks
- up to 100% with combination chemotherapy
- gastrointestinal
- nausea/vomiting
- mild to moderate, but may be severe
- dose & schedule related; more common with higher doses & after boluses
- mild to moderate, but may be severe
- anorexia
- diarrhea
- constipation
- transient increases in liver function tests
- stomatitis
- nausea/vomiting
- genitourinary
- hemorrhagic cystitis
- NEVER use without uroprotective agent (i.e. MESNA)
- hematuria
- renal tubular damage
- renal insufficiency
- may resemble Fanconi syndrome: glycosuria, amino aciduria, phosphaturia, uricosuria
- metabolic acidosis (up to 30%)
- renal tuberular acidosis type 2
- alopecia
- less common (1-10%)
- myelosuppression
- leukopenia is mild to moderate
- thrombocytopenia (rare)
- anemia (rare)
- onset 7 days
- nadir 10-14 days
- recovery 21 days
- neurologic (due to chloroacetaldehyde metabolite)
- somnolence, confusion, hallucinations (12%)
- coma (generally with higher doses)
- depressive psychoses
- phlebitis, nasal stuffiness, SIADH, immunosuppression, sterility, hyperpigmentation of the skin, pulmonary fibrosis, cardiotoxicity, dermatitis, nail ridging, possible secondary malignancy, impaired wound healing, allergic reactions
- myelosuppression
- uncommon (< 1%)
- cardiotoxicity
- pulmonary toxicity
Drug interactions
- any drug that inhibits cyt P450 3A4 may increase levels of ifosfamide
- any drug that induces cyt P450 3A4 may diminish levels of ifosfamide
- allopurinol, cimetidine, phenobarbital, phenytoin & chloral hydrate may increase ifosfamide toxicity[1]
Test interactions
increase in serum K+
Mechanism of action
- alkylating agent
- interferes with DNA template
More general terms
Additional terms
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
- mesna; 2-mercaptoethane sulfonate; 2-sulfanylethanesulfonic acid (Mesnex, Uromitexan, Mistabronco)
Component of
References
- ↑ 1.0 1.1 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
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 4.0 4.1 4.2 Deprecated Reference
- ↑ 5.0 5.1 Medical Knowledge Self Assessment Program (MKSAP) 19. American College of Physicians, Philadelphia 2021