Chemical: Drug
ifosfamide

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.



PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for ifosfamide

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs13181 NC_000019.10:g.45351661T>G, NC_000019.9:g.45854919T>G, NG_007067.2:g.23927A>C, NM_000400.3:c.2251A>C, NM_177417.2:c.*304T>G, NP_000391.1:p.Lys751Gln, XM_005258536.1:c.*128T>G, XM_005258536.3:c.*128T>G, XM_005258537.1:c.*128T>G, XM_005258538.1:c.*304T>G, XM_005258539.1:c.*304T>G, XM_005258639.1:c.2179A>C, XM_005258640.1:c.2017A>C, XM_005258641.1:c.1513A>C, XM_011526611.1:c.2173A>C, XP_005258696.1:p.Lys727Gln, XP_005258697.1:p.Lys673Gln, XP_005258698.1:p.Lys505Gln, XP_011524913.1:p.Lys725Gln, rs1052559, rs17285142, rs17355147, rs17359310, rs3170171, rs3859422, rs60606175
T > G
SNP
K751Q
No VIP available No Clinical Annotations available VA
rs1799793 NC_000019.10:g.45364001C>T, NC_000019.9:g.45867259C>T, NG_007067.2:g.11587G>A, NM_000400.3:c.934G>A, NM_001130867.1:c.862G>A, NP_000391.1:p.Asp312Asn, NP_001124339.1:p.Asp288Asn, XM_005258639.1:c.862G>A, XM_005258640.1:c.700G>A, XM_005258641.1:c.196G>A, XM_005258642.1:c.934G>A, XM_011526611.1:c.856G>A, XP_005258696.1:p.Asp288Asn, XP_005258697.1:p.Asp234Asn, XP_005258698.1:p.Asp66Asn, XP_005258699.1:p.Asp312Asn, XP_011524913.1:p.Asp286Asn, XR_935763.1:n.981G>A, rs3916814, rs58989209
C > T
SNP
D312N
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • Asta Z 4942
  • I-Phosphamide
  • Ifosfamid
  • Ifosfamide Sterile
  • Ifsofamide
  • Iphosphamid
  • Iphosphamide
  • Isofosfamide
  • Isophosphamide
  • ifosphamide
Trade Names
  • Cyfos
  • Holoxan 1000
  • IFEX
  • Ifex/Mesnex Kit
  • Ifosfamide/Mesna Kit
  • Isoendoxan
  • Mitoxana
  • Naxamide
Brand Mixture Names

PharmGKB Accession Id

PA449964

Type(s):

Drug

Description

Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent.

Source: Drug Bank

Indication

Used as a component of various chemotherapeutic regimens as third-line therapy for recurrent or refractory germ cell testicular cancer. Also used as a component of various chemotherapeutic regimens for the treatment of cervical cancer, as well as in conjunction with surgery and/or radiation therapy in the treatment of various soft tissue sarcomas. Other indications include treatment of osteosarcoma, bladder cancer, ovarian cancer. small cell lung cancer, and non-Hodgkin's lymphoma.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The exact mechanism of ifosfamide has not been determined, but appears to be similar to other alkylating agents. Ifosfamide requires biotransformation in the liver by mixed-function oxidases (cytochrome P450 system) before it becomes active. After metabolic activation, active metabolites of ifosfamide alkylate or bind with many intracellular molecular structures, including nucleic acids. The cytotoxic action is primarily through the alkylation of DNA, done by attaching the N-7 position of guanine to its reactive electrophilic groups. The formation of inter and intra strand cross-links in the DNA results in cell death.

Source: Drug Bank

Pharmacology

Ifosfamide requires activation by microsomal liver enzymes to active metabolites in order to exert its cytotoxic effects. Activation occurs by hydroxylation at the ring carbon atom 4 to form the unstable intermediate 4-hydroxyifosfamide. This metabolite than rapidly degrades to the stable urinary metabolite 4-ketoifosfamide. The stable urinary metabolite, 4-carboxyifosfamide, is formed upon opening of the ring. These urinary metabolites have not been found to be cytotoxic. N, N-bis (2-chloroethyl)-phosphoric acid diamide (ifosphoramide) and acrolein are also found. The major urinary metabolites, dechloroethyl ifosfamide and dechloroethyl cyclophosphamide, are formed upon enzymatic oxidation of the chloroethyl side chains and subsequent dealkylation. It is the alkylated metabolites of ifosfamide that have been shown to interact with DNA. Ifosfamide is cycle-phase nonspecific.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Primarily hepatic

Source: Drug Bank

Protein Binding

Minimal

Source: Drug Bank

Half-Life

7-15 hours

Source: Drug Bank

Toxicity

LD 50 (mouse) = 390-1005 mg/kg, LD 50 (rat) = 150-190 mg/kg. Side effects include nausea, vomiting and myelosuppression. Toxic effects include central nervous system toxicity (confusion, hallucinations) and urotoxic effects (cystitis, blood in urine).

Source: Drug Bank

Route of Elimination

Ifosfamide is extensively metabolized in humans and the metabolic pathways appear to be saturated at high doses. After administration of doses of 5 g/m2 of 14C-labeled ifosfamide, from 70% to 86% of the dosed radioactivity was recovered in the urine, with about 61% of the dose excreted as parent compound. At doses of 1.6-2.4 g/m2 only 12% to 18% of the dose was excreted in the urine as unchanged drug within 72 hours.

Source: Drug Bank

Chemical Properties

Chemical Formula

C7H15Cl2N2O2P

Source: Drug Bank

Isomeric SMILES

C1CN(P(=O)(OC1)NCCCl)CCCl

Source: OpenEye

Canonical SMILES

ClCCNP1(=O)OCCCN1CCCl

Source: Drug Bank

Average Molecular Weight

261.086

Source: Drug Bank

Monoisotopic Molecular Weight

260.02481966

Source: Drug Bank

SMILES

ClCCNP1(=O)OCCCN1CCCl

Source: Drug Bank

InChI String

InChI=1S/C7H15Cl2N2O2P/c8-2-4-10-14(12)11(6-3-9)5-1-7-13-14/h1-7H2,(H,10,12)

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Ifosfamide Pathway, Pharmacokinetics
    Model human liver cell showing genes involved in the metabolism of ifosfamide.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
DNMT1 (source: Drug Bank)

Drug Interactions

Interaction Description
aprepitant - ifosfamide Aprepitant may change levels of the chemotherapy agent, ifosfamide. (source: Drug Bank)
telithromycin - ifosfamide Telithromycin may reduce clearance of Ifosfamide. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Ifosfamide if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
ticlopidine - ifosfamide Ticlopidine may decrease the metabolism and clearance of Ifosfamide. Consider alternate therapy or monitor for adverse/toxic effects of Ifosfamide if Ticlopidine is initiated, discontinued or dose changed. (source: Drug Bank)
tranylcypromine - ifosfamide Tranylcypromine, a strong CYP2A6 inhibitor, may decrease the metabolism and clearance of Ifosmadine. (source: Drug Bank)
trastuzumab - ifosfamide Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)
voriconazole - ifosfamide Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ifosfamide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of ifosfamide if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to ifosfamide: 14

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: ifosfamide pathways, pharmacokinetics and pharmacodynamics. Pharmacogenetics and genomics. 2014. Lowenberg Daniella, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: very important pharmacogene information for GSTT1. Pharmacogenetics and genomics. 2012. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Nucleotide excision repair gene variants and association with survival in osteosarcoma patients treated with neoadjuvant chemotherapy. The pharmacogenomics journal. 2011. Biason P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line. Cancer chemotherapy and pharmacology. 2010. Harmsen Stefan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Glutathione S-transferase polymorphisms in osteosarcoma patients. Pharmacogenetics and genomics. 2010. Salinas-Souza Carolina, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for CYP2B6. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Structure, function, regulation and polymorphism of human cytochrome P450 2A6. Current drug metabolism. 2009. Di Yuan Ming, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Current drug metabolism. 2009. Mo Sui-Lin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme. Current drug metabolism. 2008. Wang Hongbing, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP450 pharmacogenetics for personalizing cancer therapy. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 2008. van Schaik Ron H N. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ribonucleotide reductase messenger RNA expression and survival in gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004. Rosell Rafael, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Human cytochrome P4502B6: interindividual hepatic expression, substrate specificity, and role in procarcinogen activation. Drug metabolism and disposition: the biological fate of chemicals. 1997. Code E L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Glutathione conjugation of the cytostatic drug ifosfamide and the role of human glutathione S-transferases. Chemical research in toxicology. 1995. Dirven H A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer research. 1993. Chang T K, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0703-3427-11
DrugBank:
DB01181
ChEBI:
5864
KEGG Drug:
D00343
PubChem Compound:
3690
PubChem Substance:
162510
46508335
Drugs Product Database (DPD):
2246565
ChemSpider:
3562
Therapeutic Targets Database:
DAP000537
FDA Drug Label at DailyMed:
14f535d7-4593-4cee-94fb-54ee239d95d2

Clinical Trials

These are trials that mention ifosfamide and are related to either pharmacogenetics or pharmacogenomics.

No trials found.

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Sources for PharmGKB drug information: DrugBank, PubChem.