Ifosfamide

Ifosfamide Brand Name– Ifex

What is Ifosfamide

Ifosfamide is an intravenous alkylating agent related to the nitrogen mustards; it is a prodrug requiring activation by CYP3A4 for its cytotoxic activity.

It is a synthetic analog of cyclophosphamide, although it has a different spectrum of activity. Ifosfamide carries a black box warning for myelosuppression, neurotoxicity, nephrotoxicity, and hemorrhagic cystitis; it should be administered with mesna and high volume IV fluids.

Ifosfamide is FDA approved for the treatment of advanced testicular cancer; however, it also has several off-label uses including sarcoma, non-Hodgkin lymphoma, and other cancers

Indications

  1. acute lymphocytic leukemia (ALL)
  2. bladder cancer
  3. desmoid tumor
  4. Ewing’s sarcoma
  5. non-Hodgkin’s lymphoma (NHL)
  6. osteogenic sarcoma
  7. penile cancer
  8. rhabdomyosarcoma
  9. soft-tissue sarcoma
  10. stem cell transplant preparation
  11. testicular cancer
  12. thymic carcinoma
  13. thymoma
  14. Wilms’ tumor

For use as a third line chemotherapeutic agent in the treatment of germ cell testicular cancer

NOTE: Ifosfamide has been designated an orphan drug by the FDA for the treatment of testicular cancer.

Side Effects

  1. abdominal pain
  2. acute cerebellar syndrome
  3. acute respiratory distress syndrome (ARDS)
  4. agitation
  5. agranulocytosis
  6. alopecia
  7. amenorrhea
  8. amnesia
  9. anaphylactoid reactions
  10. anemia
  11. angina
  12. angioedema
  13. anorexia
  14. anovulation
  15. anuria
  16. anxiety
  17. aphasia
  18. arthralgia
  19. asterixis
  20. asthenia
  21. ataxia
  22. atrial fibrillation
  23. atrial flutter
  24. atrial tachycardia
  25. azoospermia
  26. azotemia
  27. bleeding
  28. blurred vision
  29. bone marrow suppression
  30. bradycardia
  31. bronchospasm
  32. bundle-branch block
  33. capillary leak syndrome
  34. cardiac arrest
  35. cardiomyopathy
  36. cardiotoxicity
  37. chest pain (unspecified)
  38. chills
  39. cholestasis
  40. colitis
  41. coma
  42. confusion
  43. conjunctivitis
  44. constipation
  45. cough
  46. cylindruria
  47. delirium
  48. depression
  49. diabetes insipidus
  50. diarrhea
  51. disseminated intravascular coagulation (DIC)
  52. dizziness
  53. drowsiness
  54. dysarthria
  55. dysesthesia
  56. dyspnea
  57. dysuria
  58. edema
  59. elevated hepatic enzymes
  60. encephalopathy
  61. enterocolitis
  62. erythema
  63. Fanconi syndrome
  64. fatigue
  65. fecal incontinence
  66. fever
  67. flushing
  68. GI bleeding
  69. glycosuria
  70. growth inhibition
  71. hallucinations
  72. headache
  73. hearing loss
  74. heart failure
  75. hematuria
  76. hemolytic anemia
  77. hemolytic-uremic syndrome
  78. hemorrhagic cystitis
  79. hepatic failure
  80. hepatotoxicity
  81. hyperbilirubinemia
  82. hyperglycemia
  83. hyperhidrosis
  84. hypersalivation
  85. hypertension
  86. hypocalcemia
  87. hypoesthesia
  88. hypokalemia
  89. hyponatremia
  90. hypophosphatemia
  91. hypotension
  92. hypoxia
  93. ileus
  94. immunosuppression
  95. impaired cognition
  96. impaired wound healing
  97. infection
  98. infertility
  99. injection site reaction
  100. interstitial nephritis
  101. jaundice
  102. lethargy
  103. leukoencephalopathy
  104. leukopenia
  105. maculopapular rash
  106. malaise
  107. mania
  108. memory impairment
  109. metabolic acidosis
  110. methemoglobinemia
  111. myalgia
  112. myocardial infarction
  113. myocarditis
  114. myoclonia
  115. nausea
  116. nephrotoxicity
  117. neurotoxicity
  118. new primary malignancy
  119. ocular irritation
  120. oligospermia
  121. oliguria
  122. oral ulceration
  123. osteomalacia
  124. palmar-plantar erythrodysesthesia (hand and foot syndrome)
  125. palpitations
  126. pancreatitis
  127. paranoia
  128. paresthesias
  129. pericardial effusion
  130. pericarditis
  131. peripheral neuropathy
  132. petechiae
  133. phlebitis
  134. phosphaturia
  135. pleural effusion
  136. pneumonitis
  137. polydipsia
  138. polyuria
  139. premature atrial contractions (PACs)
  140. proteinuria
  141. pruritus
  142. psychosis
  143. pulmonary edema
  144. pulmonary embolism
  145. pulmonary fibrosis
  146. pulmonary hypertension
  147. pulmonary toxicity
  148. radiation recall reaction
  149. rash
  150. renal failure (unspecified)
  151. renal tubular acidosis (RTA)
  152. renal tubular necrosis
  153. restlessness
  154. rhabdomyolysis
  155. seizures
  156. SIADH
  157. sinusoidal obstruction syndrome (SOS)
  158. skin hyperpigmentation
  159. skin necrosis
  160. spermatogenesis inhibition
  161. ST-T wave changes
  162. Stevens-Johnson syndrome
  163. stomatitis
  164. supraventricular tachycardia (SVT)
  165. testicular atrophy
  166. thrombocytopenia
  167. thrombosis
  168. tinnitus
  169. toxic epidermal necrolysis
  170. tremor
  171. tumor lysis syndrome (TLS)
  172. urinary incontinence
  173. urticaria
  174. vasculitis
  175. veno-occlusive disease (VOD)
  176. ventricular fibrillation
  177. ventricular tachycardia
  178. vertigo
  179. visual impairment
  180. vomiting

Monitoring Parameters

  • CBC
  • serum creatinine/BUN
  • serum phosphate
  • serum potassium
  • urinalysis

Contraindications

  • anemia
  • bladder obstruction
  • bone marrow suppression
  • breast-feeding
  • cardiac disease
  • cardiotoxicity
  • children
  • chronic lung disease (CLD)
  • contraception requirements
  • encephalopathy
  • females
  • geriatric
  • hematuria
  • hemorrhagic cystitis
  • herpes infection
  • hypoalbuminemia
  • immunosuppression
  • infection
  • infertility
  • leukopenia
  • nephrotoxicity
  • neurotoxicity
  • pregnancy
  • pulmonary disease
  • pulmonary toxicity
  • radiation therapy
  • renal failure
  • renal impairment
  • reproductive risk
  • thrombocytopenia
  • urinary tract infection (UTI)
  • urinary tract obstruction
  • vaccination
  • varicella

Interactions

  • Acetaminophen; Butalbital
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Amiodarone
  • Amobarbital
  • Amoxicillin; Clarithromycin; Lansoprazole
  • Amoxicillin; Clarithromycin; Omeprazole
  • Apalutamide
  • Aprepitant, Fosaprepitant
  • Articaine; Epinephrine
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Atazanavir
  • Atazanavir; Cobicistat
  • Atropine; Hyoscyamine; Phenobarbital; Scopolamine
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Bexarotene
  • Bosentan
  • Bupivacaine
  • Bupivacaine Liposomal
  • Bupivacaine; Lidocaine
  • Butabarbital
  • Carbamazepine
  • Cenobamate
  • Ceritinib
  • Chloramphenicol
  • Chloroprocaine
  • Ciprofloxacin
  • Cisplatin
  • Clarithromycin
  • Cobicistat
  • Conivaptan
  • Crizotinib
  • Dabrafenib
  • Danazol
  • Darunavir
  • Darunavir; Cobicistat
  • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
  • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
  • Delavirdine
  • Dexamethasone
  • Diltiazem
  • Docetaxel
  • Dronedarone
  • Duvelisib
  • Efavirenz
  • Efavirenz; Emtricitabine; Tenofovir
  • Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
  • Enzalutamide
  • Erythromycin
  • Erythromycin; Sulfisoxazole
  • Eslicarbazepine
  • Etravirine
  • Fedratinib
  • Fluconazole
  • Fluoxetine
  • Fluoxetine; Olanzapine
  • Fluvoxamine
  • Fosamprenavir
  • Fosphenytoin
  • grapefruit juice
  • Idelalisib
  • Imatinib
  • Indinavir
  • Isavuconazonium
  • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
  • Isoniazid, INH; Rifampin
  • Itraconazole
  • Ketoconazole
  • Lefamulin
  • Letermovir
  • Lidocaine
  • Lidocaine; Prilocaine
  • Live Vaccines
  • Lopinavir; Ritonavir
  • Lorlatinib
  • Lumacaftor; Ivacaftor
  • Mephobarbital
  • Mepivacaine
  • Mepivacaine; Levonordefrin
  • Mitotane
  • Modafinil
  • Nafcillin
  • Nefazodone
  • Nelfinavir
  • Netupitant, Fosnetupitant; Palonosetron
  • Nevirapine
  • Nilotinib
  • Ombitasvir; Paritaprevir; Ritonavir
  • Omeprazole; Amoxicillin; Rifabutin
  • Palifermin
  • Penicillamine
  • Penicillin G Benzathine; Penicillin G Procaine
  • Penicillin G Procaine
  • Phenobarbital
  • Phenytoin
  • Posaconazole
  • Prilocaine
  • Prilocaine; Epinephrine
  • Primidone
  • Quinine
  • Ribociclib
  • Ribociclib; Letrozole
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Ritonavir
  • Ropivacaine
  • Saquinavir
  • St. John’s Wort, Hypericum perforatum
  • Telithromycin
  • Tetracaine
  • Tipranavir
  • Trandolapril; Verapamil
  • Tuberculin Purified Protein Derivative, PPD
  • Tucatinib
  • Vasopressin, ADH
  • Verapamil
  • Voriconazole
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