Ifosfamide

Mechanism :

Ifosfamide is an oxazaphosphorine alkylating agent linked to nitrogen mustards. It is a prodrug that requires activation through the cytochrome P450 3A4 group of enzymes. The mechanism of ifosfamide’s cytotoxicity has not been established, but its cytotoxic action is thought to occur through DNA crosslinking at the guanine N-7 position. These crosslinks facilitate cellular damage and death. The activation occurs by hydroxylation at the ring carbon atom forming the unstable intermediate 4-hydroxyifosfamide Ifosfamide which later decomposes to form the cytotoxic and urotoxic compound acrolein which is an alkylating isophosphoramide mustard with multiple nontoxic products.

Indication :

For the treatment of testicular cancer.
For the treatment of Nonhodgkins lymphoma.
For the treatment of soft tissue sarcoma.
For the treatment of osteogenic sarcoma.
For the treatment of Ewings sarcoma.
For the treatment of Rhabdomyosarcoma.
For the treatment of Desmoid tumour.
For the treatment of bladder cancer.
For the treatment of Thymoma.
For the treatment of Wilms tumour.
For the treatment of relapsed Acute Lymphocytic leukemia.

Contraindications :

Anemia, bone marrow suppression, herpes simplex virus, immunosuppression, infection, leukopenia, thrombocytopenia, Hematuria, hemorrhagic cystitis, urinary tract infection (UTI), Bladder obstruction, nephrotoxicity, renal failure, renal impairment, Encephalopathy, Pregnancy, neurotoxicity, cardic diseases, chronic lung diseases, cardiotoixity

Dosing :

For the treatment of soft tissue sarcoma:

2.5 grams/m2 per day continuous IV infusion over 24 hours on the first 5 days of therapy (along with hydration and mesna 1.5 grams/m2 per day continuous IV infusion).

For the treatment of Ewings sarcoma:

ifosfamide 3000 mg/m2/day IV was given on days 1 to 3 plus mesna 3000 mg/m2/day continuous IV infusion on days 1 to 3

For the treatment of Rhabdomyosarcoma:

Ifosfamide 6000 mg/m2 continuous IV infusion over 48 hours on days 1, 29 and 50 in combination with mesna 6000 mg/m2/day continuous IV infusionover 48 hours.

For the treatment of wilms tumour:

Ifosfamide 1800 mg/m2/day IV for the first 5 days.

For the treatment of ALL:

ifosfamide 3,000 mg/m2/day IV on days 3, 4, and 5 (mesna is given with every dose 600 mg/m2 IV, followed by mesna 600 mg/m2 IV over 15 minutes at 3, 6, 9, and 12 hours after the start of ifosfamide).

Adverse Effect :

Hemorrhagic cystitis ,hepatotoxicity ,cardiotoxicity ,toxic epidermal necrolysis ,Stevens-Johnson syndrome ,skin necrosis ,ileus ,enterocolitis ,pancreatitis ,GI bleeding ,renal tubular acidosis (RTA) ,renal failure ,azotemia ,diabetes insipidus ,oliguria ,nephrotoxicity

anuria ,interstitial nephritis ,Fanconi syndrome ,renal tubular necrosis ,visual impairment acute cerebellar syndrome ,seizures ,coma ,leukoencephalopathy ,pulmonary edema atrial flutter ,bradycardia ,heart failure ,pericardial effusion ,atrial fibrillation ,atrial tachycardia ,myocardial infarction ,ventricular tachycardia ,cardiac arrest ,pericarditis ,cardiomyopathy ,ventricular fibrillation ,new primary malignancy rhabdomyolysis veno-occlusive disease , sinusoidal obstruction syndrome , hepatic failure anaphylactoid reactions ,angioedema , SIADH , tumor lysis syndrome hearing loss

pulmonary embolism thrombosis vasculitis acute respiratory distress syndrome (ARDS)

pulmonary toxicity ,pulmonary fibrosis , bronchospasm ,pulmonary hypertension, pleural effusion disseminated intravascular coagulation, agranulocytosis , hemolytic-uremic syndrome ,methemoglobinemia

hemolytic anemia

Interaction :

Major drug interactions with Anti-viral medicstions, Anti-TB medications, Aminoglycoside class of antibiotics, Anti-fungal group of medications, Non nucleoside reverse transcriptase inhibitors, Penicillamine, Olanzapine, St. Johns Wort etc

Hepatic Dose :

No dose adjustment required