Cyclophosphamide
Mechanism :
Cyclophosphamide is bio transformed principally in the liver to active alkylating metabolites by microsomal oxidase system. These metabolites interfere with the growth of susceptible rapidly proliferating malignant cells. The mechanism of action is thought to involve cross-linking of tumor cell DNA.
Indication :
- Rhabdomyosarcoma
- Sarcoma
- Neuroblastoma stage IV
- Ewing tumor
- Non-Hodgkin’s lymphoma
- Bone marrow transplantation
- Medulloblastoma
- Neuroectodermal tumors
- Infant brain tumours
- Vasculitis
- Systemic lupus erythematosus
- Nephrotic syndrome
- Juvenile rheumatoid arthritis
Contraindications :
Continued use of cyclophosphamide is contraindicated in patients with severely depressed bone marrow function. Cyclophosphamide is contraindicated in patients who have demonstrated a previous hypersensitivity to it.
Dosing :
Children cancer chemotherapy:
IV Intermittent therapy:
40-50 mg/kg (400-1800 mg/m²) in divided doses over 2-5 days; at intervals of 2-4 weeks, it may be repeated.
IV Continuous daily therapy:
60-120 mg/m²/day (1-2.5 mg/kg/day).
Oral Intermittent therapy:
400-1000 mg/m² divided doses over four to five days.
Oral continuous daily therapy:
50-100 mg/m²/day.
Juvenile Idiopathic Arthritis/Vasculitis:
10 mg/kg IV every two weeks.
Nephrotic Syndrome:
2-3 mg/kg/day oral up to 12 weeks (if corticosteroids unsuccessful).
SLE:
500-750 mg/m² IV monthly; maximum: 1 g/m².
Adverse Effect :
Nausea and vomiting, alopecia, myelosuppression, mucositis/enteritis, chemical or hemorrhagic cystitis if administered without mesna or with inadequate hydration and micturition. Rarely cardiotoxicity presenting as CCF, pericardial effusion and tamponade.
Interaction :
Phenobarbital: The rate of metabolism and the leukopenic activity of cyclophosphamide reportedly are increased.
Succinylcholine: Marked and persistent inhibition of cholinesterase activity, potentiates the effect of succinylcholine.
Dexamethasone: Concurrent treatment may increase cyclophosphamide metabolism.
Allopurinol: Administration may decrease cyclophosphamide metabolism.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | 75–100% of normal dose depending on clinical indication and local protocol |
| <10 | 50–100% of normal dose depending on clinical indication and local protocol |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Dialysed. Dose as in GFR<10 mL/ min. Following dose, do not perform CAPD exchange for 12 hours |
| HD | Dialysed. Dose as in GFR<10 mL/ min. Dose at minimum of 12 hours before HD session |
| HDF/High flux | Dialysed. Dose as in GFR<10 mL/ min. Dose at minimum of 12 hours before HDF session |
| CAV/VVHD | Dialysed. Dose as in GFR=10– 20 mL/min |
Hepatic Dose :
No dosage adjustment is necessary.