Generic Name

Cyclophosphamide

Precaution

Blood disorders. Elderly or debilitated patients. Diabetic patients. Renal or hepatic impairment or who have gone adrenaloctomy. Previous treatment with x-ray or cytotoxic agents. Monitor haematological profile and presence of RBCs in urine regularly. Maintain adequate hydration and frequent micturition to reduce the risk of cystitis. Lactation: Drug excreted in breast milk; do not nurse

Indication

Bone marrow transplantation, malignancies, lymphomas, brain cancer, leukemia, systemic lupus erythematosus, minimal change disease, severe rheumatoid arthritis, wegener's granulomatosis, multiple sclerosis, multiple myeloma, carcinoma of the breast, ovarian carcinoma, neuroblastoma, retinoblastoma.

Contra Indication

Bladder haemorrhage. Patients with bone-marrow aplasia, acute infection, drug- or radiation-induced urothelial toxicity. Porphyria. Pregnancy and lactation.

Dose

N/A

Side Effect

Alopecia, skin and nails hyperpigmentation, nausea and vomiting, mucositis, inappropriate antidiuretic hormone secretion, carbohydrate metabolism disturbances, gonadal suppression, interstitial pulmonary fibrosis. Potentially Fatal: Anaphylactic reactions, bone marrow failure, severe immunosuppression, urotoxicity, cardiotoxicity, hyponatraemia, haemorrhagic cystitis.

Pregnancy Category

Mode of Action

Cyclophosphamide is a prodrug which is converted in the body to the active metabolites. It acts at any stage of the cell cycle but its main action is blockage at the G2 stage. It arrests cell division by alkylating the DNA in a dose-dependent manner. It also exerts immunosuppressive effects possibly due to a cytotoxic effect on lymphocytes.

Interaction

Increased risk of cardiotoxicity w/ doxorubicin or other cardiotoxic drugs. May increase incidence of mucositis w/ protease inhibitors. May increase haematotoxicity and/or immunosuppression w/ ACE inhibitors, natalizumab, paclitaxel, thiazide diuretics, zidovudine. May increase pulmonary toxicity w/ amiodarone. May increase nephrotoxicity w/ amphotericin B. May result to acute water intoxication w/ indometacin. May increase risk of hepatotoxicity w/ azathioprine. May increase incidence of hepatic veno-occlusive disease and mucositis w/ busulfan. May increase risk of haemorrhagic cystitis w/ previous or concomitant radiotherapy. May result to acute encephalopathy w/ metronidazole. May increase risk of thromboembolic complications. May alter the effect of warfarin. May increase immunosuppressive effect of ciclosporin. May result to prolonged apnoea w/ depolarising muscle relaxants (e.g. suxamethonium).

Pregnancy Category Note

Pregnancy Based on mechanism of action and published reports of effects in pregnant patients or animals, drug can cause fetal harm when administered to pregnant woman; exposure to cyclophosphamide during pregnancy may cause fetal malformations, miscarriage, fetal growth retardation, and toxic effects in the newborn; drug is teratogenic and embryo-fetal toxic in mice, rats, rabbits and monkeys; advise pregnant women and females of reproductive potential of the potential risk to the fetus Verify the pregnancy status of females of reproductive potential prior to the initiation of therapy Contraception Therapy can cause fetal harm; advise females of reproductive potential to use effective contraception during treatment for up to 1 year after completion of therapy Based on findings in genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 4 months after completion of therapy Infertility Amenorrhea, transient or permanent, associated with decreased estrogen and increased gonadotropin secretion develops in a proportion of women treated with cyclophosphamide Affected patients generally resume regular menses within a few months after cessation of therapy; risk of premature menopause with cyclophosphamide increases with age Oligomenorrhea has also been reported in association with cyclophosphamide treatment Men treated with cyclophosphamide may develop oligospermia or azoospermia, which are normally associated with increased gonadotropin but normal testosterone Lactation Drug is present in breast milk; neutropenia, thrombocytopenia, low hemoglobin, and diarrhea have been reported in infants breast fed by women treated with cyclophosphamide; because of potential for serious adverse reactions in a breastfed child from therapy, advise lactating women not to breastfeed during treatment and for 1 week after last dose

Adult Dose

Malignant Diseases IV (intermittent therapy): 40-50 mg/kg (400-1800 mg/m²) divided over 2-5 days; may be repeated at intervals of 2-4 weeks IV (continuous daily therapy): 60-120 mg/m²/day (1-2.5 mg/kg/day) PO (intermittent therapy): 400-1000 mg/m² divided over 4-5 days PO (continuous daily therapy): 50-100 mg/m²/day or 1-5 mg/kg/day Nephrotic Syndrome 2-3 mg/kg/day for up to 12 weeks when corticosteroids unsuccessful Non-Hodgkin Lymphoma 600-1500 mg/m² IV with other antineoplastics (part of CHOP regimen); dose intensification possible Breast Cancer 600 mg/m² IV with other antineoplastics; dose intensification possible

Child Dose

Malignant Diseases IV (intermittent therapy): 40-50 mg/kg (400-1800 mg/m²) divided over 2-5 days; may be repeated at intervals of 2-4 weeks IV (continuous daily therapy): 60-120 mg/m²/day (1-2.5 mg/kg/day) PO (intermittent therapy): 400-1000 mg/m² divided over 4-5 days PO (continuous daily therapy): 50-100 mg/m²/day uvenile Idiopathic Arthritis/Vasculitis 10 mg/kg IV every 2 weeks Nephrotic Syndrome 2-3 mg/kg/day for up to 12 weeks when corticosteroids unsuccessful Systemic Lupus Erythematosus 500-750 mg/m² IV monthly; not to exceed 1 g/m²

Renal Dose

N/A

Administration

Should be taken on an empty stomach. Preferably taken on an empty stomach, but may be taken w/ meals to minimise GI irritation. Ensure adequate fluid intake. Swallow whole. IV Preparation Maximum concentration of cyclophosphamide is limited to 20 mg/mL because of solubility IV push: Reconstitute with NS (do not use SWI, because it is hypotonic) Infusion: Reconstitute with SWI to concentration of 20 mg/mL May dilute further with D5W, NS, lactated Ringer solution, or other compatible fluids IV Administration Infusions may be administered over 1-2 hours Doses >500 mg up to ~1 g may be administered over 20-30 minutes To minimize bladder toxicity, increase normal fluid intake during and for 1-2 days after cyclophosphamide therapy; most adult patients will require fluid intake of at least 2 L/day; high-dose regimens should be accompanied by vigorous hydration with or without mesna therapy