Makindo Medical Notes.com

Potentially highly toxic - Must be experienced and specialist use and supervision only. Famously causes Haemorrhagic cystitis

About: Always check the BNF link here

• Akylating agent with significant marrow depression
• At the risk of infections and bleeding and a teratogen

Mode of action

• Prodrug activated by cytochrome p450 to 4 hydroxy-cyclophosphamide
• Effects are often delayed (up to 6 weeks in Rheumatological causes)
• Metabolites bind to DNA, thereby inhibiting DNA replication

Malignant Indications

• Malignant lymphomas (Stages III and IV of the Ann Arbor staging system), Hodgkin's disease, lymphocytic lymphoma (nodular or diffuse), mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's lymphoma.
• Leukaemias: Chronic lymphocytic leukaemia, chronic granulocytic leukaemia (it is usually ineffective in acute blastic crisis), acute myelogenous and monocytic leukaemia, acute lymphoblastic (stem-cell) leukaemia in children (CYTOXAN given during remission is effective in prolonging its duration).
• Multiple myeloma, Mycosis fungoides (advanced disease), Neuroblastoma (disseminated disease).
• Adenocarcinoma of the ovary, Retinoblastoma, Carcinoma of the breast

Other Indications

• Severe, refractory rheumatoid arthritis
• Severe complications of lupus, myositis, scleroderma, or vasculitis.
• Severe Autoimmune diseases
• Vasculitis, SLE, steroid-resistant nephrotic syndrome, progressive IgA-nephropathy

Dose - Check specialist literature: needs expert assessment

• Cyclophosphamide is often used for 3-6 months to treat a condition and put it into remission
• RA with severe systemic manifestations: Cyclophosphamide 1-1.5 mg/kg/day PO for specific duration depending on indication
• RA with severe systemic manifestations: Cyclophosphamide 0.5-1 g every 2 weeks then 0.5-1 g monthly
• Leukaemia, lymphomas, and solid tumour s: see local protocols

Interactions

• Avoid live vaccines such as yellow fever

Contraindications

• Possible or Proven Pregnancy, Breastfeeding

Side effects

• Nausea, Vomiting, Myelosuppression and later produces AML
• Lung fibrosis and Cardiac toxicity in high doses
• Haemorrhagic cystitis: prevent by good hydration and drinking 2-3 L /day and treatment with MESNA
• Long term risk of bladder carcinoma, lymphomas and tumour of the skin, for the myelodysplastic syndrome and permanent infertility.
• Advise seeking help if any sore throat, fever, symptoms of infection unexplained bruising or bleeding
• Reduced fertility, hair loss, mouth ulcers and irregular menstrual periods.
• Seek medical support if you haven't had chickenpox and you come into contact with someone who has chickenpox or shingles or you develop chickenpox or shingles.

References

• Package Insert