Cyclophosphamide

Cyclophosphamide is an anti-cancer medication. It is an alkylating agent which works by damaging the genetic material (DNA and RNA) of the cancer cells, thereby stopping their growth and multiplication. It is also used to treat kidney disease known as nephrotic syndrome in children after other treatments have not worked. Cyclophosphamide is a prodrug which is converted in the body to 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.

• Malignant lymphomas (Hodgkin's disease, lymphocytic lymphoma, mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's lymphoma)
• Multiple myeloma
• Leukemias (chronic lymphocytic leukemia, chronic granulocytic leukemia, acute myelogenous and monocytic leukemia, acute lymphoblastic leukemia in children)
• Mycosis fungoides
• Neuroblastoma
• Adenocarcinoma of the ovary
• Retinoblastoma
• Carcinoma of the breast
• Minimal Change Nephrotic Syndrome in children

Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites by a mixed function 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. Cyclophosphamide is well absorbed after oral administration with a bioavailability greater than 75%. The unchanged drug has an elimination half-life of 3 to 12 hours. It is eliminated primarily in the form of metabolites, but from 5 to 25% of the dose is excreted in urine as unchanged drug.

Cyclophosphamide is a prodrug which is converted in the body to 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.

Adult - Malignant Diseases (IV intermittent): 40-50 mg/kg (400-1800 mg/m²) divided over 2-5 days; may be repeated at intervals of 2-4 weeks.

Adult - Malignant Diseases (IV continuous): 60-120 mg/m²/day (1-2.5 mg/kg/day)

Adult - Malignant Diseases (PO intermittent): 400-1000 mg/m² divided over 4-5 days

Adult - Malignant Diseases (PO continuous): 50-100 mg/m²/day or 1-5 mg/kg/day

Nephrotic Syndrome (children): 2.5-3 mg/kg/day for 60-90 days

Non-Hodgkin Lymphoma: 600-1500 mg/m² IV (part of CHOP regimen)

Breast Cancer: 600 mg/m² IV

Take with food, preferably in the morning at the same time every day. Swallow it as a whole. Do not chew, crush or break it. Take in the dose and duration as advised by your doctor.

If you miss a dose of Cyclophosphamide, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Common Side Effects:

• Nausea and vomiting
• Anorexia
• Abdominal discomfort or pain
• Diarrhea
• Alopecia
• Skin rash
• Leukopenia
• Thrombocytopenia
• Anemia
• Fever
• Blood in urine

Serious Side Effects:

• Hemorrhagic cystitis
• Interstitial pneumonitis
• Pulmonary fibrosis
• Anaphylactic reactions
• SIADH
• Hepatotoxicity
• Hemorrhagic colitis

• May affect your ability to drive (dizziness, blurred vision).
• Drink plenty of fluids and urinate frequently to prevent bladder problems.
• Regular blood tests are required to monitor blood counts.
• Consult your doctor before getting any vaccines.
• Contact your doctor immediately if you experience difficulty in urinating or blood in urine.
• Use with caution in patients with liver or kidney disease.

• Severely depressed bone marrow function
• Bladder hemorrhage
• Bone-marrow aplasia
• Acute infection
• Drug- or radiation-induced urothelial toxicity
• Porphyria
• Pregnancy and lactation
• Hypersensitivity

Doxorubicin/cardiotoxic drugs: Increased risk of cardiotoxicity.

Protease inhibitors: May increase incidence of mucositis.

ACE inhibitors, natalizumab, paclitaxel, thiazide diuretics, zidovudine: May increase hematotoxicity and/or immunosuppression.

Amiodarone: May increase pulmonary toxicity.

Amphotericin B: May increase nephrotoxicity.

Indomethacin: May result in acute water intoxication.

Azathioprine: May increase risk of hepatotoxicity.

Busulfan: May increase incidence of hepatic veno-occlusive disease and mucositis.

Metronidazole: May result in acute encephalopathy.

Warfarin: May alter the effect.

Ciclosporin: May increase immunosuppressive effect.

Suxamethonium: May result in prolonged apnoea.

Phenobarbital: May increase metabolism and leukopenic activity.

It is unsafe to consume alcohol with Cyclophosphamide. Can be taken with food.

Pregnancy Category D. Cyclophosphamide is unsafe during pregnancy as there is definite evidence of risk to the developing baby. May be prescribed in life-threatening situations if benefits outweigh risks. Please consult your doctor.

Cyclophosphamide is unsafe during breastfeeding. The drug may cause toxicity to the baby.

The safety profile in pediatric patients is similar to that of the adult population. For nephrotic syndrome: 2.5-3 mg/kg/day for 60-90 days.

Elderly patients may be more susceptible to cyclophosphamide toxicities. Dose selection should be cautious, usually starting at the low end of the dosing range.

Renal impairment: Use with caution. Dose adjustment may be needed. Please consult your doctor.

Hepatic impairment: Use with caution. Dose adjustment may be needed. Please consult your doctor.

No specific antidote is known. Overdosage should be managed with supportive measures, including appropriate treatment for concurrent infection, myelosuppression, or cardiac toxicity.

Store at a temperature not exceeding 25°C in a dry place. Protect from light and moisture. Do not freeze.

Cyclophosphamide