CYCRAM

Indications

• Hodgkin's lymphoma
• Non-Hodgkin's lymphoma
• Acute lymphoblastic leukemia
• Multiple myeloma
• Breast cancer
• Ovarian cancer
• Neuroblastoma
• Autoimmune diseases (e.g., systemic lupus erythematosus, vasculitis)
• Organ transplantation (to prevent rejection)

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations, as

Adults: Refer to the BNF for specific dosing information based on the condition being treated, as doses vary widely depending on the cancer type and treatment regimen.

Mechanism of action

Cyclophosphamide is a prodrug that is metabolized in the liver to its active form, phosphoramide mustard. The active metabolite forms covalent bonds with DNA, leading to cross-linking of DNA strands. This cross-linking inhibits DNA replication and transcription, ultimately resulting in cell cycle arrest and apoptosis of malignant and rapidly dividing normal cells.

Pharmacodynamics

As an alkylating agent, cyclophosphamide primarily affects rapidly dividing cells, such as cancer cells and bone marrow cells. Its cytotoxic effects are dose-dependent, with higher doses leading to more significant toxicity, including myelosuppression and gastrointestinal disturbances. The immunosuppressive effects make it useful in treating autoimmune disorders, as it reduces the proliferation of immune cells.

Pharmacokinetics

Cyclophosphamide is administered orally or intravenously. It is rapidly absorbed and extensively metabolized in the liver, primarily by cytochrome P450 enzymes. The half-life of cyclophosphamide varies based on the route of administration and patient factors but generally ranges from 3 to 12 hours. The drug and its metabolites are excreted mainly in the urine. Dosing adjustments may be necessary in patients with impaired liver or kidney function.

Contra-indications

• Hypersensitivity to cyclophosphamide or any of its components
• Severe bone marrow suppression
• Active infections
• Pregnancy (except in life-threatening situations)

Adverse effects

• Nausea and vomiting
• Bone marrow suppression leading to neutropenia, anemia, or thrombocytopenia
• Hemorrhagic cystitis
• Alopecia
• Secondary malignancies
• Cardiotoxicity
• Pulmonary toxicity

Interactions

• Allopurinol may increase the toxicity of cyclophosphamide
• Barbiturates may decrease the effectiveness of cyclophosphamide
• Live vaccines may pose a risk in patients on cyclophosphamide due to immunosuppression

Precautions

• Monitor blood counts regularly due to the risk of bone marrow suppression
• Use with caution in patients with a history of bladder problems
• Hydration is important to prevent hemorrhagic cystitis
• Consider potential for long-term carcinogenic effects

Pregnancy

Cyclophosphamide is contraindicated during pregnancy due to potential teratogenic effects and risk of fetal harm.

Breast-feeding

Cyclophosphamide is excreted in breast milk; breastfeeding is not recommended during treatment.

Storage

Store at room temperature, away from moisture and light. Keep out of reach of children.

Formulations

• Oral tablets
• Intravenous injection
• Intramuscular injection