Cyclophosphamide, Fluorouracil, Methotrexate (Adverse effects)

The combination of cyclophosphamide, fluorouracil and methotrexate is a therapy used in cancer treatment. The presence of certain polymorphisms in the MTHFR gene has been associated with an increased risk of toxicity.

Cyclophosphamide is an alkylating cytostatic agent with a broad antineoplastic spectrum (immunosuppressant). It is an electrophilic agent, which acts specifically during the S phase of the cell cycle (phase in which the DNA is duplicated). Reacts with nucleophilic atoms of the nucleic bases, forming inter and intra-chain bridges in the double hélix DNA, causing important interferences in the processes of transcription and DNA replication.

Cyclophosphamide is contraindicated in patients who have hypersensitivity to the drug. Likewise, it should not be administered during the first three months of pregnancy or in patients with anemia, leukopenia or thrombocytopenia. Prolonged use of cyclophosphamide can lead to severe marrow depression, porphyria and hemorrhagic cystitis.

During the supply of cyclophosphamide one of the precautions that must be taken is to avoid extravasation.

Side effects of cyclophosphamide include nausea, vomiting, bladder irritation, and alopecia. Other more severe side effects are leukopenia, gastrointestinal toxicity, hepatotoxicity, myelodysplasia and acute myeloid leukemia.


The toxicity of cyclophosphamide is increased by the intake of barbiturates.

The efficacy of cyclophosphamide is diminished by the intake of phenothiazines.

Cyclophosphamide increases the risk of spinal depression with concomitant intake with allopurinol.


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