Alkylating cytotoxic agent (antineoplastic/immunosuppressant)
Cyclophosphamide is a cytotoxic drug used to treat several cancers (lymphomas, leukaemias, solid tumours) and as an immunosuppressant in autoimmune diseases. It is a prodrug: it must be activated in the liver. Because it affects dividing cells, it has important adverse effects — mainly on the bone marrow, the bladder (haemorrhagic cystitis) and fertility — so it is always used under specialist supervision.
Also known as: Ciclofosfamida, Endoxan
Cyclophosphamide + ritonavir: protease inhibitors may increase the concentration of cytotoxic metabolites and enhance cyclophosphamide toxicity.
Ritonavir, a potent CYP450 inhibitor, may interfere with cyclophosphamide metabolism, which is activated by hepatic hydroxylation (CYP2A6, 2B6, 3A, 2C9, 2C19) — the FDA label documents that protease inhibitors "may increase the concentration of cytotoxic metabolites and may enhance the toxicities of cyclophosphamide, including higher incidence of infections, neutropenia, and mucositis". The practical consequence is an increased risk of haematological and infectious toxicity in the oncology patient. In patients with HIV or receiving ritonavir as a pharmacokinetic booster, monitor the blood count and signs of infection, and consider cyclophosphamide dose adjustment. This is not a clinically trivial interaction — it requires active vigilance throughout the cycle.
Cyclophosphamide + ritonavir: monitor for enhanced toxicity (myelosuppression, infections, mucositis) — protease inhibitors may raise cytotoxic metabolites.
Ritonavir (potent CYP450 inhibitor) may reduce conversion of cyclophosphamide to inactive metabolites and increase exposure to active cytotoxic metabolites — the FDA label documents: "Concomitant use of protease inhibitors may increase the concentration of cytotoxic metabolites and may enhance the toxicities of cyclophosphamide".
Regular blood count (neutrophils, platelets), monitoring for infections and mucositis during the combination.
Fever, neutropenia, signs of infection or severe mucositis during combined therapy.
Monitor for signs of enhanced toxicity (myelosuppression, neutropenia, mucositis, infections) in patients receiving cyclophosphamide with protease inhibitors; consider cyclophosphamide dose adjustment.
DailyMed/FDA (NIH/NLM) — approved Cyclophosphamide label (EVER Pharma): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=571a5a63-fb66-0617-e063-6394a90a2d04 ; approved Ritonavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=38d0cf24-e81e-4fe6-a6e5-e7d61193f8d6
Alcohol increases the risk of hepatotoxicity and may worsen gastrointestinal effects (nausea, vomiting) during cyclophosphamide treatment.
Avoid or strongly limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Cyclophosphamide label (EVER Pharma): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=571a5a63-fb66-0617-e063-6394a90a2d04
Teratogenic and fetotoxic — "may cause birth defects, miscarriage, fetal growth retardation, and fetotoxic effects in the newborn" (label); gametogenesis may be severely affected.
Contraindicated in pregnancy; require a pregnancy test and effective contraception in women of childbearing potential before, during and after treatment.
DailyMed/FDA (NIH/NLM) — approved Cyclophosphamide label (EVER Pharma): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=571a5a63-fb66-0617-e063-6394a90a2d04
Renal elimination of cyclophosphamide and its metabolites is important — in renal impairment there is a risk of accumulation and increased toxicity.
Reduce the dose in renal impairment and monitor renal function and blood count.
DailyMed/FDA (NIH/NLM) — approved Cyclophosphamide label (EVER Pharma): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=571a5a63-fb66-0617-e063-6394a90a2d04
The Prontuário indicates avoiding cyclophosphamide in porphyria (porphyrinogenic drug).
Avoid in porphyria; use a therapeutic alternative.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Cyclophosphamide, 16.1.1
Teratogenic and fetotoxic — "may cause birth defects, miscarriage, fetal growth retardation, and fetotoxic effects in the newborn" (label).
Contraindicated in any trimester; never use during pregnancy.
Excreted in breast milk — do not breastfeed during treatment.
Effective contraception mandatory in women of childbearing potential before, during and after treatment (prior pregnancy test).
DailyMed/FDA (NIH/NLM) — approved Cyclophosphamide label (EVER Pharma): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=571a5a63-fb66-0617-e063-6394a90a2d04
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Alkylating cytotoxic agent that interferes with DNA replication in dividing cells; also used as an immunosuppressant (lympholytic) in autoimmune diseases and transplant rejection prevention.
Prodrug activated in the liver by hydroxylation (CYP2A6, 2B6, 3A, 2C9, 2C19) to active metabolites (phosphoramide mustard) that alkylate DNA, forming cross-links and preventing cell replication. The acrolein metabolite causes haemorrhagic cystitis.
Administration by oral or IV route; hepatic activation is required for activity, so oral bioavailability depends on liver function.
Activated in the liver by CYP450 isoenzymes (CYP2A6, 2B6, 3A, 2C9, 2C19); metabolites and unchanged drug are eliminated in urine — renal clearance is an important route.
Half-life of 3 to 12 hours ("half-life (t½) of cyclophosphamide ranges from 3 to 12 hours"); clearance of 4–5 L/h. Excretion is renal (unchanged drug and metabolites).
