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Cyclophosphamide: Indications, Dosing, Side Effects and Interactions
Cyclophosphamide clinical drug profile including indications, dosing, side effects, cautions and interactions.
MedNext Academy | 4 min read
Cyclophosphamide: Indications, Dosing, Side Effects and Interactions
Cyclophosphamide clinical drug profile including indications, dosing, side effects, cautions and interactions.
Indications and dose
**Rheumatoid arthritis with severe systemic manifestations (under expert supervision)**
- **Adult** (By Mouth): 1-1.5 mg/kg daily.
**Severe systemic rheumatoid arthritis (under expert supervision),Other connective tissue diseases (especially with active vasculitis) (under expert supervision)**
- **Adult** (By Intravenous Injection): 0.5-1 g every 2 weeks, then reduced to 0.5-1 g every month, frequency adjusted according to clinical response and haematological monitoring. To be given with prophylactic mesna.
**Malignant disease (specialist use only)**
- **Adult** (By Mouth, Or By Intravenous Infusion): Specialist indication - access specialist resources for dosing information.
**Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, retinoblastoma, neuroblastoma, rhabdomyosarcoma, soft-tissue sarcomas, Ewing tumour, neuroectodermal tumours (including medulloblastoma), infant brain tumours, ependymona, high-dose conditioning for bone marrow transplantation, lupus nephritis (specialist use only) for cyclophosphamide**
- **Child** (By mouth, or by intravenous infusion): Specialist indication - access specialist resources for dosing information.
**Steroid-sensitive nephrotic syndrome (under expert supervision) for cyclophosphamide**
- **Child 3 months-17 years** (By mouth): 2-3 mg/kg daily for 8 weeks.
- **Child 3 months-17 years** (By intravenous infusion): 500 mg/m2 once a month for 6 months.
Cautions
Avoid in Acute porphyrias ; diabetes mellitus; haemorrhagic cystitis; previous or concurrent mediastinal irradiation-risk of cardiotoxicity
Side effects
General side-effects: Common or very common Agranulocytosis; alopecia; anaemia; asthenia; bone marrow disorders; cystitis; decreased leucocytes; fever; haemolytic uraemic syndrome; haemorrhage; hepatic disorders; immunosuppression; increased risk of infection; mucosal abnormalities; neutropenia; progressive multifocal leukoencephalopathy (PML); reactivation of infections; sperm abnormalities; thrombocytopenia Uncommon Appetite decreased; flushing; hypersensitivity; ovarian and fallopian tube disorders; sepsis Rare or very rare Bladder disorders; chest pain; confusion; constipation; diarrhoea; disseminated intravascular coagulation; dizziness; eye inflammation; fluid imbalance; headache; hyponatraemia; menstrual cycle irregularities; myocardial infarction; nail discolouration; nausea; neoplasms; oral disorders; pancreatitis acute; renal failure; rhabdomyolysis; secondary neoplasm; seizure; severe cutaneous adverse reactions (SCARs); SIADH; skin reactions; visual impairment; vomiting Frequency not known Abdominal pain; altered smell sensation; arrhythmias; arthralgia; ascites; cardiac inflammation; cardiogenic shock; cardiomyopathy; cough; deafness; dyspnoea; embolism and thrombosis; encephalopathy; excessive tearing; facial swelling; gastrointestinal disorders; heart failure; hyperhidrosis; hypoxia; infertility; influenza like illness; interstitial lung disease; multi organ failure; muscle complaints; myelopathy; nasal complaints; nephrogenic diabetes insipidus; nephrotoxicity; nerve disorders; neuralgia; neurotoxicity; oedema; oropharyngeal pain; palpitations; pericardial effusion; peripheral ischaemia; pulmonary fibrosis; pulmonary hypertension; pulmonary oedema; QT interval prolongation; radiation injuries; renal tubular disorder; renal tubular necrosis; respiratory disorders; scleroderma; sensation abnormal; sinusoidal obstruction syndrome; taste altered; testicular atrophy; tinnitus; tremor; tumour lysis syndrome; vasculitis Specific side-effects: Frequency not known With intravenous use Infusion site necrosis; injection site necrosis Side-effects, further information Haemorrhagic cystitis A urinary metabolite of cyclophosphamide, acrolein, can cause haemorrhagic cystitis; this is a rare but serious complication that may be prevented by increasing fluid intake for 24-48 hours after intravenous injection. Mesna can also help prevent cystitis when high-dose therapy (e.g. more than 2 g intravenously) is used or when the patient is considered to be at high risk of cystitis (e.g. because of pelvic irradiation). Secondary malignancy As with all cytotoxic therapy, treatment with cyclophosphamide is associated with an increased incidence of secondary malignancies.
Interactions
**Other interactions (18):**
- Cyclophosphamide is inactive, but is metabolised in the liver, mainly by CYP2A6, 2B6, 2C9, 2C19 and 3A4, into two active metabolites.
- Planned co-administration or sequential administration of other substances or treatments with cyclophosphamide that could increase the likelihood or severity of toxic effects (by means of...
- Patients being treated with cyclophosphamide and agents that reduce its activation should be monitored for a potential reduction of therapeutic effectiveness and the need for dose adjustment.
- Interactions negatively affecting the pharmacokinetics of cyclophosphamide and its metabolites Reduced activation of cyclophosphamide may alter the effectiveness of cyclophosphamide treatment.
- Substances that delay activation of cyclophosphamide include: - Aprepitant - Bupropion - Busulfan: decreased elimination of cyclophosphamide and prolonged half-life has been reported in patients who...
- Increased incidence of hepatic veno-occlusive disease and mucositis has been reported with concomitant administration (see section 4.2 and 4.4).
Pregnancy
Avoid. See also Pregnancy and reproductive function in Cytotoxic drugs .
Breast feeding
Discontinue breast-feeding during and for 36 hours after stopping treatment.
Hepatic impairment
Manufacturer advises caution (risk of decreased cyclophosphamide activation and increased risk of veno-occlusive liver disease). Dose adjustments Manufacturer advises consider dose adjustment in severe impairment-consult product literature.
Renal impairment
Dose adjustments Consider dose reduction (consult product literature). M
Medicinal forms
Tablet,Tablet,Solution
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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