NEOSAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEOSAR (NEOSAR).
Alkylating agent that inhibits DNA replication and transcription by cross-linking DNA strands, leading to cell cycle arrest and apoptosis.
| Metabolism | Primarily metabolized by hepatic CYP2B6, CYP2C9, CYP2C19, and CYP3A4 to active alkylating metabolites (4-hydroxycyclophosphamide and phosphoramide mustard). Also undergoes spontaneous degradation to acrolein. |
| Excretion | Renal: 30-60% unchanged; biliary/fecal: 10-20% as metabolites. |
| Half-life | Terminal elimination half-life: 3-5 hours; prolonged in hepatic impairment (up to 12 hours). |
| Protein binding | 98% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.5-0.8 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 70-90% due to extensive first-pass metabolism. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 2-5 minutes. |
| Duration of Action | Oral: 4-6 hours; Intravenous: 2-4 hours; clinical effect may persist longer in overdose. |
Cyclophosphamide 500-1500 mg/m² IV every 2-4 weeks; oral 50-200 mg daily.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 10-50 mL/min: reduce dose by 25%; GFR <10 mL/min: reduce dose by 50%. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25%; Child-Pugh C: contraindicated. |
| Pediatric use | 60-75 mg/kg IV every 2-4 weeks; or 20-40 mg/m² orally daily. |
| Geriatric use | Monitor renal function; initiate at lower end of dosing range (e.g., 50-75% of standard dose). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEOSAR (NEOSAR).
| Breastfeeding | Cyclophosphamide is excreted into breast milk with a milk-to-plasma (M/P) ratio of approximately 0.8. Breastfeeding during therapy is contraindicated due to potential neonatal immunosuppression, neutropenia, and carcinogenicity. An alternative feeding method should be used during treatment and for at least 36 hours after the last dose. |
| Teratogenic Risk | NEOSAR (cyclophosphamide) is a pregnancy category D drug. First trimester exposure is associated with a 20-30% risk of major congenital malformations, including craniofacial defects, cleft palate, limb anomalies, and growth restriction. Second and third trimester exposure may cause intrauterine growth restriction (IUGR), premature birth, and fetal bone marrow suppression. Neonatal complications including pancytopenia and increased infection risk have been reported. |
■ FDA Black Box Warning
Cyclophosphamide may cause hemorrhagic cystitis, cardiac toxicity (especially with high doses), secondary malignancies (e.g., bladder cancer, myelodysplasia), and severe myelosuppression.
| Common Effects | Application site reactions burning irritation itching and redness |
| Serious Effects |
Hypersensitivity to cyclophosphamide or any component, severely depressed bone marrow function, active infection (especially with varicella-zoster), urinary outflow obstruction, pregnancy (teratogenic).
| Precautions | Hemorrhagic cystitis (requires adequate hydration and mesna in high doses), cardiac toxicity (especially with prior anthracycline or high-dose regimens), myelosuppression, pneumonitis, secondary malignancies, SIADH, hepatic veno-occlusive disease, impaired fertility. |
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| Fetal Monitoring | Maternal monitoring includes complete blood counts with differential (especially absolute neutrophil count), liver and renal function tests, urinalysis for hematuria, and fluid intake/output monitoring to prevent hemorrhagic cystitis. Fetal monitoring should include serial ultrasound for growth, anatomy, and amniotic fluid volume; nonstress tests or biophysical profiles in the third trimester. Genetic counseling is recommended before therapy. |
| Fertility Effects | Cyclophosphamide is highly gonadotoxic. In females, it causes progressive ovarian failure, premature menopause, and infertility with cumulative dose-dependent risk. In males, it leads to oligospermia, azoospermia, and testicular atrophy, which may be reversible in some cases after cessation of therapy. Pre-treatment fertility preservation options (e.g., oocyte or sperm cryopreservation) should be discussed. |