URACIL MUSTARD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for URACIL MUSTARD (URACIL MUSTARD).
Uracil mustard is a nitrogen mustard alkylating agent that crosslinks DNA, inhibiting DNA replication and transcription, leading to cell death.
| Metabolism | Hepatic; primarily metabolized by cytochrome P450 enzymes |
| Excretion | Primarily renal (56-80% as unchanged drug and metabolites); minor fecal (10%) |
| Half-life | Terminal half-life approximately 6–8 hours in patients with normal renal function; may be prolonged with renal impairment |
| Protein binding | 30-40% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.5–0.6 L/kg, indicating distribution into total body water |
| Bioavailability | Oral: 30-50% (variable due to first-pass metabolism and hepatic degradation) |
| Onset of Action | Oral: 1–3 weeks for clinical response; IV: 2–4 weeks |
| Duration of Action | 3–6 weeks after oral dose; may persist longer with cumulative doses due to bone marrow effects |
| Molecular Weight | 253.64 |
1 mg orally daily for 3 weeks, then 1 mg daily every 4 weeks, or 0.15 mg/kg orally once weekly.
| Dosage form | CAPSULE |
| Renal impairment | Contraindicated in patients with GFR <30 mL/min; for GFR 30-50 mL/min, reduce dose by 50%; for GFR >50 mL/min, use with caution and monitor. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Safety and efficacy not established; use not recommended. |
| Geriatric use | Start at lower end of dosing range (0.5 mg daily) due to increased risk of myelosuppression and renal impairment; monitor blood counts and renal function frequently. |
| 1st trimester | Contraindicated; embryotoxic and teratogenic based on animal data. |
| 2nd trimester | Contraindicated; risk of fetal harm outweighs potential benefit. |
| 3rd trimester | Contraindicated; may cause neonatal toxicity and bone marrow suppression. |
Clinical note
Comprehensive clinical and safety monograph for URACIL MUSTARD (URACIL MUSTARD).
| Placental transfer | Crosses placenta; detected in fetal tissues in animal studies. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants, including immunosuppression, bone marrow suppression, and carcinogenesis. |
| Lactation Rating |
■ FDA Black Box Warning
Uracil mustard can cause severe myelosuppression, increased risk of secondary malignancies (e.g., acute leukemia), and is teratogenic.
| Serious Effects |
Hypersensitivity to uracil mustardSevere bone marrow suppressionActive infectionPregnancy
| Precautions | Monitor bone marrow function closely; increased risk of infection, bleeding, and secondary malignancies; avoid use in pregnancy; caution in patients with renal impairment |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase drug levels. No other significant food interactions known. Maintain adequate hydration. |
| Clinical Pearls |
Loading safety data…
| L5 (Contraindicated) |
| Teratogenic Risk | Uracil mustard is an alkylating agent with high teratogenic potential. First trimester exposure is associated with a significant risk of major congenital malformations, including central nervous system, skeletal, and cardiac defects. Second and third trimester exposure risks include intrauterine growth restriction, fetal myelosuppression, and teratogenic effects may still occur. The drug should be avoided during all trimesters unless maternal benefit clearly outweighs fetal risk. |
| Fetal Monitoring | Monitor complete blood counts (CBC) with differential in both mother and expectant mother throughout therapy. Assess for signs of infection, bleeding, or anemia. Perform serial ultrasounds to monitor fetal growth and anatomy. Consider amniocentesis for chromosome analysis if first trimester exposure occurred. Monitor liver and renal function tests due to maternal toxicity potential. |
| Fertility Effects | Uracil mustard can cause irreversible gonadal dysfunction. In prepubertal and adult males, it may lead to oligospermia or azoospermia. In females, it may cause ovarian suppression, amenorrhea, and premature ovarian failure. Reproductive counseling and fertility preservation options (e.g., sperm or oocyte cryopreservation) should be considered prior to therapy. |
| Uracil mustard is an alkylating agent used primarily for chronic lymphocytic leukemia and malignant lymphomas. Monitor for myelosuppression, especially leukopenia and thrombocytopenia. Cumulative dose-related pulmonary fibrosis may occur. Consider dose reduction in renal impairment. Drug interactions: may potentiate effects of other immunosuppressants. |
| Patient Advice | Take exactly as prescribed; do not adjust dose without consulting your doctor. · Avoid prolonged sun exposure and use sunscreen; this drug may cause photosensitivity. · Report any unusual bleeding, bruising, fever, or signs of infection immediately. · Do not receive live vaccines while on this medication. · Use effective contraception during treatment and for a period after discontinuation. · Swallow capsules whole; do not crush or chew. |