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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for URACIL MUSTARD (URACIL MUSTARD).
| Breastfeeding | Uracil mustard is excreted into breast milk; the M/P ratio is unknown but likely high due to its lipophilic nature. Breastfeeding is contraindicated during therapy and for at least 3 days after the last dose due to potential severe adverse effects in the infant including myelosuppression and carcinogenesis. |
| 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. |
■ FDA Black Box Warning
Uracil mustard can cause severe myelosuppression, increased risk of secondary malignancies (e.g., acute leukemia), and is teratogenic.
| Serious Effects |
History of severe hypersensitivity reaction to uracil mustard; pre-existing severe myelosuppression; pregnancy; concurrent chemotherapy or radiation therapy that depresses bone marrow
| Precautions | Monitor bone marrow function closely; increased risk of infection, bleeding, and secondary malignancies; avoid use in pregnancy; caution in patients with renal impairment |
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| 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. |