Adult Dose 1-2 mg/kg/d PO or monthly pulse IV; dosing based on body size used; usually a 6-mo treatment period used; dose adjusted to reduce WBC count to 2000-3000/mL; reports describe high-dose ablative therapy (which reduces WBC counts to 0) having efficacy in patients with otherwise severe and refractory disease
 

Pediatric Dose Not established

Contraindications Absolute: Breastfeeding; dehydration; infection

Relative: Documented hypersensitivity; bone marrow suppression; dental work; gout; hyperuricemia; hemorrhagic cystitis; pregnancy; radiation treatment; vaccinations
Interactions Other immunosuppressive agents can worsen marrow suppression; thrombolytic agent or anticoagulant can increase risk of bleeding; has additive GI effect with salicylates and NSAIDs; enzyme inducers such as phenytoin and barbiturates can increase toxic effects; multiple medications, including prednisone, can alter efficacy; can alter efficacy of vaccines

Pregnancy D - Unsafe in pregnancy
Precautions Hemorrhagic cystitis is serious complication, and vigorous hydration has to be instituted in all patients; can lead to various GI symptoms and ulcer formation with delayed healing (use with prophylactic agent); can lead to leukopenia, anemia, and thrombocytopenia (monitor blood counts); as immune suppressant, places patients at risk for infections

Teratogenic—use in pregnancy should be greatly discouraged, particularly in first trimester
Variety of other adverse effects must be monitored, and patients must be aware of them, including alopecia, allergic reactions, infertility, myocarditis and pericarditis, nephrolithiasis, and secondary malignancy