Re-MATC H Protocol Page 68 of 106 Version: 20180628 18. DESCRIPTION OF PROTOCOL DRUGS OR DEVICES 18.1 Preparation and Administration of Standard of Care Therapeutic Agents 18.2 Cyclophosphamide Source and Pharmacology Cyclophosphamide ((Cytoxan) NSC #26271) is an alkylating agent related to nitrogen mustard. Cyclophosphamide is inactive until it is metabolized by P -450 isoenzymes (CYP2B6, CYP2C9 and CYP3A4) in the liver to active compounds. The initial product is 4- hydroxycyclophosphamide (4- HC) which is in equilibrium with aldophosphamide which spontaneously releases acrolein to produce phosphoramide mustard. Phosphoramide mustard, which is an active bifunctional alkylating species, is 10 times more potent in vitro than is 4-HC and has been shown to produce interstrand DNA cross -link analogous to those produced by mechlorethamine. Approximately 70% of a dose of cyclophosphamide is excreted in the urine as the inactive carboxyphosphamide and 5- 25% as unchanged drug. Cyclophosphamide is well absorbed orally with a bioavailability greater than 75%. The plasma half -life ranges from 4.1 to 16 hours after IV administration and 1.3 to 6.8 hours after oral administration. Formulation and Stability Cyclophosphamide for Injection is available as powder for injection or lyophilized powder for injection in 500 mg, 1 gm and 2 gm vials. The powder for injection contains 82 mg sodium bicarbonate/100 mg cyclophosphamide and the lyophilized powder for injection contains 75 mg mannitol/100 mg cyclophosphamide. Storage at or below 25ºC (77ºF) is recommended.