CYCLOPHOSPHAMIDE PROTOCOL FOR RPGN

Cyclophosphamide for RPGN

  1. ONE HOUR PRIOR THE INFUSION HYDRATES WITH 500CC NORMAL SALINE FOR ONE HOUR.
  2. HALF AN HOUR PRIOR THE INFUSION GIVE :-
    • ONDANSETRON¬†8MG TAB (ONE TAB.) STAT
    • MESNA(UROMETEXAN) 200MG IN 100CC NORMAL SALINE IV OVER 30 MIN.
  3. CYCLOPHOSPHAMIDE(ENDOXAN) INFUSION AS FOLLOW:
    1000MG + MESNA 400 MG IN 500CC NORMAL SALINE TO BE INFUSED OVER ONE HOUR.

(DOSE OF CYCLOPHOSPHAMIDE IS 0.75GM/M2  BSA ).

  • FOLLOWING CYCLOPHOSPHAMIDE INFUSION, HYDRATE WITH 500CC NORMAL SALINE FOR ONE HOUR.

Cyclophosphamide

Mechanism of Action

Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent. Cyclophosphamide also possesses potent immunosuppressive activity. Cyclophosphamide is a prodrug that must be metabolized to active metabolites in the liver.

Pharmacodynamics/Kinetics

Absorption: Oral: Well absorbed

Distribution: Vd: 30 to 50 L (approximates total body water); crosses into CSF (not in high enough concentrations to treat meningeal leukemia)

Protein binding: ~20%; some metabolites are bound at >60%

Metabolism: Hepatic to active metabolites acrolein, 4-aldophosphamide, 4-hydroperoxycyclophosphamide, and nor-nitrogen mustard

Bioavailability: >75%

Half-life elimination: IV: 3 to 12 hours; Children: 4 hours; Adults: 6 to 8 hours

Time to peak: Oral: ~1 hour; IV: Metabolites: 2 to 3 hours

Excretion: Urine (10 to 20% as unchanged drug); feces (4%)

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