Doses - CYCLOPHOSPHAMIDE
For more information, refer to the protocol references found in the appendix or otherprotocols found in numerous references, including: Handbook of Small Animal Practice (Ogilvie1988), (Cotter 1988), (Stann 1988a); Handbook of Small Animal Therapeutics (Rosenthal 1985);
Current Veterinary Therapy X: Small Animal Practice (Helfand 1989), (Matus 1989); and Textbook of Veterinary Internal Medicine, 3rd Edition (Couto 1989a).Dogs:
For susceptible neoplastic diseases:
a) 50 mg/m2 PO or IV 4 days/week. (MacEwen and Rosenthal 1989)
b) 50 mg/m2 PO or IV 4 days/week or 200 mg/m2 IV weekly. (Rosenthal 1985)
c) For multiple myeloma in patients refractory to melphalan: 1 mg/kg PO once daily.
For macroglobulinemia in patients refractory to chlorambucil: 1 mg/kg PO once daily.(Hurvitz and Johnessee 1985)
As an immunosuppressant:
a) For adjunctive therapy for immune-mediated hemolytic anemia (probably should bereserved for dogs w/fulminant intravascular hemolysis, autoagglutination or those thatrequire repeated transfusion or have persistant reticulocytopenia): Initially at 2mg/kg/day IV or PO for 4 days; no treatment for 3 days and then repeat cycle.(Bucheler and Cotter 1995)
b) For immune-mediated hemolytic anemia: 50 mg/m2 for 4 consecutive days per week.
May be overtreatment; efficacy not proven. (Weiser 1989a)
c) For immune-mediated hemolytic anemia if glucocorticoids unsuccessful: Add cyclophosphamide at 2.2 mg/kg (50 mg/m2 ) PO or IV once daily for 4 consecutive daysof each week. Discontinue CTX when PCV increases significantly and attempt to slowlyreduce steroids dose and D/C eventually, if possible. (Thompson 1989b)
c) For immune-mediated hemolytic anemia: Usually steroids used initially, but cyclophosphamide (&/or azathioprine) may be indicated early in therapy for cases withsevere hemolysis and agglutination. Cyclophosphamide 2 mg/kg PO once daily for 4days, stop for 3 days, then repeat. Animals should receive steroids, CTX, and azathioprine if they exhibit massive agglutination and intravascular hemolysis (poorprognosis). (Maggio-Price 1988)
d) For immune-mediated thrombocytopenia: If corticosteroids ineffective, may use eithervincristine, azathioprine or cyclophosphamide. CTX dose: 50 mg/m2 PO once daily for3-4 days/week. May give initial doses IV. Decrease dose if renal or hepatic impairmentexists. After 1-4 weeks, taper dose and discontinue after platelet count is >100, 000/µl.
Serious bleeding secondary to thrombocytopenia and hemorrhagic cystitis can occur;use cautiously. (Young 1988)
e) For rheumatoid arthritis: In conjunction with a glucocorticoid (predniso(lo)ne); give
CTX PO once daily in the AM for 4 consecutive days each week at 2.5 mg/kg if weighs<10 kg, 2 mg/kg if 10-35 kg, and 1.5 mg/kg if >35 kg. Discontinue: 1 month afterremission of synovial inflammation (determined from joint tap), after 4 months oftreatment, or if hemorrhagic cystitis develops. If cystitis develops, switch to azathioprine.(Tangner and Hulse 1988)
f) For polymyositis: In conjunction with steroids, if steroids alone are ineffective: 1 mg/kg
PO once daily for 4 days, then off 3 days. Decrease concurrent prednisone dose to 1mg/kg/day. (Knaack 1988)Cats:
For susceptible neoplastic diseases:
a) For advanced mammary carcinoma: Doxorubicin: 30 mg/m2 IV every 3 weeks up to 4-8treatments. Cyclophosphamide: 100 mg/m2 PO once daily on days 3, 4, 5, and 6 afterdoxorubicin. (Loar 1988)
As an immunosuppressant:
a) Give 2.5 mg/kg once daily PO for 4 consecutive days out of 7 for up to 3 weeks.
Alternatively, 7 mg/kg IV may be given once a week. (Hurvitz and Johnessee 1985)
b) For immune-mediated hemolytic anemia: 50 mg/m2 for 4 consecutive days per week.
May be overtreatment; efficacy not proven. (Weiser 1989a)
c) For rheumatoid arthritis: In conjunction with a glucocorticoid (predniso(lo)ne); give
CTX PO once daily in the AM for 4 consecutive days each week at 2.5 mg/kg.
Discontinue 1 month after remission of synovial inflammation (determined from jointtap), after 4 months of treatment, or if hemorrhagic cystitis develops. If cystitis develops, switch to azathioprine. (Tangner and Hulse 1988)Sheep:
As a chemical defleecing agent:
a) 25 mg/kg PO once (McConnell and Hughey 1989)
Monitoring Parameters -1) Efficacy. See the Protocol section or refer to the references from the Dosage section above for more information. 2) Toxicity, see Adverse Effects above. Regular hemograms and urinalyses are mandatory.
Client Information - Clients must be briefed on the possibilities of severe toxicity developingfrom this drug, including drug-related mortality. Clients should contact veterinarian should theanimal exhibit any symptoms of abnormal bleeding and/or bruising.
Although no special precautions are necessary with handling intact tablets, direct exposure shouldbe avoided to split or crushed tablets, oral elixir, or the animal's urine or feces. Should exposureoccur, wash the area thoroughly with soap and water.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - Veterinary-Approved Products: None
Current Veterinary Therapy X: Small Animal Practice (Helfand 1989), (Matus 1989); and Textbook of Veterinary Internal Medicine, 3rd Edition (Couto 1989a).
Dogs: 
For susceptible neoplastic diseases: a) 50 mg/m2 PO or IV 4 days/week. (MacEwen and Rosenthal 1989)
b) 50 mg/m2 PO or IV 4 days/week or 200 mg/m2 IV weekly. (Rosenthal 1985)
c) For multiple myeloma in patients refractory to melphalan: 1 mg/kg PO once daily.
For macroglobulinemia in patients refractory to chlorambucil: 1 mg/kg PO once daily.(Hurvitz and Johnessee 1985)
As an immunosuppressant:
a) For adjunctive therapy for immune-mediated hemolytic anemia (probably should bereserved for dogs w/fulminant intravascular hemolysis, autoagglutination or those thatrequire repeated transfusion or have persistant reticulocytopenia): Initially at 2mg/kg/day IV or PO for 4 days; no treatment for 3 days and then repeat cycle.(Bucheler and Cotter 1995)
b) For immune-mediated hemolytic anemia: 50 mg/m2 for 4 consecutive days per week.
May be overtreatment; efficacy not proven. (Weiser 1989a)
c) For immune-mediated hemolytic anemia if glucocorticoids unsuccessful: Add cyclophosphamide at 2.2 mg/kg (50 mg/m2 ) PO or IV once daily for 4 consecutive daysof each week. Discontinue CTX when PCV increases significantly and attempt to slowlyreduce steroids dose and D/C eventually, if possible. (Thompson 1989b)
c) For immune-mediated hemolytic anemia: Usually steroids used initially, but cyclophosphamide (&/or azathioprine) may be indicated early in therapy for cases withsevere hemolysis and agglutination. Cyclophosphamide 2 mg/kg PO once daily for 4days, stop for 3 days, then repeat. Animals should receive steroids, CTX, and azathioprine if they exhibit massive agglutination and intravascular hemolysis (poorprognosis). (Maggio-Price 1988)
d) For immune-mediated thrombocytopenia: If corticosteroids ineffective, may use eithervincristine, azathioprine or cyclophosphamide. CTX dose: 50 mg/m2 PO once daily for3-4 days/week. May give initial doses IV. Decrease dose if renal or hepatic impairmentexists. After 1-4 weeks, taper dose and discontinue after platelet count is >100, 000/µl.
Serious bleeding secondary to thrombocytopenia and hemorrhagic cystitis can occur;use cautiously. (Young 1988)
e) For rheumatoid arthritis: In conjunction with a glucocorticoid (predniso(lo)ne); give
CTX PO once daily in the AM for 4 consecutive days each week at 2.5 mg/kg if weighs<10 kg, 2 mg/kg if 10-35 kg, and 1.5 mg/kg if >35 kg. Discontinue: 1 month afterremission of synovial inflammation (determined from joint tap), after 4 months oftreatment, or if hemorrhagic cystitis develops. If cystitis develops, switch to azathioprine.(Tangner and Hulse 1988)
f) For polymyositis: In conjunction with steroids, if steroids alone are ineffective: 1 mg/kg
PO once daily for 4 days, then off 3 days. Decrease concurrent prednisone dose to 1mg/kg/day. (Knaack 1988)
Cats: 
For susceptible neoplastic diseases: a) For advanced mammary carcinoma: Doxorubicin: 30 mg/m2 IV every 3 weeks up to 4-8treatments. Cyclophosphamide: 100 mg/m2 PO once daily on days 3, 4, 5, and 6 afterdoxorubicin. (Loar 1988)
As an immunosuppressant:
a) Give 2.5 mg/kg once daily PO for 4 consecutive days out of 7 for up to 3 weeks.
Alternatively, 7 mg/kg IV may be given once a week. (Hurvitz and Johnessee 1985)
b) For immune-mediated hemolytic anemia: 50 mg/m2 for 4 consecutive days per week.
May be overtreatment; efficacy not proven. (Weiser 1989a)
c) For rheumatoid arthritis: In conjunction with a glucocorticoid (predniso(lo)ne); give
CTX PO once daily in the AM for 4 consecutive days each week at 2.5 mg/kg.
Discontinue 1 month after remission of synovial inflammation (determined from jointtap), after 4 months of treatment, or if hemorrhagic cystitis develops. If cystitis develops, switch to azathioprine. (Tangner and Hulse 1988)
Sheep: 
As a chemical defleecing agent: a) 25 mg/kg PO once (McConnell and Hughey 1989)
Monitoring Parameters -
Client Information - Clients must be briefed on the possibilities of severe toxicity developingfrom this drug, including drug-related mortality. Clients should contact veterinarian should theanimal exhibit any symptoms of abnormal bleeding and/or bruising.
Although no special precautions are necessary with handling intact tablets, direct exposure shouldbe avoided to split or crushed tablets, oral elixir, or the animal's urine or feces. Should exposureoccur, wash the area thoroughly with soap and water.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - Veterinary-Approved Products: None