環磷醯胺
抗腫瘤藥 / 免疫抑制劑（烷化劑）
環磷醯胺是一種強效的**抗腫瘤**和**免疫抑制**藥物，廣泛應用於犬貓的獸醫學中。 * **抗腫瘤用途**：用於淋巴瘤、白血病、癌和肉瘤的聯合化療方案。低劑量節拍式（連續）療法也可用於預防肉瘤復發。 * **免疫抑制用途**：用於嚴重的免疫介導疾病，如全身性紅斑狼瘡 (SLE)、免疫介導性血小板減少症 (ITP)、免疫介導性溶血性貧血 (IMHA) 和天皰瘡。
作用機制: Cyclophosphamide is a prodrug that is metabolized in the liver by **cytochrome P450** enzymes into active metabolites, primarily **phosphoramide mustard** and **acrolein**. **Phosphoramide mustard** → acts as an alkylating agent → forms cross-links within and between DNA strands → interferes with DNA replication and RNA transcription → triggers apoptosis and cell death. **Acrolein** is a toxic byproduct that concentrates in the urinary bladder and is responsible for sterile hemorrhagic cystitis. The drug also profoundly suppresses B-cell and T-cell function, leading to its immunosuppressive effects.
各物種劑量
Cats
- Immunosuppressant (ITP or IMHA) · 50 mg/m2 PO every 2nd day · PO · q48h · Ongoing · Author prefers cyclosporine or chlorambucil in cats.
- To slow progression of FIP · 2-4 mg/kg PO four times a week · PO · 4 times/week · Ongoing
Sheep
- Chemical shearing agent · Historical use · PO/IV · Single · Single · Historical use only.
Horses
- Neoplastic diseases · 200 mg/m2 (usually 1 gram per horse per dose) IV every 1-2 weeks · IV · q1-2 weeks · Protocol dependent · Consult veterinary oncologist.
SmallMammals
- Antineoplastic (lymphoma) in rabbits · 50 mg/m2 PO daily for 3 days each week OR 100-200 mg/m2 IV every 7 days · PO/IV · Varies · Protocol dependent · Consider fully implantable vascular access device for IV.
Dogs
- To inhibit local recurrence in dogs with incompletely resected soft tissue sarcomas · 10 mg/m2 PO once daily with piroxicam at 0.3 mg/kg PO once daily · PO · q24h · Continuous (metronomic) · If unacceptable adverse effects develop, increase interval to every other day.
- Antineoplastic · 50 mg/m2 PO 4 days/week OR 250 mg/m2 PO once every 3 weeks OR 100-300 mg/m2 IV weekly · PO/IV · Varies · Protocol dependent · Consult veterinary oncologist.
- Immunosuppressant (IMHA/ITP) · 50 mg/m2 PO every 2nd day · PO · q48h · Adjust to manage side effects · Used with glucocorticoids.
- Immunosuppressant (IMHA pulse therapy) · 50 mg/m2 PO daily for 4 days on, 3 days off · PO · Pulse · Ongoing · Alternatively 50 mg/m2 PO every other day.
- Polyarthritis · 1.5 mg/kg (>30 kg), 2 mg/kg (15-30 kg), 2.5 mg/kg (<15 kg) PO daily on 4 consecutive days each week · PO · 4 days/week · 2-4 months (max 4 months) · Given with prednisolone.
- Glomerulonephritis · 2.2 mg/kg PO q24h for 4 days, discontinue for 3 days and then repeat · PO · Pulse · Ongoing
- Lymphoma (COP low dose protocol - Induction) · 50 mg/m2 · PO · alternate days OR first 4 days of each week · First 2 months · Co-administer with 1 mg/kg furosemide q12h on treatment days to reduce cystitis risk.
- Lymphoma (COP low dose protocol - Maintenance after 2 months) · 50 mg/m2 · PO · alternate days OR first 4 days of each second week · Months 2 to 6 · Alternate-week therapy.
- Lymphoma (COP low dose protocol - Maintenance after 6 months) · 50 mg/m2 · PO · q48h (one week in three) OR first 4 days of each third week · Months 6 to 12 · Stop and monitor for relapse after 12 months.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
POIV
禁忌症
- Prior anaphylactic reactions to the drug
- Severe pre-existing myelosuppression (leukopenia, thrombocytopenia)
- Active infections where immunosuppression may be dangerous
- No specific contraindications available in the monograph, but clinically contraindicated in patients with severe pre-existing myelosuppression or active haemorrhagic cystitis.
- Pre-existing severe myelosuppression
- Active haemorrhagic cystitis
不良反應
- Myelosuppression (leukopenia, thrombocytopenia, anemia)
- Gastroenterocolitis (anorexia, nausea, vomiting, diarrhea)
- Sterile hemorrhagic cystitis (induced by acrolein metabolite)
- Alopecia (especially in continuously growing coats like Poodles and Old English Sheepdogs)
- Pulmonary infiltrates and fibrosis
- Hyponatremia
- Secondary leukemia
- Myelosuppression (nadir usually 5-14 days post-therapy)
- Sterile haemorrhagic cystitis (caused by acrolein metabolite)
- Bladder fibrosis
- Transitional cell carcinoma (secondary to chronic cystitis)
- Vomiting
- Diarrhoea
- Hepatotoxicity
- Nephrotoxicity
藥物相互作用
- Allopurinol · May increase the myelosuppression caused by cyclophosphamide
- Doxorubicin · Potentiation of cardiotoxicity may occur · major
- Chloramphenicol · May inhibit cyclophosphamide metabolism · moderate
- Phenobarbital · May increase the rate of metabolism to active metabolites, increasing toxicity risk
- Thiazide Diuretics · May increase the myelosuppression caused by cyclophosphamide · major
- Succinylcholine · Metabolism may be slowed, prolonging effects due to decreased pseudocholinesterases
- Digoxin · Absorption of orally administered digoxin may be decreased (may occur several days after dosing) · moderate
- Barbiturates · Increase cyclophosphamide toxicity due to increased rate of conversion to metabolites · major
- Phenothiazines · Reduce cyclophosphamide efficacy · moderate
- Ondansetron · Reduce cyclophosphamide efficacy · moderate
- Insulin · Insulin requirements are altered by concurrent cyclophosphamide · moderate
- cimetidine · Inhibits hepatic cytochrome P450 enzyme pathway, potentially altering the metabolism and increasing toxicity of chemotherapeutics. · major
監測
- Efficacy (tumor response or remission of immune-mediated disease)
- Complete Blood Count (CBC) regularly for myelosuppression (nadir typically 7-14 days)
- Urinalysis regularly for signs of sterile hemorrhagic cystitis (hematuria)
- Uric acid levels (blood and urine)
- White Blood Cell (WBC) count (regular monitoring recommended due to myelosuppression)
- Urinalysis (monitor for haematuria indicating sterile haemorrhagic cystitis)
- Renal and hepatic function panels
- Free-catch urine by dipstick prior to and each week of treatment
- Haematology
- Biochemistry (prior to first treatment and minimum every 6 months)
過量
Limited information on acute overdoses. The lethal dose in dogs is reported as **40 mg/kg IV**. If an oral overdose occurs, perform gut emptying (emesis/lavage) if indicated and hospitalize the animal for aggressive supportive care, including IV fluids to flush the bladder and prevent hemorrhagic cystitis.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。