シクロホスファミド
Cyclophosphamide
N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
別名: Cytoxan · Neosar · Procytox · Endoxana · CPM · CTX · B-518 · ciclofosfamida · cyclophosphamidum · cyclophosphanum · NSC-26271 · WR-138719 · Cytophosphane
VetSheet 獣医チームが監修更新日 2026年4月5日エビデンスに基づく獣医学リファレンス
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
動物種別用量
🌎 NA — North America🌍 EU — Europe
犬
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| 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) | 🌎 NA |
| 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 | 🌎 NA |
| Immunosuppressant (IMHA/ITP) | 50 mg/m2 PO every 2nd day | PO | q48h | Adjust to manage side effects | 🌎 NA |
| Immunosuppressant (IMHA pulse therapy) | 50 mg/m2 PO daily for 4 days on, 3 days off | PO | Pulse | Ongoing | 🌎 NA |
| 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) | 🌎 NA |
| Glomerulonephritis | 2.2 mg/kg PO q24h for 4 days, discontinue for 3 days and then repeat | PO | Pulse | Ongoing | 🌎 NA |
| Lymphoma (COP low dose protocol - Induction) | 50 mg/m2 | PO | alternate days OR first 4 days of each week | First 2 months | 🌍 EU |
| 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 | 🌍 EU |
| 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 | 🌍 EU |
- To inhibit local recurrence in dogs with incompletely resected soft tissue sarcomas: If unacceptable adverse effects develop, increase interval to every other day.
- Antineoplastic: Consult veterinary oncologist.
- Immunosuppressant (IMHA/ITP): Used with glucocorticoids.
- Immunosuppressant (IMHA pulse therapy): Alternatively 50 mg/m2 PO every other day.
- Polyarthritis: Given with prednisolone.
- Lymphoma (COP low dose protocol - Induction): Co-administer with 1 mg/kg furosemide q12h on treatment days to reduce cystitis risk.
- Lymphoma (COP low dose protocol - Maintenance after 2 months): Alternate-week therapy.
- Lymphoma (COP low dose protocol - Maintenance after 6 months): Stop and monitor for relapse after 12 months.
猫
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| Immunosuppressant (ITP or IMHA) | 50 mg/m2 PO every 2nd day | PO | q48h | Ongoing | 🌎 NA |
| To slow progression of FIP | 2-4 mg/kg PO four times a week | PO | 4 times/week | Ongoing | 🌎 NA |
- Immunosuppressant (ITP or IMHA): Author prefers cyclosporine or chlorambucil in cats.
小型哺乳類
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| 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 | 🌎 NA |
- Antineoplastic (lymphoma) in rabbits: Consider fully implantable vascular access device for IV.
馬
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| Neoplastic diseases | 200 mg/m2 (usually 1 gram per horse per dose) IV every 1-2 weeks | IV | q1-2 weeks | Protocol dependent | 🌎 NA |
- Neoplastic diseases: Consult veterinary oncologist.
羊
| 適応 | 用量 | 経路 | 頻度 | 期間 | 地域 |
|---|---|---|---|---|---|
| Chemical shearing agent | Historical use | PO/IV | Single | Single | 🌎 NA |
- Chemical shearing agent: Historical use only.
用量は獣医専門家向けの臨床参考資料です。必ず最新の医薬品情報および個別症例に基づいて確認してください。
概要
シクロホスファミドは、犬や猫の獣医療で広く使用される強力な抗悪性腫瘍薬および免疫抑制薬です。
- 抗悪性腫瘍としての用途：リンパ腫、白血病、癌、肉腫の併用プロトコルで使用されます。肉腫の再発を防ぐための低用量メトロノミック（持続）療法も利用されます。
- 免疫抑制としての用途：全身性エリテマトーデス（SLE）、免疫介在性血小板減少症（ITP）、免疫介在性溶血性貧血（IMHA）、天疱瘡などの重篤な免疫介在性疾患に使用されます。
作用機序
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.
安全性・警告
禁忌
- 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
有害事象
- 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)
- Diarrhoea
- Hepatotoxicity
- Nephrotoxicity
- Reduction in hair growth rate / Alopecia
- Gastrointestinal toxicity
注意事項
WARNING: Cyclophosphamide is potentially teratogenic and embryotoxic. Safe use in pregnancy is not established.
- Hemorrhagic Cystitis: Up to 30% of dogs on long-term therapy may develop sterile hemorrhagic cystitis. Encourage frequent urination and water intake. Co-administration of furosemide may reduce risk.
- Myelosuppression: Monitor CBC closely. Delay doses if severe leukopenia or thrombocytopenia occurs.
- Handling: Cytotoxic precautions must be taken. Do not split or crush tablets. Avoid direct contact with urine or feces of treated animals.
医薬品相互作用
May increase the myelosuppression caused by cyclophosphamide
Potentiation of cardiotoxicity may occur
May inhibit cyclophosphamide metabolism
May increase the rate of metabolism to active metabolites, increasing toxicity risk
May increase the myelosuppression caused by cyclophosphamide
Metabolism may be slowed, prolonging effects due to decreased pseudocholinesterases
Absorption of orally administered digoxin may be decreased (may occur several days after dosing)
Increase cyclophosphamide toxicity due to increased rate of conversion to metabolites
Reduce cyclophosphamide efficacy
Reduce cyclophosphamide efficacy
Insulin requirements are altered by concurrent cyclophosphamide
Inhibits hepatic cytochrome P450 enzyme pathway, potentially altering the metabolism and increasing toxicity of chemotherapeutics.
監視
- 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)
薬物動態
半減期
吸収
Well absorbed after oral administration with peak levels occurring about 1 hour after dosing.
分布
Distributed throughout the body, including CSF (subtherapeutic levels). Minimally protein bound. Distributes into milk and crosses the placenta.
代謝
Metabolized in the liver to several active and inactive metabolites (including phosphoramide mustard and acrolein).
消失
Majority of the drug is excreted as metabolites and unchanged drug in the urine.
過剰投与
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.
製品
製剤
- Oral tablets
- Powder for injection
- Compounded oral elixir/suspension
- Injectable: 100 mg, 200 mg, 500 mg, 1000 mg powder for reconstitution
- Oral: 50 mg tablets
ヒト用医薬品
- Cyclophosphamide Tablets: 25 mg & 50 mg
- Cyclophosphamide Powder for Solution for Injection: 500 mg, 1 g and 2 g
- Endoxana 50 mg tablets
- Endoxana 100 mg, 200 mg, 500 mg, 1000 mg powder for reconstitution
規制ステータス
Often requires compounding by specialized pharmacies (e.g., ChemoPet) for accurate veterinary dosing.
Often requires compounding by specialized pharmacies (e.g., ChemoPet) for accurate veterinary dosing.
規制データなし: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
保管・安定性
Store tablets and powder for injection at <25°C (brief excursions up to 30°C permitted). Store tablets in tight containers. Reconstituted injection is stable for 24 hours at room temperature or 6 days refrigerated. Compounded oral elixir is stable for 14 days refrigerated.
飼主向け情報
重要な安全上の警告：これは強力な抗がん剤です。すべての取り扱い手順を慎重に従ってください。
- 取り扱い：錠剤を割ったり砕いたりしないでください。取り扱い後は手をよく洗ってください。ペットがこの薬を服用している間は、尿、便、吐き戻し物に直接触れないようにしてください。
- 排尿：特に朝は、排尿を促すために犬を頻繁に散歩に連れて行ってください。これにより膀胱の炎症を防ぐことができます。
- 獣医師への連絡のタイミング：血尿、排尿困難、異常な出血、あざ、重度の無気力、嘔吐、または下痢に気づいた場合は、すぐに獣医師に連絡してください。
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