甲氨蝶呤
Methotrexate
Methotrexate sodium
別名: Rheumatrex · Trexall · Methotrexate LPF · MTX · Amethopterin · 4-Amino-4-deoxy-10-methylpteroyl-L-glutamic acid · 4-Amino-10-methylfolic acid · CL-14377 · alpha-methopterin · methotrexatum · metotrexato · NSC-740 · WR-19039
由 VetSheet 獸醫團隊審訂更新於 2026年4月5日本內容以實證獸醫文獻為本
這是按體表面積（mg/m²）計算的劑量；給藥前須先把體重換算為體表面積。
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
各物種劑量
🌎 NA — North America🌍 EU — Europe
狗
| 適應症 | 劑量 | 途徑 | 頻次 | 療程 | 地區 |
|---|---|---|---|---|---|
| As part of the LMP protocol for maintenance of canine lymphoma | 2.5-5 mg/m2 PO twice a week | PO | twice a week | — | 🌎 NA |
| In combination with other antineoplastics (per protocol) | 5 mg/m2 PO twice weekly or 0.8 mg/kg IV every 21 days; alternatively 2.5 mg/m2 PO daily | PO/IV | twice weekly, every 21 days, or daily | — | 🌎 NA |
- As part of the LMP protocol for maintenance of canine lymphoma: Given with Chlorambucil 20 mg/m2 PO every 15 days and Prednisone 20 mg/m2 PO every other day. When Vincristine is added it is at a dose of 0.5-0.7 mg/m2 and is given every 15 days alternating weeks with the chlorambucil.
貓
| 適應症 | 劑量 | 途徑 | 頻次 | 療程 | 地區 |
|---|---|---|---|---|---|
| For susceptible neoplastic diseases (usually as part of a multi-drug protocol) | 2.5 mg/m2 PO 2-3 times weekly; 0.3-0.8 mg/m2 IV every 7 days | PO/IV | 2-3 times weekly (PO) or every 7 days (IV) | — | 🌎 NA |
| For non-suppurative cholangitis/cholangiohepatitis (CCHC) syndrome with fibrosis | A total dose of 0.4 mg per cat total dose given on one day in three divided doses: 0.26 mg at hour zero, 0.13 mg at the 12 and 24 hour dosing. Repeat every 7-10 days. | PO | Divided over 24 hours, repeated every 7-10 days | — | 🌎 NA |
- For non-suppurative cholangitis/cholangiohepatitis (CCHC) syndrome with fibrosis: Use in conjunction with ursodeoxycholic acid (15 mg/kg PO q24h) and folate (0.25 mg/kg PO q24h).
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
概覽
甲氨蝶呤 (MTX) 是一種強效的葉酸拮抗劑，在獸醫腫瘤學中主要用於治療犬貓的淋巴增生性疾病（如淋巴瘤）和某些實體腫瘤。
除了抗腫瘤特性外，它還具有顯著的免疫抑制能力，使其成為治療難治性免疫介導疾病（例如對標準潑尼松龍或苯丁酸氮芥治療無反應的貓非化膿性膽管炎/膽管肝炎）的寶貴選擇。
臨床要點： 由於 MTX 的治療指數非常狹窄且嚴重依賴腎臟清除，因此病患的水合狀態和腎功能對於預防嚴重毒性至關重要。它對快速分裂的細胞具有高度毒性，這意味著胃腸道上皮細胞和骨髓特別容易受到附帶損害。
作用機制
Methotrexate is an S-phase specific antimetabolite. It acts by competitively and irreversibly inhibiting the enzyme dihydrofolate reductase (DHFR).
- Folic acid → (via DHFR) → Dihydrofolate → (via DHFR) → Tetrahydrofolate (active form).
- By blocking DHFR, MTX prevents the reduction of dihydrofolate to tetrahydrofolate.
- Tetrahydrofolate is an essential cofactor for the synthesis of purines and pyrimidines (specifically thymidylate).
- The depletion of these precursors halts DNA, RNA, and protein synthesis, ultimately leading to apoptosis in rapidly proliferating cells (e.g., neoplasms, bone marrow, GI tract epithelium).
Note: DHFR has a much greater affinity for MTX than for folic acid. Therefore, coadministration of folic acid will not reverse MTX toxicity. Leucovorin calcium (a derivative of tetrahydrofolic acid that bypasses the blocked enzyme) is required as a rescue agent.
安全性與警告
禁忌症
- Preexisting bone marrow depression
- Severe hepatic insufficiency
- Severe renal insufficiency
- Hypersensitivity to the drug
- Pregnancy (Teratogenic/Embryotoxic - FDA Category X)
- Nursing mothers
- Pre-existing severe bone marrow suppression
- Severe renal impairment
- Severe hepatic impairment
- Pregnancy and lactation (teratogenic and embryotoxic)
- Patients with significant third-space fluid accumulations (e.g., ascites, pleural effusion)
不良反應
- Nausea
- Inappetence (especially in cats)
- GI toxicity (ulcers, mucosal sloughing, stomatitis)
- Hematopoietic toxicity / Myelosuppression (nadir at 4-6 days)
- Hepatopathy
- Renal tubular necrosis
- Depigmentation
- Pulmonary infiltrates and fibrosis
- CNS toxicity (encephalopathy) if given intrathecally
- Anaphylaxis (rare)
- Myelosuppression (neutropenia, thrombocytopenia, anemia)
- Gastrointestinal toxicity (anorexia, vomiting, diarrhea, stomatitis)
- Hepatotoxicity (elevated liver enzymes)
- Nephrotoxicity (especially at high doses due to tubular precipitation)
- Alopecia (rare in most animals, but possible in continuously growing coats)
注意事項
Use with extreme caution in patients susceptible to or with preexisting clinical signs of MTX adverse reactions. Handling Precautions: Wear gloves or immediately wash hands after handling. Gloves are particularly important if handling split, broken, or crushed tablets. Preparation of intravenous solutions should ideally be performed in a vertical laminar flow hood to avoid human exposure. Teratogenic and may affect spermatogenesis.
藥物相互作用
Prolonged PO administration (>2 weeks) may inhibit MTX metabolism
Given concomitantly with MTX may decrease MTX efficacy
Potential for increased risk for hepatic toxicity
May displace MTX from plasma proteins increasing risk for toxicity, but also may reduce MTX absorption and enterohepatic recirculation
May have synergistic action with MTX, but alter the renal elimination of MTX
May increase MTX levels
May reduce MTX efficacy, but folate deficiency increases MTX toxicity
May decrease the absorption of oral methotrexate if given concomitantly
Severe hematologic and GI toxicity risk; use caution in dogs also on MTX
May decrease MTX renal elimination
May inhibit the tubular secretion of MTX and increase its half-life
A similar folic acid antagonist; may increase MTX toxicity and should not be given to patients receiving MTX
Potential for increased risk for hepatic toxicity
Potential for increased risk for hepatic toxicity
May displace MTX from plasma proteins increasing risk for toxicity
May displace MTX from plasma proteins increasing risk for toxicity, but also may reduce MTX absorption and enterohepatic recirculation
MTX may reduce theophylline elimination
Rarely, may increase myelosuppression of MTX
Live virus vaccines should be used with caution, if at all during therapy
Decreased renal clearance of methotrexate, leading to increased serum levels and severe toxicity.
Additive antifolate effects, significantly increasing the risk of severe bone marrow suppression.
May delay the elimination of methotrexate.
監測
- Efficacy of treatment
- Clinical signs of GI irritation and ulceration
- Complete blood counts (with platelets) weekly early in therapy, then every 4-6 weeks (Discontinue if WBC <4000/mm3 or platelets <100,000/mm3)
- Baseline and ongoing renal function tests
- Baseline and ongoing hepatic function tests (liver enzymes)
- Complete Blood Count (CBC) - baseline and prior to each dose (monitor for nadir)
- Renal function panel (BUN, Creatinine, Urinalysis)
- Hepatic enzymes (ALT, AST, ALP, Bilirubin)
- Clinical signs of gastrointestinal toxicity (vomiting, diarrhea, anorexia)
- Hydration status
藥物動力學
半衰期
吸收
Well absorbed from the GI tract after oral administration of dosages <30 mg/m2 with a bioavailability of about 60%. Peak levels occur within 4 hours after oral dosing, and between 30 minutes and 2 hours after IM injection.
分佈
Widely distributed in the body and actively transported across cell membranes. Highest concentrations in kidneys, spleen, gallbladder, liver, and skin. Does not reach therapeutic levels in CSF unless given intrathecally. About 50% bound to plasma proteins and crosses the placenta.
代謝
Minimal hepatic metabolism is noted; primarily excreted unchanged.
排除
Excreted almost entirely by the kidneys via both glomerular filtration and active transport.
過量
Acute overdosage in dogs is associated with severe exacerbations of adverse effects, particularly myelosuppression and acute renal failure. Acute tubular necrosis occurs secondary to drug precipitation in the renal tubules.
- Toxicity Thresholds: In dogs, the maximally tolerated dose is reported to be 0.12 mg/kg q24h for 5 days. A dose of 10 mg/kg is considered lethal if leucovorin rescue is not performed.
- Decontamination: Empty the gut and prevent absorption using standard protocols if ingestion is recent. Oral neomycin has been suggested to help prevent intestinal absorption.
- Renal Protection: Forced alkaline diuresis should be considered to minimize renal damage. Maintain urine pH between 7.5-8 by adding 0.5-1 mEq/kg of sodium bicarbonate per 500 mL of IV fluid.
- Antidote: Leucovorin calcium is the specific therapy for MTX overdoses. It must be given as soon as possible (preferably within the first hour, definitely within 48 hours). Dogs treated with leucovorin at 15 mg/m2 every 3 hours IV for 8 doses, then IM q6h for 8 doses were able to tolerate very high MTX doses.
可用產品
劑型
- Tablets
- Injection solution
- Powder for injection
- 2.5 mg oral tablet
- 10 mg oral tablet
人用標示
- Methotrexate Sodium Tablets (plain & scored): 2.5 mg, 5 mg, 7.5 mg, 10 mg & 15 mg
- Methotrexate Sodium Injection: 25 mg/mL (as base) in various vial sizes
- Methotrexate Powder for Injection, lyophilized: 1 gram preservative free in single-use vials
- Matrex 2.5 mg tablets
- Methotrexate 2.5 mg tablets
- Methotrexate 10 mg tablets
各地核准狀態
Human authorized products often used off-label under the cascade.
Prescription Only Medicine. Handled under cascade regulations.
暫無法規資料: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
儲存與穩定性
Methotrexate sodium tablets should be stored at room temperature (15-30°C) in well-closed containers and protected from light. The injection and powder for injection should be stored at room temperature (15-30°C) and protected from light.
飼主須知
警告：化學治療藥物 本藥物具有高毒性，若處理不當可能對人體造成危害。
- 處理安全： 給予藥錠時（特別是壓碎或剝半的藥錠）請務必戴上拋棄式手套。若未戴手套，處理後請立即徹底洗手。孕婦或免疫力低下者應避免接觸此藥物。
- 毒性風險： 您必須了解此藥物可能引發嚴重毒性，甚至導致藥物相關的死亡風險。
- 何時應聯繫獸醫： 如果您的寵物出現極度抑鬱、嗜睡、異常出血（包括血便、黑色柏油狀糞便）、瘀傷、嘔吐或食慾不振等臨床症狀，請立即聯繫您的獸醫。
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