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メトトレキサート

Methotrexate

Methotrexate sodium

抗悪性腫瘍薬 / 免疫抑制剤（代謝拮抗薬）POIVIMIntrathecalSC犬猫

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

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

2.5-5 mg/m2 PO twice a weekPO· twice a week

これは体表面積（mg/m²）に基づく用量です。投与前に体重を体表面積へ換算してください。

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
As part of the LMP protocol for maintenance of canine lymphoma2.5-5 mg/m2 PO twice a weekPOtwice 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 dailyPO/IVtwice 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.

猫

適応用量経路頻度期間地域
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 daysPO/IV2-3 times weekly (PO) or every 7 days (IV)—🌎 NA
For non-suppurative cholangitis/cholangiohepatitis (CCHC) syndrome with fibrosisA 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.PODivided 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).

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。

診察中ですか？VetSheet の AI が薬剤・用量・投与期間を構造化された診察記録に直接記入します。VetSheet の仕組みを見る

概要

メトトレキサート（MTX）は強力な​葉酸拮抗薬​であり、獣医腫瘍学において主に犬や猫の​リンパ増殖性疾患​（リンパ腫など）および一部の固形腫瘍の治療に使用されます。

抗悪性腫瘍特性に加えて、顕著な​免疫抑制​作用も持ち合わせており、標準的なプレドニゾロンやクロラムブシル治療に反応しない猫の非化膿性胆管炎/胆管肝炎などの難治性免疫介在性疾患に対する貴重な選択肢となります。

​臨床のポイント：​ MTXは治療域が非常に狭く、腎クリアランスに大きく依存しているため、重篤な毒性を防ぐためには患者の水分補給と腎機能の維持が極めて重要です。急速に分裂する細胞に対して強い毒性を示すため、消化管上皮や骨髄は特に巻き添え被害を受けやすくなります。

作用機序

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・警告

禁忌

  • 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)

有害事象

  • 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.

医薬品相互作用

Amiodarone

Prolonged PO administration (>2 weeks) may inhibit MTX metabolism

Asparaginase

Given concomitantly with MTX may decrease MTX efficacy

Azathioprine

Potential for increased risk for hepatic toxicity

Chloramphenicol

May displace MTX from plasma proteins increasing risk for toxicity, but also may reduce MTX absorption and enterohepatic recirculation

Cisplatin

May have synergistic action with MTX, but alter the renal elimination of MTX

Cyclosporine

May increase MTX levels

Folic Acid

May reduce MTX efficacy, but folate deficiency increases MTX toxicity

Neomycin (oral)

May decrease the absorption of oral methotrexate if given concomitantly

NSAIDs / Salicylates

Severe hematologic and GI toxicity risk; use caution in dogs also on MTX

PenicillinsModerate

May decrease MTX renal elimination

ProbenecidMajor

May inhibit the tubular secretion of MTX and increase its half-life

Pyrimethamine

A similar folic acid antagonist; may increase MTX toxicity and should not be given to patients receiving MTX

Retinoids

Potential for increased risk for hepatic toxicity

Sulfasalazine

Potential for increased risk for hepatic toxicity

Sulfonamides

May displace MTX from plasma proteins increasing risk for toxicity

Tetracyclines

May displace MTX from plasma proteins increasing risk for toxicity, but also may reduce MTX absorption and enterohepatic recirculation

Theophyllines

MTX may reduce theophylline elimination

Trimethoprim/Sulfa

Rarely, may increase myelosuppression of MTX

Vaccines, Live

Live virus vaccines should be used with caution, if at all during therapy

NSAIDsMajor

Decreased renal clearance of methotrexate, leading to increased serum levels and severe toxicity.

Trimethoprim-sulfamethoxazoleMajor

Additive antifolate effects, significantly increasing the risk of severe bone marrow suppression.

OmeprazoleModerate

May delay the elimination of methotrexate.

監視

  • 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

薬物動態

半減期

猫Unknown犬<10 hours (generally between 2-4 hours)

吸収

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.

分布

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.

消失

Excreted almost entirely by the kidneys via both glomerular filtration and active transport.

過剰投与

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.

製品

製剤

  • Tablets
  • Injection solution
  • Powder for injection
  • 2.5 mg oral tablet
  • 10 mg oral tablet

ヒト用医薬品

  • 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

規制ステータス

European Union✓ 承認済み処方箋医薬品EMA
🐕 Dogs🐈 Cats

Human authorized products often used off-label under the cascade.

United Kingdom✓ 承認済み処方箋医薬品 · POMVMD
🐕 Dogs🐈 Cats

Prescription Only Medicine. Handled under cascade regulations.

規制データなし: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU

保管・安定性

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.

飼主向け情報

​警告：化学療法薬​ この薬は毒性が高く、取り扱いを誤ると人体に有害となる可能性があります。

  • ​取り扱いの安全性：​ 錠剤（特に砕いたり割ったりしたもの）を投与する際は、必ず使い捨て手袋を着用してください。手袋を使用しない場合は、取り扱い後すぐに手を徹底的に洗ってください。妊娠中の女性や免疫不全の人は、この薬の取り扱いを避けるべきです。
  • ​毒性のリスク：​ この薬によって薬物関連の死亡を含む重篤な毒性が発生する可能性があることを認識しておく必要があります。
  • ​獣医師への連絡のタイミング：​ ペットに極度のうつ状態、無気力、異常な出血（血便や黒色タール便を含む）、あざ、嘔吐、または食欲不振などの臨床症状が見られた場合は、直ちに獣医師に連絡してください。
  • ​授乳：​ この薬を服用しているペットには授乳させないでください。人工乳に切り替えてください。

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