메토트렉세이트

동물 종별 용량

용량은 면허 수의 전문가를 위한 임상 참고 자료입니다. 항상 최신 라벨과 개별 환자에 대해 확인하십시오.

투여 경로

금기

• 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)

이상반응

• Diarrhea
• Nausea
• Vomiting
• Inappetence (especially in cats)
• GI toxicity (ulcers, mucosal sloughing, stomatitis)
• Hematopoietic toxicity / Myelosuppression (nadir at 4-6 days)
• Hepatopathy
• Renal tubular necrosis
• Alopecia
• 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)

약물 상호작용

• 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
• Penicillins · May decrease MTX renal elimination · moderate
• Probenecid · May inhibit the tubular secretion of MTX and increase its half-life · major
• Pyrimethamine · A similar folic acid antagonist; may increase MTX toxicity and should not be given to patients receiving MTX

모니터링

• 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

과용량

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.