MEXATE-AQ PRESERVED
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEXATE-AQ PRESERVED (MEXATE-AQ PRESERVED).
Methotrexate is a folate analog that inhibits dihydrofolate reductase (DHFR), leading to depletion of tetrahydrofolate and inhibition of DNA synthesis, repair, and cellular replication. It also exhibits immunosuppressive and anti-inflammatory effects through inhibition of purine synthesis and modulation of cytokine release.
| Metabolism | Primarily metabolized hepatically to polyglutamated methotrexate (active form) via folylpolyglutamate synthetase; also undergoes oxidation via aldehyde oxidase. Excretion is primarily renal via glomerular filtration and active tubular secretion. |
| Excretion | Primarily renal (80-90% unchanged via glomerular filtration and active tubular secretion), with approximately 5-10% eliminated via biliary/fecal excretion. Enterohepatic recirculation occurs. |
| Half-life | Terminal elimination half-life is 3-10 hours for low-dose therapy; at high doses, half-life increases to 8-15 hours due to saturation of renal clearance. Clinical context: Prolonged half-life in renal impairment or third-space fluid accumulation. |
| Protein binding | Approximately 50-60% bound to albumin, with binding saturable at high concentrations. |
| Volume of Distribution | Vd is 0.4-0.8 L/kg, indicating distribution into total body water. Higher Vd (1-2 L/kg) in high-dose therapy due to tissue binding and polyglutamation. |
| Bioavailability | Oral: 30-90% (dose-dependent, saturable absorption; lower at high doses). IM/SubQ: 100% (complete absorption). IV: 100%. |
| Onset of Action | IV: Onset within minutes for antineoplastic effect (methotrexate inhibits dihydrofolate reductase rapidly). IM/SubQ: Onset 30-60 minutes. Oral: Onset 1-2 hours. Intrathecal: Immediate onset in CSF. |
| Duration of Action | Duration of antineoplastic effect: 1-2 days for low doses; high-dose therapy may require leucovorin rescue for 24-72 hours. Duration of immunosuppressive effect in rheumatoid arthritis: up to 1 week. |
MEXATE-AQ PRESERVED (methotrexate) is administered intramuscularly, intravenously, or subcutaneously. For neoplastic diseases, typical adult doses range from 25-100 mg/m² weekly or 5-25 mg/m² every 6-12 hours for 2-6 doses. For rheumatoid arthritis, 7.5-20 mg once weekly. For psoriasis, 10-25 mg once weekly.
| Dosage form | INJECTABLE |
| Renal impairment | Contraindicated if creatinine clearance (CrCl) <10 mL/min. For CrCl 10-30 mL/min: reduce dose by 50%. For CrCl 30-60 mL/min: reduce dose by 25%. For CrCl >60 mL/min: no adjustment needed. Monitor renal function closely; high methotrexate doses may require additional hydration and alkalinization. |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class B: reduce dose by 50%. For Child-Pugh class A: no dose adjustment. Avoid use in patients with significant liver disease or chronic hepatitis. Monitor liver enzymes. |
| Pediatric use | For acute lymphoblastic leukemia: induction doses of 3.3-5 mg/m² IV or IM, or higher doses per protocol (e.g., 100-1000 mg/m² IV). For juvenile idiopathic arthritis: 10-15 mg/m² once weekly (max 20-25 mg). Doses based on body surface area; adjust for renal function. |
| Geriatric use | Elderly patients may have reduced renal function; start at low end of dose range (e.g., 5-7.5 mg weekly for rheumatoid arthritis). Monitor CrCl, liver function, and blood counts. Increased risk of myelosuppression and hepatotoxicity. Avoid high-dose methotrexate unless renal function confirmed adequate. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEXATE-AQ PRESERVED (MEXATE-AQ PRESERVED).
| Breastfeeding | Contraindicated. Excreted in breast milk; M/P ratio unknown. Potential for infant toxicity. |
| Teratogenic Risk | Category X. First trimester: high risk of miscarriage, CNS and skeletal malformations. Second/third trimester: growth restriction, developmental delay. |
| Fetal Monitoring | Before/during pregnancy: weekly CBC, LFTs, renal function; serial ultrasound for fetal growth and anomalies. |
■ FDA Black Box Warning
Methotrexate can cause severe toxicity including myelosuppression, hepatotoxicity, nephrotoxicity, pulmonary fibrosis, and severe enterocolitis. Accidental overdose has led to fatalities. It should only be prescribed by physicians experienced with antimetabolite therapy and familiar with its toxicities.
| Common Effects | Ulcerative stomatitis Nausea Abdominal pain Increased liver enzymes Hair loss Decreased blood cells red cells white cells and platelets |
| Serious Effects |
Absolute: hypersensitivity to methotrexate; severe hepatic impairment; severe renal impairment (CrCl < 30 mL/min); severe bone marrow suppression; active infection; alcohol use disorder; pregnancy (Category X); breastfeeding. Relative: peptic ulcer disease; ulcerative colitis; obesity; diabetes.
| Precautions | Monitor for bone marrow suppression, hepatotoxicity (liver function tests), renal impairment (serum creatinine), pulmonary toxicity (pneumonia-like symptoms), gastrointestinal toxicity, neurotoxicity (especially in high-dose regimens), and increased risk of infections. Avoid concomitant NSAIDs with high-dose methotrexate. Use with caution in patients with ascites, pleural effusions, or dehydration. |
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| Fertility Effects | May cause reversible oligospermia in males and amenorrhea in females; case reports of infertility. |