MEXATE
Clinical safety rating
cautionComprehensive clinical and safety monograph for MEXATE (MEXATE).
Comprehensive clinical and safety monograph for MEXATE (MEXATE).
Rheumatoid arthritis (moderate to severe active disease in adults)Polyarticular juvenile idiopathic arthritisPsoriasis (severe, recalcitrant, disabling)Neoplastic diseases: gestational choriocarcinoma, chorioadenoma destruens, hydatidiform mole; acute lymphocytic leukemia (ALL); meningeal leukemia; Burkitt lymphoma; advanced non-Hodgkin lymphomas; mycosis fungoides; advanced head and neck cancer; osteosarcoma (adjunctive treatment)Off-label: ectopic pregnancy, inflammatory bowel disease, graft-versus-host disease, sarcoidosis, systemic lupus erythematosus, vasculitis
Abdominal pain, Indigestion, Loss of appetite, Nausea, Vomiting, Tiredness, Mouth sore
MEXATE is an antimetabolite that inhibits dihydrofolate reductase (DHFR), reducing tetrahydrofolate synthesis and interfering with DNA, RNA, and protein synthesis. It also inhibits thymidylate synthetase and has immunomodulatory and anti-inflammatory effects.
| Metabolism | Methotrexate is primarily metabolized by hepatic aldehyde oxidase to 7-hydroxymethotrexate. It undergoes polyglutamation intracellularly. Less than 10% is metabolized by cytochrome P450 enzymes. Excretion is primarily renal via glomerular filtration and active tubular secretion. |
| Excretion | Renal excretion of unchanged drug is the primary route of elimination, accounting for 80-90% of the dose. Biliary/fecal excretion is minor (<10%). |
| Half-life | Terminal elimination half-life is 3-10 hours for low-dose therapy (≤30 mg/m²). For high-dose therapy (>100 mg/m²), terminal half-life extends to 8-15 hours due to saturable elimination. A third, prolonged terminal phase (8-72 hours) is observed in some patients due to enterohepatic recirculation. |
| Protein binding | 50-60% bound, primarily to albumin. |
| Volume of Distribution | 0.4-0.8 L/kg (total body water). Vd increases with dose, indicating tissue distribution. |
| Bioavailability | Oral: 30-70% (dose-dependent, saturable absorption). Intramuscular: 80-100%. Subcutaneous: approximately 100%. |
| Onset of Action | Oral: 30-60 minutes to therapeutic effect. Intramuscular: 30-60 minutes. Intravenous: immediate (within minutes). Intrathecal: 15-30 minutes. |
| Duration of Action | Clinical effects persist for 1-3 days depending on dose and route. Weekly low-dose therapy (e.g., for rheumatoid arthritis) shows sustained suppression of inflammation up to 1 week. Antineoplastic effects persist over the dosing interval. |
| Molecular Weight | 454.44 |
| Action Class | Antimetabolite- Methotrexate |
| Brand Substitutes | MEXATE 25 MG INJECTION, Folitrax 25 Injection, Mexate 25mg Injection |
10-25 mg/m2 orally or intramuscularly once weekly for rheumatoid arthritis; 50 mg/m2 intravenously once weekly for psoriasis; 30-40 mg/m2 intravenously weekly for certain cancers (dose varies by protocol).
| Dosage form | INJECTABLE |
| Renal impairment | GFR >50 mL/min: no adjustment; GFR 10-50 mL/min: reduce dose by 50%; GFR <10 mL/min: avoid use. |
| Liver impairment | Child-Pugh A: 75% of normal dose; Child-Pugh B: 50% of normal dose; Child-Pugh C: contraindicated. |
| Pediatric use | For leukemia: 20-40 mg/m2 orally or intravenously once weekly; for juvenile idiopathic arthritis: 10-15 mg/m2 orally once weekly (max 25 mg/week). |
| Geriatric use | Start at lowest effective dose (e.g., 5-7.5 mg/week) with close monitoring of renal function, hepatic function, and hematologic parameters due to increased toxicity risk. |
| 1st trimester | Contraindicated; associated with severe fetal malformations (neural tube defects, craniofacial, limb defects) and spontaneous abortion. |
| 2nd trimester | Contraindicated; continued risk of fetal growth restriction, congenital anomalies, and neonatal toxicity. |
| 3rd trimester | Contraindicated; may cause fetal myelosuppression, immune suppression, and low birth weight. |
Clinical note
Comprehensive clinical and safety monograph for MEXATE (MEXATE).
| Placental transfer | Methotrexate actively crosses the placenta via folate transporters; placental transfer is extensive, with fetal concentrations approximating maternal levels. |
| Breastfeeding | Methotrexate is excreted in breast milk in low amounts but accumulates in neonatal tissues. Due to potential for serious adverse effects (e.g., immunosuppression, neutropenia, gastrointestinal toxicity), breastfeeding is contraindicated during therapy. Discontinue breastfeeding or avoid the drug. |
| Lactation Rating | L5 |
| Teratogenic Risk | Category X. 1st trimester: High risk of CNS, craniofacial, and skeletal malformations. 2nd and 3rd trimesters: Fetal growth restriction, oligohydramnios, and neonatal pancytopenia. |
| Fetal Monitoring | Weekly CBC, liver and renal function tests. Fetal ultrasound for growth and amniotic fluid volume every 4 weeks. |
| Fertility Effects | May cause reversible oligospermia or amenorrhea. Risk of gonadal suppression with prolonged use. |
■ FDA Black Box Warning
Boxed Warning: Methotrexate (MEXATE) can cause severe or fatal toxicities including bone marrow suppression, hepatic fibrosis/cirrhosis, pulmonary fibrosis, renal failure, and ulcerative stomatitis. Fatalities have been reported with inadvertent daily dosing instead of weekly. For rheumatoid arthritis and psoriasis, use only in patients with severe disease. Monitor for toxicity closely. Advise patients about risks of fatal toxicity.
| Serious Effects |
PregnancyBreastfeedingSevere hepatic impairmentSevere renal impairment (CrCl < 10 mL/min)Pre-existing blood dyscrasias (e.g., bone marrow hypoplasia)Alcoholism or alcoholic liver diseaseImmunodeficiency syndromesActive serious infections (e.g., tuberculosis, hepatitis B/C)
| Precautions | Severe hematologic toxicity (bone marrow suppression, pancytopenia), hepatotoxicity (fibrosis, cirrhosis, acute hepatitis), pulmonary toxicity (pneumonitis, fibrosis), renal toxicity, gastrointestinal toxicity (stomatitis, ulceration), neurotoxicity (leukoencephalopathy), opportunistic infections, tumor lysis syndrome, photosensitivity, and dermatologic reactions. Avoid concomitant NSAIDs, salicylates, and nephrotoxic drugs. Monitor CBC, LFTs, creatinine, and chest imaging. Use caution in elderly, debilitated, or patients with renal impairment, ascites, or pleural effusions. |
| Food/Dietary | Avoid alcohol due to increased hepatotoxicity risk. No specific food restrictions; however, maintain adequate hydration. Folate-rich foods do not interfere but supplemental folic acid may be prescribed to reduce side effects. |
| Clinical Pearls | Mexate (methotrexate) is a folate analog antimetabolite used in high doses for malignancy and low doses for autoimmune diseases. Reserve leucovorin rescue for high-dose protocols to prevent severe myelosuppression. Monitor renal function and methotrexate levels; adjust hydration and alkalinization to prevent precipitation in renal tubules. Avoid concurrent NSAIDs and proton pump inhibitors which reduce methotrexate clearance. Screen for pregnancy before initiation. Administer weekly in low-dose regimens for rheumatoid arthritis to avoid acute toxicity. |
| Patient Advice | Take exactly as prescribed—do not increase dose or frequency. Overdose can be fatal. · Avoid alcohol completely while on this medication. · Report any signs of infection, unusual bleeding, bruising, or mouth sores immediately. · Use effective contraception during treatment and for at least 3 months after stopping. · Do not take NSAIDs or aspirin without consulting your doctor. · Stay well hydrated; drink plenty of fluids unless otherwise instructed. · Avoid live vaccines during treatment. · Keep all follow-up appointments for blood tests and monitoring. |
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