MYTREX A
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MYTREX A (MYTREX A).
Methotrexate inhibits dihydrofolate reductase, leading to depletion of tetrahydrofolate and inhibition of DNA synthesis and cell proliferation. Also has immunomodulatory effects via adenosine release.
| Metabolism | Hepatic metabolism via aldehyde oxidase, xanthine oxidase, and hepatic hydroxylation. Minor metabolism by intestinal bacteria. |
| Excretion | Renal: 90% unchanged drug; fecal: <10% via bile; minor hepatic metabolism to inactive metabolites. |
| Half-life | Terminal elimination half-life: 12-15 hours in normal renal function; prolonged to 24-30 hours in moderate to severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 95% bound to albumin; minimal binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 0.3-0.4 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral: 60-70% (first-pass hepatic metabolism); Intramuscular: ~100%; Intravenous: 100%. |
| Onset of Action | Oral: 2-4 hours; Intravenous: 15-30 minutes; Intramuscular: 1-2 hours. |
| Duration of Action | Oral: 12-24 hours; Intravenous: 6-12 hours; Intramuscular: 12-24 hours. Duration extended in renal impairment. |
Methotrexate (MYTREX A) 7.5-25 mg orally once weekly, or 15-25 mg intramuscularly/subcutaneously once weekly for rheumatoid arthritis; in oncology, dosing varies per protocol.
| Dosage form | OINTMENT |
| Renal impairment | GFR 10-50 mL/min: reduce dose by 50%; GFR <10 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Juvenile idiopathic arthritis: 10-15 mg/m² orally or 15-20 mg/m² subcutaneously once weekly; oncology: per protocol (e.g., 20 mg/m² twice weekly). |
| Geriatric use | Start at low end of dosing range (e.g., 5-7.5 mg weekly); monitor for renal function and toxicity due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MYTREX A (MYTREX A).
| Breastfeeding | Methotrexate is excreted into breast milk in low concentrations; the milk-to-plasma ratio is approximately 0.08. Due to potential for serious adverse effects (e.g., immunosuppression, bone marrow suppression) in the nursing infant, breastfeeding is contraindicated during MYTREX A therapy. |
| Teratogenic Risk | MYTREX A is contraindicated in pregnancy. First trimester: High risk of major malformations including neural tube defects, craniofacial anomalies, and limb defects. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and fetal renal impairment. Methotrexate is an abortifacient and should be avoided throughout pregnancy. |
■ FDA Black Box Warning
BOXED WARNING: (1) Hepatotoxicity: Methotrexate can cause hepatic fibrosis, cirrhosis, and acute hepatitis, especially at high doses or prolonged use. (2) Pulmonary toxicity: Acute or chronic interstitial pneumonitis can occur. (3) Myelosuppression: Severe bone marrow suppression leading to pancytopenia. (4) Renal toxicity: High doses may cause renal failure. (5) Teratogenicity: Methotrexate is contraindicated in pregnancy and can cause fetal death or congenital anomalies. (6) Lymphoproliferative disorders: May increase risk of lymphoma. (7) Hypersensitivity reactions: Anaphylaxis and other severe allergic reactions have been reported.
| Serious Effects |
["Pregnancy and breastfeeding","Significant hepatic impairment (e.g., cirrhosis, hepatitis)","Severe renal impairment (creatinine clearance < 30 mL/min)","Severe bone marrow suppression or pre-existing blood dyscrasias","Alcoholism or alcoholic liver disease","Hypersensitivity to methotrexate or any component","Active tuberculosis or other serious infections"]
| Precautions | ["Monitor hepatic function, renal function, and blood counts regularly.","Use with caution in patients with renal impairment, hepatic disease, or ascites.","Avoid live vaccines during therapy.","Concomitant use of NSAIDs may increase methotrexate toxicity.","Pulmonary toxicity may occur even at low doses; discontinue if suspected.","Risk of opportunistic infections due to immunosuppression.","Photosensitivity reactions may occur.","Monitor for lymphoproliferative disorders; discontinue if suspected."] |
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| Fetal Monitoring | If inadvertent exposure during pregnancy occurs, monitor with high-resolution fetal ultrasound and serial growth scans. Maternal monitoring includes complete blood count, liver function tests, renal function tests, and monitoring for signs of pneumonitis. Pregnancy must be excluded before initiation and monthly thereafter. |
| Fertility Effects | Methotrexate can cause impaired spermatogenesis and oligospermia in males, and oligomenorrhea or amenorrhea in females. These effects are usually reversible upon discontinuation. Contraception is recommended during and for at least 3 months after cessation in both sexes. |