REDITREX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REDITREX (REDITREX).
REDITREX is a folate analog metabolic inhibitor that inhibits dihydrofolate reductase (DHFR), thereby blocking the conversion of dihydrofolate to tetrahydrofolate, which is essential for purine and pyrimidine synthesis. This leads to inhibition of DNA synthesis and cell proliferation.
| Metabolism | Primarily metabolized in the liver to polyglutamates, which are retained intracellularly and contribute to prolonged action. It undergoes limited hepatic metabolism via CYP450 enzymes, but the majority is excreted unchanged in the urine. |
| Excretion | Primarily renal (80-90% as unchanged drug) via glomerular filtration and active tubular secretion; minimal biliary/fecal elimination (<10%). |
| Half-life | Terminal elimination half-life is 3-10 hours in patients with normal renal function; prolonged to 20-40 hours in end-stage renal disease. |
| Protein binding | Approximately 50% bound to albumin; weakly bound to other plasma proteins. |
| Volume of Distribution | 0.4-0.8 L/kg; distributes into total body water, with higher concentrations in liver and kidneys. |
| Bioavailability | Oral: 30-40% (dose-dependent, saturable absorption); Subcutaneous: 90-100%; Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5-10 minutes; Subcutaneous: 15-30 minutes. |
| Duration of Action | Clinical effects (immunosuppression/anti-inflammatory) persist 12-24 hours after single dose; with weekly dosing, sustained effects up to 1 week. |
| Molecular Weight | 454.44 Da (methotrexate) |
15 mg/m2 intramuscularly or intravenously once weekly; maximum single dose 30 mg.
| Dosage form | SOLUTION |
| Renal impairment | GFR 10-50 mL/min: reduce dose by 50%; GFR <10 mL/min: avoid use. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | 0.5-1 mg/kg intramuscularly or intravenously once weekly; maximum initial dose 25 mg. |
| Geriatric use | Start at 5-7.5 mg intramuscularly or intravenously once weekly; monitor renal function and bone marrow suppression closely. |
| 1st trimester | Teratogenic. Associated with spontaneous abortion, major malformations (neural tube, cardiac, craniofacial). Contraindicated. |
| 2nd trimester | Teratogenic and fetotoxic. Risk of fetal growth restriction, oligohydramnios. Avoid use unless maternal benefit outweighs risk. |
| 3rd trimester | Fetal and neonatal toxicity (pancytopenia, immunosuppression). Avoid near term. Use only in life-threatening maternal conditions. |
Clinical note
Comprehensive clinical and safety monograph for REDITREX (REDITREX).
| Placental transfer | Extensive placental transfer; fetal methotrexate concentrations approximate maternal levels by 4 hours after administration. Active transport via folate receptors. |
| Breastfeeding | Methotrexate is excreted into breast milk in low amounts; however, due to potential for accumulation and adverse effects in the infant (e.g., immunosuppression, neutropenia, developmental toxicity), breastfeeding is generally contraindicated. American Academy of Pediatrics recommends avoiding breastfeeding during therapy. If use is essential, discontinue breastfeeding and wait at least 1 week after the last dose before resuming. |
■ FDA Black Box Warning
REDITREX can cause fetal death or teratogenic effects when administered to a pregnant woman. It is contraindicated in pregnant women and in women of childbearing potential unless the benefits outweigh the risks. Additionally, severe hematologic, hepatic, renal, or gastrointestinal toxicities can occur; monitoring and dose adjustment are required.
| Serious Effects |
Hypersensitivity to methotrexate or any componentPregnancy (multiple guidelines)BreastfeedingSevere renal impairment (CrCl <10 mL/min unless using low-dose protocols with caution)Severe hepatic impairment or active liver diseasePre-existing blood dyscrasias (e.g., severe anemia, leukopenia, thrombocytopenia)Active serious infection (especially tuberculosis, hepatitis B/C, HIV)Alcoholism or alcoholic liver diseaseImmunodeficiency syndromesConcurrent live vaccines
| Precautions | Monitor for myelosuppression, hepatotoxicity, nephrotoxicity, pulmonary toxicity (e.g., pneumonitis), gastrointestinal perforation, and serious skin reactions (e.g., Stevens-Johnson syndrome). Avoid concurrent use of NSAIDs due to increased methotrexate toxicity. Monitor renal function, liver function, and blood counts regularly. |
| Food/Dietary |
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| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | First trimester: Methotrexate is a known teratogen, causing craniofacial, cardiac, and CNS defects; contraindicated. Second trimester: Risk of fetal growth restriction, oligohydramnios, and preterm birth; avoid use. Third trimester: Increased risk of neonatal myelosuppression, pulmonary toxicity, and infection; contraindicated. There is no trimester with safe exposure. |
| Fetal Monitoring | Before and during therapy: complete blood count, liver function tests, renal function tests, and pregnancy test. Fetal monitoring: ultrasound for growth and anatomy if exposure occurs. Methotrexate levels if toxicity suspected. Chest X-ray for pulmonary toxicity. |
| Fertility Effects | Methotrexate can cause reversible oligospermia and menstrual dysfunction. In females, high doses may lead to ovarian failure and premature menopause. In males, sperm counts decrease but usually recover after discontinuation. Use may impair fertility in both sexes. |
| Avoid alcohol and foods containing folic acid in high amounts (e.g., liver, fortified cereals) may reduce effectiveness. Caffeine and acidic foods may increase toxicity. Grapefruit juice may increase methotrexate levels. Maintain adequate hydration. |
| Clinical Pearls | REDITREX (methotrexate) is a folate analog antimetabolite. Monitor for hepatotoxicity, myelosuppression, and pulmonary fibrosis. Administer folic acid supplementation to reduce toxicity. Do not use in pregnancy. Check renal and liver function before each dose. Hydration and urine alkalinization reduce nephrotoxicity. Do not co-administer with NSAIDs due to increased methotrexate toxicity. |
| Patient Advice | Take exactly as prescribed; do not change dose or frequency. · Avoid alcohol completely to reduce liver damage risk. · Report any signs of infection, unusual bleeding, or shortness of breath immediately. · Use effective contraception during treatment and for at least 3 months after stopping. · Take folic acid as directed to help reduce side effects. · Limit sun exposure and use sunscreen as methotrexate increases photosensitivity. |