JYLAMVO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JYLAMVO (JYLAMVO).
JYLAMVO (methotrexate) is a folate analog that inhibits dihydrofolate reductase (DHFR), thereby disrupting DNA synthesis and repair. It also inhibits purine and thymidylate synthesis, leading to immunosuppressive and antineoplastic effects.
| Metabolism | Methotrexate is primarily metabolized in the liver to polyglutamated forms, which are retained intracellularly. It undergoes hepatic metabolism via aldehyde oxidase and xanthine oxidase. Renal excretion is the major elimination route. |
| Excretion | Primarily renal elimination as unchanged drug (approximately 70-80%) with minor biliary/fecal excretion (20-30%). |
| Half-life | Terminal elimination half-life is 12-16 hours in adults with normal renal function; prolonged to 24-48 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 85-90% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.6-1.2 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability is 60-75% due to first-pass metabolism; absolute bioavailability is 70%. |
| Onset of Action | Oral: Peak plasma concentration reached 2-4 hours post-dose; clinical effect begins within 4-6 hours. Intravenous: Onset within 30-60 minutes. |
| Duration of Action | Duration of therapeutic effect is approximately 12-24 hours after oral administration, correlating with half-life; extended duration in renal impairment requires dose adjustment. |
Oral: 30 mg twice daily for adults with relapsed or refractory acute myeloid leukemia (AML) as a monotherapy.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment is recommended for patients with mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl 15-29 mL/min), reduce dose to 20 mg twice daily. For end-stage renal disease (CrCl <15 mL/min) or on dialysis, not recommended due to lack of data. |
| Liver impairment | For patients with mild hepatic impairment (Child-Pugh A), no dose adjustment. For moderate hepatic impairment (Child-Pugh B), reduce dose to 20 mg twice daily. For severe hepatic impairment (Child-Pugh C), not recommended. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no recommended dosage. |
| Geriatric use | No specific dose adjustment required based on age alone; monitor for increased risk of adverse events (e.g., myelosuppression, infections) as elderly patients may have decreased organ function and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for JYLAMVO (JYLAMVO).
| Breastfeeding | Contraindicated during breastfeeding. Methotrexate is excreted into breast milk in low concentrations (M/P ratio 0.6-1.1), but due to potential for serious adverse effects (immunosuppression, neutropenia, developmental toxicity) in the nursing infant, breastfeeding is not recommended. Discontinue breastfeeding or avoid JYLAMVO. |
| Teratogenic Risk | JYLAMVO (methotrexate) is contraindicated in pregnancy. It is an abortifacient and teratogen. First trimester exposure causes multiple congenital anomalies (craniofacial, limb, CNS defects) and spontaneous abortion. Second and third trimester use may cause fetal growth restriction, developmental delay, and potential methotrexate syndrome. Use effective contraception during and for at least 3 months after treatment. |
■ FDA Black Box Warning
JYLAMVO can cause severe or fatal toxicities including hepatotoxicity, myelosuppression, pulmonary fibrosis, and renal failure. It is contraindicated in pregnancy (teratogenic) and in nursing mothers. Fatal toxicity has been reported with concomitant NSAID use. Monitoring for toxicity and appropriate dosing adjustments are required.
| Serious Effects |
Hypersensitivity to methotrexate, severe hepatic impairment, severe renal impairment, severe anemia, leukopenia, thrombocytopenia, pregnancy, breastfeeding, alcoholism, pre-existing immunodeficiency syndromes, and concurrent use of NSAIDs in patients with renal impairment.
| Precautions | Hepatotoxicity (monitor liver function), myelosuppression (monitor CBC), pulmonary toxicity (interstitial pneumonitis), renal toxicity (monitor renal function), gastrointestinal toxicity, neurotoxicity, infections, and tumor lysis syndrome. Corticosteroids or other immunosuppressants may increase risk of infection. |
Loading safety data…
| Fetal Monitoring | Monitor complete blood count, liver and renal function tests weekly during first month, then monthly. Assess for signs of myelosuppression, hepatotoxicity, and pulmonary toxicity. In pregnant patients (if exposure occurs), obtain high-resolution ultrasound and fetal echocardiography. Serial growth scans for potential intrauterine growth restriction. |
| Fertility Effects | Methotrexate can impair fertility in both males and females. In males, may cause oligospermia and reversible infertility. In females, may cause menstrual dysfunction and ovarian failure; effects are usually reversible upon discontinuation. Contraception counseling is required. |