Jylamvo - Drug Monograph

Introduction

Jylamvo (methotrexate) oral solution is a disease-modifying antirheumatic drug (DMARD) and antimetabolite agent. It is a folate analog metabolic inhibitor indicated for the management of rheumatoid arthritis and certain neoplastic conditions. Jylamvo provides an alternative formulation to tablets, particularly beneficial for patients who have difficulty swallowing solid dosage forms or require precise dose titration.

Mechanism of Action

Methotrexate inhibits dihydrofolate reductase, the enzyme responsible for converting dihydrofolate to tetrahydrofolate. This inhibition disrupts DNA synthesis, repair, and cellular replication. In rheumatoid arthritis, methotrexate exhibits immunomodulatory effects through adenosine-mediated suppression of inflammatory cytokines and inhibition of T-cell proliferation. The drug's antineoplastic effects result from competitive inhibition of folate metabolism, ultimately impairing purine and thymidylic acid synthesis.

Indications

• Rheumatoid Arthritis: Management of active rheumatoid arthritis in adults who have had an insufficient response to or are intolerant of first-line therapy
• Polyarticular Juvenile Idiopathic Arthritis: Active disease in children who have responded inadequately to salicylates or other NSAIDs
• Psoriasis: Severe, recalcitrant, disabling psoriasis not adequately responsive to other forms of therapy
• Oncologic Uses: As part of combination chemotherapy for:

- Acute lymphoblastic leukemia - Burkitt's lymphoma - Advanced non-Hodgkin's lymphomas - Mycosis fungoides - Osteosarcoma

Dosage and Administration

• Initial dose: 7.5 mg once weekly or 2.5 mg every 12 hours for 3 doses weekly
• May gradually increase to maximum 20 mg weekly based on response and tolerability
• Administer same day each week

• Varies significantly based on protocol, tumor type, and patient factors
• Range: 10-50 mg/m² weekly to high-dose regimens (100-12,000 mg/m²) with leucovorin rescue

• Renal impairment: Reduce dose or avoid use in significant impairment (CrCl <60 mL/min)
• Hepatic impairment: Contraindicated in preexisting liver disease
• Geriatric: Consider reduced doses due to increased risk of toxicity
• Pediatric: Dosing based on body surface area or weight

Pharmacokinetics

Contraindications

• Pregnancy, lactation, or women of childbearing potential not using reliable contraception
• Preexisting blood dyscrasias
• Significant renal impairment (CrCl <60 mL/min)
• Active hepatic disease or chronic liver disease
• Preexisting immunodeficiency syndromes
• Hypersensitivity to methotrexate or any component of the formulation
• Concomitant use with live vaccines

Warnings and Precautions

• Methotrexate has been associated with fatal toxicities including bone marrow suppression, aplastic anemia, and gastrointestinal toxicity
• Must be prescribed only by physicians experienced in antimetabolite chemotherapy
• Requires close monitoring of hematologic, hepatic, renal, and pulmonary function

• Risk of hepatotoxicity including fibrosis and cirrhosis (dose- and duration-dependent)
• Pulmonary toxicity including interstitial pneumonitis
• Serious dermatologic reactions including toxic epidermal necrolysis and Stevens-Johnson syndrome
• Risk of opportunistic infections
• Potential for tumor lysis syndrome in leukemia/lymphoma patients
• Risk of neurotoxicity (especially with intrathecal administration)

Drug Interactions

• NSAIDs: Increased methotrexate toxicity risk
• Probenecid: Decreased renal clearance of methotrexate
• Penicillins: Reduced renal clearance of methotrexate
• Sulfonamides: Increased risk of bone marrow suppression
• Trimethoprim/sulfamethoxazole: Increased hematologic toxicity
• Proton pump inhibitors: May reduce methotrexate clearance
• Live vaccines: Contraindicated due to immunosuppression
• Folic acid: May reduce efficacy but decreases toxicity

Adverse Effects

• Nausea/vomiting
• Stomatitis
• Diarrhea
• Alopecia
• Rash
• Elevated liver enzymes
• Fatigue

• Bone marrow suppression (leukopenia, thrombocytopenia, pancytopenia)
• Hepatotoxicity (elevated transaminases, fibrosis, cirrhosis)
• Pulmonary fibrosis and interstitial pneumonitis
• Severe mucositis and gastrointestinal ulceration
• Renal failure
• Neurotoxicity (especially with high doses)
• Increased risk of infections
• Secondary malignancies with long-term use

Monitoring Parameters

• Complete blood count with differential
• Comprehensive metabolic panel (liver and renal function)
• Chest X-ray
• Pregnancy test in women of childbearing potential
• Hepatitis B and C screening

• CBC weekly initially, then monthly when stable
• Liver function tests every 4-8 weeks
• Renal function every 3-6 months
• Pulmonary function monitoring if symptoms develop
• Regular skin examinations for psoriasis patients
• Monitoring for signs of infection

• Annual liver biopsy consideration after cumulative dose of 1.5g or with persistent LFT abnormalities
• Periodic chest imaging if pulmonary symptoms occur
• Bone density monitoring with long-term use

Patient Education

• Take exactly as prescribed, typically once weekly (not daily)
• Understand the importance of regular blood tests
• Report signs of infection (fever, sore throat), unusual bleeding/bruising, or yellowing of skin/eyes
• Use effective contraception during treatment and for ≥3 months after discontinuation
• Avoid alcohol consumption due to increased hepatotoxicity risk
• Be aware of potential drug interactions with OTC medications
• Carry identification indicating methotrexate use
• Understand the delayed onset of effect (4-8 weeks for rheumatological effects)
• Report any new respiratory symptoms immediately

References

1. Jylamvo Prescribing Information. FDA Approved Label. 2. Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2020;79(6):685-699. 3. Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis. Drugs. 2009;69(3):289-306. 4. Weinblatt ME. Methotrexate in rheumatoid arthritis: a quarter century of development. Trans Am Clin Climatol Assoc. 2013;124:16-25. 5. American College of Rheumatology. Guidelines for monitoring methotrexate therapy. Arthritis Care Res. 2021;73(3):307-315. 6. Bleyer WA. The clinical pharmacology of methotrexate. Cancer. 1978;41(1):36-51. 7. Lopez-Olivo MA, et al. Methotrexate for rheumatoid arthritis. Cochrane Database Syst Rev. 2022;3:CD000957.