Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. The mechanism of action in rheumatoid arthritis is unknown; it may affect immune function.

Rasuvo is a folate analog metabolic inhibitor indicated for the:
• Management of patients with severe, active rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA), who are intolerant of or had an inadequate response to first-line therapy.
• Symptomatic control of severe, recalcitrant, disabling psoriasis in adults who are not adequately responsive to other forms of therapy Rasuvo is not indicated for the treatment of neoplastic diseases (Limitation of Use).

• Rasuvo is for once weekly subcutaneous use only.
• Administer Rasuvo in the abdomen or thigh.
• Use another formulation of methotrexate for patients requiring oral, intramuscular, intravenous, intra-arterial, or intrathecal dosing, doses less than 7.5 mg per week, doses above 30 mg per week, high-dose regimens, or dose adjustments of less than 2.5 mg increments.
Starting doses of methotrexate:
• RA: 7.5 mg once weekly of an oral or subcutaneous formulation.
• pJIA: 10 mg/m2 once weekly.
• Psoriasis: 10 to 25 mg once weekly of an oral, intramuscular, subcutaneous, or intravenous formulation.
• Adjust dose gradually to achieve an optimal response

Common adverse reactions are: nausea, abdominal pain, dyspepsia, stomatitis/mouth sores, rash, nasopharyngitis, diarrhea, liver function test abnormalities, vomiting, headache, bronchitis, thrombocytopenia, alopecia, leukopenia, pancytopenia, dizziness, photosensitivity, and “burning of skin lesions”

• Pregnancy.
• Nursing mothers.
• Alcoholism or liver disease.
• Immunodeficiency syndromes.
• Preexisting blood dyscrasias.
• Hypersensitivity to methotrexate.

• Organ system toxicity: Potential for serious toxicity. Only for use by physicians experienced in antimetabolite therapy.
• Embryo-fetal toxicity: Exclude pregnancy before treatment. Avoidpregnancy if either partner is receiving Rasuvo. Advise males to avoid pregnancy for a minimum of three months after therapy and females to avoid pregnancy for at least one ovulatory cycle after therapy.
• Effects on reproduction: May cause impairment of fertility, oligospermia, and menstrual dysfunction.
• Laboratory tests: Monitor complete blood counts, renal function, and liver function tests.
• Risks from improper dosing: Mistaken daily use has led to fatal toxicity.
• Patients with impaired renal function, ascites, or pleural effusions: Elimination is reduced.
• Dizziness and fatigue: May impair ability to drive or operate machinery