Methotrexate Pfizer Italia (Methotrexate Sodium)

Methotrexate is an antimetabolite used across several oncologic and autoimmune disease pathways.

• Acute lymphoblastic leukemia: induces remission by inhibiting DNA synthesis in malignant lymphoblasts.
• Acute myeloid leukemia: reduces proliferation of myeloid blasts through folate pathway blockade.
• Non‑Hodgkin lymphoma: slows tumor growth by preventing nucleotide formation.
• Rheumatoid arthritis: diminishes inflammatory activity and joint damage by modulating immune cell replication.
• Psoriasis: reduces hyperproliferation of skin cells, improving plaque severity.
• Prophylaxis/treatment of CNS leukemia: penetrates the central nervous system to eradicate leukemic cells.

• Methotrexate inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate. This blocks the synthesis of purine nucleotides and thymidylate, leading to reduced DNA, RNA and protein production. The resulting impairment of cell division preferentially affects rapidly proliferating malignant and immune cells, producing its antineoplastic and immunosuppressive effects.

Methotrexate may cause a range of adverse reactions, from mild to severe.

Common Side Effects

• Nausea and vomiting: gastrointestinal upset occurring shortly after administration.
• Fatigue: persistent tiredness that may affect daily activities.
• Mucositis: inflammation and ulceration of the oral mucosa.
• Alopecia: temporary hair loss due to reduced cell turnover.
• Elevated liver enzymes: mild hepatic irritation detectable on blood tests.
• Skin rash: mild erythema or itching at the injection site.

Serious or Rare Side Effects

• Bone marrow suppression: leading to anemia, leukopenia or thrombocytopenia.
• Pulmonary toxicity: interstitial pneumonitis presenting with cough and dyspnea.
• Severe infection: opportunistic infections due to immunosuppression.
• Hepatic fibrosis or cirrhosis: long‑term liver injury with elevated enzymes.
• Renal failure: acute nephrotoxicity from precipitation of drug crystals.
• Life‑threatening skin reactions: such as Stevens‑Johnson syndrome or toxic epidermal necrolysis.

Methotrexate requires careful monitoring and specific safety measures.

• Monitor blood counts: perform regular CBC to detect marrow suppression early.
• Assess liver function: conduct periodic LFTs to identify hepatotoxicity.
• Evaluate renal function: check serum creatinine and clearance before each dose.
• Avoid use in pregnancy: drug is teratogenic and contraindicated for pregnant patients.
• Counsel on infection risk: advise patients to report fevers or signs of infection promptly.
• Store at ambient temperature: keep in original container, protect from moisture and direct light.

Methotrexate interacts with several medicines that can alter its efficacy or toxicity.

Major Interactions (Avoid)

• NSAIDs: increase methotrexate serum levels and risk of renal toxicity.
• Penicillins: reduce methotrexate clearance, heightening toxicity.
• Sulfonamides: compete for renal tubular secretion, raising drug concentrations.
• Live vaccines: may cause severe infection due to immunosuppression.
• Proton pump inhibitors: can impair renal elimination, leading to accumulation.

Moderate Interactions (Monitor Closely)

• Azathioprine: additive bone‑marrow suppression requires CBC monitoring.
• Allopurinol: may increase methotrexate toxicity; dose adjustment may be needed.
• Warfarin: potentiates anticoagulant effect, necessitating INR checks.
• Oral contraceptives: reduced efficacy; advise alternative contraception.
• Trimethoprim‑sulfamethoxazole: may enhance myelosuppression, monitor blood counts.