Introduction
- Methotrexate is a medication used to treat a variety of autoimmune conditions and certain cancers.
- It works by inhibiting dihydrofolate reductase, interfering with DNA synthesis and cellular replication.
- Commonly prescribed for rheumatoid arthritis, psoriasis, and certain types of leukemia.
- Requires careful monitoring due to its potential toxicity.
Uses of Methotrexate
- Autoimmune Conditions
- Rheumatoid Arthritis (RA): Reduces joint inflammation and slows disease progression.
- Psoriasis: Controls severe or refractory cases by reducing skin cell turnover.
- Systemic Lupus Erythematosus (SLE): Used off-label in some cases.
- Cancer Therapy
- Acute Lymphoblastic Leukemia (ALL): High-dose therapy as part of chemotherapy regimens.
- Non-Hodgkin’s Lymphoma: Used in specific chemotherapy protocols.
- Choriocarcinoma: Effective in treating this rare cancer.
- Ectopic Pregnancy
- Used to terminate ectopic pregnancies by stopping the growth of embryonic cells.
- Other Off-Label Uses
- Crohn’s disease, sarcoidosis, and uveitis.
Mechanism of Action
- Methotrexate inhibits dihydrofolate reductase, blocking the conversion of dihydrofolate to tetrahydrofolate.
- This disrupts DNA synthesis, primarily affecting rapidly dividing cells such as immune cells and cancer cells.
Forms, Brand Names, and Costs
- Available Forms
- Tablets: 2.5 mg, 5 mg, 7.5 mg, 10 mg.
- Injectable: 25 mg/mL (subcutaneous, intramuscular, or intravenous).
- Brand Names
- USA: Rheumatrex, Trexall, Otrexup, Rasuvo.
- Manufacturers: Pfizer, Amgen, Teva Pharmaceuticals.
- Cost
- Tablets: $10–$50 per month (depending on dosage).
- Injections: $100–$500 per dose (brand-specific).
Dosing and Administration
- For Autoimmune Conditions
- Start with 7.5–15 mg orally or subcutaneously once weekly.
- Increase to a maximum of 25 mg weekly, if tolerated.
- For Cancer
- High-dose regimens (variable dosing) administered in cycles.
- For Ectopic Pregnancy
- Single-dose protocol: 50 mg/m² intramuscularly.
- Folic Acid Supplementation
- 1 mg daily to reduce methotrexate toxicity.
Contraindications
- Hypersensitivity to methotrexate.
- Severe renal or hepatic impairment.
- Active infections, including tuberculosis.
- Pregnancy and breastfeeding (teratogenic).
Precautions
- Monitor liver function and renal function regularly.
- Use contraception during treatment and for 6 months after discontinuation.
- Avoid alcohol to minimize liver toxicity.
- Increased risk of infection; counsel patients to report fever or signs of infection immediately.
Common Side Effects
- Gastrointestinal
- Nausea, vomiting, diarrhea, and mouth sores.
- Hematological
- Anemia, leukopenia, thrombocytopenia.
- Liver Toxicity
- Elevated liver enzymes, long-term fibrosis, or cirrhosis.
- Other
- Fatigue, hair thinning, and skin rash.
Serious Side Effects
- Pulmonary toxicity (pneumonitis).
- Hepatotoxicity (irreversible liver damage).
- Bone marrow suppression (life-threatening pancytopenia).
- Severe infections, including opportunistic infections.
Drug Interactions
- Increased Toxicity
- NSAIDs (e.g., ibuprofen, naproxen): Reduce methotrexate clearance.
- Antibiotics (e.g., trimethoprim, sulfonamides): Additive bone marrow suppression.
- Reduced Effectiveness
- Proton pump inhibitors (PPIs): Delay methotrexate elimination.
- Folic Acid Antagonism
- Avoid excessive folate supplementation, as it may reduce methotrexate efficacy.
Monitoring Parameters
- Blood Tests: CBC, liver function tests (LFTs), and renal function every 4–8 weeks.
- Chest X-Ray: Baseline and periodic checks for pneumonitis.
- Pregnancy Tests: For women of childbearing potential before initiating therapy.
Patient Counseling Points
- Take methotrexate exactly as prescribed; do not exceed the weekly dose.
- Use contraception during treatment and for 6 months afterward.
- Avoid alcohol and stay hydrated to protect the liver and kidneys.
- Report symptoms of infection, unusual bruising, or persistent fatigue immediately.
- Folic acid supplementation can help reduce side effects but must be taken as directed.
Use in Children
- Dosing is weight- or surface area-based, especially in juvenile idiopathic arthritis (JIA) or leukemia.
- Monitor growth and development during treatment.
Use in Pregnancy
- Contraindicated due to teratogenic effects.
- Consult a healthcare provider for alternative treatments.
Use in Elderly
- Start with a lower dose due to increased sensitivity to side effects, especially renal impairment.
FAQs About Methotrexate
Q1: What conditions is methotrexate used to treat?
- Rheumatoid arthritis, psoriasis, certain cancers, ectopic pregnancy, and off-label for Crohn’s disease.
Q2: How long does methotrexate take to work for autoimmune diseases?
- 4–6 weeks for symptom improvement, with full effects in 12 weeks.
Q3: Can methotrexate cause hair loss?
- Yes, mild hair thinning is a possible side effect.
Q4: Is alcohol allowed during methotrexate treatment?
- No, alcohol increases the risk of liver damage.
Q5: Can methotrexate be stopped suddenly?
- Discontinuation should be done under medical supervision to prevent disease flare-ups.
Q6: What should I do if I miss a dose?
- Take it as soon as possible unless it’s close to the next dose. Never double-dose.
Q7: Can methotrexate interact with over-the-counter medications?
- Yes, avoid NSAIDs without consulting your doctor.
Q8: How is methotrexate toxicity treated?
- Administer leucovorin rescue (folinic acid) to counteract toxicity.
Q9: Does methotrexate weaken the immune system?
- Yes, it suppresses the immune system, increasing infection risk.
Q10: What are the signs of methotrexate toxicity?
- Severe fatigue, mouth ulcers, shortness of breath, or dark urine.
Q11: Can methotrexate be used long-term?
- Yes, with regular monitoring to manage side effects and toxicity.
Q12: Is methotrexate safe for children?
- Yes, in conditions like juvenile idiopathic arthritis (JIA), with dose adjustments and monitoring.