• Acute lymphoblastic leukemia:
    • Adults: IV 10-5,000mg/m2/dose on specific day(s) of cycle per regimen
    • Dose dependent on disease state, patient risk category, concurrent drugs used, phase of treatment and response to treatment
    • Maintenance PO: 20mg/m2/dose weekly
  • Meningeal leukemia:
    • Adults:
      • Treatment: 12-15mg intrathecally every 2-5 days up to twice per week
      • Administer 1 additional dose after cell count on CSF returns to normal
      • Prophylaxis: 12-15 mg intrathecally no more than once weekly
      • Patients with Down syndrome should be given leucovorin rescue with methotrexate intrathecally
    • <1 year: 6mg intrathecally
    • 1-<2 years: 8mg intrathecally
    • 2-<3 years: 10mg intrathecally
    • 3-<9 years: 12mg intrathecally
    • ≥9 years: 12-15mg intrathecally
  • Mycologist fungoides:
    • Monotherapy: PO 25-75mg weekly
    • Combination therapy: PO 10mg/m2/dose twice weekly
  • Non-Hodgkin lymphoma:
    • Induction treatment: IV 1000-3,000mg/m2/dose
      • Part of multi-drug regimen
      • Administer leucovorin rescue
      • Alkalinize urine to maintain pH of 7 or higher
      • Give fluids to maintain adequate hydration and urinary output before 1st dose and throughout treatment
    • Relapsed/refractory disease: PO 2.5mg 2-4 times per week
      • Max 10mg/week
  • CNS lymphoma:
    • Monotherapy: IV 8,000mg/m2/dose *1 on specific day of cycle per regimen
    • Combination with immunotherapy: 3,000-8,000 mg/m2 IV infusion
      • Administer leucovorin rescue
      • Alkalinize urine to maintain pH of 7 or higher
      • Give fluids to maintain adequate hydration and urinary output before 1st dose and throughout treatment
  • Osteosarcoma:
    • IV 12g/m2/dose *1 at week 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45
      • Initiate 4 weeks after surgery
      • Max: 20g/dose
      • If peak serum methotrexate <454mcg/mL at end of initial infusion, dose may be increased to 15g/m2 in subsequent treatments
      • Part of multi-drug regimen
      • Administer leucovorin rescue
      • Alkalinize urine to maintain pH of 7 or higher
      • Give fluids to maintain adequate hydration and urinary output before 1st dose and throughout treatment
  • Breast cancer:
    • IV 40mg/m2/dose *1 on days 1, 8 of 28-day cycle *6 cycles
    • Part of a cyclophosphamide- and fluorouracil-based multidrug regimen
  • Squamous cell carcinoma of head and neck:
    • IV 40-60mg/m2/dose weekly
  • Gestational tophoblastic neoplasia:
    • Low-risk disease: IV/IM 30-200mg/m2 OR4-1mg/kg
    • High-risk disease: IV 300mg/m2 infused over 12 hours as a component of a multidrug regimen
  • Rheumatoid arthritis:
    • Initially PO/IV/IM 5mg as a single weekly dose OR PO 2.5mg BD *3 sequential doses per week
    • Max: 20-25mg/week
    • Give with folic acid 1mg OD or leucovorin 5mg per week
  • Severe psoriasis:
    • PO/SC/IM/IV 7.5-25mg weekly
    • Max: PO 30mg/week; SC/IM/IV 25mg/week
    • PO may give divided doses BD *3 doses weekly
    • Use lowest effective dose
    • Give with folic acid 1mg OD or leucovorin 5mg weekly
  • Active polyarticular juvenile idiopathic arthritis (pJIA) in children:
    • PO/IM/SC 10mg/m² every week
  • Ectopic pregnancy (Off-label):
    • IM/IV 50 mg/m2/dose *1
    • Repeat dose in 7 days if beta-HCG levels have not decreased at least 15% from day of first injection
  • Moderate-severe Crohn’s disease (Off-label):
    • Initially SC/IM 25mg weekly *16-25 weeks, then decrease dose to SC/IM 15mg weekly
    • For induction or remission maintenance treatment
    • Give with folic acid 1mg OD or leucovorin 5mg weekly

Injection: 25mg/mL

Tablet: 2.5mg

  • Intrathecal administration: Before administration, equal volume of CSF is usually withdrawn
    • Administer drug only if easy flow of blood-free CSF is noted
  • SC administered in abdomen or thigh
  • Specific dosing schemes vary, but high doses should be followed by leucovorin 24 hours after initiation of therapy to prevent toxicity

DMARD; Antimetabolite anticancer

Immunosuppressant: It inhibits dihydrofolate reductase and inhibits lymphocyte proliferation

  • Stomatitis
  • Leukopenia
  • Nausea
  • Abdominal discomfort
  • Infection
  • Malaise
  • Fatigue
  • Rigors
  • Fever
  • Dizziness
  • Elevated LFTs
  • Vomiting
  • Thrombocytopenia
  • Rash
  • Pruritus
  • Dermatitis
  • Diarrhea
  • Alopecia
  • Pancytopenia
  • Anemia
  • Photosensitivity
  • Headache
  • Concurrent nitrous oxide use
  • Alcohol abuse history (RA, psoriasis or JIA use)
  • Intrathecal use (benzyl alcohol-containing inj form)
  • High-dose use (benzyl alcohol-containing inj form)
  • Infants w/ low birth wt (benzyl alcohol-containing inj form)
  • Neonates (benzyl alcohol-containing inj form)
  • Pregnancy (benzyl alcohol-containing inj forms)
  • Pregnancy (RA, psoriasis or JIA use)
  • CrCl <10 (adult patients not on hemodialysis)
  • Significant renal impairment (ectopic pregnancy use)
  • Peritoneal dialysis (adult patients)
  • Significant hepatic impairment (ectopic pregnancy use)
  • Chronic hepatic disease chronic (RA, psoriasis or JIA use)
  • Blood dyscrasia (RA, psoriasis or JIA use)
  • Myelosuppression (RA, psoriasis or JIA use)
  • Immunodeficiency syndrome
  • Avoid breastfeeding during treatment and *1 week after discontinuation

 

WARNING

  • Administer only preservative-free injection form for treatment of neonates, low birth weight infants, intrathecal use or high-dose regimens
  • Known to cause embryo-fetal toxicity and death
  • Contraindicated in patients with history of severe hypersensitivity reactions to methotrexate, including anaphylaxis
  • Drug elimination reduced in renal impairment, ascites or pleural effusions
  • Unexpectedly severe and sometimes fatal myelosuppression, aplastic anemia and GI toxicity reported with methotrexate (usually high dose) in combination with some NSAIDs
  • Hepatotoxicity, fibrosis and cirrhosis generally only after prolonged use
  • Methotrexate-induced lung disease, including acute or chronic interstitial pneumonitis, may occur acutely or any time during treatment and is not always reversible
  • Diarrhea and ulcerative stomatitis require treatment interruption, otherwise intestinal perforation may lead to hemorrhagic enteritis and death
  • Malignant lymphoma may occur with low-dose treatment and may regress when treatment discontinued
  • Tumor lysis syndrome (TLS) may occur in patients with rapidly growing tumors
  • Severe, occasionally fatal reactions may occur within days after single or multiple PO, IM, IV or intrathecal doses
  • Potentially fatal opportunistic infections
  • Concomitant radiotherapy increase risk of soft tissue necrosis and osteonecrosis
  • Live vaccines
  • Acitretin
  • Cidofovir
  • Tamoligene

                          Drug Status

Availability Prescription only
Pregnancy Contraindicated in non-malignant disease
Breastfeeding Contraindicated
Schedule Not controlled
BRAND NAME STRENGTH FORMULATION PACK SIZE MANUFACTURER DISTRIBUTOR
Biotrexate 50mg/2mL Injection 1’s Zydus Healthcare Sai Pharma
Emthex 50mg Injection 1’s PSM Pharma PSM Pharma
Emthex 2.5mg Tablet 100’s PSM Pharma PSM Pharma
Methotrexate 2.5mg Tablet 100’s Pfizer Labs Pfizer Labs
Trexglo 2.5mg Tablet 30’s Globela Pharma Globela Pharma
Trexol 50mg/2mL Injection 1’s Venus Remedies Surgipharm Ltd
Unitrexate 2.5mg Tablet 1’s Veteran Pharma Veteran Pharma
Zexate 500mg/20mL Injection 1’s Fresenius Kabi Nairobi Enterprises
Zexate 50mg/2mL Injection 1’s Fresenius Kabi Nairobi Enterprises