- 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
- Adults:
- 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
- Induction treatment: IV 1000-3,000mg/m2/dose
-
- Relapsed/refractory disease: PO 2.5mg 2-4 times per week
- Max 10mg/week
- Max 10mg/week
- Relapsed/refractory disease: PO 2.5mg 2-4 times per 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
- Combination with immunotherapy: 3,000-8,000 mg/m2 IV infusion
- 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
- IV 12g/m2/dose *1 at week 4, 5, 6, 7, 11, 12, 15, 16, 29, 30, 44, 45
- 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
- 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
- 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 |