Methotrexate

Trexall, Otrexup, Rasuvo, Xatmep, Reditrex, Jylamvo

Antineoplastic • Antimetabolite / DMARD

Premium

NTIHepatotoxicNephrotoxic

Half-life

3-10 hours (dose-dependent)

Protein Binding

50%

Metabolized By

N/A

External

Drugs.com

Boxed warning

Bone marrow suppression
Hepatotoxicity
Lung disease
Renal damage
Severe skin reactions
Teratogenicity

Clinical alerts

Boxed warning

6 boxed warnings

Narrow therapeutic index

Small dose changes can cause toxicity or loss of effect

Nephrotoxic

Monitor renal function; avoid other nephrotoxins where possible

Hepatotoxic

Monitor liver function

Mechanism of action

Inhibits dihydrofolate reductase, blocking DNA and RNA synthesis

Recorded indications

From the drug index — may include conditions studied rather than approved indications

·Rheumatoid arthritis — first-line DMARD
·Psoriasis and psoriatic arthritis
·Acute lymphoblastic leukaemia (ALL)
·Non-Hodgkin lymphoma
·Ectopic pregnancy

Monitoring

Therapeutic range: 0.05–0.1 umol/L; < 0.05 umol/L at 72h post high-dose

Interactions

3 curated · 3 major or contraindicated · select a row for management

Interacting drug	Severity	Effect
trimethoprim	contraindicated	Severe pancytopenia, potentially fatal
trimethoprim-sulfamethoxazole	contraindicated	Severe methotrexate toxicity (pancytopenia, mucositis, nephrotoxicity)
ibuprofen	major	Methotrexate toxicity — myelosuppression, hepatotoxicity, mucositis.

Common adverse effects

Nausea
Stomatitis
Fatigue
Myelosuppression
Hepatotoxicity

Food, alcohol & herbal

Food

Folate-rich foods may reduce effectiveness at high doses

Alcohol · major

Significantly increases hepatotoxicity

Herbal

Echinacea (moderate) — May interfere with immunosuppression

Pharmacokinetics

Published parameters · PMID:10197600

Half-life: 3-10 hours (dose-dependent)
Protein binding: 50%
Clearance: 9 L/h; adult oncology patients (high-dose)
Volume of distribution: 25 L
Renally eliminated: 80%; Dose review in renal impairment
Model: 2-compartment

Pregnancy & lactation

Pregnancy category: X
Lactation: avoid

Sources

Assembled from: drug index, curated drug database, curated interaction pairs, published PK literature.

Not a substitute for clinical judgement

Methotrexate

Trexall, Otrexup, Rasuvo, Xatmep, Reditrex, Jylamvo

Antineoplastic • Antimetabolite / DMARD

Premium

NTIHepatotoxicNephrotoxic

Half-life

3-10 hours (dose-dependent)

Protein Binding

50%

Metabolized By

N/A

External

Drugs.com

Boxed warning

Bone marrow suppression
Hepatotoxicity
Lung disease
Renal damage
Severe skin reactions
Teratogenicity

Clinical alerts

Boxed warning

6 boxed warnings

Narrow therapeutic index

Small dose changes can cause toxicity or loss of effect

Nephrotoxic

Monitor renal function; avoid other nephrotoxins where possible

Hepatotoxic

Monitor liver function

Mechanism of action

Inhibits dihydrofolate reductase, blocking DNA and RNA synthesis

Recorded indications

From the drug index — may include conditions studied rather than approved indications

·Rheumatoid arthritis — first-line DMARD
·Psoriasis and psoriatic arthritis
·Acute lymphoblastic leukaemia (ALL)
·Non-Hodgkin lymphoma
·Ectopic pregnancy

Monitoring

Therapeutic range: 0.05–0.1 umol/L; < 0.05 umol/L at 72h post high-dose

Interactions

3 curated · 3 major or contraindicated · select a row for management

Interacting drug	Severity	Effect
trimethoprim	contraindicated	Severe pancytopenia, potentially fatal
trimethoprim-sulfamethoxazole	contraindicated	Severe methotrexate toxicity (pancytopenia, mucositis, nephrotoxicity)
ibuprofen	major	Methotrexate toxicity — myelosuppression, hepatotoxicity, mucositis.

Common adverse effects

Nausea
Stomatitis
Fatigue
Myelosuppression
Hepatotoxicity

Food, alcohol & herbal

Food

Folate-rich foods may reduce effectiveness at high doses

Alcohol · major

Significantly increases hepatotoxicity

Herbal

Echinacea (moderate) — May interfere with immunosuppression

Pharmacokinetics

Published parameters · PMID:10197600

Half-life: 3-10 hours (dose-dependent)
Protein binding: 50%
Clearance: 9 L/h; adult oncology patients (high-dose)
Volume of distribution: 25 L
Renally eliminated: 80%; Dose review in renal impairment
Model: 2-compartment

Pregnancy & lactation

Pregnancy category: X
Lactation: avoid

Sources

Assembled from: drug index, curated drug database, curated interaction pairs, published PK literature.

Not a substitute for clinical judgement

Methotrexate Drug Profile | PharmaGraphX