Methotrexate Injection and Chloral Hydrate: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Chloral Hydrate
No brand names on recordMethotrexate Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased methotrexate exposure
Interaction Deep Dive
Both chloral hydrate and methotrexate are eliminated via renal tubular excretion. Increased methotrexate exposure may be linked to competition for renal tubular transporters between methotrexate and chloral hydrate metabolites. A 2-year-old girl with acute lymphoblastic leukemia who received chloral hydrate followed by high-dose methotrexate displayed increased methotrexate AUC levels compared with AUC levels of high-dose methotrexate without chloral hydrate pretreatment. Use chloral hydrate with caution when administered concurrently with methotrexate1, and monitor closely for methotrexate adverse effects.
Why it happens (mechanism)
Decreased methotrexate renal clearance due to competition for tubular secretion
Literature reports
1 report — tap to read
a) A 2-year-old girl with acute lymphoblastic leukemia displayed decreased methotrexate clearance and grade 2 mucositis when treated concomitantly with chloral hydrate and high-dose methotrexate (HD-MTX) for the first 3 courses of consolidation chemotherapy. The patient was treated with 6 courses of methotrexate 2 g/m(2) via 4-hour infusion every 3 weeks following a standard 4-week induction protocol of dexamethasone, vincristine, and asparaginase. Chloral hydrate was used as a sedative before the first 3 courses. Methotrexate clearance was abnormally slow during the first 3 courses of HD-MTX and the patient had corresponding methotrexate AUC values of 1163, 1087, and 1153 mcmol x hr/L for courses 1, 2, and 3, respectively. Methotrexate AUC values decreased after chloral hydrate discontinuation to 642, 567, and 616 mcmol x hr/L for courses 4, 5, and 6, respectively. Increased hydration during cycles 4, 5, and 6 partially accounted for increased methotrexate clearance in these cycles. As both chloral hydrate and methotrexate are eliminated via renal tubular excretion, increased methotrexate exposure may be linked to competition for renal tubular transporters between methotrexate and chloral hydrate metabolites 1.
Common questions
Can I take Methotrexate Injection and Chloral Hydrate together?
Increased methotrexate exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methotrexate Injection and Chloral Hydrate interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Methotrexate Injection or Chloral Hydrate need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Dao K, Ivanyuk A, Buclin T, et al: Pharmacokinetic interaction between methotrexate and chloral hydrate. Pediatr Blood Cancer 2013; 60(3):518-520. PubMed
Keep reading about Chloral Hydrate
Keep reading about Methotrexate Injection
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