Methotrexate infusions (high dose) and drug interactions for oncology patients

This fact sheet has been written for parents and carers about how to use this medicine in children. This information sometimes differs from that provided by the manufacturers, because their information is usually aimed at adult patients. Please read this information carefully and keep it somewhere safe so that you can read it again.

Methotrexate is used to treat a wide range of cancers. High dose methotrexate is given in hospital as an intravenous infusion and this information sheet is NOT referring to intermediate dose methotrexate (capizzi), intrathecal methotrexate or methotrexate tablets administered at home.

Interactions with other medications

Methotrexate can interact with other medications, especially when given in high doses. For example, the following medications may affect the levels of methotrexate in the body:

  • Some antibiotics including penicillins (e.g. Amoxycillin, Flucloxacillin), trimethoprim with sulfamethoxazole (also called Septrin, Resprim and Bactrim) and ciprofloxacin.
  • Proton pump inhibitors given to protect the stomach (e.g. Omeprazole, Esomeprazole, Pantoprazole).
  • Some medicines used to treat pain and inflammation (Non-Steroidal Anti-inflammatory Drugs NSAIDs) such as Ibuprofen – Nurofen/Brufen/Advil , and Diclofenac – Voltaren.
  • Other medicines including Levetiracetam (Keppra) and other medicines used to prevent seizures. It is important NOT to stop medicines like Levetiracetam abruptly. Please discuss a plan for your child with your consultant.

These medications can reduce the body’s ability to excrete/remove methotrexate from the blood which may result in a higher chance of side effects/toxicity.

Packaging of various medications which Methotrexate can interact with.

When to withhold certain medications and for how long?

  • Proton pump inhibitors (e.g. Omeprazole, Esomeprazole, Pantoprazole) should be with-held the day your child is admitted to hospital and restart on discharge or sooner if directed by the treating team.
  • Trimethoprim with sulfamethoxazole (Septrin, Resprim and Bactrim) should be with-held for at least 48 hours prior to admission and restart on discharge or sooner if directed by the treating team.
  • Penicillin based antibiotics (e.g. Amoxycillin, Amoxycillin with clavulanic acid, Flucloxacillin and Phenoxymethylpenicillin), should be with-held from the day of admission for high dose methotrexate and should only be restarted on discharge or sooner on direction by the treating team.
  • Ciprofloxacin should be with-held from the day before admission for high dose methotrexate and should only be restarted on discharge or sooner on direction by the treating team.
  • A certain group of pain relieving medicines called Non-steroidal Anti-inflammatory Drugs- NSAIDs (including Ibuprofen – Nurofen/Brufen/Advil, and Diclofenac – Voltaren) should be AVOIDED throughout the entire chemotherapy treatment. These medications can increase the toxicity of many chemotherapy medications including methotrexate and should NOT be used unless prescribed by the oncology consultant.

Who to contact for more information

Your consultant at clinic visits or the Oncology team at the Queensland Children’s Hospital.

Contact us

Oncology pharmacy
Level 5, Queensland Children’s Hospital
501 Stanley Street, South Brisbane, QLD 4101
t: 07 3068 1989

Oncology day unit
Level 5 (5c), Queensland Children’s Hospital
501 Stanley Street, South Brisbane, QLD 4101
t: 07 3068 2060

In an emergency, always call 000.

Queensland Poisons Information Centre 13 11 26.


Developed by Pharmacy Department, Queensland Children’s Hospital.

Updated: January 2016.

For details on any other sources used to create this leaflet, please contact us via CHQMedicationSafety@health.qld.gov.au.

Disclaimer: We take great care to make sure that the information in this leaflet is correct and up-to-date. However, medicines can be used in different ways for different patients. It is important that you ask the advice of your doctor or pharmacist if you are not sure about something.

This leaflet is about the use of these medicines in Australia, and may not apply to other countries. Children’s Health Queensland Hospital and Health Service cannot be held responsible for the accuracy of information, omissions of information, or any actions that may be taken as a consequence of reading this leaflet.

Last updated: October 2023