What is the recommended timing for administering ondansetron (generic name) for methotrexate-related nausea?

From the Guidelines

Ondansetron should be given at a dose of 8 mg 2 h before the methotrexate dose and repeated 12 and 24 h later if required to effectively manage methotrexate-related nausea. This approach is based on the British Association of Dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 2016 1. The guidelines suggest that nausea tends to occur within 12–24 h of consumption of the medication and is dose-dependent.

Key Considerations

• Nausea is one of the commonest side-effects of methotrexate, occurring in up to 25% of patients 1.
• The usual advice is to take the medication before bedtime or with food; folic acid supplementation of up to 5 mg daily has been shown to reduce nausea, although this has not been replicated in other studies 1.
• Ondansetron is an effective way of managing the nausea, and granisetron is an alternative 5-HT3 antagonist that has been helpful in methotrexate-induced nausea for patients with rheumatoid arthritis 1.

Dosage and Administration

• The recommended dose of ondansetron is 8 mg, given 2 h before the methotrexate dose and repeated 12 and 24 h later if required 1.
• The dosage of methotrexate may need to be adjusted based on the patient's glomerular filtration rate (GFR), with reduced doses recommended for patients with decreased GFR 1.

Patient-Specific Factors

• Patients with severe methotrexate-induced nausea may benefit from extended ondansetron coverage for 48-72 hours after methotrexate administration if they experience delayed nausea.
• Parenteral delivery of methotrexate may also reduce nausea and should be considered for patients who experience severe nausea with oral methotrexate 1.

From the FDA Drug Label

In a double-blind US trial in 336 patients receiving a cyclophosphamide-based chemotherapy regimen containing either methotrexate or doxorubicin, ondansetron tablets 8 mg administered twice a day, was as effective as ondansetron tablets 8 mg administered 3 times a day in preventing nausea and vomiting The first 8 mg dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent 8 mg dose 8 hours after the first dose, followed by 8 mg administered twice a day for 2 days after the completion of chemotherapy

The recommended timing for administering ondansetron for methotrexate-related nausea is to give the first dose 30 minutes before the start of chemotherapy. The dosage regimen is 8 mg twice a day 2.

From the Research

Ondansetron Administration Timing for Methotrexate-Related Nausea

• The recommended timing for administering ondansetron for methotrexate-related nausea is not explicitly stated in the provided studies, but we can infer some information from the research.
• A study published in 2011 3 used a 4- to 8-week tapering schedule with methotrexate, and ondansetron was given as premedication, but the exact timing is not specified.
• Another study from 1993 4 administered ondansetron orally, 8 mg three times a day for 15 days, starting at the same time as cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy.
• A 1995 study 5 compared the efficacy and tolerability of ondansetron 8 mg twice daily for 3 days with placebo in preventing nausea and vomiting in patients receiving cyclophosphamide-doxorubicin-based chemotherapy, with the first dose of study drug administered 30 minutes before the initiation of chemotherapy.
• A 2017 study 6 recorded nausea severity, timing of emetic episodes, and administration of antiemetics beginning immediately prior to intrathecal methotrexate administration, for the next 24 hours (acute phase), and for a maximum of 7 additional days (delayed phase), but does not specify the exact timing of ondansetron administration.

Key Findings

• Ondansetron is effective in preventing nausea and vomiting associated with methotrexate and other chemotherapy agents 3, 4, 5.
• The optimal timing for administering ondansetron for methotrexate-related nausea is not clearly established, but it is often given as premedication or shortly before chemotherapy administration 3, 4, 5.
• Further research is needed to determine the most effective timing and dosage of ondansetron for preventing methotrexate-related nausea 6.