From the Guidelines
Methotrexate toxicity can indeed cause fever, and patients should be advised to seek urgent medical attention if they develop this symptom. According to the British Association of Dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 1, patients should be warned about the signs and symptoms of methotrexate toxicity, including fever or flu-like illness. This is crucial because methotrexate is an antimetabolite that can affect rapidly dividing cells, leading to tissue damage and potentially life-threatening complications when it reaches toxic levels in the bloodstream.
Key points to consider when evaluating methotrexate toxicity include:
- The onset of therapeutic benefit may not be apparent for 3–12 weeks, during which time patients should be closely monitored for signs of toxicity 1.
- Patients should be advised to seek urgent medical attention if they develop symptoms such as fever, mouth ulceration, tiredness, unexplained bruising or bleeding, nausea, vomiting, abdominal pain, or dark urine 1.
- Methotrexate toxicity can lead to bone marrow suppression, liver impairment, and increased risk of infections due to compromised immune function.
- Treatment for methotrexate toxicity often involves leucovorin (folinic acid) rescue therapy, which helps counteract the toxic effects of methotrexate [not explicitly stated in (1), but a well-established medical practice].
In clinical practice, it is essential to prioritize patient safety and take a proactive approach to managing potential methotrexate toxicity. This includes regular blood tests to monitor for signs of toxicity, advising patients on the importance of seeking urgent medical attention if they develop concerning symptoms, and providing guidance on limiting alcohol intake and avoiding potential drug interactions 1. By taking these precautions, healthcare providers can help minimize the risks associated with methotrexate therapy and ensure the best possible outcomes for their patients.
From the FDA Drug Label
The most frequently reported adverse reactions include ... chills and fever... After the intrathecal use of methotrexate, the central nervous system toxicity which may occur can be classified as follows: acute chemical arachnoiditis manifested by such symptoms as ... and fever; Although clinically variable, the typical patient with methotrexate induced lung disease presents with fever, cough, dyspnea, hypoxemia, and an infiltrate on chest X-ray; Yes, methotrexate toxicity can cause fever 2, 2, 2.
From the Research
Methotrexate Toxicity and Fever
- Methotrexate (MTX) toxicity can cause a range of symptoms, including fever, as reported in a case of methotrexate neurotoxicity presented as status epilepticus, encephalopathy, and high fever 3.
- High-dose methotrexate is used to treat various cancers and can cause significant neurotoxicity, including symptoms such as high fever, in 1% to 4.5% of patients 3.
- Methotrexate toxicity can also lead to other symptoms such as bone marrow suppression, pulmonary toxicity, nephrotoxicity, hematologic toxicity, and an increased risk of infections 4.
- Fever is not a commonly reported symptom of methotrexate toxicity in all studies, but it is mentioned as a possible symptom in cases of methotrexate neurotoxicity 3.
Risk Factors for Methotrexate Toxicity
- Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions 5.
- Patients with compromised renal function are at a higher risk of developing methotrexate toxicity, and a lower initial dose is recommended for these patients 4.
- Monitoring of serum creatinine, urine output, and serum methotrexate concentration is essential to assess renal clearance and prevent toxicity 5.
Treatment of Methotrexate Toxicity
- Treatment of severe methotrexate toxicity has three main goals: clearance of methotrexate from the bloodstream, folinic acid therapy, and organ treatment 4.
- Leucovorin is highly beneficial in preventing myelosuppression, gastric toxicity, and neurotoxic effects after high-dose methotrexate therapy 4.
- Glucarpidase has been licensed for the treatment of high plasma methotrexate levels in patients with compromised renal function 4.