Methotrexate

High-dose methotrexate therapy used in cancer treatment is monitored with one or more methotrexate blood tests that are typically requested at 24 hours, 48 hours, and as needed at 72 hours after a person's methotrexate dose has been administered. Testing is performed to detect toxic concentrations of methotrexate at these time points. A drug called leucovorin (folinic acid) can be given as a "rescue" treatment to protect a person from the toxic effects of methotrexate. The methotrexate blood tests help to identify the need for leucovorin and guides the timing and amount of its administration.

Low-dose methotrexate therapy is rarely monitored by a methotrexate blood test. It is usually monitored by assessing the function of the kidney, the liver, and bone marrow cell production. Testing may include a Full Blood Count (FBC) to measure red blood cell counts, white blood cell counts, and platelets; a blood urea and creatinine to evaluate kidney function; and liver function tests to evaluate liver function. The development of liver fibrosis on long-term treatment may also be evaluated with a blood test called procollagen III N-terminal peptide (P3NP), which is normally checked annually.

A methotrexate test is typically requested at 24 hours, 48 hours, and at 72 hours as needed after high-dose methotrexate is administered. Tests to monitor blood cell counts and kidney and liver function are also requested at regular intervals during methotrexate therapy. The test is rarely used to monitor low-dose methotrexate. A methotrexate blood test may also be requested whenever a person has symptoms or signs that suggest methotrexate toxicity.

Common side effects associated with methotrexate use (that may be seen without toxic concentrations of methotrexate) include:

• Loss of appetite
• Nausea or vomiting
• Thinning hair
• Sore mouth/mouth ulcers
• Fatigue
• Diarrhoea
• Sensitivity to sunlight
• Headaches

More serious signs and symptoms seen with methotrexate toxicity include:

• Dark stools or urine
• Jaundice
• Bruising and bleeding
• Drug-induced hepatitis
• Cough
• Sore throat
• Fever and chills
• Shortness of breath
• Chest pain
• Abdominal pain
• Bacterial septicaemia
• Severe skin rash
• Seizures

With therapeutic drug monitoring, there is typically a "therapeutic range”, with a lower concentration limit that is associated with effectiveness and an upper limit associated with unacceptable side effects and toxicity. In the case of methotrexate, the primary focus is on the upper concentration limit – the drug's toxic effects on the kidney, liver, and blood cell counts, and on unacceptable side effects.

When methotrexate is given in high doses, toxic concentrations are generally considered to be:

above 5 µmol/L at 24 hours after the dose

above 0.5 µmol/L at 48 hours

above 0.05 µmol/L at 72 hours

Test results are used to guide the amount and timing of leucovorin (folinic acid) given as a "rescue" treatment.

Low-dose methotrexate therapy is rarely monitored with a methotrexate blood test. The therapeutic concentration of the drug depends upon the condition and the timing of the blood collection.

Although the risks of side effects and organ damage increase with increasing doses of methotrexate, a person may experience side effects from methotrexate use without having high blood concentrations of the drug.

A variety of prescription and over-the-counter medications and supplements can interfere or interact with methotrexate, including: phenytoin, theophylline, digoxin, ciclosporin, warfarin, omepraxole, diuretics and certain antibiotics (trimethoprim, co-trimoxazole). These substances may need to be avoided, or the dosages of methotrexate and other medications may need to be adjusted.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and salicylates (aspirin) can reduce the excretion of methotrexate. Excessive alcohol use can increase the risk of methotrexate-associated liver damage.

Methotrexate must not be taken while a woman is pregnant or breast-feeding. It is important to avoid getting pregnant or fathering a child while taking methotrexate, and for 6 months afterwards (consult your doctor).

Doctors may perform blood tests to assess kidney and liver function and blood cell counts prior to initiating methotrexate therapy.

Sensitivity to methotrexate and associated side effects increase with age.

Response to methotrexate therapy varies. Some of the variation in effectiveness and toxicity is thought to be due to genetic variations. This concept is being researched and may lead to the clinical use of one or more genetic tests to help predict a person's response to methotrexate.

Some of the side effects associated with methotrexate use are due to decreased folate levels. Doctors may recommend folate supplementation to help protect healthy cells in your body and minimise symptoms like nausea and diarrhoea.