From the FDA Drug Label
In cases of massive overdosage, hydration and urinary alkalinization may be necessary to prevent the precipitation of methotrexate and/or its metabolites in the renal tubules Alkalinize urine to maintain pH above 7. 0 during methotrexate infusion and leucovorin calcium therapy.
It is important to watch the patient's urine pH level when they are on methotrexate because urinary alkalinization is necessary to prevent the precipitation of methotrexate and/or its metabolites in the renal tubules. This can be achieved by maintaining a urine pH above 7.0. Monitoring urine pH helps to ensure that the urine is adequately alkalinized, reducing the risk of renal toxicity. 1 1
From the Research
Monitoring urine pH is crucial for patients on methotrexate because acidic urine can significantly decrease methotrexate excretion, potentially leading to toxic drug levels. Methotrexate and its metabolites are less soluble in acidic urine, which increases the risk of precipitation in the renal tubules, causing kidney damage and further reducing drug clearance. Ideally, urine pH should be maintained above 7.0 during high-dose methotrexate therapy, as supported by a study published in 2021 2, which found that a urine pH < 7.0 at day 1 was a significant risk factor for methotrexate-induced nephrotoxicity. This can be achieved by administering sodium bicarbonate or acetazolamide before and during treatment to alkalinize the urine. Adequate hydration is also crucial, with a recommended fluid intake of at least 2-3 liters per day to promote drug excretion. Healthcare providers should regularly monitor urine pH, especially during high-dose therapy, and adjust alkalinization measures accordingly. Some studies have suggested that the urine pH threshold can be reduced to 7 without significantly affecting hospital length of stay, MTX clearance, or rates of nephrotoxicity 3. However, it is essential to consider the potential risks and benefits of reducing the urine pH threshold and to closely monitor patients for signs of nephrotoxicity. In addition to urine alkalinization, other methods such as enteral alkalinization using sodium bicarbonate tablets and sodium citrate/citric acid solution can be effective in achieving the desired urine pH levels 4. Overall, the goal is to prevent methotrexate-induced nephrotoxicity and reduce the risk of other serious adverse effects that could result from delayed drug clearance and prolonged exposure to high methotrexate levels. Key considerations for healthcare providers include:
- Regularly monitoring urine pH, especially during high-dose therapy
- Adjusting alkalinization measures accordingly
- Ensuring adequate hydration
- Considering the potential risks and benefits of reducing the urine pH threshold
- Closely monitoring patients for signs of nephrotoxicity.