Methotrexate

At high concentrations methotrexate and its 7-hydroxy metabolite
may cause tubular nephropathy.

  • Overview
  • Hydration Process
  • Urine Alkalinisation
  • Post Hydration

Overview

Methotrexate and its 7-hydroxy metabolite are not very soluble in acid pH. At high concentrations they may precipitate in the renal tubules causing damage (tubular nephropathy). A high fluid throughput and alkalinisation of the urine to pH 6.5 - 7 is required to minimise this.

Depending on the protocol being used high dose methotrexate may be administered over a period of 3-4 hours or 24 hours.

Click to remove information.

Why Alkalinise?

Alkalinising the urine increases the solubility of methotrexate and its 7-hydroxy metabolite, promotes excretion and reduces damage.

Click to remove information.

Hydration Process

Patients receiving methotrexate high dose (doses > 250mg/m2) should be well hydrated prior to its administration and hydration maintained until the methotrexate levels have fallen to 0.2micromol/l. Levels are not usually measured for patients receiving doses less than 500mg/m2.

man boy

In adult patients a couple of litres of fluid (usually Sodium chloride 0.9% with potassium 20mmol/l) over 4 hours are usually prescribed.

In paediatric patients where a much closer eye is kept on fluid balance, an intravenous intake of 125ml/m2/hr is considered to be adequate.

Click to remove information.

Urine Alkalinisation

Urine alkalinisation may be carried out by:

The administration of oral sodium bicarbonate (3g 4-6 hourly).
The addition of intravenous bicarbonate to the hydration fluid
(50-70mmol of bicarbonate per litre of fluid).
Or the use of acetazolamide, a carbonic anhydrase inhibitor at a dose of 500mg qds (unlicensed use).

The urine pH is kept at >7.0 throughout administration of the methotrexate and for a minimum of 48 hours post dose.

Click to remove information.

Reference

Acetazolamide for alkalinisation of urine in patients receiving high-dose methotrexate.
Samash J, Earl H, Rouhami R.
Cancer Chemother Pharmacol 1991, 28: 150-151

Click to remove information.

Post Hydration

Post hydration is continued for 24-28 hours and a combined oral and/or intravenous intake greater than 3l/m2/24 hours maintained until the methotrexate levels are below 0.2µmol/l.

Click to remove information.