Methotrexate TDM

1. Methotrexate TDM
1. Guidelines for administration of high dose methotrexate
Hydration pre-hydrate with sodium bicarbonate beginning the evening prior to administration of
HDMTX
D5W 1/4 NS + Na bicarbonate40mEq/L + KCl 10mEq/L
IV fluids should run at a rate of >100 ml/m2/hr for a minimum of 12 hours prior to
startingHDMTX
Urine pH Check urine pH with each void
A urinary pH>6.5 must be achieved before startingMTX infusion
Maintain until serumMTX level is <1 uM
2. Methotrexate Leucovorin Guidelines
- Obtain MTX levels atthe end of infusion (Hr 4), 24 and 48 hrs from the startof the infusion
4 hr MTX level goal 1000 microM If > 1500 microM, keep IVF rate at 200ml/m2/hr until 24 hr
level known
24 hr MTX level goal < 10 microM Adjust IVF hydration rate and leucovorin per protocol
48 hr MTX level goal < 1 microM If > 1 microM, adjust IVF hydration rate and leucovorin per
protocol
72 hr MTX level goal < 0.1 microM If < 0.1 microM, adjust IVF fluid hydration and leucovorin
per protocol
* if patient has any fluid collection,monitor MTX levels until MTX is below level of detection x 2 days
3. Increased MTX concentrations and leucovorin rescue
MTX level Threshold for action Recommended LV rescue IV fluids (mL/m2/hr)
24 hr < 10uM Protocol leucovorin rescue 150
10.1 - 20.1 uM 100 mg/m2 IV q 6 hrs - startat hr 30 200
20.1 - 30.0 uM 250 mg/m2 IV q 6 hrs - start immediately,
admit patient
200
30.1 - 50.0 500 mg/m2 IV q6 hrs - start immediately,
admit patient
200
> 50 uM Individualised, check that hydration and
alkalnization are adequate, check for
nephrotoxic drugs, check creatinine,
consider glucarpidase
200
48 hr < 1 uM Protocol leucovorin rescue 150
1.1 - 5 uM 30 mg/m2 PO/IV q6 hrs - and keep
checkinguntil MTX level < 0.1 uM
150
5.1 - 10 uM 100 mg/m2 IV q6 hrs - and keep checking
until MTX level < 0.1 uM
200
10.1 - 20 uM 200 mg/m2 IV q6 hrs - and keep checking
until MTX level < 0.1 uM
200
20.1 - 50 uM 500 mg/m2 IV q6 hrs - and keep checking
until MTX level < 0.1 uM
200
> 50 uM Individualized, check that hydration and
alkalinzation are adequate, check for
nephrotoxic drugs, check creatinine,
consider glucarpidase
72 hr < 0.1 uM No further leucovorin - stop checking
MTX levels ***
Stop IV fluids
0.11 - 0.5 uM 15 mg/m2 PO q12 hrs - and keep 100

2. checkinguntil MTX < 0.1 uM
0.51 - 1.0 uM 15 mg/m2 PO q12 hrs - and keep
checkinguntil MTX < 0.1 uM
150
1.1 - 2.0 uM 30 mg/m2 PO/IV q6 hrs - and keep
checkinguntil MTX < 0.1 uM
150
2.1 - 5.0 uM 50 mg/m2 PO/IV q6 hrs - and keep
checkinguntil MTX < 0.1 uM
150
5.1 - 10 uM 100 mg/m2 IV q6hrs - and keep checking
until MTX level < 0.1 uM
150
> 10 uM Individualized, check that hydration and
alkalinization are adequate, check for
nephrotoxic drugs, check creatinine,
consider glucarpidase
4. How longto continue leucovorin
- Initiatewithin first48 hours
- Until MTX conc < 0.01 uM in patients athigh risk for toxicity
5. High risk factors for closetherapeutic monitoringof MTX
Ascites/pleural effusions - Third spacing
Poor renal function Concurrent therapy with nephrotoxic agents
Patient with emesis during infusion
Patient with delayed clearanceduringprevious course
6. Patient case- HDMTX monitoring
- AS is a 17 - year old male with osteosarcoma.He is receivinghis 3rd courseof HDMTX (12g/m2). He
has previously received 2 courses of cisplatin (120mg/m2 per course)
- End of infusion [MTX] = 1069uM
- 24 hr [MTX] = 19.4 uM
What would you do for AS?
- Begin leucovorin at100mg/m2 IV Q6 hours
- Hydrate at200ml/hr/m2
- Continue to check urinepH until [MTX] < 1uM
- Check [MTX] at48 hrs and adjustleucovorin per guidelines
- Continue to monitor [MTX] until 0.01 uM
(Source from
http://bvsms.saude.gov.br/bvs/publicacoes/inca/farmacocinetica_do_metotrexato_kristine_crews.pd
f)