Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Traceability

In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded.

Paediatric population

No formal evaluation of the effect of age on the pharmacokinetics of glucarpidase has been performed.
No data are available in children aged less than 28 days.

It is important to measure baseline plasma MTX concentations and renal function and to continue to monitor these throughout treatment with high dose MTX therapy, as described below.

A high performance chromatography (HPLC) method is recommended for measuring MTX concentrations following glucarpidase administration. Current immunoassays are unreliable for samples collected following glucarpidase administration due to 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA), an inactive metabolite of MTX formed following glucarpidase administration, interfering with the measurement of MTX concentration. This interference results in an overestimation of the MTX concentration. The effect of DAMPA interference will decline over time as DAMPA is eliminated.

DAMPA concentrations in patients treated with glucarpidase fell within a mean half-life of 8.6 hours.
In the majority of patients DAMPA concentrations had fallen to below 1 µmol/l within 48 hours of administration of glucarpidase. In clinical studies, DAMPA concentrations above 1 µmol/L have been observed beyond 3 days in a small minority (≤3%) of patients.

In the absence of more specific HPLC assay it is recommended that the dose of folinic acid used in a 48 hour-period after glucarpidase should be based on the MTX concentration from a sample taken prior to glucarpidase administration. Within 48 hours after glucarpidase administration MTX concentrations determined by immunoassay may not be reliably used to monitor for rebound and confirmatory HPLC data should be considered.

Over 48 hours after glucarpidase administration immunoassay results will be reliable in the majority of patients and so can be used to adjust the folinic acid dose or monitor for rebound. In clinical studies, ~9% patients with baseline MTX concentration ≥ 50µmol/l had DAMPA levels that persisted above 1 µmol/l beyond 4 days.

Routine monitoring of plasma MTX concentrations should be continued in accordance with local guidelines.

Glucarpidase does not reverse pre-existing renal damage or renal failure that occurs as a consequence of MTX administration, but instead removes MTX to reduce the risk of sustaining further renal toxicity. As such, other supportive care, including hydration and alkalinisation of the urine, should be started at the onset of MTX administration and continued in accordance with local treatment guidelines.

Allergic type hypersensitivity reactions are possible following adminstration of glucarpidase see section 4.8.

Effects on Driving

4.7    Effects on ability to drive and use machines

Glucarpidase has no or negligible influence on the ability to drive and use machines.