Interaction between Leucovorin and Glucarpidase
Moderate
Antagonism
| ID | DDInter1041 and DDInter828 |
| Interaction | INTERVAL: Concomitant administration of glucarpidase may decrease the plasma concentrations of leucovorin, which is a substrate for glucarpidase. Conversely, leucovorin may interfere with the action of glucarpidase in the treatment of toxic plasma methotrexate concentrations in patients with impaired renal function by reducing the availability of glucarpidase, a recombinant bacterial enzyme that provides an alternate nonrenal pathway for methotrexate elimination by converting methotrexate to an inactive metabolite and glutamate. |
| Management | Leucovorin should be continued following treatment with glucarpidase; however, it should not be administered within two hours before or two hours after a dose of glucarpidase. For the first 48 hours after glucarpidase administration, the same leucovorin dose as given prior to glucarpidase treatment is appropriate. Beyond 48 hours, the leucovorin dose should be based on the measured methotrexate concentration. Do not discontinue leucovorin based on the determination of a single methotrexate concentration below the leucovorin treatment threshold. Therapy with leucovorin should be continued until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days. Hydration and alkalinization of the urine should be continued as indicated. |
| References | |
| Alternative for Leucovorin |
V03A
More
|
| Alternative for Glucarpidase |
V03A
More
|
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.