Interaction between Apalutamide and Lorlatinib
Major
Metabolism
| ID | DDInter107 and DDInter1094 |
| Interaction | Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of lorlatinib, which has been found to be metabolized primarily by CYP450 3A4 and UGT1A4 in vitro. In addition to the potential for diminished efficacy of lorlatinib, the risk of serious hepatotoxicity may be increased due to activation of the pregnane X receptor (PXR) by both lorlatinib and CYP450 3A4 inducers. |
| Management | Concomitant use of lorlatinib with potent CYP450 3A4 inducers is considered contraindicated. Lorlatinib should not be initiated until after discontinuation of potent CYP450 3A4 inducers for at least 3 plasma half-lives. |
| References | |
| Alternative for Apalutamide |
L02B
|
| Alternative for Lorlatinib |
L01X
Binimetinib
Tagraxofusp
Asparaginase Escherichia coli
Aminolevulinic acid
Methyl aminolevulinate (topical)
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.