Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIL642J1R)
  Drug Name Eltrombopag Drug Info Lorlatinib Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Platelet-Stimulating Agents Multikinase Inhibitors
  Structure

 Mechanism of Eltrombopag-Lorlatinib Interaction (Severity Level: Moderate)
     UGT induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Eltrombopag Lorlatinib
      Mechanism UGT substrate UGT inducer
      Key Mechanism Factor 1
Factor Name UDP-glucuronosyltransferase Structure Sequence
Protein Family UDP-glycosyltransferase family
Protein Function
[Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558).
    Click to Show/Hide
      Mechanism Description
  • Increased metabolism of Eltrombopag caused by Lorlatinib mediated induction of UGT

Recommended Action
      Management Caution is advised when lorlatinib is used concurrently with drugs that are known UGT substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever lorlatinib is added to or withdrawn from therapy.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3 Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.