Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDICFOB0HK)
  Drug Name Methylnaltrexone Drug Info Risdiplam Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Peripheral Opioid Receptor Antagonists Mrna Splicing Modifier
  Structure

 Mechanism of Methylnaltrexone-Risdiplam Interaction (Severity Level: Moderate)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Methylnaltrexone Risdiplam
      Mechanism 1 MATE1 substrate MATE1 inhibitor
      Key Mechanism Factor 1
Factor Name Solute carrier family 47 member 1
×
Structure Sequence
MEAPEEPAPVRGGPEATLEVRGSRCLRLSAFREELRALLVLAGPAFLVQLMVFLISFISSVFCGHLGKLELDAVTLAIAVINVTGVSVGFGLSSACDTLISQTYGSQNLKHVGVILQRSALVLLLCCFPCWALFLNTQHILLLFRQDPDVSRLTQTYVTIFIPALPATFLYMLQVKYLLNQGIVLPQIVTGVAANLVNALANYLFLHQLHLGVIGSALANLISQYTLALLLFLYILGKKLHQATWGGWSLECLQDWASFLRLAIPSMLMLCMEWWAYEVGSFLSGILGMVELGAQSIVYELAIIVYMVPAGFSVAASVRVGNALGAGDMEQARKSSTVSLLITVLFAVAFSVLLLSCKDHVGYIFTTDRDIINLVAQVVPIYAVSHLFEALACTSGGVLRGSGNQKVGAIVNTIGYYVVGLPIGIALMFATTLGVMGLWSGIIICTVFQAVCFLGFIIQLNWKKACQQAQVHANLKVNNVPRSGNSALPQDPLHPGCPENLEGILTNDVGKTGEPQSDQQMRQEEPLPEHPQDGAKLSRKQLVLRRGLLLLGVFLILLVGILVRFYVRIQ
Gene Name MATE1
Uniprot ID S47A1_HUMAN
KEGG Pathway hsa:55244
Protein Family Multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family
Protein Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Methylnaltrexone due to the transporter inhibition by Risdiplam 
      Mechanism 2 MATE2K substrate MATE2K inhibitor
      Key Mechanism Factor 2
Factor Name Multidrug and toxin extrusion protein 2
×
Structure Sequence
MDSLQDTVALDHGGCCPALSRLVPRGFGTEMWTLFALSGPLFLFQVLTFMIYIVSTVFCGHLGKVELASVTLAVAFVNVCGVSVGVGLSSACDTLMSQSFGSPNKKHVGVILQRGALVLLLCCLPCWALFLNTQHILLLFRQDPDVSRLTQDYVMIFIPGLPVIFLYNLLAKYLQNQGWLKGQEEESPFQTPGLSILHPSHSHLSRASFHLFQKITWPQVLSGVVGNCVNGVANYALVSVLNLGVRGSAYANIISQFAQTVFLLLYIVLKKLHLETWAGWSSQCLQDWGPFFSLAVPSMLMICVEWWAYEIGSFLMGLLSVVDLSAQAVIYEVATVTYMIPLGLSIGVCVRVGMALGAADTVQAKRSAVSGVLSIVGISLVLGTLISILKNQLGHIFTNDEDVIALVSQVLPVYSVFHVFEAICCVYGGVLRGTGKQAFGAAVNAITYYIIGLPLGILLTFVVRMRIMGLWLGMLACVFLATAAFVAYTARLDWKLAAEEAKKHSGRQQQQRAESTATRPGPEKAVLSSVATGSSPGITLTTYSRSECHVDFFRTPEEAHALSAPTSRLSVKQLVIRRGAALGAASATLMVGLTVRILATRH
Gene Name MATE2
Uniprot ID S47A2_HUMAN
KEGG Pathway hsa:146802
Protein Family Multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family
Protein Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, and ganciclovir. Responsible for the secretion of cationic drugs across the brush border membranes.
    Click to Show/Hide
      Mechanism Description
  • Decreased clearance of Methylnaltrexone due to the transporter inhibition by Risdiplam 

Recommended Action
      Management Coadministration of risdiplam with drugs that are substrates of MATE1 and/or MATE2K should generally be avoided. However, if concomitant use is unavoidable, monitor for drug-related toxicities and consider dosage reduction of the MATE1 or MATE2K substrate (based in the labeling of that drug) as needed.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Product Information. Evrysdi (risdiplam). Genentech, South San Francisco, CA.
3 Yonezawa A, Inui K "Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics." Br J Pharmacol 164 (2011): 1817-25. [PMID: 21457222]