Details of Drug-Drug Interaction
| Drug General Information (ID: DDIY7R19TB) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Drug Name | Probenecid | Drug Info | Baricitinib | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Uricosuric Agents | Antirheumatics | |||||||
| Structure | |||||||||
| Mechanism of Probenecid-Baricitinib Interaction (Severity Level: Major) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Transporter inhibition Click to Show/Hide Mechanism Graph | |||||||||
 |
|||||||||
| Drug Name | Probenecid | Baricitinib | |||||||
| Mechanism | OAT3 inhibitor | OAT3 substrate | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Solute carrier family 22 member 8 |
×
Structure
Sequence
MTFSEILDRVGSMGHFQFLHVAILGLPILNMANHNLLQIFTAATPVHHCRPPHNASTGPWVLPMGPNGKPERCLRFVHPPNASLPNDTQRAMEPCLDGWVYNSTKDSIVTEWDLVCNSNKLKEMAQSIFMAGILIGGLVLGDLSDRFGRRPILTCSYLLLAASGSGAAFSPTFPIYMVFRFLCGFGISGITLSTVILNVEWVPTRMRAIMSTALGYCYTFGQFILPGLAYAIPQWRWLQLTVSIPFFVFFLSSWWTPESIRWLVLSGKSSKALKILRRVAVFNGKKEEGERLSLEELKLNLQKEISLAKAKYTASDLFRIPMLRRMTFCLSLAWFATGFAYYSLAMGVEEFGVNLYILQIIFGGVDVPAKFITILSLSYLGRHTTQAAALLLAGGAILALTFVPLDLQTVRTVLAVFGKGCLSSSFSCLFLYTSELYPTVIRQTGMGVSNLWTRVGSMVSPLVKITGEVQPFIPNIIYGITALLGGSAALFLPETLNQPLPETIEDLENWSLRAKKPKQEPEVEKASQRIPLQPHGPGLGSS
|
|||||||
| Gene Name | OAT3 | ||||||||
| Uniprot ID | S22A8_HUMAN | ||||||||
| KEGG Pathway | hsa:9376 | ||||||||
| Protein Family | Major facilitator (TC 2.A.1) superfamily | ||||||||
| Protein Function |
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Click to Show/Hide
|
||||||||
| Mechanism Description |
|
||||||||
| Recommended Action | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Management | The dosage of baricitinib should be reduced by one-half during coadministration with potent OAT3 inhibitors. For the treatment of rheumatoid arthritis, baricitinib dosage should be reduced from 2 mg once daily to 1 mg once daily. For the treatment of COVID-19, the FDA Emergency Use Authorization fact sheet recommends reducing the baricitinib dosage as follows: (1) If the recommended dosage is 4 mg once daily, reduce to 2 mg once daily (2) If the recommended dosage is 2 mg once daily, reduce to 1 mg once daily (3) If the recommended dosage is 1 mg once daily, consider discontinuing the OAT3 inhibitor. Patients should be monitored for adverse effects of baricitinib such as infections, malignancies, thrombosis, hematologic abnormalities, gastrointestinal perforations, hyperlipidemia, and hepatic transaminase elevations. | ||||||||