SUMMARY

• Please refer to the local labeling for information on drug interactions with icotrokinra.
• Icotrokinra demonstrates no clinically relevant drug-drug interactions (DDIs). In nonclinical studies, icotrokinra was not a substrate or inhibitor of major drug transporters or cytochrome P450 (CYP) enzymes.^1,2 

Company Core Data Sheet

Interactions

• No formal DDI studies have been conducted with icotrokinra.¹ 
• Based on in vitro studies, icotrokinra is not a CYP enzyme substrate, inhibitor, or inducer.
• Icotrokinra is not a substrate or inhibitor of P-glycoprotein (P-gp) or other major drug transporters. Therefore, no clinically relevant drug interactions have been identified.

Live Vaccines/Therapeutic Infectious Agents

• Live vaccines should not be administered to patients during treatment with icotrokinra. Live vaccines may be administered 3 days after discontinuation of icotrokinra.¹ 

IN VITRO DATA

Knight et al (2025)² conducted studies to assess the potential for DDIs of icotrokinra.

Study Design/Methods

• In vitro assays assessed permeability, plasma protein binding, and interactions with drug transporters and metabolic enzymes.
• The following transfected cell systems or vesicles were used to evaluate whether icotrokinra is a substrate or inhibitor of various transporters:
  • Human embryonic kidney (HEK) 293 mock-transfected (control) cells and organic anion transporter (OAT)P1B1-, OATP1B3-, OAT1-, and organic cation transporter (OCT)2-overexpressing cells
  • Madin-Darby canine kidney (MDCK)-II parental (control) cells and OAT3-, multidrug and toxin extrusion (MATE)1-, or MATE2-K-overexpressing cells
  • Lilly Laboratories cell-porcine kidney (LLC-PK1) mocktransfected cells or cells expressing human breast cancer resistance protein (BCRP)
  • Inside-out membrane vesicles overexpressing the human bile salt export pump (BSEP)
  • Cryopreserved human hepatocytes at concentrations were used to evaluate the ability of icotrokinra to inhibit major human CYP isoforms (CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4) and the potential mRNA induction of human CYP1A2, CYP2B6, and CYP3A4.

Results

Nonclinical In Vitro Assays

• Icotrokinra was neither a substrate for P-gp, OATP1B1, OATP1B3, OAT1, OAT3, OCT2, MATE1, MATE2-K, and BCRP, nor an inhibitor of P-gp, OAT1, OAT3, OCT2, MATE1, MATE2-K, BCRP, or BSEP activity.
  • At the highest tested concentrations (24.7 µM for OATP1B1 and 24.2 µM for OATP1B3), 43.9% and 48.0% inhibition of OATP1B1 and OATP1B3 activity, respectively, was observed. At clinically relevant concentrations (maximum plasma concentration for a 200 mg dose of icotrokinra is ~0.002 uM), interactions with these transporters and effect on the pharmacokinetics of drugs that are substrates of these transporters is not anticipated.
  • Icotrokinra did not show concentrationdependent inhibition of major human CYP enzymes (up to 100 µM).
  • All CYP isoforms exhibited half-maximal inhibitory concentrations of ≥100 µM, indicating minimal potential for CYP-mediated DDIs.
  • At the highest concentration tested (100 µM), maximum inhibition was <10% for most CYP isoforms, with weak inhibition observed only for CYP1A2 (19%) and CYP2E1 (30%).
  • Cultured human hepatocytes were used to evaluate the potential for icotrokinra to induce CYP1A2, CYP2B6, and CYP3A4 mRNA expression.
    • Icotrokinra caused no induction (<2-fold change in mRNA expression) and showed a minimal response compared with the positive control (<5% at 90 µM).
• Across the concentration of 1-300 µM, icotrokinra showed low, nonsaturable permeability in polarized cell monolayer models expressing multidrug resistance protein 1 (MDR1, the gene encoding P-gp]).
  • In the absence or presence of the P-gp inhibitor, the efflux ratios (ERs) remained <2 across the concentration range, confirming there was no change in permeability with P-gp inhibition and indicating that icotrokinra is not a substrate of P-gp.
• Mean protein bound percentage ranged from 49.7% to 55.2% in human plasma.
  • No concentration‑dependent differences were observed across the tested range of concentrations (0.01-1 µM).
  • Mean percent binding values were 25.7-35.9% for 4% human albumin.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 5 February 2026.

REFERENCES