Olumiant® (Baricitinib)

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Baricitinib: Comparison of DDI With Dupilumab

There have been no head-to-head clinical trials between baricitinib and dupilumab. Drug-drug interaction studies have been performed independently for each product as part of their respective clinical development programs.

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Baricitinib - Interaction With Other Medicinal Products

Cytochrome P450 Enzymes

In in vitro studies, BARI is a substrate for CYP3A4.1 In clinical pharmacology studies, no clinically meaningful changes were observed in the PK of BARI when BARI was coadministered with the CYP450 substrates

  • ketoconazole (CYP3A inhibitor)
  • rifampin (CYP3A inducer), or
  • fluconazole (CYP3A/CYP2C19/CYP2C9 inhibitor).2

In vitro studies showed that BARI did not significantly inhibit or induce a panel of CYP450 enzymes which included

  • CYP3A
  • CYP1A2
  • CYP2B6
  • CYP2C8
  • CYP2C9
  • CYP2C19, and
  • CYP2D6.2

In clinical pharmacology studies, coadministration of BARI with CYP3A substrates resulted in no clinically meaningful changes in the PK of

  • simvastatin
  • ethinyl estradiol, or
  • levonorgestrel.2

Organic Anion Transporters

In vitro studies indicate that BARI

  • is a substrate for OAT3, and
  • inhibits the activity of OAT1, OAT2, and OAT3.3,4

In a clinical pharmacology study,

  • dosing with probenecid (OAT3 inhibitor with strong inhibition potential) resulted in
    • approximately a 2-fold increase in AUC (0-∞), and
    • no effect on Cmax or Tmax of BARI, and
  • simulations with diclofenac and ibuprofen (OAT3 inhibitors with less inhibition potential) predicted minimal effect on BARI exposure.2,4

The recommended dose of BARI in patients taking OAT3 inhibitors with a strong inhibition potential, such as probenecid, is 2 mg once daily.

Other Transporters

In vitro, BARI is a substrate for Pgp, BCRP, and MATE2-K.2

In in vitro studies,

  • BARI did not inhibit the transporters Pgp or OATP1B1.
  • BARI inhibited the activity of
    • organic cation transporters OCT1, OCT2
    • OATP1B3,
    • BCRP, and
    • multidrug and toxic extrusion proteins MATE1 and MATE2-K.1,2

In clinical pharmacology studies, there were no clinically meaningful effects when BARI was coadministered with

  • digoxin (Pgp substrate), or
  • MTX (substrate of several transporters).2

There were no clinically meaningful effects on BARI exposure when BARI was coadministered with

  • cyclosporine (Pgp/BCRP inhibitor), or
  • MTX (substrate of several transporters).2

Immunizations

No data are available on the response to vaccination with live vaccines in patients receiving BARI.2

Baricitinib use with live vaccines is not recommended and immunizations should be updated in agreement with current immunization guidelines prior to initiating BARI therapy.2

Dupilumab: Interaction With Other Medicaments

Please refer to the dupilumab label for all product information.5

Cytochrome P450 Enzymes

In a clinical study of AD patients, dupilumab had no clinically relevant effects on the PK of CYP450 substrates for the enzymes

  • CYP1A2
  • CYP3A
  • CYP2C19
  • CYP2D6, or
  • CYP2C9.5,6

Immunizations

Live Vaccine

Clinical safety and efficacy have not been established for live and live-attenuated vaccines given concurrently with dupilumab. Patients are recommended to update live and live-attenuated immunizations in agreement with current immunization guidelines prior to treatment with dupilumab.5

Nonlive Vaccine

No adverse interactions were noted between dupilumab and nonlive vaccine, T-cell–dependent tetanus and meningococcal polysaccharide vaccines in patients with AD treated with dupilumab. After 12 weeks of 300-mg once weekly dupilumab administration, patients were vaccinated and immune responses were assessed 4 weeks later. Antibody responses were similar in dupilumab-treated and placebo-treated patients.5

Other Medications

Based on population analysis, commonly coadministered medications had no effect on dupilumab PK on patients with moderate-to-severe asthma.5

References

1Payne C, Zhang X, Shahri N, et al. Evaluation of potential drug-drug interactions with baricitinib. Ann Rheum Dis. 2015;74(suppl 2):1063. European League Against Rheumatism abstract AB0492. https://doi.org/10.1136/annrheumdis-2015-eular.1627

2Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3Zhao X, Payne C, Wang F, Cui Y. THU0199 pharmacokinetics, safety and tolerability of single- and multiple-dose once-daily baricitinib in Chinese healthy volunteers – a randomized placebo-controlled study. Ann Rheum Dis. 2019;78(suppl 2);378. https://ard.bmj.com/content/78/Suppl_2/378.1

4Posada MM, Cannady EA, Payne CD, et al. Prediction of transporter-mediated drug-drug interactions for baricitinib. Clin Transl Sci. 2017;10(6):509-519. https://dx.doi.org/10.1111/cts.12486

5Dupixent: EPAR - product information. European Medicines Agency. Updated July 2, 2020. Accessed September 10, 2020. https://www.ema.europa.eu/en/medicines/human/EPAR/dupixent

6Davis JD, Bansal A, Hassman D, et al. Evaluation of potential disease-mediated drug-drug interaction in patients with moderate-to-severe atopic dermatitis receiving dupilumab. Clin Pharmacol Ther. 2018;104(6):1146-1154. http://dx.doi.org/10.1002/cpt.1058

Glossary

AD = atopic dermatitis

AUC = area under the concentration-time curve

BARI = baricitinib

BCRP = breast cancer resistance protein

Cmax = maximum concentration

CYP = cytochrome P450

DDI = drug-drug interaction

MATE = multidrug and toxin extrusion protein

MTX = methotrexate

OAT = organic anion transporter

OCT = organic cation transporter

Pgp = P-glycoprotein

PK = pharmacokinetic

tmax = time of maximum observed drug concentration

Fecha de la última revisión: 2020 M09 02


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