Taltz ® (ixekizumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Taltz Summary of Product Characteristics (SmPC)

Taltz® (ixekizumab): Drug-Drug Interactions

Information on drug-drug interactions of ixekizumab are summarized in this response.

Drug-Drug Interaction Summary

Hepatic metabolizing enzymes and drug transporters are not presumed to be

  • involved in ixekizumab elimination, as ixekizumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins, or

  • directly affected by ixekizumab.1

Interaction with other Medicinal Products and other Forms of Interaction

In plaque psoriasis studies, the safety of ixekizumab in combination with other immunomodulatory agents or phototherapy has not been evaluated.2

In PsA clinical trials, no interaction was seen when ixekizumab was administered concomitantly with methotrexate.1

In population pharmacokinetic analyses, clearance of ixekizumab was not affected by concomitant administration of

  • oral corticosteroids,

  • NSAIDs,

  • sulfasalazine, or

  • methotrexate.2

Cytochrome P450 Substrates

Cytochrome P450 enzymes are downregulated in diseases with inflammatory conditions due to overexpression of proinflammatory cytokines or cytokine modulators that directly and indirectly modify CYP enzyme formation, stability, and activity. Therefore, therapeutic antibodies targeting these cytokines may alter the metabolism of small-molecule drugs that are substrates for CYP enzymes.3,4

Ixekizumab binds with high affinity and specificity to IL-17A, a proinflammatory cytokine. The IL-17A cytokine was shown to have no appreciable effect on CYP expression or activity in vitro.1

Results from an interaction study in patients with moderate-to-severe psoriasis determined that 12 weeks of administration of ixekizumab with substances metabolised by

  • CYP3A4 (i.e., midazolam),

  • CYP2C9 (i.e., warfarin),

  • CYP2C19 (i.e., omeprazole),

  • CYP1A2 (i.e., caffeine) or

  • CYP2D6 (i.e., dextromethorphan)

does not have a clinically significant impact on the pharmacokinetics of these substances.2

Immunisations

Ixekizumab should not be used with live vaccines. No data are available on the response to live vaccines; there are insufficient data on response to inactive vaccines.2

In a study in healthy subjects, no safety concerns were identified of two inactivated vaccines (tetanus and pneumococcal), received after two doses of ixekizumab (160 mg followed by a second dose of 80 mg two weeks later).

  • However, the data concerning immunisation were insufficient to conclude on an adequate immune response to these vaccines following administration of ixekizumab.2

References

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

2. Taltz [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

3. Morgan ET. Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics. Clin Pharmacol Ther. 2009;85(4):434-438. http://dx.doi.org/10.1038/clpt.2008.302

4. Wang J, Wang YMC, Ahn HY. Biological products for the treatment of psoriasis: therapeutic targets, pharmacodynamics and disease-drug-drug interaction implications. AAPS J. 2014;16(5):938-947. http://dx.doi.org/10.1208/s12248-014-9637-0

Glossary

axSpA = axial spondyloarthritis

CYP = cytochrome P450

IL-17A = interleukin-17A

nr-axSpA = nonradiographic axial spondyloarthritis

NSAID = nonsteroidal anti-inflammatory drug

PsA = psoriatic arthritis

Date of Last Review: March 13, 2020


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