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Drug Interactions between ixekizumab and Neoral

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

cycloSPORINE ixekizumab

Applies to: Neoral (cyclosporine) and ixekizumab

GENERALLY AVOID: The use of interleukin blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections.

MANAGEMENT: Concomitant use of interleukin blockers with other immuno- or myelosuppressive agents should be avoided if possible.

MONITOR: Plasma concentrations of drugs that are CYP450 substrates may decrease following the initiation of interleukin inhibitors in patients with chronic inflammatory diseases. Because the formation of hepatic CYP450 enzymes is down-regulated during infection and chronic inflammation by increased levels of certain cytokines (e.g., interleukins-1, -6, and -10; tumor necrosis factor alpha; interferons), treatment with interleukin inhibitors may restore or normalize CYP450 enzyme levels resulting in increased metabolism of these drugs. In vitro studies showed that tocilizumab, an inhibitor of interleukin-6, has the potential to impact expression of various hepatic microsomal enzymes including CYP450 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4. Its effects on CYP450 2C8 or transporters is unknown. In vivo studies with omeprazole (a substrate of CYP450 2C19 and 3A4) and simvastatin (a substrate of CYP450 3A4) showed decreases of up to 28% and 57% in systemic exposure, respectively, one week following a single dose of tocilizumab. A role for other interleukins such as IL-12, IL-17A, or IL-23 in the regulation of CYP450 enzymes has not been established, and it is not known whether antagonists of these interleukins (e.g., ixekizumab, secukinumab, ustekinumab) would similarly affect CYP450 metabolism.

MANAGEMENT: Caution is advised when interleukin inhibitors are prescribed to patients receiving concomitant drugs that are CYP450 substrates, particularly those with narrow therapeutic ranges such as immunosuppressants or antineoplastic agents. Clinical and/or laboratory monitoring should be considered following the initiation or withdrawal of interleukin inhibitor therapy, and the dosage(s) of these drugs adjusted accordingly. Clinicians should note that the effects of interleukin inhibitors on CYP450 activities may persist for several weeks after stopping therapy.

References

  1. "Product Information. Amevive (alefacept)." Biogen (2003):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. "Product Information. Arcalyst (rilonacept)." Regeneron Pharmaceuticals Inc (2008):
  4. "Product Information. Stelara (ustekinumab)." Centocor Inc (2009):
  5. "Product Information. Ilaris (canakinumab)." Novartis Pharmaceuticals (2009):
  6. "Product Information. Actemra (tocilizumab)." Genentech (2010):
  7. "Product Information. Sylvant (siltuximab)." Janssen Biotech, Inc. (2014):
  8. "Product Information. Cosentyx (secukinumab)." Novartis Pharmaceuticals (2015):
  9. "Product Information. Taltz Autoinjector (ixekizumab)." Eli Lilly and Company (2016):
View all 9 references

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Drug and food interactions

Moderate

cycloSPORINE food

Applies to: Neoral (cyclosporine)

GENERALLY AVOID: Administration with grapefruit juice (compared to water or orange juice) has been shown to increase blood concentrations of cyclosporine with a relatively high degree of interpatient variability. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

GENERALLY AVOID: Administration with red wine or purple grape juice may decrease blood concentrations of cyclosporine. In 12 healthy volunteers, 12 ounces total of a merlot consumed 15 minutes prior to and during cyclosporine administration (single 8 mg/kg dose of Sandimmune) decreased cyclosporine peak blood concentration (Cmax) and systemic exposure (AUC) by 38% and 30%, respectively, compared to water. The time to reach peak concentration (Tmax) doubled, and oral clearance increased 50%. Similarly, one study were 12 healthy patients were administered purple grape juice and a single dose of cyclosporine showed a 30% and a 36% decrease in cyclosporine systemic exposure (AUC) and peak blood concentration (Cmax), respectively. The exact mechanism of interaction is unknown but may involve decreased cyclosporine absorption.

MONITOR: Food has been found to have variable effects on the absorption of cyclosporine. There have been reports of impaired, unchanged, and enhanced absorption during administration with meals relative to the fasting state. The mechanisms are unclear. Some investigators found an association with the fat content of food. In one study, increased fat intake resulted in significantly increased cyclosporine bioavailability and clearance. However, the AUC and pharmacodynamics of cyclosporine were not significantly affected, thus clinical relevance of these findings may be minimal.

MANAGEMENT: Patients receiving cyclosporine therapy should be advised to either refrain from or avoid fluctuations in the consumption of grapefruits and grapefruit juice. Until more data are available, the consumption of red wine or purple grape juice should preferably be avoided or limited. All oral formulations of cyclosporine should be administered on a consistent schedule with regard to time of day and relation to meals so as to avoid large fluctuations in plasma drug levels.

References

  1. Honcharik N, Yatscoff RW, Jeffery JR, Rush DN "The effect of meal composition on cyclosporine absorption." Transplantation 52 (1991): 1087-9
  2. Ducharme MP, Provenzano R, Dehoornesmith M, Edwards DJ "Trough concentrations of cyclosporine in blood following administration with grapefruit juice." Br J Clin Pharmacol 36 (1993): 457-9
  3. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  4. Hollander AAMJ, Vanrooij J, Lentjes EGWM, Arbouw F, Vanbree JB, Schoemaker RC, Vanes LA, Vanderwoude FJ, Cohen AF "The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients." Clin Pharmacol Ther 57 (1995): 318-24
  5. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  6. Tan KKC, Trull AK, Uttridge JA, Metcalfe S, Heyes CS, Facey S, Evans DB "Effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine in kidney transplant recipients." Clin Pharmacol Ther 57 (1995): 425-33
  7. Yee GC, Stanley DL, Pessa LJ, et al. "Effect of grrapefruit juice on blood cyclosporin concentration." Lancet 345 (1995): 955-6
  8. Ducharme MP, Warbasse LH, Edwards DJ "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice." Clin Pharmacol Ther 57 (1995): 485-91
  9. Ioannidesdemos LL, Christophidis N, Ryan P, Angelis P, Liolios L, Mclean AJ "Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases." J Rheumatol 24 (1997): 49-54
  10. Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF, Hunsicker LG "Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients." Transplantation 62 (1996): 123-5
  11. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  12. Tsunoda SM, Harris RZ, Christians U, et al. "Red wine decreases cyclosporine bioavailability." Clin Pharmacol Ther 70 (2001): 462-7
  13. Oliveira-Freitas VL, Dalla Costa T, Manfro RC, Cruz LB, Schwartsmann G "Influence of purple grape juice in cyclosporine availability." J Ren Nutr 20 (2010): 309-13
View all 13 references

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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