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Drug Interactions between cyclosporine and guselkumab

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

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Interactions between your drugs

Moderate

cycloSPORINE guselkumab

Applies to: cyclosporine and guselkumab

MONITOR: Coadministration of interleukin (IL) inhibitors with CYP450 substrates that are also immunosuppressants could result in an alteration of the plasma concentration of the CYP450 substrate and an increased risk of shared side effects, such as infection or myelosuppression. In general, inflammation is associated with an elevation of pro-inflammatory cytokines like IL-1 beta and IL-6, which can bind to receptors present on hepatocytes and affect the expression level of the CYP450 isoenzyme. Agents that target these cytokines may affect the levels of CYP450 isoenzymes and result in altered drug metabolism of their substrates. The therapeutic target and disease state being treated may play a role in the significance of this interaction. The most evidence is currently for agents targeting the actions of IL-6 and in disease states with high levels of inflammation, such as rheumatoid arthritis (RA), rather than in patients with psoriasis and atopic dermatitis. Clinical data are limited, variable, and not available for all agents that reduce cytokine production. Studies involving the IL-6 inhibitors tocilizumab and sarilumab in RA patients showed similar results on the CYP450 3A4 probe, simvastatin, with reductions in the systemic exposure (AUC) of simvastatin and its metabolite (simvastatin acid) of 45% to 57% and 36% to 39%, respectively. Smaller reductions in the AUC of other probe substrates, omeprazole (2C19) and dextromethorphan (2D6), were also observed following treatment with tocilizumab. However, the AUC of CYP450 substrates is not always reduced. A study with brodalumab showed an increase in the AUC of midazolam (3A4) by 24%. Alternatively, some IL inhibitors (e.g., risankizumab and tildrakizumab) have not been shown to affect any CYP450 substrates when evaluated with probe substrates.

MANAGEMENT: Caution may be advisable when IL inhibitors are prescribed to patients receiving concomitant drugs that are both CYP450 substrates and immunosuppressants. Clinical and/or laboratory monitoring may be appropriate following the initiation or withdrawal of such treatments, and the dosage(s) of the CYP450 substrate(s) adjusted accordingly. Clinicians should note that the effects of IL inhibitors on CYP450 activities may persist for several weeks after stopping therapy. Individual product labeling should be consulted for these products. Some manufacturers no longer recommend general precautions with CYP450 substrates due to updated study data indicating no clinically significant changes in the exposure of probe CYP450 substrates. However, CYP450 substrates that are also immunosuppressants may still require additional precautions given a similar adverse effect profile to the IL inhibitor.

References (15)
  1. (2003) "Product Information. Amevive (alefacept)." Biogen
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. (2008) "Product Information. Arcalyst (rilonacept)." Regeneron Pharmaceuticals Inc
  4. (2009) "Product Information. Stelara (ustekinumab)." Centocor Inc
  5. (2009) "Product Information. Ilaris (canakinumab)." Novartis Pharmaceuticals
  6. (2010) "Product Information. Actemra (tocilizumab)." Genentech
  7. (2014) "Product Information. Sylvant (siltuximab)." Janssen Biotech, Inc.
  8. (2015) "Product Information. Cosentyx (secukinumab)." Novartis Pharmaceuticals
  9. (2016) "Product Information. Taltz Autoinjector (ixekizumab)." Eli Lilly and Company
  10. (2023) "Product Information. Bimzelx (bimekizumab)." UCB Australia Pty Ltd T/A UCB Pharma Division of UCB Australia
  11. (2023) "Product Information. Bimzelx (bimekizumab)." UCB Pharma Ltd
  12. (2023) "Product Information. Bimzelx Prefilled Syringe (bimekizumab)." UCB Pharma Inc
  13. (2023) "Product Information. Bimzelx (bimekizumab)." UCB Canada Inc
  14. Bruin G, Hasselberg A, Koroleva I, et al. (2019) "Secukinumab treatment does not alter the pharmacokinetics of the cytochrome P450 3A4 substrate midazolam in patients with moderate to severe psoriasis." Clin Pharmacol Ther, 106, p. 1380-8
  15. de Jong LM, Klomp SD, Treijtel N, Rissmann R, Swen JJ, Manson ML (2022) "A systematic review on disease-drug-drug interactions with immunomodulating drugs: a critical appraisal of risk assessment and drug labelling." Br J Clin Pharmacol, 88, p. 4387-402

Drug and food interactions

Moderate

cycloSPORINE food

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

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.

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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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