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Drug Interactions between ETH-Oxydose and Sylvant

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

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Interactions between your drugs

Moderate

oxyCODONE siltuximab

Applies to: ETH-Oxydose (oxycodone) and Sylvant (siltuximab)

MONITOR: Plasma concentrations of drugs that are CYP450 substrates may decrease following the initiation of interleukin (IL) inhibitors, tumor necrosis factor (TNF) blockers, or interferon (IFN) 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 targeting these cytokines may restore or normalize CYP450 enzyme levels resulting in increased metabolism of these drugs. In vitro studies showed that tocilizumab, an IL-6 inhibitor, 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 and OATP 1B1) showed decreases of up to 28% and 57% in systemic exposure, respectively, one week following a single dose of tocilizumab. Likewise, simvastatin and simvastatin acid exposures decreased by 45% and 36%, respectively, in 17 patients with rheumatoid arthritis one week following a single 200 mg subcutaneous dose of sarilumab, another IL-6 inhibitor. 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 would similarly affect CYP450 metabolism. Risankizumab and tildrakizumab, both IL-23 antagonists, demonstrated no clinically significant effects when tested with CYP450 probe substrates such as caffeine (1A2), warfarin (2C9), omeprazole (2C19), dextromethorphan (2D6), metoprolol (2D6), and midazolam (3A4) in study subjects with plaque psoriasis.

MANAGEMENT: Caution is advised when treatments targeting cytokines such as interleukins, tumor necrosis factors, or interferons are prescribed to patients receiving concomitant drugs that are CYP450 substrates, particularly those with narrow therapeutic ranges (e.g., antiarrhythmics, anticonvulsants, immunosuppressants, theophylline) or sensitive substrates where decreases in plasma levels may be significant or undesirable (e.g., oral contraceptives, statins, benzodiazepines, opioids). Clinical and/or laboratory monitoring should be considered 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, TNF blockers, and IFN inhibitors on CYP450 activities may persist for several weeks after stopping therapy.

References

  1. "Product Information. Remicade (infliximab)." Centocor Inc PROD (2001):
  2. "Product Information. Amevive (alefacept)." Biogen (2003):
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. "Product Information. Arcalyst (rilonacept)." Regeneron Pharmaceuticals Inc (2008):
  5. "Product Information. Stelara (ustekinumab)." Centocor Inc (2009):
  6. "Product Information. Simponi (golimumab)." Centocor Inc (2009):
  7. "Product Information. Ilaris (canakinumab)." Novartis Pharmaceuticals (2009):
  8. "Product Information. Actemra (tocilizumab)." Genentech (2010):
  9. "Product Information. Sylvant (siltuximab)." Janssen Biotech, Inc. (2014):
  10. "Product Information. Cosentyx (secukinumab)." Novartis Pharmaceuticals (2015):
  11. "Product Information. Taltz Autoinjector (ixekizumab)." Eli Lilly and Company (2016):
  12. "Product Information. Kevzara (sarilumab)." sanofi-aventis (2017):
  13. "Product Information. Ilumya (tildrakizumab)." Merck & Co., Inc (2018):
  14. "Product Information. Gamifant (emapalumab)." Sobi Inc (2018):
  15. "Product Information. Skyrizi (risankizumab)." AbbVie US LLC (2019):
View all 15 references

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Drug and food interactions

Major

oxyCODONE food

Applies to: ETH-Oxydose (oxycodone)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oxycodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of oxycodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of oxycodone by certain compounds present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for 5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and 56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when prescribing oxycodone, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with oxycodone may also want to avoid or limit the consumption of grapefruit and grapefruit juice.

References

  1. Nieminen TH, Hagelberg NM, Saari TI, et al. "Grapefruit juice enhances the exposure to oral oxycodone." Basic Clin Pharmacol Toxicol 107 (2010): 782-8

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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.

Further information

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