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Drug Interactions between Rythmol SR and Sylvant

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

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Interactions between your drugs

Moderate

propafenone siltuximab

Applies to: Rythmol SR (propafenone) 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

Moderate

propafenone food

Applies to: Rythmol SR (propafenone)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of propafenone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. In over 90% of patients, propafenone is rapidly and extensively converted to 2 active metabolites: 5-hydroxypropafenone via CYP450 2D6 and N-depropylpropafenone (norpropafenone) via CYP450 3A4 and 1A2. In less than 10% of patients (approximately 6% of Caucasians in the U.S. population), however, metabolism of propafenone is slower because the 5-hydroxy metabolite is not formed, or minimally formed, due to a genetic deficiency in CYP450 2D6. In these poor metabolizers of CYP450 2D6, clearance of propafenone via the CYP450 3A4 and 1A2 metabolic pathways becomes more important, and inhibition of these pathways may substantially increase systemic exposure to propafenone. Likewise, patients taking concomitant inhibitors of CYP450 2D6 and 3A4 may experience similar pharmacokinetic effects. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to propafenone may result in proarrhythmic events and exaggerated beta-adrenergic blocking activity.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with propafenone.

References

  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK "Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites." Mol Pharmacol 43 (1993): 120-6
  2. "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline (2011):
  3. "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated (2023):
  4. "Product Information. Propafenone (propafenone)." Accord-UK Ltd (2022):
View all 4 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.

Further information

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