Drug Interactions between Arcalyst and lurbinectedin
This report displays the potential drug interactions for the following 2 drugs:
- Arcalyst (rilonacept)
- lurbinectedin
Interactions between your drugs
rilonacept lurbinectedin
Applies to: Arcalyst (rilonacept) and lurbinectedin
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
- (2003) "Product Information. Amevive (alefacept)." Biogen
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2008) "Product Information. Arcalyst (rilonacept)." Regeneron Pharmaceuticals Inc
- (2009) "Product Information. Stelara (ustekinumab)." Centocor Inc
- (2009) "Product Information. Ilaris (canakinumab)." Novartis Pharmaceuticals
- (2010) "Product Information. Actemra (tocilizumab)." Genentech
- (2014) "Product Information. Sylvant (siltuximab)." Janssen Biotech, Inc.
- (2015) "Product Information. Cosentyx (secukinumab)." Novartis Pharmaceuticals
- (2016) "Product Information. Taltz Autoinjector (ixekizumab)." Eli Lilly and Company
Drug and food interactions
lurbinectedin food
Applies to: lurbinectedin
GENERALLY AVOID: Grapefruit and Seville oranges may increase the plasma concentrations of lurbinectedin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit and Seville oranges. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit or Seville oranges, but pharmacokinetic data are available for potent and moderate CYP450 3A4 inhibitors. In a clinical drug interaction study, coadministration of itraconazole, a potent CYP450 3A4 inhibitor, increased the systemic exposure (AUC) of total lurbinectedin by 2.7-fold and unbound lurbinectedin by 2.4-fold. In a Phase 1 study, coadministration of aprepitant, a moderate CYP450 3A4 inhibitor, decreased lurbinectedin plasma clearance by 33% compared to lurbinectedin alone. In general, the effect of grapefruit and Seville oranges is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice and Seville oranges (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 exposure may increase the incidence and severity of adverse reactions of lurbinectedin, such as myelosuppression and hepatotoxicity.
MANAGEMENT: Patients should avoid consumption of grapefruit, grapefruit juice, and Seville oranges during treatment with lurbinectedin.
References
- (2020) "Product Information. Zepzelca (lurbinectedin)." Jazz Pharmaceuticals
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
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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