Drug–Drug Interaction Between Isavuconazole and Tacrolimus: Is Empiric Dose Adjustment Necessary?

Kufel, Wesley D; Armistead, Paul M.; Daniels, Lindsay M.; Ptachcinski, Jonathan; Alexander, Mhairi E.; Shaw, J. Ryan

doi:10.1177/0897190018790688

Cited by 11 publications

(9 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, no affected isavuconazole trough concentration was documented. The measured steady-state drug level was 4 µg/mL, which was in line with the previously described studies [136]. The authors also recommended TDM of tacrolimus to guide drug dosing.…”

Section: Immunosuppresive Agentssupporting

confidence: 84%

The Overview on the Pharmacokinetic and Pharmacodynamic Interactions of Triazoles

et al. 2021

View full text Add to dashboard Cite

Second generation triazoles are widely used as first-line drugs for the treatment of invasive fungal infections, including aspergillosis and candidiasis. This class, along with itraconazole, voriconazole, posaconazole, and isavuconazole, is characterized by a broad range of activity, however, individual drugs vary considerably in safety, tolerability, pharmacokinetics profiles, and interactions with concomitant medications. The interaction may be encountered on the absorption, distribution, metabolism, and elimination (ADME) step. All triazoles as inhibitors or substrates of CYP isoenzymes can often interact with many drugs, which may result in the change of the activity of the drug and cause serious side effects. Drugs of this class should be used with caution with other agents, and an understanding of their pharmacokinetic profile, safety, and drug-drug interaction profiles is important to provide effective antifungal therapy. The manuscript reviews significant drug interactions of azoles with other medications, as well as with food. The PubMed and Google Scholar bases were searched to collect the literature data. The interactions with anticonvulsants, antibiotics, statins, kinase inhibitors, proton pump inhibitors, non-nucleoside reverse transcriptase inhibitors, opioid analgesics, benzodiazepines, cardiac glycosides, nonsteroidal anti-inflammatory drugs, immunosuppressants, antipsychotics, corticosteroids, biguanides, and anticoagulants are presented. We also paid attention to possible interactions with drugs during experimental therapies for the treatment of COVID-19.

show abstract

Section: Immunosuppresive Agentssupporting

confidence: 84%

The Overview on the Pharmacokinetic and Pharmacodynamic Interactions of Triazoles

et al. 2021

View full text Add to dashboard Cite

show abstract

“…found no TAC dose reduction is needed. 14,15 In another study in 22 HSCT patients, the authors found ISA initiation leads to a 42% increase in TAC concentration/dose ratio, but this result was not statistically significant. 16 In our study, the reduction in TAC doses between our ISA and FLC groups was similar, which is consistent with the fact that both antifungals are moderate CYP3A4 inhibitors.…”

Section: Discussionmentioning

confidence: 98%

Comparative effects of fluconazole, posaconazole, and isavuconazole upon tacrolimus and cyclosporine serum concentrations

Lewis

et al. 2021

J Oncol Pharm Pract

View full text Add to dashboard Cite

Introduction Calcineurin inhibitors are commonly used in hematopoietic stem cell transplant (HSCT) patients to prevent graft versus host disease, but as CYP3A4 substrates they are frequently involved in drug-drug interactions. The purpose of this study is to characterize the effects of isavuconazole, fluconazole, and posaconazole on tacrolimus and cyclosporine serum concentrations and dose adjustments in allogeneic HSCT patients. Methods This retrospective study included patients admitted to Oregon Health and Science University between April 2008 and December 2018 who underwent hematopoietic stem cell transplantation and received concomitant tacrolimus or cyclosporine and fluconazole, isavuconazole or posaconazole therapy. Data on patient characteristics, drug dosing, and serum drug concentrations were collected through chart review, and descriptive statistics were used to summarize the results. Results A total of 139 patients were included in this study. We found fluconazole initiation leads to a 25% reduction in both tacrolimus and cyclosporine doses in order to maintain goal serum concentrations. Posaconazole and isavuconazole initiation requires tacrolimus dose reductions by 53% and 21%, respectively. Conclusions Based on our experience, FLC, POS, and ISA initiation may require CNI dose reductions and close monitoring of CNI levels to ensure levels remain within goal serum concentrations. Larger studies are needed to fully quantify the percentage in CNI dose reductions and characterize differences among these antifungals.

show abstract

“…One study and one case report in solid organ transplant patients also indicated increases in tacrolimus exposure when combined with isavuconazole . However, one case report in an alloHSCT patient indicated that no empiric dose reduction in tacrolimus was needed when combined with isavaconazole …”

Section: Introductionmentioning

confidence: 99%

Effect of isavuconazole on tacrolimus and sirolimus serum concentrations in allogeneic hematopoietic stem cell transplant patients: A drug‐drug interaction study

Kieu

Jhangiani

Dadwal

et al. 2018

Transplant Infectious Dis

View full text Add to dashboard Cite

Introduction Isavuconazole, a triazole antifungal, is an inhibitor of cytochrome P450 3A4, which also metabolizes tacrolimus and sirolimus. In previous studies, isavuconazole administration increased tacrolimus and sirolimus area under the curve values by 2.3‐fold and 1.8‐fold, respectively, in healthy adults and tacrolimus concentration/dose (C/D) ratio by 1.3‐fold in solid organ transplant patients. We aimed to determine the magnitude of effect of isavuconazole administration on tacrolimus and sirolimus C/D ratios in allogeneic hematopoietic stem cell transplant (alloHSCT) patients. Methods A retrospective, single‐center, single‐arm study in adult alloHSCT patients who received at least 10 days of combination therapy with isavuconazole and tacrolimus and/or sirolimus as inpatients or outpatients was conducted. Tacrolimus and sirolimus trough serum concentrations were measured up to twice weekly for up to 4 weeks. Results Twenty‐two patients receiving tacrolimus and twenty patients receiving sirolimus met the inclusion criteria. The mean C/D ratio increased from baseline by 1.42‐fold for tacrolimus during week 1 (P = 0.002) and up to 1.56‐fold for sirolimus during week 2 (P = 0.02). For the remaining timepoints, tacrolimus and sirolimus C/D ratios were not statistically significantly different from baseline. Conclusion In alloHSCT patients, modest increases in tacrolimus and sirolimus C/D ratios from baseline were observed within the first 2 weeks after initiation of isavuconazole.

show abstract

Drug–Drug Interaction Between Isavuconazole and Tacrolimus: Is Empiric Dose Adjustment Necessary?

Cited by 11 publications

References 18 publications

The Overview on the Pharmacokinetic and Pharmacodynamic Interactions of Triazoles

The Overview on the Pharmacokinetic and Pharmacodynamic Interactions of Triazoles

Comparative effects of fluconazole, posaconazole, and isavuconazole upon tacrolimus and cyclosporine serum concentrations

Effect of isavuconazole on tacrolimus and sirolimus serum concentrations in allogeneic hematopoietic stem cell transplant patients: A drug‐drug interaction study

Contact Info

Product

Resources

About