Rhabdomyolyse unter der Kombination Atorvastatin, Amiodaron und Fluconazol

Franz, Carmen C.; Bruggisser, Marcel; Krähenbühl, Stephan; Bravo, Alexandra E. Rätz

doi:10.1024/1661-8157/a000491

Cited by 8 publications

(3 citation statements)

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“…Wang et al in 2017 reported a case of sudden cardiac arrest in a patient treated simultaneously with uconazole and amiodarone [29]. Another reported life-threatening side effect of multiple therapies in a patient taking atorvastatin, amiodarone, and uconazole was rhabdomyolysis [30]. These reports question the safety of treatment with azole in patients with polypharmacy.…”

Section: Discussionmentioning

confidence: 99%

Assessment of potential drug-to-drug interaction with antifungal agents in men with cardiovascular disease – a cross-sectional study of Polish population

Ryś-Czaporowska

Szykut-Badaczewska

Ulc

et al. 2023

Preprint

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Background Treatment of dermatological diseases in patients with concomitant cardiovascular is difficult due to reported interactions between antimycotic and cardiac drugs. The aim of the study was to assess the prescription frequency of drugs, causing potential interaction with antifungal drugs of superficial mycoses in patients with cardiovascular disease. Methods The study consisted of 166 consecutive men discharged from a tertiary cardiac department who were screened for topical fungal infections and were analyzed for drugs prescribed at discharge, with possible interference with typically used antimycotic treatment. Results The mean age of the study population was 62.8 ± 12.1 years. 57 (49.1%) of patients had a clinical suspicion of superficial mycosis and were referred for further dermatological investigation. The use of cardiovascular drugs was frequent, with 24.5% taking NOACs, 54.8% receiving diuretics and 76.5% receiving statins. No difference in the use of any drug was noted according to the mycosis status. Conclusions Polypharmacy with drugs exhibiting a potential for drug-to-drug interaction with antifungal agents is common in patients with cardiovascular disease. When choosing the appropriate option for superficial mycoses treatment, the knowledge of potential interaction is crucial in dermatologists and cardiologists to avoid their harmful consequences including serious bleeding or live threatening arrhythmias.

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Section: Discussionmentioning

confidence: 99%

Assessment of potential drug-to-drug interaction with antifungal agents in men with cardiovascular disease – a cross-sectional study of Polish population

Ryś-Czaporowska

Szykut-Badaczewska

Ulc

et al. 2023

Preprint

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“…Although triazole antifungal agents are poorly metabolized by one-step oxidative biotransformation and are excreted through the kidneys in the urine in the form of prototype drugs (Lass-Florl, 2011), they showed definite inhibitory effects on CYPs and significantly increased systemic exposure to drugs metabolized by CYP3A4, such as fentanyl and diazepam (Saari et al, 2007;Saari et al, 2008). In addition, as a moderate CYP3A inhibitor, fluconazole may lead to rhabdomyolysis in some clinical cases with concomitant use of ATO or simvastatin (Kahri et al, 2005;Franz et al, 2011). VOR is a derivative of fluconazole and has been identified as an inhibitor of CYP3A (Kim et al, 2019), which may be a critical factor in the elevated serum levels of tacrolimus (Imamura et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Interaction and potential mechanisms between atorvastatin and voriconazole, agents used to treat dyslipidemia and fungal infections

Xun

Rong

et al. 2023

Front. Pharmacol.

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Purpose: Voriconazole (VOR) is combined with atorvastatin (ATO) to treat fungal infections in patients with dyslipidemia in clinical practice. However, the pharmacokinetic interactions and potential mechanisms between them are unknown. Therefore, this study aimed to investigate the pharmacokinetic interactions and potential mechanisms between ATO and VOR.Patients and methods: We collected plasma samples from three patients using ATO and VOR. Rats were administered either VOR or normal saline for 6 days, followed by a single dose of 2 mg/kg ATO, and then plasma samples were collected at different time points. The incubation models of human liver microsomes or HepG2 cells were constructed in vitro. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system was developed to determine the concentration of ATO, 2-hydroxy-ATO, 4-hydroxy-ATO, and VOR.Results: In patients, VOR significantly reduced the metabolism of ATO and slowed the formation of 2-hydroxy- and 4-hydroxy-ATO. In rats pretreated with orally administered VOR for 6 days or normal saline given a single dose of 2 mg/kg ATO administered orally on Day 6, the t1/2 of ATO was significantly prolonged from 3.61 to 6.43 h, and the area under the concentration-time curve (AUC0–24h) values of ATO increased from 53.86 to 176.84 h μg.L−1. However, the pharmacokinetic parameters of VOR (20 mg/kg) with or without pretreatment with ATO (2 mg/kg) only slightly changed. In vitro studies indicated that VOR inhibited the metabolism of ATO and testosterone, and the IC50 values were 45.94 and 49.81 μM. However, no significant change in transporter behaviors of ATO was observed when VOR or transporter inhibitors were co-administered.Conclusion: Our study demonstrated that VOR has significant interactions with ATO, probably due to VOR’s inhibition of the CYP3A4-mediated metabolism of ATO. Based on the clinical cases and potential interactions, the basic data obtained in our study are expected to help adjust the dose of ATO and promote the design of rational dosage regimens for pharmacotherapy for fungal infections in patients with dyslipidemia.

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“…Interactions between ketokonazole and simvastatin (49-51) or lovastatin (52) have also been described. Rhabdomyolysis as a consequence of fluconazole interaction with statins has been reported as well (53)(54)(55)(56).…”

Section: Major Statin-drug Interactionsmentioning

confidence: 99%

Drug interactions with statins

Causevic-Ramosevac¹,

Semiz²

2013

Acta Pharmaceutica

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All important drug interactions, with the possible exception of idiosyncratic or allergic reactions, have a pharmacokinetic or pharmacodynamic basis, or both (1). A study of the mechanisms of drug interactions is of much value in selecting proper drug combinations in order to provide rational therapy, especially for drugs that have a narrow margin of safety and where drugs are used for a prolonged period of time. Most recently, pharmacogenetics has linked drug interaction outcomes to variations in genes encoding cytochrome P450 (CYP) enzymes (2) and transporter genes.Statins (or HMG-CoA reductase inhibitors) represent a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. As of 2010, a number of statins have been on the market: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin (3).Statins are associated with two uncommon, but important, adverse effects, asymptomatic elevation in liver enzyme activity and myopathy. In 2001, cerivastatin was withdrawn from the market worldwide because of an unacceptably high incidence of serious The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are generally well tolerated as monotherapy. Statins are associated with two important adverse effects, asymptomatic elevation in liver enzymes and myopathy. Myopathy is most likely to occur when statins are administered with other drugs. Statins are substrates of multiple drug transporters (including OAT--P1B1, BCRP and MDR1) and several cytochrome P450 (CYP) enzymes (including CYP3A4, CYP2C8, CYP2C19, and CYP2C9). Possible adverse effects of statins can occur due to interactions in concomitant use of drugs that substantially inhibit or induce their methabolic pathway. This review summarizes the most important interactions of statins.

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Rhabdomyolyse unter der Kombination Atorvastatin, Amiodaron und Fluconazol

Cited by 8 publications

References 0 publications

Assessment of potential drug-to-drug interaction with antifungal agents in men with cardiovascular disease – a cross-sectional study of Polish population

Assessment of potential drug-to-drug interaction with antifungal agents in men with cardiovascular disease – a cross-sectional study of Polish population

Interaction and potential mechanisms between atorvastatin and voriconazole, agents used to treat dyslipidemia and fungal infections

Drug interactions with statins

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