Prevalence of Potentially Severe Drug-Drug Interactions in Ambulatory Patients with Dyslipidaemia Receiving HMG-CoA Reductase Inhibitor Therapy

Bravo, Alexandra E. Rätz; Tchambaz, Lydia; Krähenbühl-Melcher, Anita; Hess, Lorenzo; Schlienger, Raymond G.; Krähenbühl, Stephan

doi:10.2165/00002018-200528030-00007

Cited by 72 publications

(29 citation statements)

References 52 publications

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“…These results were expected, because the highest number of patients-3488 (78.1%) used cardiovascular drugs (B. Nikolic, unpublished data). Also, the results were consistent with the results of previous studies [29,40,41]. In the research report by Björkman et al which was conducted to detect the frequency of potential DDIs in elderly outpatient in 6 European countries was presented that 9 of 10 most commonly drugcombinations that might need dose adjustment, and 4 of 9 drug-combinations recommended to be avoided, included drugs with ATC code C [23].…”

Section: Discussionsupporting

confidence: 88%

Prevalence and predictors of potential drug-drug interactions

Nikolic¹,

Janković

Stojanov³

et al. 2014

Open Medicine

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Section: Discussionsupporting

confidence: 88%

Prevalence and predictors of potential drug-drug interactions

Nikolic¹,

Janković

Stojanov³

et al. 2014

Open Medicine

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“…A similar tendency was found in Swiss ambulatory patients (Rätz Bravo et al 2005). While we found no significant difference in the total proportion of pSDIs between patients at hospital admission and discharge, there was a significant increase of simvastin coprescriptions for inpatients compared to outpatients.…”

Section: Discussionsupporting

confidence: 82%

“…There are few studies reporting the incidence of pSDIs (Einarson et al 2002; Rätz Bravo et al 2005; Egger et al 2007; Stang et al 2007; Tirkkonen et al 2008). They all differ in their design, number and nature of interacting drugs, as well as in the patient sample size.…”

Section: Discussionmentioning

confidence: 99%

Potential statin-drug interactions: prevalence and clinical significance

2014

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BackgroundStatins are cholesterol-lowering drugs widely used for cardiovascular prevention. Although safe when used alone, in combination with other drugs the likelihood of adverse drug reactions increases significantly. The exposure of the Bulgarian population to coprescriptions leading to potential statin-drug interactions is currently unknown.ObjectiveThe aim of this study was to investigate the incidence of coprescriptions involving statins and to compare the exposure of outpatients and inpatients to potential statin-drug interactions.SettingA cardiology clinic of the teaching University hospital in Varna, Bulgaria.MethodThis observational retrospective study examined the medical records of hospitalized patients prescribed a statin in combination with potentially interacting drugs. Patients who entered the hospital with a statin coprescription (considered outpatients) were compared with those coprescribed a statin at discharge from hospital (considered inpatients). Potentially interacting drugs included inhibitors and inducers of cytochrome P450 (CYP) enzymes and drugs of narrow safety margin (coumarin anticoagulants, digitalis).Main outcome measureThe proportion of patients exposed to statin coprescriptions with potentially interacting drugs at hospital admission and discharge. Secondary outcome measures: laboratory evidence supporting possible statin-drug interactions.ResultsOut of 1641 hospitalized patients examined, 572 were prescribed a statin, either at hospital admission or discharge. Simvastatin was most commonly prescribed and simvastatin-drug coprescription predominated, especially at discharge. The exposure to all potential statin-drug interactions was similar at hospital admission (26.1%) and discharge (24.4%), as was the exposure to statin combinations with CYP inhibitors, 6.4% and 4%, correspondingly. Overall, more coprescriptions were generated, than were eliminated by hospital physicians. Amiodarone was the CYP inhibitor most frequently coprescribed. Of all interacting drugs acenocoumarol was the most commonly found, the proportions of statin-acenocoumarol coprescriptions being roughly the same at hospital entry (11.5%) and discharge (12.4%). In 7 patients out of 69 exposed to the combination, INR was found to be higher than 3, indicating a risk of over-anticoagulation.ConclusionsPotential statin-drug interactions are common. Although they do not differ between outpatient and inpatient settings, new hazardous coprescriptions are more frequently generated in hospital. Caution is required when acenocoumarol is coprescribed with statins, especially simvastatin.

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“…Two well established risk factors include a high systemic exposure [1] and underlying metabolic muscle disease [43,44]. High systemic exposures in patients treated with a therapeutic dose can result from inherited malfunction of the transport mechanism into hepatocytes [7] or from drug-statin interactions [42,45,46]. Regarding drug-statin interactions, mainly (but not exclusively) the lipophilic statins are affected and the increase in the systemic exposure can be substantial, leading to serum concentrations in the low micromolar range [42].…”

Section: Discussionmentioning

confidence: 99%

The AKT/mTOR signaling pathway plays a key role in statin-induced myotoxicity

Bonifacio

Sanvee

Bouitbir

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Statins are drugs that lower blood cholesterol levels and reduce cardiovascular morbidity and mortality. They are generally well-tolerated, but myopathy is a potentially severe adverse reaction of these compounds. The mechanisms by which statins induce myotoxicity are not completely understood, but may be related to inhibition of the AKT signaling pathway. The current studies were performed to explore the down-stream effects of the statin-associated inhibition of AKT within the AKT signaling pathway and on myocyte biology and morphology in C2C12 myotubes and in mice in vivo. We exposed C2C12 myotubes to 10 μM or 50 μM simvastatin, atorvastatin or rosuvastatin for 24 h. Simvastatin and atorvastatin inhibited AKT phosphorylation and were cytotoxic starting at 10 μM, whereas similar effects were observed for rosuvastatin at 50 μM. Inhibition of AKT phosphorylation was associated with impaired phosphorylation of S6 kinase, ribosomal protein S6, 4E-binding protein 1 and FoxO3a, resulting in reduced protein synthesis, accelerated myofibrillar degradation and atrophy of C2C12 myotubes. Furthermore, impaired AKT phosphorylation was associated with activation of caspases and PARP, reflecting induction of apoptosis. Similar findings were detected in skeletal muscle of mice treated orally with 5 mg/kg/day simvastatin for 3 weeks. In conclusion, this study highlights the importance of the AKT/mTOR signaling pathway in statin-induced myotoxicity and reveals potential drug targets for treatment of patients with statin-associated myopathies.

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Prevalence of Potentially Severe Drug-Drug Interactions in Ambulatory Patients with Dyslipidaemia Receiving HMG-CoA Reductase Inhibitor Therapy

Cited by 72 publications

References 52 publications

Prevalence and predictors of potential drug-drug interactions

Prevalence and predictors of potential drug-drug interactions

Potential statin-drug interactions: prevalence and clinical significance

The AKT/mTOR signaling pathway plays a key role in statin-induced myotoxicity

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