Rosuvastatin-acenocoumarol interaction.
TL;DR: A 36-year-old male patient receiving long-term oral treatment with acenocoumarol, a synthetic coumarin anticoagulant, who experienced an increase in international normalized ratio (INR) and a hematoma in the left leg approximately 45 days after the initiation of treatment with rosuvastatin is described.
About: This article is published in Clinical Therapeutics.The article was published on 2005-06-01. It has received 13 citations till now. The article focuses on the topics: Acenocoumarol & Rosuvastatin.
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01 Jan 2005
TL;DR: Compare your culture to one of the cultures discussed in this unit, and list as many similarities and differences between the two as you can think of.
Abstract: Compare your culture to one of the cultures discussed in this unit. On a sheet of paper, list the cultures you are comparing and make one column titled “similarities,” and a second column titled “differences.” Now, list as many similarities and differences between the two as you can think of. Are there more similarities or differences between the two cultures you selected? Have you ever met anyone from this culture? How can you use this information to build greater respect between cultures?
1,000 citations
TL;DR: Evidence with regard to the safety and interactions of rosuvastatin is reviewed, which appears to be relatively safe and well tolerated, sharing the adverse effects that are considered class effects of statins.
Abstract: HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with any of these drugs. Rosuvastatin therefore appears to be relatively safe and well tolerated, sharing the adverse effects that are considered class effects of statins. Practitioners of all medical practices should be alert when rosuvastatin is prescribed concomitantly with agents that may increase the risk of rosuvastatin-associated toxicity.
88 citations
Cites background or result from "Rosuvastatin-acenocoumarol interact..."
...anticoagulant agents from protein-binding sites, could explain such an interaction.([65]) 9....
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...Discontinuation of both drugs resulted in a rapid decrease in INR, suggesting that a rebound effect on the INR may occur after simultaneous discontinuation of both drugs.([65]) Two small clinical studies investigated whether there was a potential drug-drug interaction between rosuvastatin and warfarin, with conflicting results....
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...To date, three cases of potential drug-drug interactions between rosuvastatin and vitaminK antagonists have been reported.([4,64,65]) One patient in the JUPITER study, who was receiving long-term warfarin treatment, developed increased bruising, hematuria, light-headedness and an increase in INR (international normalized ratio), 4 weeks after the initiation of rosuvastatin....
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...Another case report described a potentiation of the anticoagulant effect of acenocoumarol after rosuvastatin administration, in a patient who had a significantly increased INR along with a hematoma in the leg.([65]) Discontinuation of both drugs resulted in a rapid decrease in INR, suggesting that a rebound effect on the INR may occur after simultaneous discontinuation of both drugs....
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Journal Article•
TL;DR: It is not currently possible to predict which patients will manifest clinically important drug-drug interactions, nor what concentration of an HMG-CoA reductase inhibitor will cause rhabdomyolysis, so until prescribers have better scientific information from which to develop a ‘therapeutic range’ for each agent, caution should be exercised.
Abstract: The present review outlines the clinical relevance of pharmacokinetic drug interactions within the HMG-CoA reductase inhibitor class. These interactions can result in markedly increased or decreased plasma concentrations of some drugs within this class. However, the relationship between altered plasma concentrations and adverse effects or toxicity may not be linear. It is likely that other variables affect this concentration-effect relationship including: rapid changes in the concentration, concomitant lipid-lowering therapy or host genetic factors that code for different forms or amounts of metabolising enzymes and drug receptors.It is not currently possible to predict which patients will manifest clinically important drug-drug interactions, nor what concentration of an HMG-CoA reductase inhibitor will cause rhabdomyolysis. Thus, until prescribers have better scientific information from which to develop a ‘therapeutic range’ for each agent, caution should be exercised. In particular, patients taking a CYP3A4-metabolised agent, e.g. atorvastatin, simvastatin and lovastatin, should not be started on a CYP3A4 inhibitor or inducer without close monitoring.
51 citations
TL;DR: In this article, the etiology of drug-drug interactions between warfarin and statins was investigated through case studies for many years, but the biochemical mechanisms causing these interactions have not been explained fully.
35 citations
TL;DR: The efficacy and safety of rosuvastatin, the newest and most potent of the approved statins, are reviewed, with results suggesting that Tolerability is comparable with other statins.
Abstract: Background: The HMG Co-A reductase inhibitors (statins) are the most efficacious agents for lowering cholesterol. Statins reduce clinical cardiovascular events and are generally well tolerated. Objective: To review the efficacy and safety of rosuvastatin, the newest and most potent of the approved statins. Methods: A comprehensive (PubMed) search was performed to identify relevant publications up to May 2007. Results/conclusions: Rosuvastatin reduces LDL cholesterol (LDL-C) by up to 50%, and by 70% when combined with ezetimibe. Rosuvastatin also reduces plasma triglycerides and increases HDL-C, and slows atherosclerosis progression in coronary and carotid arteries in both low-risk and high-risk individuals. Tolerability is comparable with other statins. Clinical trials to evaluate cardiovascular outcomes have recently been published (CORONA) or are underway.
22 citations
Cites background from "Rosuvastatin-acenocoumarol interact..."
...It is therefore recommended that the INR be monitored appropriately following the initiation of concomitant coumarin anticoagulant and rosuvastatin therapy [67] and the dose of rosuvastatin adjusted accordingly....
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...3 Interactions with anticoagulants In common with other statins, concomitant rosuvastatin and warfarin may be associated with an increased International Normalized Ratio (INR) [65,66] ; also rosuvastatin may enhance the anticoagulant effect of acenocoumarol [67] ....
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References
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TL;DR: It was shown that the ADR probability scale has consensual, content, and concurrent validity and may be applicable to postmarketing drug surveillance.
Abstract: The estimation of the probability that a drug caused an adverse clinical event is usually based on clinical judgment. Lack of a method for establishing causality generates large between-raters and within-raters variability in assessment. Using the conventional categories and definitions of definite, probable, possible, and doubtful adverse drug reactions (ADRs), the between-raters agreement of two physicians and four pharmacists who independently assessed 63 randomly selected alleged ADRs was 38% to 63%, kappa (k, a chance-corrected index of agreement) varied from 0.21 to 0.40, and the intraclass correlation coefficient of reliability (R[est]) was 0.49. Six (testing) and 22 wk (retesting) later the same observers independently reanalyzed the 63 cases by assigning a weighted score (ADR probability scale) to each of the components that must be considered in establishing causal associations between drug(s) and adverse events (e.g., temporal sequence). The cases were randomized to minimize the influence of learning. The event was assigned a probability category from the total score. The between-raters reliability (range: percent agreement = 83% to 92%; κ = 0.69 to 0.86; r = 0.91 to 0.95; R(est) = 0.92) and within-raters reliability (range: percent agreement = 80% to 97%; κ = 0.64 to 0.95; r = 0.91 to 0.98) improved (p < 0.001). The between-raters reliability was maintained on retesting (range: r = 0.84 to 0.94; R(est) = 0.87). The between-raters reliability of three attending physicians who independently assessed 28 other prospectively collected cases of alleged ADRs was very high (range: r = 0.76 to 0.87; R(est) = 0.80). It was also shown that the ADR probability scale has consensual, content, and concurrent validity. This systematic method offers a sensitive way to monitor ADRs and may be applicable to postmarketing drug surveillance.
Clinical Pharmacology and Therapeutics (1981) 30, 239–245; doi:10.1038/clpt.1981.154
9,840 citations
01 Jan 2005
TL;DR: Compare your culture to one of the cultures discussed in this unit, and list as many similarities and differences between the two as you can think of.
Abstract: Compare your culture to one of the cultures discussed in this unit. On a sheet of paper, list the cultures you are comparing and make one column titled “similarities,” and a second column titled “differences.” Now, list as many similarities and differences between the two as you can think of. Are there more similarities or differences between the two cultures you selected? Have you ever met anyone from this culture? How can you use this information to build greater respect between cultures?
1,000 citations
TL;DR: The liver is the target organ for the statins, since it is the major site of cholesterol biosynthesis, lipoprotein production and LDLcatabolism, and the adverse effects of HMG-reductase inhibitors during long term treatment may depend in part upon the degree to which they act in extrahepatic tissues.
Abstract: Hypercholesterolaemia plays a crucial role in the development of atherosclerotic diseases in general and coronary heart disease in particular. The risk of progression of the atherosclerotic process to coronary heart disease increases progressively with increasing levels of total serum cholesterol or low density lipoprotein (LDL) cholesterol at both the individual and the population level. The statins are reversible inhibitors of the microsomal enzyme HMG-CoA reductase, which converts HMG-CoAto mevalonate. This is an early rate-limiting step in cholesterol biosynthesis. Inhibition of HMG-CoA reductase by statins decreases intracellular cholesterol biosynthesis, which then leads to transcriptionally upregulated production of microsomal HMG-CoA reductase and cell surface LDL receptors. Subsequently, additional cholesterol is provided to the cell by de novo synthesis and by receptor-mediated uptake of LDL-cholesterol from the blood. This resets intracellular cholesterol homeostasis in extrahepatic tissues, but has little effect on the overall cholesterol balance. There are no simple methods to investigate the concentration-dependent inhibition of HMG-CoA reductase in human pharmacodynamic studies. The main clinical variable is plasma LDL-cholesterol, which takes 4 to 6 weeks to show a reduction after the start of statin treatment. Consequently, a dose-effect rather than a concentration-effect relationship is more appropriate to use in describing the pharmacodynamics. Fluvastatin, lovastatin, pravastatin and simvastatin have similar pharmacodynamic properties; all can reduce LDL-cholesterol by 20 to 35%, a reduction which has been shown to achieve decreases of 30 to 35% in major cardiovascular outcomes. Simvastatin has this effect at doses of about half those of the other 3 statins. The liver is the target organ for the statins, since it is the major site of cholesterol biosynthesis, lipoprotein production and LDLcatabolism. However, cholesterol biosynthesis in extrahepatic tissues is necessary for normal cell function. The adverse effects of HMG-reductase inhibitors during long term treatment may depend in part upon the degree to which they act in extrahepatic tissues. Therefore, pharmacokinetic factors such as hepatic extraction and systemic exposure to active compound(s) may be clinically important when comparing the statins. Different degrees of liver selectivity have been claimed for the HMG-CoA reductase inhibitors. However, the literature contains confusing data concerning the degree of liver versus tissue selectivity. Human pharmacokinetic data are poor and incomplete, especially for lovastatin and simvastatin, and it is clear that any conclusion on tissue selectivity is dependent upon the choice of experimental model. However, the drugs do differ in some important aspects concerning the degree of metabolism and the number of active and inactive metabolites. The rather extensive metabolism by different cytochrome P450 isoforms also makes it difficult to characterise these drugs regarding tissue selectivity unless all metabolites are well characterised. The effective elimination half-lives of the hydroxy acid forms of the 4 statins are 0.7 to 3.0 hours. Protein binding is similar (>90%) for fluvastatin, lovastatin and simvastatin, but it is only 50% for pravastatin. The best characterised statins from a clinical pharmacokinetic standpoint are fluvastatin and pravastatin. The major difference between these 2 compounds is the higher liver extraction of fluvastatin during the absorption phase compared with pravastatin (67 versus 45%, respectively, in the same dose range). Estimates of liver extraction in humans for lovastatin and simvastatin are poorly reported, which makes a direct comparison difficult.
519 citations