Lack of Effect of Gemfibrozil on Cyclosporine Blood Concentrations in Kidney-Transplanted Patients

Pisanti, N; Stanziale, P.; Imperatore, P.; D'alessandro, R.; Marino, V. De; Capone, Domênico; Marino, Vincenzo

doi:10.1159/000013337

Cited by 13 publications

(4 citation statements)

References 9 publications

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“…Studies of fibrate class drugs have shown that neither gemfibrozil nor fenofibrate alters cyclosporine levels and therefore do not require modification of cyclosporine doses (60, 61). Ezetemibe also does not affect levels of cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil and can therefore be safely used with these immunosuppressive therapies (54).…”

Section: Hyperlipidaemiamentioning

confidence: 99%

Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors, incidence and management

Desai

Hong

Saab

2009

Liver International

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Background: Liver transplantation is the standard of care for acute and chronic causes of end-stage liver disease. Advances in medical therapy and surgical techniques have led to improvement of patient and graft survival rates following orthotopic liver transplantation. However, the prevalence of posttransplant cardiovascular complications has been rising with increased life expectancy after liver transplantation. Aims: To determine the incidences, risk factors, and treatment for hypertension, hyperlipidaemia, diabetes, and obesity in the post-liver transplantation population. Methods: We performed a review of relevant studies available on the PubMed database that provided information on the incidence, risk factors and treatment for cardiovascular complications that develop in the post-liver transplantation population. Results: Current immunosuppressive agents have improved patient and graft survival rates. However, long-term exposure to these agents has been associated with development of systemic and metabolic complications including hypertension, hyperlipidaemia, diabetes mellitus and obesity. Cardiovascular disease remains one of the most common causes of death in liver transplant patients with functional grafts. Conclusions: Liver transplant recipients have a higher risk of cardiovascular complications compared with the nontransplant population. Post-transplant cardiac risk stratification and aggressive treatment of cardiovascular complications, including modification of risk factors and tailoring of immunosuppressive regimen, is imperative to prevent serious complications.Liver transplantation is the standard of care for acute and chronic causes of end-stage liver disease. Advances in medical therapy and surgical techniques have led to improvement of patient and graft survival rates following orthotopic liver transplantation (OLT), with 1-and 5-year patient survival rates of 84 and 67% respectively (1). However, the prevalence of medical complications such as hypertension, hyperlipidaemia, weight gain and diabetes has been rising along with increased life expectancy after liver transplantation (2). Liver transplant recipients have a higher risk of cardiovascular death and ischaemic events as compared with an age-and sex-matched population without liver transplant (3). This elevated cardiovascular event rate ranges from 9% at 5 years post-transplant (4) to 25% at 10 years post-transplant (5). Cardiovascular disease causes 21% of deaths among liver transplant patients with functioning grafts surviving more than 3 years (6) and remains a common cause of death in OLT patients (7).Post-OLT cardiovascular complications result from a combination of factors that include pre-existing disease before transplantation and chronic exposure to immunosuppressive agents following OLT (8). Current immunosuppressive regimens include a combination of a calcineurin inhibitor, such as cyclosporine or tacrolimus, along with corticosteroids, mycophenolate mofetil or sirolimus, and have been associated with both exacerbati...

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Section: Hyperlipidaemiamentioning

confidence: 99%

Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors, incidence and management

Desai

Hong

Saab

2009

Liver International

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“…In addition to pathophysiological causes (kidney diseases, obesity, diabetes) [1,10], it has been also reported that the administration of Cs-A and steroids, used as immunosuppressive agents in organ-transplanted patients, is responsible for hyperlipidemia [11][12][13]. The hypothesized mechanisms by which these drugs increase cholesterol and triglyceride serum concentrations have been described in our previous study [8]. According to the European Atherosclerosis Society, hyperlipidemia was treated with two HMG-CoARIs, simvastatin and pravastatin [9].…”

Section: Discussionmentioning

confidence: 82%

“…On the basis of these evidences, several authors [5][6][7][8] suggested treatment of hyperlipidemia with lipid-lowering drugs in organ transplant recipients to prevent these risks.…”

Section: Introductionmentioning

confidence: 99%

Effects of Simvastatin and Pravastatin on Hyperlipidemia and Cyclosporin Blood Levels in Renal Transplant Recipients

Capone¹,

Stanziale

Gentile³

et al. 1999

Am J Nephrol

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Thirty-one renal transplant recipients, submitted to treatment with cyclosporin in association with other immunosuppressive agents, were also treated for 9 months with two hydroxymethylglutaryl coenzyme A reductase inhibitors, simvastatin (10 mg/day) or pravastatin (20 mg/day), for concomitant hypercholesterolemia and hypertriglyceridemia. Both drugs significantly decreased total cholesterol and triglyceride serum levels, but they did not modify whole-blood trough concentrations of polyclonal and monoclonal cyclosporin or polyclonal/monoclonal cyclosporin ratio. No alterations of the clinical and laboratory parameters investigated were found. The results of this study show the efficacy and safety of hydroxymethylglutaryl coenzyme A reductase inhibitors in the treatment of hyperlipidemia in kidney transplant patients.

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“…47 Data demonstrating potential drug interaction between gemfibrozil or fenofibrate and CSA are conflicting. 48 Studies suggest an 18% to 27% reduction in CSA trough levels with concomitant fibric acid use. 49,50 Although reports of myotoxicity with CSA are few, the potential exists.…”

Section: Antihypertensivesmentioning

confidence: 99%

Drug Therapy in the Heart Transplant Recipient

2005

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With improving survival, the heart transplant recipient faces an increasing number of medical problems caused by both aging and the cumulative complications of immunosuppressive drugs. 1 The availability of new drugs to treat infection, obesity, hypertension, hyperlipidemia, renal insufficiency, diabetes, osteoporosis, gout, and malignancies has resulted in the heart transplant recipient and their physicians facing an almost overwhelming number of important drug-drug interactions. In parts 1 through 3 of this series, we reviewed commonly used immunosuppressive drugs and their pharmacology, as well as the common medical problems faced by the heart transplant recipient. In this article, we provide an overview of the mechanisms of common and important potential drug-drug interactions and guidelines for avoiding these interactions. Principles of Drug-Drug InteractionsThe risk for drug-drug interactions is increased by advanced age, polypharmacy, medications with a narrow therapeutic index, or medications requiring intensive monitoring. All of these factors except advanced age are present in the heart transplant recipient. A 10-fold interpatient variability may exist in the magnitude of a drug interaction resulting from patient-related and drug-related factors. 2 Patient-related factors predisposing to drug interactions include concomitant diseases, genetics, diet, and environmental exposures. For example, commonly used immunosuppressants, antifungal agents, and lipid-lowering medications are metabolized through the cytochrome P450 (CYP450) enzyme system and effluxed from cells by the multiple drug resistance transporter protein p-glycoprotein (P-gp). Both systems are found in the liver and gastrointestinal tract and exhibit genetic polymorphism. 2 The CYP450 enzymes belong to a superfamily of oxygenases; the primary purpose of these oxygenases is to add a functional group to a drug to increase its polarity and to promote its excretion from the body. If enzymes possess Ͼ40% homology, they are grouped together into families designated by an Arabic numeral (eg, the CYP1 family). Families are further divided into subfamilies, which are designated by a letter after the number (eg, CYP2C and CYP2D subfamilies); members of each subfamily have Ͼ55% homology with each another. Individual members are given an additional number (eg, CYP3A4) to identify a specific enzyme pathway. 2 CYP3A4 is particularly important because 60% of oxidized drugs, including the calcineurin inhibitors (CIs) cyclosporine (CSA) and tacrolimus (TAC), sirolimus (SIR), and everolimus (EVER), undergo biotransformation through this particular enzyme system. 3 P-gp is a membrane-bound glycoprotein belonging to the superfamily of ATP-binding cassette transporters. Like the CYP450 enzyme system, P-gp acts in a protective capacity by "effluxing" drug from the cell membrane or cytoplasm. P-gp density is highest within the small intestine, proximal tubules of the kidney, and biliary canalicular membranes. Some medications such as CIs and SIR use both the CYP450...

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Lack of Effect of Gemfibrozil on Cyclosporine Blood Concentrations in Kidney-Transplanted Patients

Cited by 13 publications

References 9 publications

Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors, incidence and management

Cardiovascular risk factors following orthotopic liver transplantation: predisposing factors, incidence and management

Effects of Simvastatin and Pravastatin on Hyperlipidemia and Cyclosporin Blood Levels in Renal Transplant Recipients

Drug Therapy in the Heart Transplant Recipient

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