Drug interactions in transplant patients: what everyone should know

Manitpisitkul, Wana; McCann, Erin; Lee, Sabrina; Weir, Matthew R.

doi:10.1097/mnh.0b013e32832edcb2

Cited by 58 publications

(38 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of potent drug-drug interactions have been described with the use of immunosuppressive drugs that are substrates of CYP3A (15,18). The dosing regimens of these drugs, which display broad interpatient variability in terms of clearance and a narrow therapeutic window, can be optimized using therapeutic drug monitoring (13,14,24).…”

Section: Discussionmentioning

confidence: 99%

Practical Management of Boceprevir and Immunosuppressive Therapy in Liver Transplant Recipients with Hepatitis C Virus Recurrence

Coilly

Furlan

Roche

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

f Hepatitis C virus (HCV) recurrence is the most important complication in HCV liver transplant patients. Boceprevir with pegylated interferon and ribavirin (PegIFN/RBV) enabled improvement in sustained virological response rates of patients with genotype 1 HCV. Boceprevir interacts with immunosuppressive therapy (IT) by inhibiting the cytochrome P450 3A enzyme. Our aim was to study interactions and assess the safety of boceprevir in the context of HCV recurrence. Boceprevir (800 mg three times a day) initiated after a 4-week lead-in phase was associated with cyclosporine (three patients), tacrolimus (two patients), and everolimus (one patient) in five liver transplant patients with genotype 1 HCV infection who experienced HCV recurrence. The mean follow-up period after HCV therapy was 14.8 ؎ 3.1 weeks. Estimated oral clearances of IT decreased on average by 50%, requiring reduced dosing regimens. Anemia occurred in all patients, with a mean fall in hemoglobin levels between baseline and week 12 of 3.12 ؎ 2.27 g/dl. All patients required administration of ␤-erythropoietin (n ‫؍‬ 5), three needed ribavirin dose reduction, and one needed a blood transfusion. A virological response was observed in all patients (mean HCV viral load [HVL] decrease at week 12, 6.64 ؎ 0.35 log 10 IU/ml). These preliminary results in liver transplant patients with HCV recurrence demonstrate the feasibility and safety of coadministration of boceprevir and IT. E nd-stage liver disease due to hepatitis C virus (HCV) is still a common indication for liver transplantation (LT) (6). However, a recurrence of HCV infection is the most frequent cause of death and graft loss, accounting for two-thirds of graft failures. The natural history of HCV is accelerated after LT, leading to cirrhosis in 20 to 30% of patients 5 years post-LT (4). The decompensation rate is higher than 70% at 3 years in liver transplant recipients with established cirrhosis, versus less than 10% in immunocompetent patients (4). Progression from decompensation to death is also accelerated after LT, with a 3-year survival rate of Ͻ10% following the onset of HCV-related allograft failure (4). Few patients (Ͻ5%) experience cholestatic hepatitis, but their prognosis is the poorest (7). To prevent or to treat these occurrences, standard anti-HCV therapy, represented by pegylated interferon and ribavirin, can achieve a sustained virological response (SVR) in 30% of patients, who have a less severe outcome and lower mortality than nonresponders (21). Boceprevir is a novel peptidometic NS3 protease inhibitor that forms a covalent and reversible complex with the NS3 protease in vitro in the HCV replicon system. Recently, two phase III trials showed that combining boceprevir with pegylated interferon and ribavirin increased SVR rates in naive and previously treated nontransplant patients with genotype 1 HCV from 38% to 66% (SPRINT-2) and 21% to 66% (RESPOND-2), respectively (2, 20). The administration of such drugs in the context of HCV recurrence on the liver graft is one of the most...

show abstract

Section: Discussionmentioning

confidence: 99%

Practical Management of Boceprevir and Immunosuppressive Therapy in Liver Transplant Recipients with Hepatitis C Virus Recurrence

Coilly

Furlan

Roche

et al. 2012

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Cyclosporine can increase plasma levels of statins via a complex mechanism, possibly involving competitive inhibition of CYP3A4mediated drug metabolism by cyclosporine. It is therefore recommended that, when used in combination with cyclosporine, the statin dose should be significantly reduced to prevent serious adverse reactions such as rhabdomyolysis [52] . The pharmacokinetics of atorvastatin has not been found to be influenced by tacrolimus [53] , although further studies are needed before this can be generalised to all types of statin.…”

Section: Dyslipidaemiamentioning

confidence: 99%

Cardiovascular risk factors following renal transplant

Neale

Smith

2015

WJT

117

View full text Add to dashboard Cite

Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Nontraditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population. Core tip: Cardiovascular disease (CVD) is the leading cause of death and disability in patients following a renal transplant. Identification of risk factors for CVD and strategies for their improvement are required in order to prevent graft failure in this complex patient

show abstract

“…This is particularly relevant in kidney transplant recipients who often have reduced estimated glomerular filtration rate (GFR) where medication dosage adjustment may be required, and there is increased risk of drug: drug interactions 4 . Moreover it remains unanswered how precautionary statements issued by Micromedex about potential drug-drug interactions in transplant recipients translate into patient safety events in this population.…”

Section: Introductionmentioning

confidence: 99%

Safety Events in Kidney Transplant Recipients

et al. 2015

Self Cite

View full text Add to dashboard Cite

Background Kidney transplant recipients are at increased risk for adverse safety events related to their reduced renal function and many medications. Methods We determined the incidence of adverse safety events based on previously defined Agency for Healthcare and Research Quality (AHRQ) ICD-9 code-derived patient safety indicators (PSI) in the Folic Acid for Vascular Outcome Reduction in Transplant (FAVORIT) trial participants who had a hospitalization stratified by tertiles of estimated glomerular filtration rate. We also examined the frequency of Micromedex defined two precautionary drug-drug interactions, and two medications whose use may be contraindicated due to reduced GFR from the FAVORIT trial Medication Thesaurus at baseline, and annually among 4110 participants. Logistic regression was used to examine the relationship between patient safety events and baseline demographic and clinical variables at a participant level. Event rates were estimated at participant and visit levels. Results Of the 2514 patients with a hospitalization, 978 (38.9%) experienced an AHRQ PSI. Factors which were associated with more common AHRQ PSI included: US location, history of cardiovascular disease or diabetes, and lower tertile of estimated GFR. At a participant level, 2524 of the 4110 participants (61.4%) were taking a CNI and a statin, 378 (9.2%) were taking azathioprine and an ACE inhibitor, 171 (12.9%) were taking a sulfonylurea ), 45 (3.4%) were taking metformin despite a baseline GFR below 40 ml/min/1.73m2. Conclusions We conclude that patient safety events are not uncommon in kidney transplant recipients. Careful monitoring is necessary to prevent adverse outcomes.

show abstract

Drug interactions in transplant patients: what everyone should know

Abstract: Close therapeutic drug monitoring and evaluation of drug-specific side effects continue to be an important key to minimize adverse events due to drug-drug interactions.

Cited by 58 publications

References 104 publications

Practical Management of Boceprevir and Immunosuppressive Therapy in Liver Transplant Recipients with Hepatitis C Virus Recurrence

Practical Management of Boceprevir and Immunosuppressive Therapy in Liver Transplant Recipients with Hepatitis C Virus Recurrence

Cardiovascular risk factors following renal transplant

Safety Events in Kidney Transplant Recipients

Contact Info

Product

Resources

About