Antihypertensive agents: a long way to safe drug prescribing in children.

Recently updated clinical guidelines have highlighted the gaps in our understanding and management of pediatric hypertension. With increased recognition and diagnosis of pediatric hypertension, the use of antihypertensive agents is also likely to increase. Drug selection to treat hypertension in the pediatric patient population remains challenging. This is primarily due to a lack of large, well-designed pediatric safety and efficacy trials, limited understanding of pharmacokinetics in children, and unknown risk of prolonged exposure to antihypertensive therapies. With newer legislation providing financial incentives for conducting clinical trials in children, along with publication of pediatric-focused guidelines, literature available for antihypertensive agents in pediatrics has increased over the last 20 years. The objective of this article is to review the literature for safety and efficacy of commonly prescribed antihypertensive agents in pediatrics. Thus far, the most data to support use in children was found for angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB). Several gaps were noted in the literature, particularly for beta blockers, vasodilators, and the long-term safety profile of antihypertensive agents in children. Further clinical trials are needed to guide safe and effective prescribing in the pediatric population.

Continuous-Flow Left Ventricular Assist Device Survival Improves With Multidisciplinary Approach.

BACKGROUND: Continuous-flow left ventricular assist devices have revolutionized the management of advanced heart failure. Device complications continue to limit survival, but enhanced management strategies have shown promise. This study compared outcomes for HeartMate II recipients before and after implementation of a multidisciplinary continuous support heart team (HTMCS) strategy. METHODS: Between January 2012 and December 2016, 124 consecutive patients underwent primary HeartMate II implantation at our institution. In January 2015, we instituted a HTMCS approach consisting of (1) daily simultaneous cardiology/cardiac surgery/critical care/pharmacy/coordinator rounds, (2) pharmacist-directed anticoagulation, (3) speed optimization echocardiogram before discharge, (4) comprehensive device thrombosis screening and early intervention, (5) blood pressure clinic with pulsatility-adjusted goals, (6) early follow-up after discharge and individual long-term coordinator/cardiologist assignment, and (7) systematic basic/advanced/expert training and credentialing of ancillary in-hospital providers. All patients completed 1-year of follow-up. RESULTS: Demographic characteristics for pre-HTMCS (n = 71) and HTMCS (n = 53) groups, including age (55.8 ± 12.1 versus 52.5 ± 14.1 years, p = not significant), percentage of men (77.5% versus 71.7%, p = not significant), and Interagency Registry for Mechanically Assisted Circulatory Support class 3 (84.5% versus 83.0%, p = not significant), were comparable. One-year survival was 74.6% versus 100% for the pre-HTMCS and HTMCS groups, respectively (p = 0.0002). One-year survival free of serious adverse events (reoperation to replace device or disabling stroke) was 70.4% versus 84.9% for the pre-HTMCS and HTMCS groups, respectively (p = 0.059). Event per patient-year rates for disabling stroke (0.15 versus 0, p = 0.019), gastrointestinal bleeding (0.87 versus 0.51, p = 0.11), and driveline infection (0.24 versus 0.10, p = 0.18) were lower for the HTMCS group, whereas pump thrombosis requiring device exchange was higher (0.09 versus 0.18, p = 0.14). CONCLUSIONS: Implementing a comprehensive multidisciplinary approach substantially improved outcomes for recipients of continuous-flow left ventricular assist devices.

The effect of MMF dose and trough levels on adverse effects in pediatric heart transplant recipients.

Limited pharmacokinetic and safety data exist for MMF in pediatric HTR. Previously targeted MPA-TL are 1.5-3.0 µg/mL. The objective of this study was to assess the outcomes targeting MPA-TL of 0.8-2.0 µg/mL in pediatric HTR. MPA-TL were retrospectively collected 2-12 months post-transplant. Acute rejection, infection, leukopenia, and GI complaints were then correlated with MPA-TL. A total of 355 MPA-TL from 22 HTR were included. Median age was 2.5 yr. Primary indication for transplant was dilated cardiomyopathy (64%). Mean MPA-TL was 1.7 ± 0.9 µg/mL. African American patients received significantly higher doses (702 ± 235 mg/m(2) ) compared with other races (p = 0.035). Leukopenia was less common in patients with SUB MPA vs. others (p = 0.01). MMF was discontinued for GI complaints in one patient and leukopenia in two patients. One SUB patient had acute rejection, and one SUP patient had infection. One-yr survival was 100%. Targeting a lower range for MPA-TL was not associated with significant rejection or infection. Despite lower MPA-TL, MMF was discontinued in 3/22 patients for adverse effects.

Clinically significant drug-drug interaction between tacrolimus and phenobarbital: the price we pay.

PURPOSE: The case of a 57-year-old male who experienced acute renal transplant rejection due to subtherapeutic tacrolimus levels as a result of drug interaction with phenobarbital. SUMMARY: Drug interactions with tacrolimus due to its metabolism through the CYP 450 3A4 enzymatic pathway have led to several reports of altered tacrolimus levels, which can lead to acute rejection in renal transplant recipients. We describe the case of a 57-year-old male initiated on immunosuppressive therapy with tacrolimus in addition to his anticonvulsant medications. CONCLUSION: Upon tacrolimus dose increases, discontinuation of carbamazepine, and minimization of phenobarbital dose, effective tacrolimus trough levels were achieved in our patient. Identification and elimination of such drug-drug interactions is necessary to assure adequate immunosuppression in renal transplant recipients.