Lingtak Neander Chan

Proposal for a New Tool to Evaluate Drug Interaction Cases

The assessment of causation for a potential drug interaction requires thoughtful consideration of the properties of both the object and precipitant drugs, patient-specific factors, and the possible contribution of other drugs that the patient may be taking. The Naranjo nomogram was designed to evaluate single-drug adverse events, not drug–drug interactions. Several of the questions on the Naranjo nomogram do not apply to potential drug–drug interactions, while others do not specify object or precipitant drug. Nevertheless, it has been inappropriately used to evaluate drug–drug interactions. The Drug Interaction Probability Scale (DIPS) was developed to provide a guide to evaluating drug interaction causation in a specific patient. It is intended to be used to assist practitioners in the assessment of drug interaction–induced adverse outcomes. The DIPS uses a series of questions relating to the potential drug interaction to estimate a probability score. An accurate assessment using the DIPS requires knowledge of the pharmacologic properties of both the object and precipitant drugs. Inadequate knowledge of either the drugs involved or the basic mechanisms of interaction will be a limitation for some users. The DIPS can also serve as a guide in the preparation of articles describing case reports of drug interactions, as well as in the evaluation of published case reports.

Pharmacokinetics of the etonogestrel contraceptive implant in obese women.

OBJECTIVE We sought to examine the pharmacokinetics and acceptability of the etonogestrel contraceptive implant in obese women. STUDY DESIGN We developed and validated a plasma etonogestrel concentration assay and enrolled 13 obese (body mass index ≥30) women and 4 normal-weight (body mass index <25) women, who ensured comparability with historical controls. Etonogestrel concentrations were measured at 50-hour intervals through 300 hours postinsertion, then at 3 and 6 months to establish a pharmacokinetic curve. RESULTS All obese participants were African American, while all normal-weight participants were white. Across time, the plasma etonogestrel concentrations in obese women were lower than published values for normal-weight women and 31-63% lower than in the normal-weight study cohort, although these differences were not statistically significant. The implant device was found highly acceptable among obese women. CONCLUSION Obese women have lower plasma etonogestrel concentration than normal-weight women in the first 6 months after implant insertion. These findings should not be interpreted as decreased contraceptive effectiveness without additional considerations.

Drug-nutrient interactions

Drug-nutrient interactions are defined as physical, chemical, physiologic, or pathophysiologic relationships between a drug and a nutrient. The causes of most clinically significant drug-nutrient interactions are usually multifactorial. Failure to identify and properly manage drug-nutrient interactions can lead to very serious consequences and have a negative impact on patient outcomes. Nevertheless, with thorough review and assessment of the patients history and treatment regimens and a carefully executed management strategy, adverse events associated with drug-nutrient interactions can be prevented. Based on the physiologic sequence of events after a drug or a nutrient has entered the body and the mechanism of interactions, drug-nutrient interactions can be categorized into 4 main types. Each type of interaction can be managed using similar strategies. The existing data that guide the clinical management of most drug-nutrient interactions are mostly anecdotal experience, uncontrolled observations, and opinions, whereas the science in understanding the mechanism of drug-nutrient interactions remains limited. The challenge for researchers and clinicians is to increase both basic and higher level clinical research in this field to bridge the gap between the science and practice. The research should aim to establish a better understanding of the function, regulation, and substrate specificity of the nutrient-related enzymes and transport proteins present in the gastrointestinal tract, as well as assess how the incidence and management of drug-nutrient interactions can be affected by sex, ethnicity, environmental factors, and genetic polymorphisms. This knowledge can help us develop a true personalized medicine approach in the prevention and management of drug-nutrient interactions.

When Is Parenteral Nutrition Appropriate

Parenteral nutrition (PN) represents one of the most notable achievements of modern medicine, serving as a therapeutic modality for all age groups across the healthcare continuum. PN offers a life-sustaining option when intestinal failure prevents adequate oral or enteral nutrition. However, providing nutrients by vein is an expensive form of nutrition support, and serious adverse events can occur. In an effort to provide clinical guidance regarding PN therapy, the Board of Directors of the American Society for Parenteral and Enteral Nutrition (ASPEN) convened a task force to develop consensus recommendations regarding appropriate PN use. The recommendations contained in this document aim to delineate appropriate PN use and promote clinical benefits while minimizing the risks associated with the therapy. These consensus recommendations build on previous ASPEN clinical guidelines and consensus recommendations for PN safety. They are intended to guide evidence-based decisions regarding appropriate PN use for organizations and individual professionals, including physicians, nurses, dietitians, pharmacists, and other clinicians involved in providing PN. They not only support decisions related to initiating and managing PN but also serve as a guide for developing quality monitoring tools for PN and for identifying areas for further research. Finally, the recommendations contained within the document are also designed to inform decisions made by additional stakeholders, such as policy makers and third-party payers, by providing current perspectives regarding the use of PN in a variety of healthcare settings.

Pharmacokinetic and Pharmacodynamic Drug Interactions with Ethanol (Alcohol)

Ethanol (alcohol) is one of the most widely used legal drugs in the world. Ethanol is metabolized by alcohol dehydrogenase (ADH) and the cytochrome P450 (CYP) 2E1 drug-metabolizing enzyme that is also responsible for the biotransformation of xenobiotics and fatty acids. Drugs that inhibit ADH or CYP2E1 are the most likely theoretical compounds that would lead to a clinically significant pharmacokinetic interaction with ethanol, which include only a limited number of drugs. Acute ethanol primarily alters the pharmacokinetics of other drugs by changing the rate and extent of absorption, with more limited effects on clearance. Both acute and chronic ethanol use can cause transient changes to many physiologic responses in different organ systems such as hypotension and impairment of motor and cognitive functions, resulting in both pharmacokinetic and pharmacodynamic interactions. Evaluating drug interactions with long-term use of ethanol is uniquely challenging. Specifically, it is difficult to distinguish between the effects of long-term ethanol use on liver pathology and chronic malnutrition. Ethanol-induced liver disease results in decreased activity of hepatic metabolic enzymes and changes in protein binding. Clinical studies that include patients with chronic alcohol use may be evaluating the effects of mild cirrhosis on liver metabolism, and not just ethanol itself. The definition of chronic alcohol use is very inconsistent, which greatly affects the quality of the data and clinical application of the results. Our study of the literature has shown that a significantly higher volume of clinical studies have focused on the pharmacokinetic interactions of ethanol and other drugs. The data on pharmacodynamic interactions are more limited and future research addressing pharmacodynamic interactions with ethanol, especially regarding the non-central nervous system effects, is much needed.

The Science and Practice of Micronutrient Supplementations in Nutritional Anemia An Evidence-Based Review

Nutritional anemia is the most common type of anemia, affecting millions of people in all age groups worldwide. While inadequate access to food and nutrients can lead to anemia, patients with certain health status or medical conditions are also at increased risk of developing nutritional anemia. Iron, cobalamin, and folate are the most recognized micronutrients that are vital for the generation of erythrocytes. Iron deficiency is associated with insufficient production of hemoglobin. Deficiency of cobalamin or folate leads to impaired synthesis of deoxyribonucleic acid, proteins, and cell division. Recent research has demonstrated that the status of copper and zinc in the body can significantly affect iron absorption and utilization. With an increasing number of patients undergoing bariatric surgical procedures, more cases of anemia associated with copper and zinc deficiencies have also emerged. The intestinal absorption of these 5 critical micronutrients are highly regulated and mediated by specific apical transport mechanisms in the enterocytes. Health conditions that persistently alter the histology of the upper intestinal architecture, expression, or function of these substrate-specific transporters, or the normal digestion and flow of these key micronutrients, can lead to nutritional anemia. The focus of this article is to review the science of intestinal micronutrient absorption, discuss the clinical assessment of micronutrient deficiencies in relation to anemia, and suggest an effective treatment plan and monitoring strategies using an evidence-based approach.

Proximal Roux‐en‐Y Gastric Bypass Alters Drug Absorption Pattern But Not Systemic Exposure of CYP3A4 and P‐glycoprotein Substrates

To evaluate the effect of Roux‐en‐Y gastric bypass surgery (RYGB) on the pharmacokinetics of midazolam (a CYP3A4 substrate) and digoxin (a P‐glycoprotein substrate).

Probiotics for neonates: safety for prime time questioned without regulatory changes.

Purpose: Necrotizing enterocolitis (NEC) is the most common acquired disease of the gastrointestinal tract in preterm infants, whereas probiotic supplementation might reduce NEC risk and potentially provide benefits to preterm infants. We performed an updated meta-analysis of all relevant randomized, controlled trials to assess the benefits of probiotic supplementation for preterm very low-birth-weight (VLBW) infants. Methods:We searched in PubMed, Embase, and Chinese BioMedical Literature Database (CBM) databases, and 20 randomized, controlled trials (a total of 3816 preterm VLBW infants) were finally included into this meta-analysis. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model depending on the heterogeneity of the included studies. Results: Probiotic supplement was associated with a significantly decreased risk of NEC in preterm VLBW infants (RR = 0.33; 95% confidence interval [CI], 0.24-0.46; P < .00001). Risk of death was also significantly reduced in the probiotic group (RR = 0.56; 95% CI, 0.43-0.73; P < .0001). There was no difference in the risk of sepsis between the probiotic group and placebo group (RR = 0.90; 95% CI, 0.71-1.15; P = .40) Conclusions: Probiotic supplement can reduce risk of NEC and mortality in preterm VLBW infants. However, the optimum type of probiotic supplement and the long-term effects need further study.

Effect of intravenous iron supplementation on hepatic cytochrome P450 3A4 activity in hemodialysis patients: A prospective, open-label study

BACKGROUND Cytochrome P450 (CYP) 3A4 is an enzyme with activity dependent on the reduction of heme iron that is responsible for the metabolism of many drugs. CYP3A4 activity is reduced in hemodialysis (HD) patients and thus may be related to functional iron deficiency. OBJECTIVE The purpose of this study was to investigate the effect of IV iron supplementation on hepatic is CYP3A4 activity in HD patients. METHODS This prospective, open-label study was conducted in 12 iron-deficient (transferrin saturation <20% or ferritin <100 ng/L) HD patients on stable medication regimens. To probe for hepatic CYP3A4 activity, an erythromycin breath test (ERMBT) was administered before and after 1 g IV iron sucrose (administered as a 100-mg dose [20 mg/mL]), at each of 10 consecutive HD sessions). CYP3A4 activity was estimated by the percentage of administered (14)C exhaled in a single-breath collection after the test dose of erythromycin underwent demethylation by CYP3A4. The ERMBT was also administered to 7 age-, sex-, and race-matched healthy controls. RESULTS Twelve HD patients (6 Hispanic, 3 white, 3 Native American; 8 men, 4 women; mean [SEM] age, 56.2 [5.0] years; mean [SEM] weight, 77.0 [5.6] kg; and 7 controls (4 men, 3 women; mean [SEM] age, 51.3 [5.0] years; mean [SEM] weight, 77.5 [7.4] kg) were enrolled in the study. In the total HD population studied, mean (SEM) CYP3A4 activity did not change significantly after IV iron replacement (1.46 [0.27] vs 1.57 [0.24] (14)C exhaled/h). A subgroup of 7 HD patients had significantly lower CYP3A4 activity before IV iron replacement compared with the other 5 HD patients and controls (mean [SEM] 0.86 [0.24] vs 2.30 [0.26] and 2.10 [0.26] (14)C exhaled/h; P < 0.01). After IV iron replacement, mean (SEM) CYP3A4 activity increased in these 7 HD patients (120.1% [67.1%]); P = 0.04) and it was not statistically different from that of controls (1.50 [0.36] vs 2.10 [0.26]). CONCLUSIONS Overall, IV iron administration had no significant effect on hepatic CYP3A4 activity. However, in a subset of HD patients with low baseline CYP3A4 activity indicated by low ERMBT values, IV iron supplementation was associated with a potentially clinically relevant increase in hepatic CYP3A4 activity. Further studies are needed to clarify mechanisms and clinical implications of this interaction.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2016

Purpose: To assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2016 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the paper was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 out of 8) considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not scored, were also included. Results: A total of 103 articles were identified; 10 from the primary literature were voted by the group to be of high importance. An additional 11 organizational guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were reviewed. Conclusion: It is recommended that pharmacists, engaged in nutrition support therapy, be familiar with the majority of these articles as it pertains to their practice.