Tracy M. Hagemann

Deferasirox—An Oral Agent for Chronic Iron Overload

Objective: To review the available literature on the pharmacology, pharmacokinetics, efficacy, toxicology, adverse effects, drug interactions, and dosage guidelines for deferasirox, an oral iron chelator, in Phase III trials. Data Sources: Reviewers searched the following databases for English-language studies: MEDLINE (1966—April 2006), International Pharmaceutical Abstracts (1970–April 2006), and the Cochrane Library Database. Key search terms included iron chelation, chelation, iron overload, deferasirox, and ICL670. Study Selection and Data Extraction: Data on efficacy, toxicology, adverse effects, and pharmacokinetics for deferasirox were obtained from randomized, open-label, blinded clinical trials. Other information was obtained from the manufacturer, including unpublished studies in abstract form as well as available data on deferasirox. Data Synthesis: Deferasirox is an orally active iron chelator. In clinical trials, deferasirox demonstrated efficacy at dosages of 20 and 30 mg/kg/day in treating iron overload in patients with β-thalassemia. Deferasirox has been studied in patients older than 2 years and appears to be safe, with the most common adverse effects reported being mild, transient nausea, gastrointestinal disturbances, and rash. There were no reports of serious adverse effects in trials to date. Conclusions: Deferasirox represents a new approach to the management of chronic iron overload in patients with chronic anemias who require blood transfusions. The available literature suggests that deferasirox is safe and as effective as the current standard of therapy at dosages of 20–30 mg/kg/day for β-thalassemia. Further studies are needed to confirm its efficacy in other chronic transfusion-requiring diseases.

Purified Poloxamer 188 for Sickle Cell Vaso-Occlusive Crisis

OBJECTIVE To review available literature on the pharmacology, pharmacokinetics, efficacy, toxicology, adverse effects, drug interactions, and dosage guidelines for purified poloxamer 188, a product in Phase III trials. DATA SOURCES Reviewers searched the following databases for English-language studies: MEDLINE (1966–November 2003), International Pharmaceutical Abstracts (1970–November 2003), and the Cochrane Library Database (3rd quarter 2003). Key search terms included purified poloxamer 188, Flocor, CRL-5861, poloxamer 188, RheothRx, and pluronic F-68. STUDY SELECTION AND DATA EXTRACTION Data on efficacy, adverse effects, and pharmacokinetics were obtained from randomized, open-label, and blinded clinical trials. Toxicology data were obtained from unpublished studies with purified poloxamer 188 and from available data on poloxamer 188 (nonpurified form). DATA SYNTHESIS Purified poloxamer 188 is a highly purified form of the nonionic block copolymer poloxamer 188. It lowers blood viscosity, decreases red blood cell (RBC) aggregation, and decreases friction between RBCs and vessel walls to increase microvascular blood flow and decrease cell injury. In clinical trials, purified poloxamer 188 demonstrated safety, but little efficacy for the treatment of sickle cell vaso-occlusive crisis. Increased efficacy has been shown in patients on concurrent hydroxyurea therapy and those <15 years of age. CONCLUSIONS Purified poloxamer 188 represents a new approach to the management of the sickle cell vaso-occlusive crisis. Children and patients on hydroxyurea may benefit most from purified poloxamer 188 therapy. Further studies are needed to confirm its efficacy and to determine whether the drug decreases sickle cell disease severity and complications.

Prevention and treatment of oral mucositis in children with cancer.

Oral mucositis affects more than three-fourths of patients undergoing chemotherapy and represents a significant burden to patients and caregivers. Lesions develop as a result of chemotherapeutic agents attacking the rapidly dividing cells of the gastrointestinal tract. Severity can range from mild, painless tissue changes to bleeding ulcerations that prevent oral intake and require narcotic pain relievers. Oral mucositis also leads to an increased risk of infection and can often delay further chemotherapy treatment. A number of assessment scales have been developed to better qualify the symptoms associated with this condition. Few pharmacologic agents have been approved to either prevent the development or alleviate the symptoms of oral mucositis. Current options include the use of antimicrobial mouthwashes, amino acid rinses, and topical healing agents. Palifermin, a keratinocyte growth factor, may be a future option after its use in children is explored. With achievements in other areas of supportive care in patients undergoing chemotherapy, oral mucositis should represent the forefront of new research. This review will provide a comprehensive examination of available options for children who have oral mucositis.

Vancomycin dosage in overweight and obese children

PURPOSE Vancomycin dosages in overweight and obese children were evaluated. METHODS This retrospective study evaluated data for children who were age 2-17 years, received i.v. vancomycin, and were admitted to a childrens hospital from September 1, 2007, through October 31, 2009. Patients were then stratified into two groups: normal-weight patients and overweight or obese patients. The primary objective was to compare the number of vancomycin regimens between groups with a trough concentration of 5-15 μg/mL. Secondary objectives included a comparison of dosage changes and toxicities. Multivariate, conditional logistic regression was performed to assess the relationship between attaining optimal vancomycin concentrations (5-15 μg/mL) and independent variables. RESULTS Data were collected for 232 courses of vancomycin, representing 187 patients. The mean ± S.D. initial dose for the normal-weight and overweight or obese groups differed significantly (461.3 ± 303.1 mg and 658.4 ± 389.6 mg, respectively; p < 0.01); the milligram-per-kilogram initial vancomycin dose did not. The multivariate analysis revealed that every-eight-hour regimens had increased odds of achieving therapeutic concentrations (p < 0.001), while obese children had decreased odds of achieving therapeutic concentrations (p = 0.037). CONCLUSION A study of prescribing behavior in one hospital revealed no significant difference in the size of vancomycin doses (in milligrams per kilogram) given to normal-weight children compared with overweight or obese children. Regimens using every-eight-hour dosing were significantly more likely than other regimens to result in a vancomycin trough concentration of 5-15 μg/mL, and regimens for obese children, compared with regimens for nonobese children, were less likely to produce trough concentrations in the same range of 5-15 μg/mL.

Promethazine Treatment of Steroid-Induced Psychosis in a Child

OBJECTIVE: To report a case of steroid-induced psychosis in a child that resolved with the treatment of promethazine, a phenothiazine derivative. CASE SUMMARY: A 2-year-old white boy with a history of relapsed acute lymphoblastic leukemia underwent a bone marrow transplant and developed graft-versus-host disease, which was treated with methylprednisolone. Within 24 hours of initiation of the methylprednisolone, the patient developed symptoms associated with steroid-induced psychosis including mania, head-banging, and excessive crying. Because the corticosteroid could not be discontinued, promethazine, a phenothiazine derivative, was used to treat the psychotic symptoms. Symptoms resolved with use of promethazine. DISCUSSION: A number of published reports describe the appearance of psychological symptoms with corticosteroid use. While the mechanism is unclear, the reaction is usually reversible with dose reduction or discontinuation of the corticosteroid. In cases where this cannot be done, typical treatment involves an antipsychotic medication. Most antipsychotic medications, such as the phenothiazine class, have not been evaluated in very young childen. Promethazine is a phenothiazine derivative that has been used in children for a number of nonpsychiatric indications. CONCLUSIONS: Promethazine may be effective in treating steroid-induced psychosis in pediatric patients.

Evaluation of Inpatient Admissions and Potential Antimicrobial and Analgesic Dosing Errors in Overweight Children

BACKGROUND The prevalence of overweight/obesity in US children has increased over the past several decades. Routine use of weight-based dosing of medications could potentially result in over- or underdosing in these children. OBJECTIVE To determine the percentage of admissions of children with a body mass index (BMI) greater than or equal to the 85th percentile for age and sex and the mean error rate per admission in the overweight versus control group. METHODS We performed a retrospective, preliminary study of children aged 5–12 years who were admitted to a childrens hospital over a period of 6 months. The overweight group included children with a BMI greater than or equal to the 85th percentile; the control group included children with a BMI less than the 85th percentile. Dose appropriateness was assessed, using 2 references. An overdose was defined as: (1) total mg/kg/day or mg/kg/dose greater than or equal to 110% of the maximum recommended pediatric dose, (2) total mg/day greater than the adult maximum recommended dose, or (3) greater than the recommended number of doses per day. An underdose was defined as: (1) total mg/kg/day or mg/kg/dose less than or equal to 90% of the minimum recommended pediatric dose, or (2) fewer than the recommended number of doses per day. Baseline comparisons between groups were done via Students t-tests and χ2 analysis, when appropriate, with an a priori α of p less than or equal to 0.05. RESULTS A total of 839 admissions representing 699 patients were included. The overweight group included 278 (33.1%) admissions. Comparison of overall mean error rate per admission revealed a statistically significant increase in dosing errors for overweight patients (0.4 ± 0.6 vs 0.3 ± 0.6; p = 0.030), with underdose errors occurring more frequently than overdose errors (0.3 ± 0.6 vs 0.2 ± 0.5; p = 0.010). CONCLUSIONS Overweight children accounted for one-third of admissions, and the results of this study suggest that these patients are at greater risk for errors in dosing than are children of age- and sex-appropriate weight. This study did not assess clinical outcomes; however, overweight children could be at increased risk for therapeutic failures or adverse effects.

Gastrointestinal Medications and Breastfeeding

Medications used to treat gastrointestinal symptoms are increasingly being used as more have been gained nonprescription status. Most of the gastrointestinal medications, such as laxatives, antacids, and antidiarrheal agents, are used short term. Women who breastfeed should be aware of the risks of taking any medications, whether prescription or nonprescription. There is little information describing transfer into breast milk for many of these products. Cimetidine, atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the only products identified by the AAP as compatible with breast feeding. Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is unknown but may be of potential concern, although studies published to date have not reported any adverse effects. The safest laxatives and antidiarrheals are those that are not absorbed and should be considered first-line therapy for conditions of constipation or loose stools. Famotidine and nizatidine are excreted into breast milk to a lesser extent than cimetidine or ranitidine and may be the preferred histamine antagonists. Despite the limited data on the use of cisapride in nursing women, it is considered safe by the AAP and may be preferred over metoclopramide for first-line prescription treatment of heartburn. Although most of these agents appear safe in the nursing infant, caretakers should be aware of the potential adverse reactions that may occur in infants whose mothers require these products.

Recommendations for meeting the pediatric patient's need for a clinical pharmacist: A joint opinion of the pediatrics practice and research network of the american college of clinical pharmacy and the pediatric pharmacy advocacy group

Children warrant access to care from clinical pharmacists trained in pediatrics. The American College of Clinical Pharmacy Pediatrics Practice and Research Network (ACCP Pediatrics PRN) released an opinion paper in 2005 with recommendations for improving the quality and quantity of pediatric pharmacy education in colleges of pharmacy, residency programs, and fellowships. Although progress has been made in increasing the availability of pediatric residencies, there is still much to be done to meet the direct care needs of pediatric patients. The purpose of this joint opinion paper is to outline strategies and recommendations for expanding the quality and capacity of pediatric clinical pharmacy practitioners by elevating the minimum expectations for pharmacists entering pediatric practice, standardizing pediatric pharmacy education, expanding the current number of pediatric clinical pharmacists, and creating an infrastructure for development of pediatric clinical pharmacists and clinical scientists. These recommendations may be used to provide both a conceptual framework and action items for schools of pharmacy, health care systems, and policymakers to work together to increase the quality and quantity of pediatric training, practice, and research initiatives.

Introductory and advanced pharmacy practice experiences within campus-based influenza clinics.

Objective. To describe the development, implementation, and assessment of an introductory and an advanced pharmacy practice experience (IPPE and APPE) integrated within campus-based influenza clinics. Design. The influenza clinics were designed to incorporate the learning objectives for the IPPE and APPE, and included preparatory sessions, online learning, and direct patient interactions tailored to the appropriate education level of the learner. Assessment. The clinics provided influenza vaccinations to 2,292 and 2,877 individuals in 2010 and 2011, respectively. The clinics allowed for experiential education of 39 students earning a total of 467 IPPE and APPE hours in 2010 and 58 students earning a total of 656 IPPE and APPE hours in 2011. Third-year students were assessed before and after completing the IPPE, and improvement was seen in knowledge and self-ratings of perceptions and attitudes toward administering immunizations. Conclusions. Integrating pharmacy practice experiences within campus-based influenza clinics was an effective way to provide students with direct patient care experience and preventive health services knowledge.

Sedation and analgesia in critically ill children.

The interplay of pain, discomfort, and fear can cause agitation in critically ill children. Therefore, sedation and analgesia are essential components in the intensive care unit setting and are best managed with a multidisciplinary team approach. No one standard approach exists to assess and manage pain and anxiety. Many tools are available for the assessment of pain and sedation, but each tool has its advantages and disadvantages. Clinicians should consider adopting a validated tool for routine continuous assessment. Multiple pharmacological therapies are available to manage pain, anxiety, fear, and agitation. Dosing of these agents can be influenced by age-related pharmacokinetic and pharmacodynamic changes. Agents should be selected on the basis of the childs disease state, desired level of sedation, and cardiac and respiratory status.