Priti N. Patel

Methylene Blue for Management of Ifosfamide-Induced Encephalopathy

Objective: To evaluate the use of methylene blue for the treatment of ifosfamide-induced encephalopathy. Data Sources: MEDLINE (1966–August 2005) and International Pharmaceutical Abstracts (1971–August 2005) were searched, using the terms methylene blue, ifosfamide, encephalopathy, and neurotoxicity. Data Synthesis: Several case reports and one retrospective chart review described the use of methylene blue for ifosfamide-induced encephalopathy, but no controlled clinical trials were found. Methylene blue appeared to aid in the resolution of encephalopathic symptoms as rapidly as within 10 minutes of administration in some patients, but it had modest efficacy in most patients. Symptoms in patients who did not receive methylene blue resolved in the same time frame; this indicates that ifosfamide-induced encephalopathy may resolve without treatment. Conclusions: Available data from case reports indicate that methylene blue is an option in the treatment of ifosfamide-induced encephalopathy, especially in patients with severe symptoms of toxicity. However, the lack of controlled clinical trials and the possibility of spontaneous resolution of encephalopathy make the usefulness of methylene blue unclear.

Access to multilingual medication instructions at New York City pharmacies

An essential component of quality care for limited English proficient (LEP) patients is language access. Linguistically accessible medication instructions are particularly important, given the serious consequences of error and patient responsibility for managing often complex medication regimens on their own. Approximately 21 million people in the U.S. were LEP at the time of the 2000 census, representing a 50% increase since 1990. Little information is available on their access to comprehensible medication instructions. In an effort to address this knowledge gap, we conducted a telephone survey of 200 randomly selected NYC pharmacies. The primary focus of the survey was translation need, capacity, and practice. The majority of pharmacists reported that they had LEP patients daily (88.0%) and had the capacity to translate prescription labels (79.5%). Among pharmacies serving LEP patients on a daily basis, just 38.6% translated labels daily; 22.7% never translated. In multivariate analysis, pharmacy type (OR=4.08, 95%CI=1.55–10.74, independent versus chain pharmacies) and proportion of Spanish-speaking LEP persons in the pharmacy’s census tract (OR=1.09, 95%CI=1.05–1.13 for each 1% increase in Spanish LEP population) were associated with increased label translation. Although 88.5% of the pharmacies had bilingual staff, less than half were pharmacists or pharmacy interns and thus qualified to provide medication counseling. More than 80% of the pharmacies surveyed lacked systematic methods for identifying linguistic needs and for informing patients of translation capabilities. Consistent with efforts to improve language access in other health care settings, the critical gap in language appropriate pharmacy services must be addressed to meet the needs of the nation’s large and ever-growing immigrant communities. Pharmacists may require supplemental training on the need and resources for meeting the verbal and written language requirements of their LEP patients. Dispensing software with accurate translation capability and telephonic interpretation services should be utilized in pharmacies serving LEP patients. Pharmacists should post signs and make other efforts to inform patients about the language resources available to them.

Effect of acetaminophen on international normalized ratio in patients receiving warfarin therapy.

Warfarin is known to have extensive interactions with many classes of drugs. The literature suggesting a relevant interaction between acetaminophen and warfarin is inconsistent. Considering the ubiquitous use of acetaminophen, a review of the effects on international normalized ratio (INR) in patients taking warfarin was necessary. Thus, we performed a search of the PubMed (1966‐November 2010) and International Pharmaceutical Abstracts (1970‐November 2010) databases to review the available literature addressing an acetaminophen‐warfarin interaction and its possible mechanisms. A sample of case reports, in addition to all English‐language studies were evaluated, and relevant references were examined for additional articles. Reports of nonwarfarin coumarin anticoagulants were excluded. Published documentation reporting an interaction between acetaminophen and warfarin is limited. Small prospective studies of various designs and case studies describe aberrant INR results in patients using acetaminophen while receiving warfarin. These INR elevations typically involved acetaminophen ingestion of at least 2 g/day for several consecutive days. In several small prospective studies, INR results were elevated to a statistically significant extent that would require a change in warfarin dosing and monitoring in clinical practice. The mechanism for this interaction remains to be elucidated yet is suggested to occur through alterations in hepatic metabolism. The use of moderate‐to‐high doses of acetaminophen while receiving warfarin results in supra‐therapeutic INRs in some patients. The characteristics that may predispose a patient to this interaction are unclear, yet the widespread use of acetaminophen calls for enhanced clinician awareness and reinforcement of patient education about this interaction.

Seasonal, Avian, and Novel H1N1 Influenza: Prevention and Treatment Modalities

Objective: To review the pathophysiology, pandemics/epidemics, transmissibility, clinical presentation, treatment, prevention/immunization, and resistance associated with seasonal, avian, and swine influenza. Data Sources: Literature was obtained from MEDLINE (1966–October 2009) and International Pharmaceutical Abstracts (1971–October 2009) using the search terms influenza, seasonal influenza, avian influenza, swine influenza, H1N1, novel H1N1, H3N2, and H5N1. Study Selection and Data Extraction: Available English-language articles were reviewed, along with information obtained from the Centers for Disease Control and Prevention, the Food and Drug Administration, and the World Health Organization. Data Synthesis: The influenza virus has caused disease in birds, swine, and humans for many centuries. Pandemics and epidemics have occurred throughout history and reports of new strains continue to emerge. Two major surface antigenic glycoproteins, hemagglutinin and neuraminidase, have various subtypes, resulting in numerous combinations of these proteins. For example, combinations occur when an influenza strain from a bird “mixes” with a strain from a human. This mixing occurs in a host, often in pigs, resulting in a new strain. This new strain can cause pandemics since people have no immunity to the new strain. An H1N1 subtype pandemic occurred in 1918, causing millions of deaths. Simultaneously, veterinary reports of “influenza” in pigs also emerged. It is postulated that humans infected pigs with this H1N1 virus. H1N1 reappeared in humans in 1976, and more recently in 2009. Other pandemics have occurred with H2N2 and H3N2 strains. In 1997, strain H5N1, which usually causes disease in fowl, was able to infect humans. Conclusions: Influenza subtypes continue to change, causing disease in animals and humans. Utilization of immunization and antiviral treatment options are available to prevent, treat, and contain the spread of this infection.

Telavancin: A Novel Lipoglycopeptide Antibiotic

Objective To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical applications, and safety of telavancin, a new lipoglycopeptide antibiotic. Data Sources Literature was obtained from MEDLINE (1966–April 2009) and International Pharmaceutical Abstracts (1971–April 2009) using the search terms telavancin and TD-6424, and also from Theravance, Inc., and Astellas Pharma US, Inc. Study Selection And Data Extraction Available English-language articles were reviewed, as well as information obtained from Theravance, Inc., and Astellas Pharma US, Inc. Data Synthesis Telavancin has rapid bactericidal activity against gram-positive aerobic and anaerobic bacteria through multiple mechanisms of action. In vitro and Phase 2 in vivo data support the efficacy of telavancin against antibiotic-resistant gram-positive organisms. On March 4, 2008, the Food and Drug Administration (FDA) accepted as complete for review Theravances response to the October 19, 2007, New Drug Application approvable letter for telavancin to be used as treatment for complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria. QTc interval prolongation has been reported, although the clinical impact of this has not been determined. Drug interactions have not been identified as of yet. Conclusions Telavancin is currently under review by the FDA for the treatment of cSSSIs caused by gram-positive bacteria. The completion of Phase 3 trials will determine whether telavancin will have a role in the treatment of other infections caused by resistant gram-positive bacteria.

Caring for patients with celiac disease: The role of the pharmacist

OBJECTIVE To review the epidemiology, pathophysiology, diagnosis, treatment, and complications of celiac disease, in order to provide guidance to pharmacists. DATA SOURCES Published articles identified through Medline using search terms such as celiac disease, gluten sensitivity, and gluten enteropathy. Additional resources were identified from personal bibliographies collected by the authors and bibliographies from gathered articles. DATA SYNTHESIS Celiac disease is an autoimmune disorder that is characterized by intolerance to gluten and affects approximately 3 million Americans. Although the most common manifestations of the disease are gastrointestinal, including diarrhea, steatorrhea, and weight loss, the disease is a multisystem disorder. Malabsorption is common, often leading to vitamin and mineral deficiencies and resulting in anemia and osteoporosis. Diagnosis is initiated through serology testing and confirmed by intestinal biopsy. The only treatment for celiac disease is strict, lifelong adherence to a gluten-free diet, which includes avoidance of foods, prescription and nonprescription pharmaceutical products, and cosmetics containing wheat, barley, and rye. Adherence to the gluten-free diet will promote intestinal healing and symptom relief and usually prevent complications of celiac disease. CONCLUSION Pharmacists can play an important role by identifying patients who may have celiac disease, providing information for gluten-free foods and pharmaceutical products, and encouraging adherence to the gluten-free diet.

Eculizumab in paroxysmal nocturnal haemoglobinuria.

Eculizumab is a monoclonal antibody that binds with high affinity to the complement protein C5, preventing terminal complement-mediated intravascular haemolysis in patients with paroxysmal nocturnal haemoglobinuria (PNH). In three well designed clinical trials in patients with PNH, eculizumab blocked serum haemolytic activity and decreased transfusion rates. Pooled data from the three clinical trials demonstrated that eculizumab treatment decreased the overall thromboembolism rate in patients with PNH. Eculizumab carries a black box warning for the potential increased risk of meningococcal infections and requires patients to receive the meningococcal vaccine at least 2 weeks before starting treatment. Eculizumab is the first drug to be approved by the US FDA for the treatment of PNH and is a novel treatment that offers a new option for patients with PNH.

Medical Resident Choices of Electronic Drug Information Resources

Objective: To determine medical residents’ day-to-day use of drug information resources since their choices of these resources, when faced with common questions, are unknown. Methods: An online survey including simulated drug information questions was administered to 146 medical residents in the Department of General Internal Medicine during July 2012. Residents were given a wide range of choices in drug information resources to answer these questions and were instructed to select what they would choose in actual practice. A score was assigned to each resource corresponding to a “best,” “intermediate,” or “not good” choice. Results: Seventy-three respondents completed the survey and results were analyzed for statistical significance. Fifty-seven percent of respondents reported receiving no formal training regarding drug information. Statistical analyses revealed there were no significant differences in performance based on postgraduate year (P = .43) or extent of prior training (P = .45). Individual question responses revealed a generally infrequent selection of “best” choices. Less than 10% of the respondents chose the “best” answer for drug information questions related to drug interactions, herbal supplements, adverse events, and medication identification. Conclusion: Further training in drug information resource selection is warranted in the medical residency program to increase the frequency of use of higher quality resources.

Role of Proton Pump Inhibitors in Calcium Absorption, Bone Resorption, and Risk of Hip Fracture

Objective: To review the influence of proton pump inhibitors (PPIs) on calcium absorption, bone remodeling, and fracture risk. Data Sources: A search via MEDLINE (1966–April 2007) was performed using the search terms proton pump inhibitors, omeprazole, calcium absorption, calcium malabsorption, bone resorption, and fracture risk. Study Selection and Data Extraction: English-language literature, including abstracts, preclinical and clinical trials, and review articles, were identified from the data sources and reviewed. Data Synthesis: Data on the effect of PPIs on calcium absorption are conflicting; however, the majority of data indicate that PPIs decrease intestinal calcium absorption, which could negatively affect bone strength. In particular, calcium carbonate may be more difficult to absorb in an environment with elevated pH due to PPI use. Data on the role of PPIs in osteoclast function are also conflicting, with one human study indicating decreased bone resorption due to inhibition of osteoclast function and another human study indicating no association between PPIs and osteoclast function. The risk of fracture with PPI use was evaluated in 2 studies, and both studies found an increased risk of fracture of 14–44% after PPI use. Conclusions: PPI use may increase a patients risk of fracture. Additional studies are needed before causality can be established.

Meclizine: Safety and Efficacy in the Treatment and Prevention of Motion Sickness

Motion sickness is a self-limiting but uncomfortable phenomenon experienced by many people. It is common during civilian travel and also among professionals during travel or military manoeuvres. Meclizine is a piperzine antihistamine that is effective for the prevention and treatment of motion sickness, particularly during mild civilian travel. It is well tolerated with few adverse effects and its oral dosage form is convenient for patients to take prior to exposure to motion as a preventative measure.