Pharmacy

Alshehri, A.M., Barner, J.C., Wong, S.L., Ibrahim, K.R. and Qureshi, S. (2021). “Perceptions among Muslims regarding fasting, medication use and provider engagement during Ramadan in the United States.” Int J Health Plann Manage Mar 12. [Epub ahead of print].

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BACKGROUND: Muslims with chronic diseases tend to fast during Ramadan, although Islam allows them not to fast. Therefore, understanding their perceptions and how they manage their health, especially as a minority population, is very important. OBJECTIVE: To examine Muslims’ (1) perceptions of fasting exemptions, (2) medication usage behaviour, (3) perceptions of relationships with healthcare providers and (4) factors impacting health management during Ramadan. METHOD: This was a qualitative study employing four focus groups (two groups of women and two groups of men). Adult Muslims (aged 18 years or more) with chronic diseases were invited to participate. Participants were asked open-ended questions about their fasting ability, medication usage behaviours, healthcare access and collaboration with providers during Ramadan. Trained researchers conducted the focus groups interviews in both English and Arabic. Each focus group was recorded, and three investigators independently transcribed the data and extracted themes and categories. Coding terminology issues were resolved through discussion. RESULTS: Twenty-five Muslims with chronic diseases (e.g., diabetes, hypertension, renal failure and anaemia) participated. The most prominent themes/subthemes were as follows: (1) fasting exemption (e.g., uncontrolled medical conditions), (2) fasting nonexemption (e.g., controlled medical conditions), (3) nonoral medication use during Ramadan, (4) healthcare provider involvement during Ramadan, and (5) factors impacting health management during Ramadan. CONCLUSION: Muslim patients perceive fasting as an important religious practice, so they tend to self-modify their medication-taking behaviours. Educating pharmacists and other healthcare providers about Muslim culture, especially their strong desire to fast, may lead to Muslims better managing their medications and viewing pharmacists and other healthcare providers as knowledgeable healthcare providers.

Walters, D.C., Jansen, E.E.W., Salomons, G.S., Arning, E., Ashcraft, P., Bottiglieri, T., Roullet, J.B. and Gibson, K.M. (2020). “Preferential accumulation of the active S-(+) isomer in murine retina highlights novel mechanisms of vigabatrin-associated retinal toxicity.” Epilepsy Res Dec 29;170:106536. [Epub ahead of print].

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((S)-(+)/(R)-(-)) vigabatrin (Sabril(R); γ-vinyl GABA), an antiepileptic irreversibly inactivating GABA-transaminase, was administered to male C57Bl6 J mice via continuous infusion (0, 40, 80 mg/kg/d) for 12 days. Our study design pooled retina, eye (minus retina), whole brain and plasma from n = 24 animals for each dose to provide n = 8 triplicates per treatment group. Hypothesizing that (S)-(+) VGB (active isomer) would preferentially accumulate in retina, we determined VGB isomers, comprehensive amino acids, and pharmacokinetic parameters. In brain, eye and plasma, the ((S)-(+)/(R)-(-)) ratio varied from 0.73 to 1.29 and 13.3 in retina, accompanied by a partition coefficient (tissue/plasma, ((S)-(+);(R)-(-))) of 5.8;0.34, 0.63;0.49, and 0.51;0.34 in retina, eye and brain, respectively. Racemic VGB (nmol/g; plasma, nmol/mL, range of means for dose) content was: retina, 25-36; eye (minus retina), 4.8-8.0; brain, 3.1-6.8 and plasma, 8.7-14.9. GABA tissue content (nmol/g) was 1246-3335, 18-64 and 2615-3200 as a function of VGB dose for retina, eye (minus retina) and brain, respectively. The retinal glial cell toxin 2-aminoadipic acid also increased with VGB dose (76-96 nmol/g). Partitioning of active (S)-(+) VGB to retina suggests the involvement of a stereospecific transporter, the identification of which could reveal new therapeutic paradigms that might mitigate VGB’s well-known retinal toxicity and expand its clinical utility.

Jacob, A., Shook, J. and Hutson, T. (2021). “The implementation of lenvatinib/everolimus or lenvatinib/pembrolizumab combinations in the treatment of metastatic renal cell carcinoma.” Expert Rev Anticancer Ther Jan 4. [ Epub ahead of print].

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Introduction: There are 400,000 new cases of Renal Cell Carcinoma (RCC) and 175,000 deaths worldwide every year. Currently available frontline therapies to treat RCC have less toxicity than previously employed therapeutic agents, but drug resistance is still a clinically significant problem. Drug resistance occurs through angiogenic escape by the activation of pathways that are independent of the VEGF targets of most first-line therapies. The lenvatinib/everolimus and lenvatinib/pembrolizumab are part of a new generation of combinations that can combat this method of resistance to extend both progression-free survival and overall survival in patients with metastatic RCC. Areas covered: This article discusses the evolution of current data on the efficacy and safety of these two combinations and future directions for their implementation in the treatment of advanced renal cell carcinoma. Expert opinion: Future research will focus on these combinations in contrast with other currently approved regimens. Once specific biomarkers that predict response to treatment are identified, the future of treatment of RCC will involve specifically tailored therapies for a patient’s genotype. Therapies unique only to the patient undergoing treatment will increase both efficacy and safety of new treatments, and that is the truly exciting future that awaits this field.

Collier, T.E., Farrell, L.B., Killian, A.D. and Kataria, V.K. (2020). “Effect of Adjunctive Dexmedetomidine in the Treatment of Alcohol Withdrawal Compared to Benzodiazepine Symptom-Triggered Therapy in Critically Ill Patients: The EvADE Study.” J Pharm Pract Dec 10;897190020977755. [Epub ahead of print].

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OBJECTIVE: This study evaluated the safety and efficacy of adjunctive dexmedetomidine for alcohol withdrawal syndrome (AWS) treatment compared to symptom-triggered benzodiazepine therapy. METHODS: This single-center, retrospective, cohort study evaluated patients admitted to an intensive care unit (ICU) with AWS. Patients were divided into 2 groups: adjunctive dexmedetomidine or symptom-triggered therapy (control). Primary outcome was change in Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) score. Secondary outcomes assessed cumulative ICU benzodiazepine requirement and ICU/hospital length of stay (LOS). Safety outcomes evaluated incidence of adverse events, new onset seizures, and intubation. Propensity matching was performed to minimize differences between study groups. RESULTS: Overall, 147 patients were included, 56 in the dexmedetomidine group and 91 in the control group. Patient demographics were similar, however baseline CIWA-Ar score was statistically higher in the dexmedetomidine group. Following propensity matching, 55 patients were included in each group. No significant difference was noted for change in CIWA-Ar score (median, IQR) [3.8 (-0.4-12.3) dexmedetomidine vs. 5.4 (1.4-12.9) control, p = 0.223]. Secondary endpoints revealed increased benzodiazepine requirements (p = 0.001), prolonged ICU LOS (p = 0.050), and more frequent use of physical restraints (p = 0.001) in the dexmedetomidine group. While not statistically significant, the development of new onset seizures (p = 0.775) and intubation (p = 0.294) occurred more frequently in the dexmedetomidine group. CONCLUSION: The addition of dexmedetomidine to symptom-triggered benzodiazepines for AWS did not produce a significant change in CIWA-Ar scores from baseline compared to symptom-triggered therapy alone. The increased rate of new onset seizures and intubation warrant further investigation into the safety of dexmedetomidine in AWS.

Uhm, S.J., Hall, J.A. and Herrington, J.D. (2020). “Severe and prolonged hypocalcemia after a single dose of denosumab for metastatic breast cancer with diffuse bone involvement without prior calcium/vitamin D supplementations.” J Oncol Pharm Pract Oct 21;1078155220964550. [Epub ahead of print].

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INTRODUCTION: Denosumab is a human monoclonal antibody antiresorptive agent used for the treatment of bone metastasis in different cancer types, including breast cancer. Hypocalcemia is a known adverse effect of denosumab, and early supplementation plays an important role in the prevention and management of hypocalcemia. CASE REPORT: A 63-year-old female with stage IV estrogen receptor-positive breast cancer with diffuse bone metastasis experienced severe, prolonged hypocalcemia following a single dose of denosumab. The patient also had several risk factors for denosumab-associated hypocalcemia. Despite not receiving additional doses of denosumab, the patient required multiple hospitalizations and outpatient infusions of calcium to resolve her symptomatic hypocalcemia.Management and outcome: Severe hypocalcemia associated with denosumab can be prevented or mitigated by recognizing the risk factors for hypocalcemia and supplementing with vitamin D/calcium. Proposed risk factors include poor renal function, hypoparathyroidism, insufficient calcium intake, and diffuse metastatic bone disease. Studies suggest that early supplementation before starting denosumab can lower this risk. DISCUSSION: Several cases of severe hypocalcemia associated with denosumab have been reported. However, to the authors’ knowledge, this is the first report that highlights the importance of early vitamin D/calcium supplementations for a patient with diffuse metastatic bone disease with pre-existing low levels of calcium.