Stefanie C. Nigro, PharmD, BCACP, CDCES

: A medical resident working in a hospital asks a clinical pharmacist about the use of empagliflozin in a patient with heart failure with preserved ejection fraction (HFpEF). Patient KE is a 58-year-old Black man with generalized anxiety disorder, HFpEF (EF 50%, NT-proBNP 400 pg/
mL), hypertension (BP 124/76 mmHg), and type 2 diabetes (HbA1c 7.8%). His HFpEF is treated with losartanandmetoprolol,and he takes escitalopram hydrochlorothiazide (HCTZ), and metformin. The medical resident wants to know whether the addition of empagliflozin could be beneficial ,given the results of the new EMPEROR-Preserved trial (NCT03057951).

: In the EMPEROR-Preserved study, the primary composite outcome of cardiovascular death or hospitalizations related to heart failure (HF) was reduced by 21% in patients receiving empagliflozin 10 mg daily compared with the placebo (NNT=31). This reduction was driven by a 29% reduction in HF- related hospitalizations. Use of empagliflozin did not reduce cardiovascular mortality or overall hospitalizations, nor did it improve HF-related quality of life, so it is important to clarify KE’s goals of therapy. Black patients were highly underrepresented in this study, so it is hard to draw firm conclusions about whether he specifically would benefit. However, because KE also has uncontrolled type 2 diabetes, use of a sodium-glucose cotransporter-2 inhibitor can provide glycemic benefits. If he begins taking empagliflozin, monitor his blood pressure closely. A dose reduction of HCTZ may be necessary because the combination could further reduce KE’s blood pressure.

Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. 

. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038

: PL, a 36-year-old woman, began taking lamotrigine 6 months ago to manage her focal seizures. After several successful dose titrations, she has been seizure-free for the past 5 months on 100 mg daily of lamotrigine taken orally. At PL’s latest clinic visit, she said she experiences dizziness throughout the day and wants to know what she can do to minimize this adverse effect.

: Dizziness is an expected adverse effect (AE) of all antiepileptic drugs and is often dose-related. Because PL has been seizure-free, it is best to keep her on lamotrigine at the current dose, if possible. One way to mitigate the AE is to spread out the daily dosage over smaller but more frequent doses. For example, PL can try taking 50 mg orally twice daily to see whether that improves her symptoms. Other strategies include dosing the medication closer to bedtime or using an extended-release preparation because lamotrigine peaks 1 to 5 hours post dose. If PL’s symptoms do not improve, she should contact her neurologist or primary care provider for further evaluation.

Schachter SC. Managing side effects. Epilepsy Foundation. November 30, 2003. Accessed March 8, 2022. https://www.epilepsy.com/learn/professionals/diagnosis-treatment/treatment/9-steps-treatment/ managing-side-effects

 at the University of Connecticut School of Pharmacy in Storrs.

, is an associate clinical professor in the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy.

Articles

How would you handle these patients' questions?

Case Studies: April 2022

CS is a 44-year-old woman who calls with questions about zinc supplements. She recently listened to a podcast and heard that zinc may be helpful in managing COVID-19 infections, and she first tested positive for COVID-19 more than a week ago. Despite some symptomatic improvement, CS continues to test positive and wants to know if taking zinc will shorten the duration of illness.

Zinc purportedly inhibits viral replication and attachment to the nasopharyngeal mucous. Evidence from in vitro studies suggests that zinc modifies the effects of several respiratory pathogens, including SARS-CoV-2. However, no reputable studies have evaluated zinc for COVID-19 management. Advise CS that consumption of zinc is not likely to improve her recovery time or symptoms. If she chooses to take zinc, advise her to avoid the nasal preparation because of reports of permanent loss of smell and taste. Oral zinc can cause adverse effects, including dose-related diarrhea, gastrointestinal upset, and metallic taste. Oral doses should not exceed the tolerable upper limit of 40 mg daily.

Adams KK, Baker WL, Sobieraj DM. Myth busters: dietary supplements and COVID-19. 

. 2020;54(8):820-826. doi:10.1177/1060028020928052

 TN is a 37-year-old man with a body mass index (BMI) of 36 kg/m2, who recently went to his primary care physician (PCP) for a wellness visit. TN takes ergocalciferol 50,000 units once weekly. He generally feels well and has
no complaints today. His medical history is significant for morbid obesity, obstructive sleep apnea, tobacco abuse, and vitamin D deficiency. TN has had laboratory work done, and the results were unremarkable, apart from an glycated hemoglobin A1C level of 5.7% (eAG = 117 mg/ dL), a fasting glucose level of 108 mg/dL, and a TG level of 154 mg/dL. The PCP asks the pharmacist if TN should start taking metformin for the management of prediabetes.

TN should start on metformin if no other contraindications exist. Evidence from the Diabetes Prevention Program (DPP) shows that metformin can lower the chance of developing type 2 diabetes (T2D) by 31%. In the DPP trial, metformin was most effective for individuals aged between 25 and 44 years, patients with obesity with a BMI of 35 or higher, and women with a history of gestational diabetes. In addition to metformin therapy, the pharmacist should counsel TN on lifestyle modifications, including an individualized reduced-calorie meal plan and weight loss efforts. These lifestyle modifications can also delay the progression to T2D.

Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. 

. 2002;346(6):393- 403. doi:10.1056/NEJMoa012512

, is an associate clinical professor in the Department of Pharmacy Practice at the University of Connecticut School of Pharmacy in Storrs.

Case Studies: March 2022

NT is a 39-year-old man who is scheduled to get his COVID-19 booster the next day, but he has had an upper respiratory tract infection during the past week. His primary care provider prescribed medications for congestion and cough. NT does not have arthralgia or a fever. He asks whether he is still eligible to receive his booster dose the next day or if he should reschedule.

. A mild acute illness, such as diarrhea or a mild upper respiratory tract infection, with or without fever, is not a precaution for vaccine administration, whereas a moderate to severe illness is. The concern in vaccinating an individual with moderate or severe illness is that a fever following the vaccine could cause complications. For example, it could be difficult to determine whether the fever resulted from the acute illness or the vaccine. The pharmacist should determine the severity of NT’s illness to determine whether deferring the booster could increase his risk of getting COVID-19. If his symptoms are mild and/or he is at risk for getting COVID-19, he should receive his booster as scheduled. If not, NT can defer his booster dose until the upper respiratory tract symptoms improve.

Ask the experts: administering vaccines. Immunization Action Coalition. Updated August 15, 2021. Accessed January 7, 2022. https://www.immunize.org/askexperts/administering-vaccines.asp

MN, a 67-year-old woman, is requesting a pneumonia vaccine at the advice of her primary care provider. She is being treated for hypertension, hypothyroidism, occasional heartburn, and osteoporosis. MN does not smoke and has no known drug allergies. She recalls getting influenza and shingles vaccines prior to recently moving from a different state, but she does not remember whether she has ever had a pneumonia vaccine. The pharmacy has Pneumovax 23 (PPSV23), Prevnar 13 (PCV13), and Prevnar 20 (PCV20) in stock.

Which is the most appropriate to administer to MN?

. Adults 65 years or older who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown should receive a pneumococcal conjugate vaccine (either PCV15 or PCV20), according to the Advisory Committee on Immunization Practices. If PCV15 is used, it should be followed by a dose of PPSV23. Based on the in-stock options, the pharmacist should administer the PCV20 vaccine to MN. A single dose (0.5 mL) should be administered intramuscularly.

Advisory Committee on Immunization Practices votes to recommend routine use of Pfizer’s Prevnar 20 (pneumococcal 20-valent conjugate vaccine) in adults. News release. Pfizer; October 20, 2021. Accessed January 21, 2021. https://www.businesswire.com/news/ home/20211020006069/en/Advisory-Committee-on-Immunization-Practices-Votes-to-Recommend-Routine-Use-of-Pfizer%E2%80%99s- PREVNAR-20%E2%84%A2-Pneumococcal-20-valent-Conjugate-Vaccine-in-Adults

How would you respond to these patient questions?

Interactive Case Studies: February 2022

 PJ, a nurse practitioner aged 44 years, asks whether she should get the Moderna booster dose for COVID-19. She has had a significant allergic reaction to MiraLAX (polyethylene glycol [PEG] 3350) consisting of hives and hypotension. PJ has already received the first 2 doses of the Moderna vaccine without incident. Since she learned that messenger RNA (mRNA) vaccines contain PEG, she has wondered whether she should be concerned about getting the Moderna booster or whether she should get a booster from a different manufacturer.

 This ingredient is thought to cause severe allergic reactions, including anaphylaxis. There may be some concerns about cross-reactivity of PEG. However, limited information is available concerning cross-reactivity between PEG 2000 and PEG 3350. Because PJ received the first 2 doses with no issues, it would be appropriate to recommend administering the booster dose. CDC guidelines recommend 30-minute monitoring if there is a history of an immediate allergic reaction to an injectable therapy or vaccine or a history of anaphylaxis related to any cause.

 Although her previous allergic reaction to MiraLAX does not classify as
a reaction to an injectable therapy, it would be appropriate to recommend that she receive the booster dose but with 30-minute monitoring as a precaution. Alternatively, PJ can opt to receive the Johnson & Johnson booster, which does not contain PEG.

1. Lauritano D, Martinelli M, Baj A, et al. Drug-induced gingival hyperplasia: an in vitro study using amlodipine and human gingival fibroblasts. 

2. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 

 2018;71(6):e13-e115. doi:10.1161/HYP.0000000000000065

3. Williams B, MacDonald TM, Morant S, et al; British Hypertension Society’s PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. 

 2015;386(10008):2059-2068. doi:10.1016/S0140-6736(15)00257-3

A clinical pharmacist working for an integrated health care network is told by an advanced practice registered nurse (APRN) about her patient, RT, a Black woman aged 58 years with uncontrolled hypertension. RT takes chlorthalidone 25 mg, losartan 100 mg, and metoprolol succinate 200 mg. Despite proper adherence, she has consistently elevated blood pressure (BP), averaging 158/84 mm Hg. Other laboratory results and vitals are unremarkable. The APRN is interested in starting nifedipine because she knows calcium channel blockers (CCBs) are recommended for Black patients. However, the APRN says that in the past RT had gingival hyperplasia on amlodipine and stopped taking it. The APRN wants to know whether nifedipine would carry the same risk and, if so, what other treatment options are suitable for RT.

All CCBs have been associated with gingival enlargement. The mechanism is poorly understood but is thought to involve collagen accumulation, fibroblasts, and proinflammatory cytokines. Gingival overgrowth usually manifests within 1 to 3 months after CCB initiation.

 Because nifedipine is the most frequently implicated CCB in drug- induced gingival hyperplasia, the pharmacist should advise against its use for RT. The best approach to manage her resistant hypertension is to screen for secondary causes, such as drug-induced hypertension, obstructive sleep apnea, primary hyperaldosteronism, renal parenchymal disease, and renovascular disease.

 Adding an aldosterone antagonist such as spironolactone would be advisable, assuming there are no contraindications. Findings from the PATHWAY-2 study show that spironolactone is superior to bisoprolol, doxazosin, and a placebo for lowering BP in resistant hypertension.

1. Sellaturay P, Nasser S, Islam S, Gurugama P, Ewan PW. Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer/BioNTech mRNA COVID‐19 vaccine. 

. 2021;51(6):861-863. doi:10.1111/cea.13874

2. Moderna COVID-19 vaccine. CDC. Updated December 1, 2021. Accessed December 13, 2021. 

https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/index.html

3. COVID-19 vaccines for people with allergies. CDC. Updated December 14, 2021. Accessed December 14, 2021. 

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/specific-groups/allergies.html

, is an associate clinical professor at the University of Connecticut School of Pharmacy in Storrs.

How would you respond to these patients' questions?

Interactive Case Studies: January 2022

The pharmacist on duty receives a call from BB, a 65-year-old woman with type 2 diabetes who says that her primary care provider (PCP) increased her dose of metformin from extended-release (ER) 750 mg daily to ER 1000 mg daily approximately 1 month ago. Since then, BB has noticed a metallic taste in her mouth, which she did not experience at the lower dose. She says that she did not start any new medications during that time, nor did she have any additional dose changes. BB’s other chronic medications include a daily multivitamin and amlodipine 5 mg daily ,both of which she has taken for years without incident. She wants to know if the situation could be elated to metformin and what advice, if any, the pharmacist has.

Metformin is transported via the organic cation transporter 3 transporter, which is highly expressed in the saliva.1 This may explain metformin’s ability to secrete and accumulate in the saliva, predisposing patients to a metallic taste. Although the medication can independently cause the metallic taste, so, too, can having poorly controlled diabetes. Prolonged hyperglycemia can damage nerves in the mouth and/or cause poor oral hygiene, such as cavities and gingivitis. Thus, poor oral hygiene can cause taste disturbances as well. The pharmacist should ask whether BB is bothered by the taste. If so, her PCP should lower her dose back to ER 750 mg daily. If further glycemic control is needed, other antidiabetic options can be explored. If BB wishes to continue the current dose, the pharmacist can advise on nondrug strategies, such as chewing sugarless gum, drinking plenty of water, and rinsing with mouthwash to reduce the unpleasant taste. The pharmacist should also encourage her to maintain euglycemia.

Lee N, Duan H, Hebert MF, Liang CJ, Rice KM, Wang J. Taste of a pill: organic cation transporter-3 (OCT3) mediates metformin accumulation and secretion in salivary glands. 

. 2014;289(39):27055-27064. doi:10.1074/jbc.M114.570564

SW, a 34-year-old man, has started on the following insulin regimen: 22 units of neutral protamine Hagedorn (NPH) and 10 units of regular insulin before breakfast and 5 units of regular insulin and 10 units of NPH before dinner. He brings in his glucometer for review at a follow-up visit 2 weeks later, noting that he tests his sugar once daily in the morning before breakfast. A review of SW’s glucometer data shows a 7-day average of 150 mg/dL. Individual daily readings include 147 mg/dL, 176 mg/dL, 156 mg/dL, 161 mg/dL, 138 mg/dL, and 145 mg/dL. SW denies any signs or symptoms of hypoglycemia.

What changes to his insulin regimen should the pharmacist recommend to help the patient reach his glycemic goals?

The fasting plasma glucose (FPG) goal for SW is 80 to 130 mg/dL, per the American Diabetes Association. His elevated FPG suggests a need to adjust his basal insulin (eg, NPH). Given the pharmacokinetic profile of NPH, an adjustment of SW’s predinner NPH dose is warranted. The pharmacist can recommend increasing the predinner NPH dose by 2 to 6 units.

 SW should monitor closely for hypoglycemia. The pharmacist should encourage the patient to test his blood sugars before dinner and 2 hours after breakfast and dinner to assess if his other insulin doses are appropriate. If SW is bothered by fingerstick testing, he can discuss obtaining a continuous glucose monitor with his provider.

American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: 

Standards of Medical Care in Diabetes-2021

. 2021;44(suppl 1):S111-S124. doi:10.2337/dc21-S009

Riddle MC, Rosenstock J, Gerich J; Insulin Glargine 4002 Study Investigators. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. 

. 2003;26(11):3080-3086. doi:10.2337/diacare.26.11.3080

, is a clinical pharmacy specialist at ProHealth Physicians/OptumCare in Farmington, Connecticut.

Interactive Case Studies: December 2021

TN, 35-year-old obese woman with a body mass index (BMI) of 32.4 kg/m2 and uncontrolled type 2 diabetes is starting on an atypical antipsychotic today for the management of schizophrenia. The pharmacist receives a call from TN’s psychiatric nurse practitioner (NP), who has questions about drug selection. The NP mentions that TN’s drug formulary lists aripiprazole, haloperidol, olanzapine, and quetiapine as tier 1, preferred options. The NP wants the pharmacist’s opinion on which atypical antipsychotic may be most appropriate to prescribe.

Atypical antipsychotics can increase the risk of metabolic effects because of antagonism of the H1 and 5-HT2C receptors. Because TN has glucose dysfunction and is obese, the pharmacist should recommend the atypical antipsychotic with the least potential for metabolic adverse effects. Haloperidol is a conventional antipsychotic and should not be prescribed if the intent is to select an atypical antipsychotic. In a recent systematic review and network meta-analysis, aripiprazole was the only antipsychotic to show no evidence of change or improvement in metabolic parameters, such as dyslipidemia, glucose dysfunction, or weight gain compared with the placebo.

 Olanzapine and quetiapine were associated with increases in BMI and weight, whereas olanzapine was also associated with changes in glucose. The pharmacist can recommend aripiprazole for TN and suggest that the NP monitor for metabolic changes at baseline and every 12 weeks thereafter.

Pillinger T, McCutcheon RA, Vano L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. 

. 2020;7(1):64-77. doi:10.1016/S2215-0366(19)30416-X

American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. 

. 2004;12(2):362-368. doi:10.1038/oby.2004.46

JB is a 65-year-old man who has had a swollen big toe and extreme pain for the past 4 days. The area is erythematous and tender. Laboratory results show elevated uric acid levels. Urate crystals are found in the synovial space, confirming a physician assistant’s (PA) suspicion of gout. JB has a medical history that includes severe renal insufficiency and well-controlled hypertension. The PA wants an opinion on the best treatment for gouty arthritis.

Guidelines suggest treating acute gout flares with colchicine, glucocorticoids, or nonsteroidal anti-inflammatory drugs (NSAIDs). No agent is preferred to another, so the choice should be based on patient-specific factors. Before making a recommendation, the pharmacist should collect additional information from the PA, such as JB’s renal function, the stability of his renal function, concomitant medications, and history of gout flares. Because JB has been in pain for 4 days, colchicine may not be the best choice because its efficacy may be reduced if not taken within the first 12 to 36 hours. Because he has documented renal dysfunction, avoiding NSAIDs would also be advisable. The pharmacist should recommend prednisone 40 mg daily until the flare resolves. Tapering may be required depending on the duration of use. Applying ice to the affected area can also help minimize inflammation and pain.

FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. 

. 2020;72(6):744-760. doi:10.1002/acr.24180

Stefanie C. Nigro, PharmD, BCACP, CDCES, 

is an associate clinical professor at the University of Connecticut School of Pharmacy in Storrs.