Stefanie C. Nigro, PharmD, BCACP, CDE

TR is a 68-year-old man who was discharged from the hospital 3 days ago after being diagnosed with new onset heart failure (HF) with reduced ejection fraction. He goes to the pharmacy to fill his new prescriptions, including carvedilol. The pharmacy intern is concerned about the use of carvedilol for TR because he has a long history of chronic obstructive pulmonary disorder (COPD), although it is well controlled. The intern wonders whether she should call TR’s primary care provider (PCP) to obtain a prescription for a cardioselective β-blocker instead. How should the pharmacist respond?

The ambulatory-care pharmacist in a clinic is seeing MN, a 61-year-old Black woman today. MN has a long history of hypertension (HTN), stage 3 chronic kidney disease (CKD), and type 2 diabetes (T2D). Her estimated glomerular filtration rate is 39 mL/min/1.73m

 and has been stable over the past year. Despite excellent control of her HTN (average blood pressure < 120/70 mmHg) and T2D (A1c 6.8%), her urine albumin:creatinine ratio remains elevated at 280 mg/g. MN takes losartan 100 mg daily for her CKD. She does not smoke and does not take any drugs known to be nephrotoxic. MN’s primary care provider wants to know if adding a sodium-glucose cotransporter 2 (SGLT2) inhibitor would be beneficial for MN. How should the pharmacist respond?

Cardioselective β-blockers, such as bisoprolol and metoprolol succinate, are preferred for patients with comorbid HF and COPD to minimize the potential risk of bronchoconstriction. However, nonselective β-blockers with α-blocking properties, such as carvedilol, have been shown to be appropriate for patients with COPD because the α-blocking properties can cause a mild bronchodilating effect and may offset any bronchoconstriction caused by the β-blocker.

 The intern and pharmacist should advise TR to monitor at home for changes to his breathing. His PCP should also consider slow titrations of carvedilol if needed and closely monitor his lung function routinely.

An SGLT2 inhibitor may be an appropriate option for further managing MN’s CKD. Results from the CREDENCE and DAPA-CKD trials suggest that these 2 agents have nephroprotective benefits in patients with CKD+/- comorbid diabetes. In the CREDENCE study, results showed that use of canagliflozin 100 mg daily resulted in a 30% reduced risk of the composite renal end point of end-stage renal disease, doubling of serum creatinine, or renal or cardiovascular death.

In the DAPA-CKD study, results showed a 39% reduction in the primary composite outcome for patients taking dapagliflozin 10 mg daily.

 It would be important to learn more about other medications that MN may take. For example, if she is on a diuretic, she may need dose modifications to prevent against dehydration or hypotension. If MN takes other antidiabetic medications, she may need dose adjustments to reduce the risk of hypoglycemia. Nonetheless, SGLT2 inhibitor use should be considered because she shows signs of macroalbuminuria.

Foresi A, Cavigioli G, Signorelli G, Pozzoni MB, Olivieri D. Is the use of beta-blockers in COPD still an unresolved dilemma? 

2010;80(3):177-187. doi:10.1159/000318583

Perkovic V, Jardine MJ, Neal B, et al; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. 

. 2019;380(24):2295-2306. doi:10.1056/NEJMoa1811744

Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in patients with chronic kidney disease. 

. 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816

SINDORELA FRROKU-DIDO is a PharmD candidate at the University of Connecticut School of Pharmacy in Storrs.

STEFANIE C. NIGRO, PHARMD, BCACP, CDE, is an associate clinical professor at the University of Connecticut School of Pharmacy.

Articles

Interactive case studies from March 2021. 

Interactives Case Studies (March 2021)

RJ is a 68-year-old man with type 2 diabetes (T2D) who calls the pharmacy with concerns about hyperglycemia. His fasting blood glucose level increased to more than 200 mg/dL from an average of 133 mg/dL over the past week. Prior to this week, RJ’s blood sugar levels were greatly improving ever since he lost 8 lb. He noticed his blood sugar levels rising a week ago, after he started tamsulosin 0.4 mg daily, which was prescribed by his primary care physician (PCP) to help with his urinary symptoms. No other medications were started or discontinued during that time. RJ says that his PCP had never heard that this medication causes hyperglycemia but suggested that he call the pharmacy team to further inquire.

The pharmacist on duty at a local community pharmacy is working with AF, a pharmacy intern in his second professional year of pharmacy school. AF tells the pharmacist that he just finished reading the DAPA-CKD trial1 for his upcoming journal club presentation. He read the results and noted that the number needed to treat (NNT) for the primary outcome (eg, sustained decline in estimated glomerular filtration rate of at least 50%, end-stage kidney disease, or death from renal of cardiovascular cases) was 19. AF is unsure what this means and how it was calculated, as he missed his drug literature and evaluation class last week. The pharmacist reviews the results section of the paper and notes that over a median of 2.4 years, the primary outcome occurred in 197 of 2152 participants (9.2%) in the dapaglifloizin group and 312 of 2152 participants (14.5%) in the placebo group [HR, 0.61 (0.51-0.72); P < .001].

 AF asks the pharmacist to explain this concept to him.

 Hyperglycemia is not a listed adverse effect in the package insert for tamsulosin. There are, however, documented case reports suggesting that the 2 may be linked.

 These reports note that hyperglycemia was induced 1 to 2 days after the initiation of tamsulosin in patients with T2D. Discontinuation led to full resolution of symptoms. It has been suggested that α1 receptors can contribute to glucose uptake through non-insulin—dependent pathways.

By blocking these peripheral receptors, glucose uptake is hampered. RJ should be screened to ensure that no other identifiable causes, such as illness, infection, or stress, can be contributing to his hyperglycemia. His PCP can recommend that RJ hold the dose of his tamsulosin for a few days to see whether his glucose levels return to normal.

Borgsteede S, Bruggeman R, Hoefnagel R,M Huiskes, van PuijenbroekE. Tamsulosin and hyperglycaemia in patients with diabetes. 

Boyda HN, ProcyshynRM, Pang CCY, Barr AM. Peripheral adrenoceptors: the impetus behind glucose dysregulation and insulin resistance. 

. 2013;25(3):217-228. doi:10.1111/jne.12002

The pharmacist can teach AF that the NNT is the number of patients who need to be treated with a specified intervention/drug for 1 patient to benefit from it. So in this case, 19 patients need to be treated with dapagliflozin over 2.4 years for 1 patient to benefit. The NNT is the inverse of the absolute risk reduction (ARR) and is calculated as NNT = 100/ARR (%).

The ARR is the absolute difference in outcome rates between the control group (14.5%) and the treatment group (9.2%). In this case, the ARR is 5.3%. Therefore, the NNT is 100/5.3 =18.867. Because NNTs are normally rounded up to the nearest whole number, the NNT for this trial would be 19.

Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816

, is an assistant professor/clinical pharmacist at Massachusetts College of Pharmacy and Health Sciences in Boston.

Two interactive case studies are presented in the January 2021 issue of Pharmacy Times®. 

Interactives: Case Studies (January 2021)

A community pharmacist receives a call from a local nurse practitioner inquiring about a potential drug interaction. She wants to prescribe duloxetine for a patient, PD, who recently received a diagnosis of neuropathy. Upon ordering the duloxetine, the practitioner received an alert that the medication can interact with the patient’s apixaban prescription. Because the practitioner is unfamiliar with this interaction, she calls the pharmacist to inquire about the nature of the interaction and wants to know if the 2 medications can be coprescribed or if an alternative medication for neuropathy is needed.

 Patients who are prescribed selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitor (SNRIs), such as duloxetine, may be at an increased risk of bleeding. Serotonin is released from platelets when vascular injury is present. Serotonin promotes vasoconstriction, which assists with platelet aggregation. SNRIs and SSRIs inhibit the serotonin transporter, which is responsible for the uptake of serotonin into platelets. It is reasonable to suspect that their use may precipitate bleeding and impair clot formation. This risk appears higher for patients who take concomitant aspirin, nonsteroidal inflammatory drugs, or warfarin, and may be clinically meaningful.

 Other anticoagulants, such as direct thrombin inhibitors and factor Xa inhibitors, also may increase risk. Providers should screen for risk factors that may further elevate bleeding risk, such as age, chronic alcohol use, and a previous history of bleeding. The combination is not contraindicated. However, counsel patients who are exposed to SNRIs in addition to oral anticoagulants to report any evidence of bleeding to their providers.

Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. 

 2008;27(1):31-40. doi:10.1111/j.1365-2036.2007.03541.x

Cochran KA, Cavallari LH, Shapiro NL, Bishop JR. Bleeding incidence with concomitant use of antidepressants and warfarin. 

. 2011;33(4):433-438. doi:10.1097/FTD.0b013e318224996e

A pharmacist receives a phone call from FS, a patient who recently received a diagnosis of major depressive disorder. She has questions regarding her antidepressant medication. Three weeks ago, her provider started FS on fluoxetine 20 mg daily and has titrated her up to 40 mg daily over the past week. After the dose increase, FS has been experiencing more dizziness and fatigue, which is bothersome. She wants to know if this is normal. In addition to fluoxetine 40 mg daily, FS takes aspirin 81 mg daily, atorvastatin 40 mg daily, lisinopril 10 mg daily, and metoprolol succinate 50 mg daily. FS also reports concern that she is still experiencing some symptoms of depression, despite being on fluoxetine for a month.

The patient’s symptoms may be the result of a pharmacokinetic drug interaction. Metoprolol is a CYP2D6 substrate and fluoxetine is a CYP2D6 inhibitor, so coadministration can lead to bradycardia. The patient’s symptoms of dizziness and fatigue are consistent with bradycardia, so her pulse should be evaluated for confirmation. The pharmacist should ask whether FS experienced these symptoms at the 20-mg dose. A dose reduction of fluoxetine back to 20 mg can be considered, but given the patient’s concern that some of her symptoms are not improving, this may not be the best option. The pharmacist can contact the provider and recommend a switch to a noninteracting SSRI, such as escitalopram 10 mg daily. Counsel FS that selective serotonin reuptake inhibitors can take 4 to 8 weeks for a clinical response. However, if her symptoms are worsening, she should call the provider immediately.

 is a PharmD candidate at the University of Connecticut School of Pharmacy in Storrs.

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

Two interactive case studies for the October 2020 issue of Pharmacy Times.

Interactives: Case Studies (October 2020)

LR, a 43-year-old man, is complaining of mouth sores and receding gum lines. He has been using chewing tobacco for the past 20 years and asks if there is a way to quit. LR's medical history includes alcohol abuse, though he is now sober; hypertension; and major depressive disorder. His conditions are stable, as he takes fluoxetine 40 mg daily and losartan 50 mg daily. LR has been receiving behavioral therapy to help quit but says he needs additional assistance. He asks if there are medications that can help him. 

A systematic review completed by the Cochrane Library presented data from 34 different randomized trials on treatment for smokeless tobacco. The results showed that neither nicotine gum nor the patch increased abstinence. However, behavioral interventions, nicotine lozenges, and varenicline showed some benefit.

 Varenicline showed the highest rates of long-term nicotine abstinence, with rates up to 34% versus a placebo.

 Nicotine lozenges may not be the best choice for LR, given his dental complaints. Although he has a history of alcohol abuse and psychiatric illness, both conditions appear stable. Therefore, varenicline can be tried. The pharmacist should counsel LR about the possible adverse effects of varenicline, including nausea and worsening of his mood. Nicotine withdrawal symptoms should also be discussed. The pharmacist should reinforce LR's abstinence, as alcohol use is not recommended while on varenicline, encourage him to continue with behavioral therapy, and follow up with his primary care provider routinely.

Ebbert JO, Elrashidi MY, Stead LF. Interventions for smokeless tobacco use cessation. 

. 2015;2015(10):CD004306. doi:10.1002/14651858.CD004306.pub5

SP is a 68-year-old woman who was discharged 3 weeks ago from the hospital with newly diagnosed nonvalvular atrial fibrillation. An ambulatory care pharmacist is assessing her medications posthospitalization. SP's medical history also includes gastroesophageal reflux disease, hypertension, macular degeneration, and obesity. Upon discharge, she was prescribed warfarin for stroke prevention. SP's medications include amlodipine 10 mg daily, omeprazole 20 mg daily, OTC calcium supplements, and warfarin 5 mg daily per the international normalized ratio (INR). She expresses concern because, given her macular degeneration, she is unable to drive and does not think she will be able to come in for monthly INR monitoring. SP asks if there are alternatives to warfarin that may be suitable for her. 

Guidelines for nonvalvular AF recommend direct-acting oral anticoagulants (DOACs) over warfarin when possible. Apixaban and rivaroxaban are most commonly used in practice. Compared with warfarin, rivaroxaban was noninferior for stroke prevention but was associated with a lower risk of intracranial and fatal bleeding.

 In another study that compared apixaban with warfarin, apixaban demonstrated lower rates of all-cause mortality, bleeding, and stroke.

 No prospective, randomized trials have compared the 2 DOACs, but a recent retrospective cohort study did compare their efficacy and safety. Apixaban was found to have fewer rates of gastrointestinal bleeding, intracranial hemorrhage, stroke, and systemic emboli.

 Additionally, rivaroxaban is listed on the American Geriatrics Society Beers Criteria for Potentially Inappropriate Medical Use in Older Adults as potentially inappropriate in older adults because of the increased risk of bleeding. SP can likely benefit from apixaban 5 mg twice daily to lower her risk of stroke.

Avezum A, Lopes RD, Schulte PJ, et al. Apixaban in comparison with warfarin in patients with atrial fibrillation and valvular heart disease: findings from the aixaban for reduction in stroke and other thromboembolic events in atrial fibrillation (ARISTOTLE) trial. 

. 2015;132(8):624-632. doi:10.1161/CIRCULATIONAHA.114.014807

Bansilal S, Bloomgarden Z, Halperin JL, et al; ROCKET AF Steering Committee and Investigators. Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: the rivaroxaban once-daily, oral, direct factor xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF trial). 

. 2015;170(4):675-682.e8. doi:10.1016/j.ahj.2015.07.006

Fralick M, Colacci M, Schneeweiss S, Huybrechts KF, Lin KJ, Gagne JJ. Effectiveness and safety of apixaban compared with rivaroxaban for patients with atrial fibrillation in routine practice: a cohort study. 

. 2020;172(7):463-473. doi:10.7326/M19-2522

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

What would you recommend to these patients?