Sindorella Frroku-Dido

EP is a patient with epilepsy. He has been taking phenytoin at a therapeutic dose for
4 years. EP was recently prescribed valproic acid because he has had breakthrough seizures over the past few months. After taking valproic acid for several days, he calls the pharmacy expressing concern about some new adverse effects. EP describes feeling confused, dizzy, and off balance, and he says he has been slurring his words. He asks whether his new therapy can cause these symptoms.

SA, a 36-year-old man, presents with a 4-month history of heartburn and intermittent difficulty swallowing. The pain is not relieved by eating or by positional changes, and he has tried OTC famotidine and Tums (antacid tablets) with minimal relief. SA takes amlodipine 5 mg orally daily for hypertension and ibuprofen 200 mg as needed for occasional headaches. He has no known drug allergies. He wants to know whether he should try Prilosec (omeprazole) OTC.

Based on EP’s report, his symptoms are consistent with phenytoin toxicity. Both phenytoin and valproic acid are highly bound to plasma proteins. Valproic acid can displace phenytoin from its binding site on protein, leading to higher concentrations of unbound (eg, pharmacologically active) phenytoin. The pharmacist can advise EP to call his prescriber as soon as possible to have a free phenytoin level ordered. A modification to his antiepileptic drug therapy will likely be required.

The pharmacist should advise against further OTC therapies and refer SA to his primary care provider for further evaluation. There are several reasons why SA is not a good candidate for self-treatment. First, his symptoms have persisted for more than 3 months despite treatment with 2 OTC therapies.1 Second, SA has difficulty swallowing (dysphagia), a red flag that may indicate more severe disease, such as cardiac disease.2 The pharmacist can counsel on nonpharmacological interventions, such as avoiding eating close to bedtime and spicy foods, as well as eating smaller meals, but should discourage use of Prilosec OTC.

Perucca E, Hebdige S, Frigo GM, Gatti G, Lecchini S, Crema A. Interaction between phenytoin and valproic acid: plasma protein binding and metabolic effects. Clin Pharmacol Ther. 1980;28(6):779-789. doi:10.1038/ clpt.1980.235

Whetsel T, Garofoli G. Heartburn and Dyspepsia. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care. Krinsky DL, ed. 20th ed. American Pharmacists Association: 2020.


Katz PO, Gerson LB, Vela MF. Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2013;108(3):308-328. doi:10.1038/ajg.2012.444

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 in Storrs.

Articles

Interactive case studies from April 2021.

Interactives: Case Studies (April 2021)

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

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

Interactive case studies from March 2021. 