NAPLEX Question of the Week: Fungus Among Us

This week's question focuses on a newly diagnosed fungal infection. Or does it...
NAPLEX Question of the Week: Fungus Among Us
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CB is a 55-year-old man who presents to the pulmonary clinic with two weeks of progressive shortness of breath, fatigue, and wart-like lesions on his skin. For work he does construction and lives in Mississippi. He was recently hospitalized a month ago after a COPD exacerbation where he received prednisone and doxycycline for 7 days. He reports being adherent to his medications, but he is worried he is experiencing another exacerbation. Chest radiograph shows nodular opacities in the upper lobes. Appropriate workup determined the patient has Blastomyces dermatitidis. The pulmonologist requests a pharmacotherapy consult after recommending Liposomal Amphotericin B for 1 week followed by itraconazole for approximately 6 months.

PMH: COPD, HFrEF (EF 30%), Obesity; Former smoker (quit 5 years ago)

Current Medications: Trelegy Ellipta QD, Combivent Respimat 1 inhalation four times daily, Entresto 49 mg/51 mg twice daily; Lisinopril 20 mg daily, Aldactone 25 mg daily, Toprol XL 100 mg daily, Farxiga 10 mg daily.

Pertinent Labs:

  • Na 136 mEq/L; K 3.4 mEq/L; Cl 95 mEq/L; BUN 10 mg/dL; SCr 1.0 mg/dL; Glucose 125 mg/dL; AST 24U/L; ALT 26U/L
  • Vitals: BP 135/80 mmHg; HR 75; RR: 23; Temp: 100.4°F
  • Weight 95 kg; Height: 70 in
  • HIV test: negative

Based on the patient’s profile and current infection, which of the following would be considered contraindications in his current as well as future medication regimens with amphotericin and/or itraconazole? Select all that apply.

A. Concurrent use of Entresto and Lisinopril

B. Aldactone (serum potassium level less than 3.5 mEq/L)

C. Itraconazole therapy 

D. Toprol XL therapy

E. Concurrent use of Trelegy Ellipta and Combivent

Rationale:

Brands/Generics covered: Trelegy (Fluticasone/Umeclidinium/Vilanterol); Combivent (Ipratropium/Albuterol); Entresto (Sacubitril/Valsartan); Aldactone (Spironolactone); Toprol XL (Metoprolol Succinate); Farxiga (dapagliflozin)

Explanation:

Blastomyces dermatitidis is an invasive fungal infection that typically affects the lungs, causing blastomycosis. Patients may have self-limiting respiratory symptoms. However, some patients experience severe pneumonia or disseminated disease, both of which require treatment. Disseminated blastomycosis may present as cutaneous, osteoarticular, genitourinary, or CNS disease. The preferred treatment for immunocompetent patients with blastomycosis is lipid formulation Amphotericin B for 1-2 weeks followed by itraconazole 6-12 months.

However...this question is not as much about the current infection as understanding contraindications within the patient's current regimen as well as his potential regimen for his infection. Sometimes when you are treating a primary problem, you may notice medication contraindications on the current profile that deserve addressing. 

Correct Answers: A, C, E

Answer choice A is correct: Entresto is a combination medication that consist of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin receptor blocker (ARB). Lisinopril is an angiotensin converting enzyme (ACE) inhibitor. While both medications have been shown to reduce mortality in heart failure patients with reduced ejection fraction, concomitant use of both medications is contraindicated due to the increased risk of angioedema. When switching between Entresto and an ACE inhibitor, Entresto should not be administered within 36 hours of the ACE inhibitor. 

Answer choice B is incorrect: Aldactone is a competitive inhibitor of the aldosterone receptor with an indication for heart failure with reduced ejection fraction. As an aldosterone receptor antagonist, it prevents potassium excretion in the distal convoluted renal tubule, which can lead to hyperkalemia. Aldactone is contraindicated in hyperkalemia; and it should not be used when potassium levels are > 5.5 mEq/L.

Answer choice C is correct: Itraconazole is an antifungal agent that interferes with fungal cell membrane formation by inhibiting ergosterol synthesis. It has a black box warning for exacerbation of congestive heart failure due to its negative ionotropic effects. Since CB has a history of HFrEF, itraconazole is contraindicated and an alternative antifungal agent should be chosen.

Answer choice D is incorrect: COPD and CHF are common comorbidities. Beta agonists are mainstays in the treatment of COPD. Similarly, there are beta-blockers that reduce mortality in HFrEF. While there is a concern for beta-blockers exacerbating symptoms of COPD and reducing the efficacy of some inhalers, this is typically seen with non-selective beta-blockers. Beta-1 receptors are primarily located in the heart and kidneys, whereas beta-2 receptors are found in the lungs. Bisoprolol, carvedilol, and metoprolol succinate are the three beta-blockers that have been proven to reduce mortality in HFrEF. However, only bisoprolol and metoprolol succinate are selective for beta-1 receptors, or cardio-selective. Therefore, it would be reasonably safe to use Toprol XL in a patient with COPD and would provide mortality decreasing therapy for his HFrEF.

Answer choice E is correct: Trelegy Ellipta is a triple therapy inhaler for COPD that combines an inhaled corticosteroid (fluticasone), a long-acting muscarinic antagonist (umeclidinium), and a long-acting beta agonist (vilanterol). Combivent Respimat is also a combination inhaler that consists of a short-acting muscarinic antagonist (ipratropium) and a short-acting beta agonist (albuterol). While Combivent can be used a rescue inhaler for COPD, concomitant use of a long-acting muscarinic antagonist with a short-acting muscarinic antagonist, especially both as scheduled medications, is contraindicated due to the increased risk of anticholinergic effects. Anticholinergic side effects include dry mouth, dry eyes, urinary retention, constipation, and tachycardia.

Because of the high number of various asthma/COPD medicatons, including products that contain more than one medication, pharmacy students should spend time ensuring they know specific brand/generics contained as well as proper dosing regimens within as it can become confusing fairly quickly. Some of these products contain similar drugs with different salt forms causing even more confusion. A number of medication dispensing errors have occurred with the Ellipta products specifically as there are a number of products with various drug classes that use the same device. 

NAPLEX Competencies Covered:

Area 2 (Identify Drug Characteristics), 2.1 Pharmacology, mechanism of action, or therapeutic class. 2.2 Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied. 2.3 Boxed warnings or REMS

Area 3 (Develop or Manage Treatment Plans), 3.6 Drug contraindications, allergies, or precautions. 3.7 Adverse drug effects, toxicology, or overdose. 3.8 Drug interactions.

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