What is the best add-on blood pressure medication for a patient taking amlodipine (10mg) and Bystolic (nebivolol, 20mg), who has a hypersensitivity to Angiotensin-Converting Enzyme inhibitors (ACE inhibitors) and thiazide diuretics?

From the Guidelines

For a patient already on maximum doses of amlodipine (10mg) and nebivolol (Bystolic 20mg) who needs additional blood pressure control but has allergies to ACE inhibitors, ARBs, and thiazides, I recommend adding spironolactone 25mg once daily. This potassium-sparing diuretic works through a different mechanism by blocking aldosterone receptors, making it an effective option when other medication classes are contraindicated, as suggested by the 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 1. Start at 25mg daily and monitor potassium levels and renal function after 1-2 weeks, as hyperkalemia is a potential side effect. Some key points to consider when adding spironolactone include:

• Monitoring for signs of hyperkalemia, such as muscle weakness, palpitations, or arrhythmias
• Regularly checking renal function, as spironolactone can cause acute renal failure in patients with severe bilateral renal artery stenosis
• Being aware of the potential for gynecomastia and impotence, especially in older adults If the patient cannot tolerate spironolactone or if it's contraindicated due to kidney disease or elevated potassium, alternative options include:
• Eplerenone, a more selective aldosterone antagonist with fewer side effects, at 25mg daily
• Hydralazine, a direct vasodilator, starting at 10mg three times daily and titrating up as needed, although it may cause sodium and water retention and reflex tachycardia
• Clonidine, a central alpha2-agonist, at 0.1mg twice daily, though it may cause sedation and rebound hypertension if stopped abruptly. These medications work through different pathways than the contraindicated drug classes, providing complementary antihypertensive effects to the calcium channel blocker (amlodipine) and beta-blocker (nebivolol) already prescribed, as outlined in the guideline 1.

From the FDA Drug Label

The fourth placebo-controlled trial demonstrated additional antihypertensive effects of nebivolol tablets at doses ranging from 5 to 20 mg when administered concomitantly with up to two other antihypertensive agents (ACE inhibitors, angiotensin II receptor antagonists, and thiazide diuretics) in patients with inadequate blood pressure control Nebivolol tablets, 5 mg to 20 mg, administered once daily concomitantly with stable doses of up to two other antihypertensive agents resulted in significant additional antihypertensive effects over placebo compared to baseline blood pressure.

The patient can be considered for nebivolol as an add-on blood pressure medication, given their allergy to ACE inhibitors and thiazides. The dosage can range from 5 mg to 20 mg once daily, as demonstrated in the study 2.

From the Research

Current Medication Regimen

• The patient is currently taking Amlodipine 10mg and Bystolic 20mg (Nebivolol) for blood pressure management.
• Amlodipine has been shown to have a low renal clearance and a long half-life, allowing it to sustain its anti-hypertensive effect for more than 24 hours 3.
• The combination of Amlodipine and Nebivolol has been studied, and results show that it can significantly reduce central blood pressure, peripheral blood pressure, and pulse wave velocity with minor and tolerable side effects 4.

Allergies and Intolerances

• The patient is allergic to ACE inhibitors and thiazides, which limits the options for add-on blood pressure medications.
• Alternative medication options need to be considered, taking into account the patient's current medication regimen and allergies.

Potential Add-on Medication Options

• Considering the patient's current regimen and allergies, other classes of blood pressure medications such as beta blockers, calcium channel blockers, or direct renin inhibitors could be explored.
• However, since the patient is already taking a beta blocker (Nebivolol) and a calcium channel blocker (Amlodipine), the options may be limited.
• Further research is needed to determine the best course of action for this patient, as there are no direct studies providing guidance on add-on medications for patients with these specific allergies and medication regimen 3, 4.