Can Breztri (formoterol) cause hypertension (HTN) in patients, particularly those with a history of cardiovascular disease or hypertension?

Can Breztri (Formoterol) Cause Hypertension?

Yes, formoterol (a component of Breztri) can cause increases in blood pressure, particularly systolic hypertension, though this effect is generally modest and dose-dependent. 1

Mechanism and Clinical Evidence

Formoterol, as a beta2-agonist, produces cardiovascular effects including increases in systolic and/or diastolic blood pressure through sympathomimetic activity. 1 The FDA label explicitly warns that formoterol "can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic and/or diastolic blood pressure, and/or symptoms." 1

Magnitude of Blood Pressure Effects

• In healthy volunteers, formoterol causes dose-dependent increases in systolic blood pressure, with this effect occurring more rapidly than with salmeterol. 2 The cardiovascular effects manifest within the first few hours after inhalation. 2

• The blood pressure elevation is typically modest but can be clinically significant in susceptible patients. 3 When compared to other beta2-agonists, formoterol demonstrates similar cardiovascular effects to salbutamol but is more selective than fenoterol. 3

• In COPD patients receiving formoterol 12 mcg twice daily (the typical therapeutic dose), vital signs including blood pressure remained similar to placebo over 8 weeks of treatment. 4 However, this does not exclude individual susceptibility or effects at higher doses.

High-Risk Populations Requiring Caution

The FDA explicitly states that formoterol should be used with caution in patients with hypertension, cardiovascular disorders, coronary insufficiency, and cardiac arrhythmias. 1

Patients with Pre-existing Hypertension

• If blood pressure increases occur with formoterol, the drug may need to be discontinued. 1 This is particularly important because uncontrolled hypertension is a major risk factor for heart failure, accounting for 39% of heart failure cases in men and 59% in women. 5

• Patients with hypertension and additional cardiovascular risk factors are at especially high risk for developing heart failure, and optimal blood pressure control should remain the primary goal. 5 The guidelines recommend blood pressure targets of <130/80 mmHg for most patients. 6

Monitoring Strategy

Monitor blood pressure within 2-4 weeks after initiating formoterol-containing products in patients with pre-existing hypertension or cardiovascular disease. 6 Key monitoring points include:

• Baseline blood pressure measurement before starting therapy 1
• Early reassessment (within 2-4 weeks) to detect blood pressure increases 6
• Ongoing monitoring if the patient has multiple cardiovascular risk factors 5

Clinical Decision-Making Algorithm

For patients with uncontrolled hypertension (≥140/90 mmHg):

• Optimize antihypertensive therapy before or concurrent with starting formoterol 5
• Consider adding or intensifying diuretic therapy, ACE inhibitors, or calcium channel blockers as first-line agents 5
• Avoid beta-blockers as routine antihypertensive therapy in COPD unless compelling indications exist (post-MI, heart failure with reduced ejection fraction) 6

For patients with controlled hypertension on treatment:

• Formoterol can be used but requires blood pressure monitoring 1
• If blood pressure rises above target, adjust antihypertensive regimen rather than discontinuing necessary COPD therapy 1

For patients with severe cardiovascular disease:

• The risk-benefit ratio must be carefully considered 1
• Alternative COPD therapies (anticholinergics, inhaled corticosteroids alone) may be preferable if blood pressure cannot be controlled 1

Important Caveats

The therapeutic window for formoterol is relatively modest, meaning the difference between therapeutic and toxic doses is small. 2 This increases the importance of:

• Not exceeding recommended doses (typically 12-24 mcg twice daily) 1
• Avoiding use with other long-acting beta2-agonists 1
• Recognizing that excessive use can cause clinically significant cardiovascular effects and has been associated with fatalities 1

Other systemic effects that may compound cardiovascular risk include hypokalemia and hyperglycemia, though these are usually transient. 1 The decrease in serum potassium can potentially produce adverse cardiovascular effects and should be monitored in high-risk patients. 1