What adjustments should be made to the medication regimen of a patient with a history of heart failure, currently taking Furosemide (Lasix) 40mg orally twice daily, Carvedilol 6.25mg orally twice daily, and Sacubitril/Valsartan (Entresto) 24-26mg orally twice daily, who presents with tongue swelling?

Immediate Medication Management for Tongue Swelling in Heart Failure Patient

Discontinue Entresto (sacubitril/valsartan) immediately and permanently—this is angioedema, a potentially life-threatening adverse effect of drugs acting on the renin-angiotensin system that requires urgent airway assessment and drug cessation. 1

Immediate Actions

Discontinue the Causative Agent

• Stop Entresto immediately and do not restart—sacubitril/valsartan acts on the renin-angiotensin system and inhibits neprilysin (which degrades bradykinin), creating a dual mechanism for angioedema 1, 2
• The FDA label explicitly warns of angioedema risk with sacubitril/valsartan, particularly affecting the tongue, glottis, and larynx 1
• Do not substitute with an ACE inhibitor or ARB, as these also cause angioedema through similar mechanisms 3, 4

Assess Airway Urgency

• Evaluate for signs of airway compromise: stridor, difficulty swallowing, voice changes, or respiratory distress 3
• If airway compromise is present or progressing, secure the airway immediately (may require fiberoptic intubation or surgical airway) 3
• Administer epinephrine, corticosteroids, and antihistamines for acute management 3

Medication Adjustments After Stabilization

Continue Current Medications

• Maintain Lasix (furosemide) 40 mg PO BID—diuretic therapy is essential for volume management and has no role in angioedema 5
• Continue Carvedilol 6.25 mg PO BID—beta-blockers do not cause angioedema and are critical for mortality reduction in heart failure 5
• Beta-blockers should never be stopped abruptly due to risk of rebound ischemia, myocardial infarction, and arrhythmias 5

Replace Entresto with Alternative Heart Failure Therapy

After the angioedema resolves (typically 48-72 hours), you face a challenging situation since the patient cannot receive:

• ACE inhibitors (cause angioedema) 3
• ARBs (can cause angioedema despite different mechanism) 4
• Sacubitril/valsartan (already caused angioedema) 1

The safest approach is to optimize the medications that can be used:

Optimize Beta-Blocker Therapy

• Uptitrate carvedilol from 6.25 mg BID toward target dose of 25-50 mg BID over several weeks as tolerated 5, 6
• Carvedilol has proven mortality benefit in heart failure and should be maximized 6, 7
• Increase dose every 2 weeks, monitoring for heart rate <50 bpm, symptomatic hypotension, or worsening congestion 5

Add Aldosterone Antagonist

• Initiate spironolactone 12.5-25 mg daily for patients with NYHA class III-IV symptoms 5
• Monitor potassium and creatinine closely (check at 1 week, then 1 month, then every 3 months) 5

Consider Hydralazine-Nitrate Combination

• Add hydralazine/isosorbide dinitrate as an alternative vasodilator strategy that does not affect the renin-angiotensin system 2
• This combination has mortality benefit, particularly in African American patients, and avoids angioedema risk 2

Optimize Diuretic Therapy

• Continue current furosemide dose unless signs of congestion develop 5
• If congestion worsens, double the diuretic dose before adjusting other medications 5

Critical Washout Period

If considering any future renin-angiotensin system blocker (which is NOT recommended after angioedema), a 36-hour washout period is mandatory between stopping one agent and starting another 1

However, given this patient has already experienced angioedema, do not attempt rechallenge with any ACE inhibitor, ARB, or sacubitril/valsartan 1, 3, 4

Monitoring Plan

• Observe for angioedema resolution over 48-72 hours 3
• Check blood pressure and heart rate before each carvedilol dose increase 5
• Monitor electrolytes and renal function 1-2 weeks after adding spironolactone 5
• Educate patient to weigh daily and report weight gain >1.5-2 kg over 2 days 5

Common Pitfall to Avoid

Do not switch to an ARB (like valsartan alone or losartan) thinking it will be safer—ARBs can also cause angioedema despite not affecting bradykinin levels, challenging previous theories about angioedema pathophysiology 4. The cross-reactivity rate is approximately 10%, but given the life-threatening nature of this patient's presentation, the risk is unacceptable 4.