What are the next steps for a patient experiencing leg weakness while taking Entresto (sacubitril/valsartan)?

Leg Weakness in Patients Taking Entresto

If you are experiencing leg weakness while taking Entresto (sacubitril/valsartan), immediately check your blood pressure and potassium levels, as hypotension and hyperkalemia are common side effects that can manifest as weakness, and contact your physician to assess whether dose adjustment or medication discontinuation is necessary. 1

Immediate Assessment Required

Check for Entresto-Related Adverse Effects

The FDA label for Entresto specifically identifies several side effects that can present as or contribute to leg weakness:

• Low blood pressure (hypotension) is common during Entresto treatment and can cause dizziness, lightheadedness, and extreme tiredness/fatigue that may be perceived as weakness 1
• Hyperkalemia (elevated potassium) is common with Entresto and can cause muscle weakness as a primary symptom 1
• Kidney problems are common during Entresto treatment and can lead to electrolyte imbalances and weakness 1
• Your risk of hypotension is greater if you are also taking diuretics (water pills) 1

Measure Vital Signs and Laboratory Values

• Obtain orthostatic blood pressures (lying, sitting, standing) to assess for hypotension 1
• Check serum potassium level urgently, as hyperkalemia requires immediate management 1
• Assess kidney function (creatinine, BUN, eGFR) as renal impairment can worsen electrolyte abnormalities 1
• Review all concurrent medications, particularly diuretics, which increase hypotension risk 1

Rule Out Serious Neuromuscular Conditions

While Entresto side effects are the most likely cause, leg weakness requires systematic evaluation to exclude life-threatening conditions:

Assess Pattern and Severity of Weakness

• Bilateral ascending weakness with sensory changes suggests Guillain-Barré syndrome requiring immediate ICU-level monitoring and treatment with IVIG or plasmapheresis 2, 3
• Fluctuating weakness worsening with activity, especially with ocular symptoms suggests myasthenia gravis requiring acetylcholine receptor antibody testing and treatment with pyridostigmine 2, 4
• Proximal muscle weakness with muscle pain suggests myositis requiring CPK, aldolase, and inflammatory marker testing 2, 3

Check for Red Flags Requiring Emergency Intervention

• Measure respiratory function (negative inspiratory force, vital capacity) as respiratory compromise can develop rapidly in neuromuscular disorders 2, 4, 3
• Assess for bulbar symptoms (dysphagia, dysarthria, facial weakness) indicating impending respiratory failure 2, 4, 3
• Evaluate for autonomic instability (blood pressure fluctuations, heart rate abnormalities) suggesting Guillain-Barré syndrome 2, 3

Management Algorithm

If Hypotension is Present (Systolic BP <90 mmHg or symptomatic)

• Reduce or temporarily discontinue Entresto until blood pressure stabilizes 1
• Ensure adequate salt and fluid intake 5
• Consider reducing or discontinuing concurrent diuretics 1
• Avoid medications that aggravate hypotension 5
• Use compressive garments over legs and abdomen for orthostatic symptoms 5

If Hyperkalemia is Present (K+ >5.5 mEq/L)

• Reduce or temporarily discontinue Entresto depending on severity 1
• Discontinue potassium supplements and potassium-sparing diuretics 1
• Initiate potassium-lowering therapy if K+ >6.0 mEq/L (calcium gluconate, insulin/glucose, sodium polystyrene sulfonate) based on general medical knowledge
• Recheck potassium within 24-48 hours 1

If Kidney Function is Declining

• Reduce Entresto dose or temporarily discontinue based on severity of renal impairment 1
• Ensure adequate hydration and avoid nephrotoxic medications based on general medical knowledge
• Monitor creatinine and potassium closely 1

If No Entresto-Related Cause is Identified

• Proceed with comprehensive neuromuscular evaluation including CPK, aldolase, inflammatory markers (ESR, CRP), and troponin to assess for myocardial involvement 2, 3
• Obtain urgent neurology consultation for all grades of suspected neuromuscular weakness given potential for rapid deterioration 3
• Consider hospital admission with ICU-level monitoring capability if progressive weakness, sensory loss, or respiratory symptoms are present 3

Common Pitfalls to Avoid

• Do not abruptly discontinue Entresto without physician guidance, as this may worsen heart failure 5, 6
• Do not attribute all weakness to deconditioning without first excluding hypotension, hyperkalemia, and serious neuromuscular conditions 5, 2
• Do not delay respiratory monitoring in patients with progressive weakness, as deterioration can be sudden in neuromuscular disease 4, 3
• Do not overlook cardiac involvement in patients with weakness and elevated CPK, as myocarditis can be life-threatening 3

Follow-Up Monitoring

• Your physician should check kidney function and potassium levels during ongoing Entresto treatment 1
• Blood pressure should be monitored regularly, especially if diuretics are also prescribed 1
• Report any worsening weakness, difficulty breathing, swallowing problems, or facial weakness immediately 4, 3