What are the potential side effects of Lisinopril in a patient with Hypertension and how can they be managed?

Potential Side Effects of Lisinopril and Their Management

Most Common Side Effects

Lisinopril is generally well-tolerated, with the most frequent adverse effects being cough (the most common class-specific effect), dizziness, headache, hypotension, and hyperkalemia. 1

Cough

• Dry, persistent cough occurs due to bradykinin accumulation (ACE normally degrades bradykinin) and is the most common reason for discontinuation 1, 2
• Reported in approximately 6.1% of hypertensive patients leading to drug discontinuation 2
• Management approach:
  • If cough is intolerable, switch directly to an angiotensin receptor blocker (ARB) such as valsartan, candesartan, or losartan at equivalent doses 3
  • ARBs provide equivalent cardiovascular protection without the cough side effect 3

Hypotension and Dizziness

• Symptomatic hypotension occurs most commonly in volume-depleted or salt-depleted patients 1
• First-dose hypotension reported in 1.3% of hypertensive patients and 4.8% of heart failure patients 2
• Peak blood pressure reduction occurs at 6 hours post-dose, with effects lasting 24 hours 1, 4
• Management approach:
  • Ensure adequate hydration before initiating therapy 1
  • Start with lower doses (2.5-5 mg daily) in volume-depleted patients or those with heart failure 5
  • Avoid concurrent use of high-dose diuretics during initiation 1
  • Monitor blood pressure 6 hours post-dose when effects peak 4

Hyperkalemia

• Mean serum potassium increase is approximately 0.1 mEq/L, but 15% of patients experience increases >0.5 mEq/L 1
• Risk is higher in patients with chronic kidney disease, diabetes, or concurrent use of potassium-sparing diuretics 5
• Management approach:
  • Monitor serum potassium and renal function within 1-2 weeks of initiation and periodically thereafter 5
  • If potassium rises above 5.5 mEq/L, consider adding an SGLT2 inhibitor which reduces hyperkalemia risk 5
  • Alternatively, switch to sacubitril/valsartan (ARNi) which has lower hyperkalemia rates than ACE inhibitors 5
  • Use potassium binders (patiromer) if hyperkalemia persists but GDMT needs to be maintained 5
  • Avoid potassium supplements and potassium-sparing diuretics unless specifically indicated 5

Renal Function Deterioration

• Acute increases in serum creatinine may occur, particularly in patients with bilateral renal artery stenosis or severe heart failure 5, 1
• Lisinopril is excreted unchanged by the kidneys; accumulation occurs when GFR <30 mL/min 1, 4
• Management approach:
  • Monitor serum creatinine and eGFR at baseline, 1-2 weeks after initiation, and periodically 5
  • Acute creatinine increases up to 30% above baseline are acceptable and often stabilize 5
  • Reduce dose by 50% when creatinine clearance is 10-30 mL/min 4
  • Contraindicated in bilateral renal artery stenosis 5

Serious but Rare Side Effects

Angioedema

• Angioedema is a life-threatening complication occurring in <1% of patients 5, 6
• Results from bradykinin accumulation causing swelling of face, lips, tongue, or airway 1
• Management approach:
  • Discontinue lisinopril immediately if angioedema occurs 5
  • Do NOT switch to an ARB as cross-reactivity can occur in rare cases 3
  • Consider alternative classes: calcium channel blockers or beta-blockers 3
  • This is a compelling contraindication to all ACE inhibitors 5

Pregnancy-Related Risks

• ACE inhibitors are absolutely contraindicated in pregnancy due to fetal toxicity 5
• Can cause fetal renal dysfunction, oligohydramnios, and death 5
• Management approach:
  • Screen all women of childbearing age before initiating therapy 5
  • Switch immediately to methyldopa, nifedipine, or labetalol if pregnancy occurs 5

Less Common Side Effects

Gastrointestinal Effects

• Nausea and diarrhea reported in clinical trials but not always drug-related 2
• Occurred in 6.1% leading to discontinuation in hypertensive patients 2

Fatigue and Headache

• Reported but difficult to distinguish from underlying disease or placebo effects 2, 6
• Generally mild and transient 7

Laboratory Monitoring Requirements

Establish a systematic monitoring protocol:

• Baseline: Serum creatinine, eGFR, potassium, blood pressure 5
• 1-2 weeks after initiation: Repeat creatinine, eGFR, potassium 5
• Ongoing: Monitor every 3-6 months or when dose changes 5
• Blood pressure monitoring: Check at 6 hours post-dose initially to assess peak effect 4

Critical Contraindications

Absolute contraindications per guidelines:

• Pregnancy 5
• History of angioedema with any ACE inhibitor 5
• Bilateral renal artery stenosis 5

Relative contraindications requiring caution:

• Hyperkalemia (K+ >5.5 mEq/L) 5
• Severe renal impairment (GFR <30 mL/min) requires dose adjustment 1, 4
• Volume depletion 1

Drug Interactions to Monitor

• NSAIDs reduce antihypertensive efficacy and increase renal dysfunction risk 1
• Potassium-sparing diuretics and potassium supplements increase hyperkalemia risk 5
• Lithium levels may increase due to reduced renal clearance 6
• Hydrochlorothiazide combination reduces hyperkalemia risk (mean K+ decrease of 0.1 mEq/L) 1

Racial Considerations

Black patients show reduced blood pressure response to lisinopril monotherapy compared to non-Black patients 1

• This reflects the typically low-renin state in Black hypertensive populations 1
• Combination with hydrochlorothiazide eliminates racial differences in response 1
• Consider starting with combination therapy in Black patients per guidelines 5

When to Switch from Lisinopril

Consider switching to an ARB if:

• Persistent dry cough develops 3, 2
• Recurrent hyperkalemia despite management strategies 5, 3
• Patient preference after shared decision-making 3

ARBs provide equivalent cardiovascular and renal protection with better tolerability 5, 3