What is the proper titration protocol for lisinopril (angiotensin-converting enzyme inhibitor) in patients with hypertension?

Lisinopril Titration Protocol for Hypertension

For patients with hypertension, lisinopril should be initiated at 2.5-5 mg once daily and titrated upward every 1-2 weeks to a target dose of 20-40 mg daily, with monitoring of blood pressure, renal function, and electrolytes after each dose adjustment. 1, 2

Initial Dosing

• Standard starting dose: 10 mg once daily 2
• For patients on diuretics: 5 mg once daily 2
• For patients with renal impairment (CrCl ≤30 mL/min): 2.5 mg once daily 2, 3, 4
• For elderly or frail patients: Consider starting at 2.5-5 mg once daily 1

Titration Schedule

1. Start with appropriate initial dose based on patient characteristics
2. Check blood pressure, serum potassium, and creatinine 5-7 days after initiation 1
3. If tolerated with no significant adverse effects, double the dose every 1-2 weeks 1
4. Continue titration until:
   • Target blood pressure is achieved
   • Maximum dose of 40 mg daily is reached
   • Intolerable side effects occur

Monitoring Protocol

• First week: Check serum potassium and creatinine 5-7 days after starting treatment 1
• During titration: Monitor blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment 1
• After stabilization: Check at 3 months, then every 6 months 1

Target Doses

• Hypertension: 20-40 mg once daily 1, 2
• Maximum dose: 80 mg daily (though doses above 40 mg provide limited additional benefit) 2

Special Considerations

Renal Impairment

• CrCl >30 mL/min: No initial dose adjustment needed
• CrCl 10-30 mL/min: Start with 2.5 mg once daily, titrate cautiously 2, 3
• CrCl <10 mL/min or hemodialysis: Start with 2.5 mg once daily 2
• An increase in creatinine of up to 50% above baseline or to 3 mg/dL (266 μmol/L), whichever is greater, is acceptable 1

Combination Therapy

• If blood pressure is not adequately controlled with lisinopril monotherapy, add a low-dose thiazide diuretic (e.g., hydrochlorothiazide 12.5 mg) 2
• After adding a diuretic, it may be possible to reduce the dose of lisinopril 2

Management of Common Issues

Hypotension

• Asymptomatic low blood pressure usually does not require intervention 1
• For symptomatic hypotension:
  • Review need for and dose of other vasodilators (nitrates, calcium channel blockers)
  • Consider reducing diuretic dose if no signs of congestion 1

Cough

• Assess if cough is due to pulmonary edema or other causes
• ACE inhibitor-induced cough rarely requires discontinuation 1
• For intolerable cough, consider switching to an angiotensin receptor blocker 1

Worsening Renal Function

• If creatinine increases >50% or K+ >6.0 mmol/L:
  1. Stop concomitant nephrotoxic drugs (NSAIDs)
  2. Reduce/eliminate non-essential vasodilators
  3. Consider reducing diuretic dose if no congestion
  4. If problems persist, halve the ACE inhibitor dose and recheck 1

Common Pitfalls to Avoid

1. Excessive initial dosing: Starting with too high a dose, especially in patients with renal impairment, volume depletion, or those on diuretics
2. Inadequate monitoring: Failing to check renal function and electrolytes after initiation and dose increases
3. Premature discontinuation: ACE inhibitors should rarely be discontinued completely due to minor side effects, as clinical deterioration is likely 1
4. Concurrent medications: Avoid potassium-sparing diuretics during initiation and avoid NSAIDs which can worsen renal function 1
5. Inadequate titration: Failing to titrate to target doses shown to be effective in clinical trials 1

Remember that some ACE inhibitor therapy is better than none, so if maximum doses cannot be achieved, maintain the highest tolerated dose 1.