Lisinopril 40 mg BID is Too High a Dose
Lisinopril 40 mg twice daily exceeds the maximum recommended dosage and should not be prescribed, as the maximum approved dose is 40 mg once daily. 1, 2
Recommended Dosing for Lisinopril
- According to clinical guidelines, the initial daily dose of lisinopril should be 2.5-5 mg once daily, with gradual titration to higher doses as needed 1
- The maximum recommended dose of lisinopril is 20-40 mg once daily, not twice daily 1, 2
- In the ATLAS trial (a large survival study with over 3,000 patients), researchers compared 2.5 mg and 35 mg of lisinopril in heart failure patients, showing that higher doses had outcomes at least as favorable as lower doses, but did not test doses above 40 mg daily 2
- FDA-approved dosing information clearly indicates that lisinopril is administered as a once-daily medication, not twice daily 2
Pharmacokinetic Considerations
- Lisinopril has a long elimination half-life of approximately 12.6 hours, which supports once-daily dosing 3
- The antihypertensive effect begins within 2 hours, peaks around 6 hours, and lasts for at least 24 hours, making once-daily dosing appropriate 4
- Steady state is achieved in 2-3 days with little accumulation when dosed appropriately 4
- Lisinopril is excreted unchanged in the urine, and significant accumulation occurs in patients with severe renal impairment, further increasing risk with excessive dosing 4
Risks of Excessive Dosing
- Higher than recommended doses increase the risk of adverse effects such as hypotension, worsening renal function, and hyperkalemia 1
- ACE inhibitors occasionally cause worsening of renal function, hyperkalaemia, symptomatic hypotension, cough, and rarely, angioedema - risks that would be amplified with excessive dosing 1
- Doubling the maximum recommended dose could lead to dangerous hypotension, especially in patients also receiving diuretics or with volume depletion 1
- Patients with renal impairment are at particularly high risk of adverse effects with excessive dosing 5
Alternative Approaches
- If blood pressure control is inadequate with maximum lisinopril dose (40 mg once daily), guidelines recommend adding a different class of antihypertensive rather than exceeding the maximum dose 1
- For heart failure patients requiring additional renin-angiotensin system blockade, adding an aldosterone antagonist (such as spironolactone) would be more appropriate than exceeding the maximum lisinopril dose 1
- The combination of multiple renin-angiotensin system inhibitors (such as ACE inhibitors and ARBs) increases side effects without providing significant additional benefits 6
Special Considerations
- Elderly patients and those with renal impairment may require lower doses of lisinopril (not higher) due to reduced clearance 3
- For patients with heart failure, the target dose of lisinopril is 20-40 mg once daily, with careful titration from lower starting doses 1
- Patients should be monitored for hypotension, worsening renal function, and hyperkalemia, especially when using doses at the higher end of the recommended range 1