Can you take Cozaar (Losartan), Lisinopril, and Metoprolol together?

Taking Cozaar (Losartan), Lisinopril, and Metoprolol Together

The combination of losartan (Cozaar) and lisinopril is not recommended and should be avoided due to increased risks of hyperkalemia, hypotension, and renal dysfunction, while metoprolol can be used with either one of these medications but not both simultaneously. 1, 2

Why This Combination Should Be Avoided

• The combination of two renin-angiotensin system (RAS) blockers (losartan and lisinopril) is specifically contraindicated according to European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines 1
• Clinical trials (ONTARGET and ALTITUDE) demonstrated that dual RAS blockade is associated with:
  • Increased risk of end-stage renal disease 1
  • Higher incidence of hyperkalemia 2
  • Greater risk of hypotension and syncope 2
  • No additional benefit in blood pressure control or cardiovascular outcomes 1

Evidence Against Dual RAS Blockade

• The VA NEPHRON-D trial showed that patients receiving the combination of losartan and lisinopril did not obtain additional benefits compared to monotherapy but experienced increased incidence of hyperkalemia and acute kidney injury 2
• The FDA drug label for losartan explicitly warns against dual blockade of the RAS with angiotensin receptor blockers and ACE inhibitors 2
• This combination is marked with a "red continuous line" in the ESC/ESH guidelines, indicating it is "not recommended" 1

Appropriate Combinations for Hypertension Management

• Either losartan (ARB) OR lisinopril (ACE inhibitor) can be safely combined with metoprolol (beta-blocker) 1
• The ESC/ESH guidelines recommend several effective two-drug combinations for hypertension management:
  • ACE inhibitor + calcium channel blocker 3
  • ARB + calcium channel blocker 1
  • ACE inhibitor + diuretic 1
  • ARB + diuretic 1
  • Beta-blocker + diuretic 1

Special Considerations with Metoprolol

• When combining metoprolol with either losartan or lisinopril:
  • Monitor blood pressure closely, especially during the first month of therapy 3, 4
  • Be aware that beta-blockers like metoprolol may have less favorable metabolic effects compared to other antihypertensives 4
  • Consider that valsartan (another ARB) has shown better cardiovascular outcomes compared to extended-release metoprolol in some studies 4

Alternative Approaches

• If multiple agents are needed for blood pressure control, consider:
  • Using fixed-dose combinations to improve adherence 1
  • Selecting combinations that have been proven effective in clinical trials 5, 6
  • Choosing medications based on comorbidities (e.g., ACE inhibitors or ARBs for patients with diabetes or kidney disease) 1

Monitoring Recommendations

• If using metoprolol with either losartan OR lisinopril (but not both):
  • Monitor blood pressure, heart rate, and renal function regularly 7
  • Check serum potassium levels, especially when initiating therapy 2
  • Be particularly cautious in elderly patients, those with pre-existing renal impairment, or heart failure 2

Common Pitfalls to Avoid

• Never combine an ACE inhibitor (lisinopril) with an ARB (losartan) due to increased adverse effects without additional benefits 1, 2
• Don't overlook the potential for drug interactions with other medications (e.g., NSAIDs can reduce the effectiveness of both losartan and lisinopril) 8, 2
• Avoid abrupt discontinuation of beta-blockers like metoprolol, which can lead to rebound hypertension 3