Can losartan and Norvasc (amlodipine) be combined in a patient with Chronic Kidney Disease (CKD) stage 3b?

Combination of Losartan and Amlodipine in CKD Stage 3b

Yes, losartan and amlodipine (Norvasc) can be safely and effectively combined in patients with CKD stage 3b, and this combination may provide complementary benefits for blood pressure control and renoprotection. 1

Rationale for Combination Therapy

• The 2017 ACC/AHA hypertension guidelines recommend combination therapy with two agents of different classes for patients with stage 2 hypertension, which is particularly relevant for CKD patients who often require multiple agents for adequate BP control 1

• In CKD stage 3b:

  • Losartan (ARB) provides renoprotection by reducing proteinuria and slowing CKD progression
  • Amlodipine (CCB) provides effective BP control with complementary mechanisms
  • The combination addresses both hemodynamic and renoprotective goals

Benefits of This Specific Combination

1. Complementary Mechanisms:

   • Losartan blocks the renin-angiotensin system, reducing intraglomerular pressure and proteinuria
   • Amlodipine dilates peripheral arterioles, effectively lowering systemic blood pressure
   • Together they provide more comprehensive BP control than either agent alone

2. Evidence of Compatibility:

   • Amlodipine has been shown to have renoprotective effects in CKD patients, especially when paired with ARBs 1
   • Even a single dose of amlodipine can increase eGFR in CKD patients 1

3. Safety in CKD:

   • Losartan has been studied specifically in patients with renal impairment and found to be effective and well-tolerated 2
   • Amlodipine is one of the few CCBs specifically mentioned as appropriate for use in patients with reduced renal function 1

Dosing and Monitoring Considerations

1. Initial Dosing:

   • Start with lower doses of both medications:
     • Losartan 25-50 mg daily
     • Amlodipine 2.5-5 mg daily

2. Monitoring Requirements:

   • Check serum creatinine and potassium within 2-4 weeks of initiation or dose changes 1
   • Monitor for expected initial decrease in eGFR (up to 30% is acceptable) 1, 3
   • Continue monitoring periodically, especially if doses are increased

3. Dose Titration:

   • Titrate to the highest tolerated doses as needed for BP control 1
   • For losartan, aim for 50-100 mg daily if tolerated
   • For amlodipine, aim for 5-10 mg daily if needed and tolerated

Potential Concerns and Management

1. Hyperkalemia:

   • Losartan may increase serum potassium, especially in CKD 4
   • Monitor potassium levels regularly
   • Manage hyperkalemia with dietary modifications, diuretics, or potassium binders rather than discontinuing therapy 1

2. Edema:

   • Amlodipine can cause dose-related pedal edema 1
   • Losartan may help counteract this effect through its action on the renin-angiotensin system

3. Hypotension:

   • Monitor for orthostatic hypotension, especially in elderly patients
   • Consider lower initial doses if concerns about hypotension exist

Important Cautions

1. Avoid Triple RAS Blockade:

   • Never combine losartan with ACE inhibitors or direct renin inhibitors 1
   • This combination increases risk of hyperkalemia and acute kidney injury without additional benefit

2. NSAID Interactions:

   • Avoid or use caution with NSAIDs, which can reduce the effectiveness of losartan and increase risk of acute kidney injury 4

3. Continuation During eGFR Decline:

   • Continue losartan even if eGFR falls below 30 ml/min/1.73 m² unless specific contraindications develop 1
   • Only discontinue if serum creatinine rises by more than 30% within 4 weeks or if uncontrolled hyperkalemia develops 1

This combination therapy approach is supported by current guidelines and provides comprehensive management for hypertension in CKD stage 3b patients, addressing both blood pressure control and renoprotection.