What medications can be given with amlodipine and losartan?

Medications to Combine with Amlodipine and Losartan for Hypertension Management

A thiazide diuretic, particularly hydrochlorothiazide (HCTZ), is the most effective medication to add to amlodipine and losartan for hypertension management, as this creates a complementary triple therapy regimen targeting different blood pressure mechanisms. 1, 2

Rationale for Adding a Thiazide Diuretic

• Amlodipine (calcium channel blocker) and losartan (angiotensin receptor blocker) work through different mechanisms, but adding a third class of medication is often necessary to achieve blood pressure goals
• The American Heart Association recommends a combination of an ACE inhibitor/ARB, calcium channel blocker, and thiazide diuretic as an effective triple regimen for resistant hypertension 2
• Thiazide diuretics have been the foundation of antihypertensive therapy in most outcome trials showing reduction in cardiovascular disease events 1
• This triple combination targets three different pathways:
  • Losartan: blocks angiotensin II receptors
  • Amlodipine: blocks calcium channels in vascular smooth muscle
  • Thiazide diuretic: increases sodium excretion and reduces plasma volume

Evidence Supporting This Combination

• The combination of losartan/HCTZ has demonstrated significant blood pressure reductions when compared to monotherapy 3
• When losartan monotherapy is insufficient, adding HCTZ (12.5 mg) has been shown to reduce blood pressure by 12.5 mmHg (diastolic) compared to 8.7 mmHg with losartan dose doubling 4
• Amlodipine has been shown to be effective when added to ARB therapy (including losartan), reducing blood pressure by 8.1/5.4 mmHg compared to placebo 5

Specific Recommendations

1. First choice: Hydrochlorothiazide (12.5-25 mg daily)

   • Available in fixed-dose combination with losartan (Hyzaar: 50/12.5,100/25 mg) 1
   • Most extensively studied and commonly prescribed
   • Monitor for hypokalemia, hyperuricemia, and glucose intolerance

2. Alternative thiazide-type diuretic: Chlorthalidone (12.5-25 mg daily)

   • Longer half-life and potentially greater cardiovascular risk reduction than HCTZ 1
   • May require separate prescription (not available in fixed combination with losartan/amlodipine)

Special Considerations

• If thiazide diuretics are contraindicated or ineffective, consider:

  • Spironolactone (25-50 mg daily) - particularly effective for resistant hypertension 2
  • Beta-blockers (metoprolol, bisoprolol) - especially if patient has concomitant coronary artery disease 1

• Monitoring recommendations:

  • Check serum potassium and renal function within 3 months of adding a diuretic 2
  • Monitor for metabolic effects: glucose, uric acid, and lipid levels 1
  • Assess for orthostatic hypotension, especially in elderly patients 2

Cautions and Contraindications

• Avoid combining ACE inhibitors with ARBs (losartan) as this increases adverse effects without additional benefit 1
• In patients with severe renal impairment (GFR <30 mL/min), loop diuretics may be preferred over thiazides 1
• Fixed-dose combinations can improve adherence but may limit dosing flexibility 2

Practical Dosing Considerations

• Start with low dose of thiazide (HCTZ 12.5 mg or chlorthalidone 12.5 mg) and titrate as needed
• Consider timing of medications:
  • All three medications can be taken once daily
  • Taking them together in the morning may improve adherence

By adding a thiazide diuretic to the combination of amlodipine and losartan, you create a comprehensive regimen that targets multiple pathways of blood pressure regulation, maximizing efficacy while maintaining a favorable side effect profile.