Amlodipine Dose Adjustment with Dyazide
No dose adjustment of amlodipine is required when Dyazide (triamterene/hydrochlorothiazide) is added or adjusted, as these medications work through complementary mechanisms without pharmacokinetic interactions. 1
Pharmacokinetic Rationale
- Amlodipine pharmacokinetics are not significantly influenced by diuretics like hydrochlorothiazide or triamterene 1
- The combination of a dihydropyridine calcium channel blocker (amlodipine) with a thiazide diuretic is a guideline-recommended first-line combination for hypertension, providing effective blood pressure control through complementary mechanisms 2, 3
- Co-administration of antacids, cimetidine, and other common medications have no impact on amlodipine exposure, and diuretics similarly do not affect amlodipine levels 1
Appropriate Combination Therapy Strategy
When combining amlodipine with Dyazide, maintain standard dosing for both agents:
- Amlodipine: Continue usual dose of 5-10 mg once daily for hypertension 1
- Dyazide: Standard dose is one tablet daily (50 mg triamterene/25 mg hydrochlorothiazide) 4
- The combination of a dihydropyridine CCB with a thiazide/thiazide-like diuretic is one of the preferred two-drug combinations recommended by the 2024 ESC guidelines 2
Clinical Monitoring Requirements
Monitor the following parameters within 1-2 weeks of adding Dyazide:
- Serum potassium: Target 4.0-5.0 mEq/L, as triamterene is potassium-sparing while hydrochlorothiazide causes potassium loss 2, 3
- Serum sodium: Hydrochlorothiazide can cause hyponatremia, particularly in elderly patients; hold if sodium drops below 130 mEq/L 3, 5
- Renal function: Check serum creatinine and eGFR, as thiazides become less effective when eGFR <30 mL/min/1.73 m² 2
- Blood pressure: Assess for excessive hypotension from additive effects 2
Titration Strategy for Inadequate Control
If blood pressure remains uncontrolled on amlodipine plus Dyazide:
- Increase amlodipine to maximum dose of 10 mg daily if not already at this dose 1
- Consider switching to a three-drug combination by adding a RAS blocker (ACE inhibitor or ARB), which is the preferred three-drug combination per 2024 ESC guidelines 2
- Triple combination therapy with olmesartan/amlodipine/hydrochlorothiazide has demonstrated superior blood pressure reduction compared to dual combinations, with 69.9% of patients reaching <140/90 mmHg 6, 7
Important Clinical Caveats
Avoid these common pitfalls:
- Do not reduce amlodipine dose preemptively when adding Dyazide, as there is no pharmacokinetic interaction requiring adjustment 1
- In patients with hepatic insufficiency or elderly/frail patients, amlodipine clearance is decreased by 40-60%, so consider starting at 2.5 mg daily regardless of diuretic use 1
- Do not use thiazides if eGFR <30 mL/min except when prescribed synergistically with loop diuretics; switch to loop diuretics in advanced CKD 2
- Monitor for hypokalemia despite triamterene's potassium-sparing effect, as the hydrochlorothiazide component may predominate; add potassium supplementation if levels drop below 3.5 mEq/L 2, 3
Drug Interaction Considerations
Be aware of amlodipine's CYP3A4 interactions:
- Amlodipine is a weak CYP3A4 inhibitor and may increase exposure to simvastatin (77% increase), cyclosporine (40% increase), and tacrolimus (2.5-4 fold increase) 1
- Strong CYP3A4 inhibitors like diltiazem can increase amlodipine exposure by 60%, though this does not apply to Dyazide 1
- Dyazide components (triamterene and hydrochlorothiazide) do not interact with CYP3A4 pathways 1