What's the next step for a patient with uncontrolled hypertension currently taking losartan (angiotensin II receptor antagonist) 100 mg and amlodipine (calcium channel blocker) 5 mg?

Next Step: Increase Amlodipine to 10 mg Daily

For a patient on losartan 100 mg and amlodipine 5 mg with uncontrolled hypertension, increase amlodipine to 10 mg once daily before adding a third medication class. 1, 2

Rationale for Dose Optimization First

• Losartan is already at its maximum recommended dose of 100 mg daily for hypertension, so further titration is not an option 1
• Amlodipine 5 mg represents only the mid-range dose, with the FDA-approved maximum being 10 mg once daily for hypertension 2
• The guideline-recommended approach is to optimize doses of current two-drug therapy before adding a third agent from a different class 3
• Clinical trial data demonstrates that amlodipine 10 mg produces significantly greater blood pressure reductions than 5 mg, with office BP reductions averaging 12-13/6-7 mmHg at the 10 mg dose 2

Evidence Supporting Amlodipine Dose Escalation

• In patients with uncontrolled hypertension on olmesartan 20 mg and amlodipine 5 mg, guidelines explicitly recommend increasing olmesartan to 40 mg before adding a third agent—the same stepwise optimization principle applies here 3
• A randomized trial in Korean patients showed that adding amlodipine 5 mg to losartan 100 mg produced significantly greater BP reductions (11.7 mmHg DBP) compared to losartan alone, with 90% achieving BP response at 8 weeks 4
• The FDA label specifies that dose titration should occur every 7-14 days, though more rapid titration is acceptable if the patient is assessed frequently 2

When to Add a Third Agent

• If blood pressure remains uncontrolled after optimizing to losartan 100 mg/amlodipine 10 mg, add a thiazide-like diuretic (chlorthalidone 12.5-25 mg or hydrochlorothiazide 25 mg daily) as the third agent 3, 5
• This creates the guideline-recommended triple therapy combination: ARB + calcium channel blocker + thiazide diuretic, targeting three complementary mechanisms—renin-angiotensin system blockade, vasodilation, and volume reduction 3
• The International Society of Hypertension guidelines explicitly state the sequence for non-Black patients: ARB → add CCB → optimize doses → add thiazide/thiazide-like diuretic 3

Monitoring Parameters

• Reassess blood pressure within 2-4 weeks after increasing amlodipine to 10 mg 3
• Target blood pressure should be <140/90 mmHg minimum, ideally <130/80 mmHg for higher-risk patients 3
• Monitor for peripheral edema, which is more common with higher amlodipine doses but may be attenuated if an ARB is already on board 3
• The goal is to achieve target blood pressure within 3 months of initiating or modifying therapy 3

Critical Pitfalls to Avoid

• Do not add a third drug class before maximizing doses of the current two-drug regimen—this violates guideline-recommended stepwise approaches and may expose patients to unnecessary polypharmacy 3
• Do not assume treatment failure without first confirming medication adherence, as non-adherence is the most common cause of apparent treatment resistance 3, 5
• Do not combine losartan with an ACE inhibitor, as dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 3

Alternative Consideration: Combination Tablet

• If adding a diuretic becomes necessary, consider losartan/HCTZ fixed-dose combination (100/25 mg), which has demonstrated efficacy in severe hypertension with mean BP reductions of 25.4/18.4 mmHg 6
• A study comparing losartan/HCTZ versus amlodipine showed that the combination produced similar ambulatory BP reductions despite differences in office readings 7