What is the typical starting dose of Norvasc (amlodipine) and chlorthalidone for a patient with hypertension?

Starting Doses for Amlodipine (Norvasc) and Chlorthalidone in Hypertension

For most adults with hypertension, start amlodipine at 5 mg once daily and chlorthalidone at 12.5-25 mg once daily, with 12.5 mg preferred initially to minimize metabolic adverse effects while maintaining proven cardiovascular benefit. 1, 2, 3

Amlodipine (Norvasc) Dosing

Standard Starting Dose:

• 5 mg once daily is the usual initial antihypertensive dose for most adults 1
• Maximum dose is 10 mg once daily 1

Modified Starting Doses for Special Populations:

• 2.5 mg once daily for small, fragile, or elderly patients, or those with hepatic insufficiency 1
• This lower dose may also be used when adding amlodipine to other antihypertensive therapy 1

Titration Strategy:

• Wait 7-14 days between titration steps in general 1
• May titrate more rapidly if clinically warranted with frequent patient assessment 1

Chlorthalidone Dosing

Starting Dose:

• 12.5 mg once daily is the evidence-based starting dose that balances efficacy with safety 3, 4
• Alternative starting dose of 25 mg once daily may be used, though this carries higher risk of metabolic adverse effects 2, 5
• The doses validated in successful morbidity trials were 12.5-25 mg of chlorthalidone 5, 4

Titration Strategy:

• If blood pressure remains uncontrolled after 4 weeks, increase to 25 mg once daily 3
• Do not exceed 25 mg daily, as higher doses increase metabolic adverse effects without additional antihypertensive benefit 3
• Dosages above 100 mg daily usually do not increase effectiveness for hypertension 2

Administration:

• Single dose given in the morning with food is recommended 2

Critical Monitoring Requirements

For Chlorthalidone:

• Check serum potassium, sodium, and creatinine within 2-4 weeks of initiating therapy or any dose escalation 3, 4
• Chlorthalidone carries a 3-fold higher risk of hypokalemia compared to hydrochlorothiazide, even at 12.5 mg dose 3, 4
• Monitor uric acid and calcium levels, as chlorthalidone can precipitate gout and cause hypercalcemia 3, 4

Combination Therapy Considerations

When Using Both Agents Together:

• Start with amlodipine 5 mg plus chlorthalidone 12.5 mg once daily 3
• This combination represents a preferred first-line strategy for most patients with confirmed hypertension 5, 3
• The combination of a calcium channel blocker with a thiazide diuretic is effective and well-tolerated 5

Evidence from Clinical Trials:

• Both amlodipine 5-10 mg and chlorthalidone 15-30 mg showed comparable efficacy in reducing systolic blood pressure by approximately 14 mm Hg in stage 1 isolated systolic hypertension 6
• Triple combination therapy including these agents (with telmisartan) achieved target blood pressure in 53.8% of patients at standard doses 7

Important Clinical Pitfalls

Avoid These Common Errors:

• Do not start elderly or frail patients on standard 5 mg amlodipine dose—use 2.5 mg instead 1
• Do not use chlorthalidone doses above 25 mg for hypertension, as this increases adverse effects without improving blood pressure control 5, 3
• Do not neglect electrolyte monitoring with chlorthalidone—hypokalemia can contribute to ventricular ectopy and sudden death 4

Guideline-Based Rationale

Why Chlorthalidone Over Hydrochlorothiazide:

• Chlorthalidone is the preferred thiazide-type diuretic based on its prolonged half-life and proven reduction in cardiovascular disease in clinical outcome trials 3, 4
• Network meta-analyses demonstrate superior clinical outcomes with chlorthalidone over hydrochlorothiazide 4
• The ALLHAT trial showed no differences in primary coronary heart disease outcomes between chlorthalidone, amlodipine, and lisinopril, but chlorthalidone reduced heart failure incidence compared to both agents 5

Why These Starting Doses:

• Thiazide-type diuretics at doses equivalent to 12.5-25 mg chlorthalidone were used in successful morbidity trials demonstrating cardiovascular protection 5
• Starting with lower doses minimizes metabolic adverse effects (hypokalemia, hyperuricemia, hyperglycemia) while maintaining antihypertensive efficacy 5, 3