What is the recommended dosage and usage of Amlodipine (calcium channel blocker) for an adult patient with hypertension or angina, considering their overall cardiovascular risk profile and potential comorbid conditions such as diabetes, hyperlipidemia, and smoking status?

Amlodipine Dosing and Management for Hypertension and Angina

Initial Dosing Strategy

Start amlodipine at 5 mg once daily for most adults with hypertension or angina, with a maximum dose of 10 mg once daily. 1

• For standard adults: Begin with 5 mg once daily, which is the FDA-approved initial dose for both hypertension and angina 1
• For small, fragile, or elderly patients, or those with hepatic insufficiency: Start at 2.5 mg once daily 1
• For pediatric patients (ages 6-17 years): Start at 2.5 mg once daily, with a maximum of 5 mg once daily 1

Blood Pressure Targets

Target blood pressure is <130/80 mmHg for most adults with hypertension, including those with diabetes, chronic kidney disease, or stable ischemic heart disease. 2

• For patients with stable ischemic heart disease and hypertension, the 2017 ACC/AHA guidelines recommend a BP target of <130/80 mmHg 2
• For patients with diabetes and hypertension, the American Diabetes Association recommends the same target of <130/80 mmHg 2

Dose Titration Algorithm

Wait 7-14 days between dose adjustments under normal circumstances, but titrate more rapidly if clinically warranted with frequent patient assessment. 1

Step-by-Step Titration Protocol:

1. Weeks 0-2: Start amlodipine 5 mg once daily 1
2. Week 2-6 assessment: Check blood pressure control 3
   • If BP remains ≥130/80 mmHg, confirm with home BP monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) 3
   • Check medication adherence before escalating dose, as non-adherence is the most common cause of apparent treatment failure 3
3. Week 4-6: If BP remains above target after confirming adherence, increase to 10 mg once daily 3, 1
4. Alternative strategy: Rather than maximizing amlodipine to 10 mg, consider adding a second agent after 4-6 weeks at 5 mg if BP control is inadequate 3

Critical Timing Consideration:

Do not increase the dose before 6 weeks of treatment at 5 mg once daily unless urgent BP reduction is required, as studies show no advantage to early dose escalation 4

Combination Therapy Approach

Add a second antihypertensive agent rather than maximizing amlodipine monotherapy if blood pressure remains uncontrolled after 4-6 weeks at 5 mg once daily. 3

Preferred Combination Partners:

• Amlodipine + ACE inhibitor or ARB: Recommended for patients with diabetes, chronic kidney disease (especially with albuminuria ≥30 mg/g creatinine), or coronary artery disease 2
• Amlodipine + thiazide-type diuretic: Particularly effective in black patients and as part of triple therapy 2
• Amlodipine + beta-blocker: Specifically for patients with stable ischemic heart disease, prior MI, or angina 2

Combination Dosing:

• Maximum amlodipine dose in combination: 10 mg daily 5
• When combining with enalapril: Maximum enalapril 40 mg daily (as 20 mg twice daily or 40 mg once daily) 5
• Allow at least 4 weeks between dose increases to observe full antihypertensive response 5

Monitoring Strategy

Schedule monthly follow-up visits until BP target is achieved, then transition to 90-day refills to improve adherence. 3

• Measure BP at trough (just before next dose) to ensure 24-hour control 3
• Use home BP monitoring or telehealth strategies to augment office-based management 2
• For patients on ACE inhibitor combinations, monitor serum creatinine and potassium within 7-14 days after initiation, then at least annually 2, 5

Angina-Specific Dosing

For chronic stable angina or vasospastic angina, the recommended dose is 5-10 mg once daily, with most patients requiring 10 mg for adequate symptom control. 1

• In clinical trials, 10 mg daily increased exercise time by an average of 12.8% (63 seconds) compared to 7.9% (38 seconds) with 5 mg 1
• For vasospastic angina, amlodipine decreased angina attacks by approximately 4 per week compared to placebo 1
• The drug provides sustained anti-ischemic efficacy for a full 24 hours after dosing 6

Common Pitfalls to Avoid

1. Premature dose escalation: Increasing from 5 mg to 10 mg before 4-6 weeks provides no additional benefit and increases side effects 4
2. Ignoring adherence issues: Always verify medication adherence before assuming treatment failure 3
3. Monotherapy maximization: Multiple studies show that adding a second agent at submaximal doses is more effective than maximizing single-drug therapy 5
4. Inadequate monitoring: Failing to measure BP at trough may miss inadequate 24-hour control 3

Side Effects and Tolerability

Common side effects include peripheral edema (10-30% at 10 mg dose), headache, flushing, and constipation, which are dose-dependent. 3, 7

• Peripheral edema is more common at 10 mg daily and may be reduced by combining with an ACE inhibitor or ARB rather than increasing amlodipine dose 5
• In the ALLHAT trial, amlodipine showed increased risk of heart failure compared to chlorthalidone (RR 1.38), though it was equivalent for primary cardiovascular outcomes 2

Special Populations

For elderly patients or those with hepatic insufficiency, start at 2.5 mg once daily and titrate cautiously. 1

• Amlodipine requires no dose adjustment for renal impairment due to low renal clearance (7 mL/min/mg) 3, 7
• The drug demonstrates renoprotective effects and does not worsen kidney function in patients with chronic kidney disease 3
• In pediatric patients ages 6-17 years, doses above 5 mg daily have not been studied and should not be used 1

Cardiovascular Outcomes Evidence

Amlodipine reduces cardiovascular events comparably to thiazide diuretics for primary outcomes, with particular benefit in preventing angina hospitalizations and revascularization procedures. 2

• In the CAMELOT trial, amlodipine 5-10 mg daily reduced composite cardiovascular endpoints by 31% (p=0.003) in patients with documented coronary artery disease 1
• Hospitalizations for angina were reduced by 42% (p=0.002) and coronary revascularizations by 27% (p=0.033) 1
• The ALLHAT trial showed amlodipine was equivalent to chlorthalidone for preventing fatal CHD and nonfatal MI (RR 0.98) 2