What are the dosing guidelines and potential side effects of Amlodipine (calcium channel blocker) in patients with hypertension and coronary artery disease, considering factors such as age, kidney function, and other medical conditions?

Amlodipine Dosing and Side Effects

Initial Dosing

Start amlodipine at 5 mg once daily for most adults with hypertension or coronary artery disease, with a lower starting dose of 2.5 mg once daily reserved for small, fragile, elderly patients, or those with hepatic insufficiency. 1

• The FDA-approved initial dose is 5 mg once daily, which can be titrated to a maximum of 10 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
• Amlodipine can be administered at any time of day to improve adherence 2

Dose Titration Algorithm

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

• Increase from 5 mg to 10 mg once daily if blood pressure remains ≥130/80 mmHg after 2-6 weeks of treatment 2
• Before escalating the dose, confirm inadequate control with home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) 2
• Check medication adherence before dose escalation, as non-adherence is the most common cause of apparent treatment failure 2
• Measure blood pressure at trough (just before the next dose) to ensure true 24-hour control 2

Combination Therapy Strategy

Consider adding a second antihypertensive agent rather than maximizing amlodipine to 10 mg if blood pressure control is inadequate after 4-6 weeks at 5 mg. 2

• Preferred combinations include amlodipine + ACE inhibitor/ARB or amlodipine + thiazide-type diuretic 2
• For black adults with hypertension, initial treatment should include a thiazide-type diuretic or calcium channel blocker like amlodipine 2
• Fixed-dose single-pill combinations are recommended when using combination therapy 2

Special Populations

Elderly Patients

• Start at 2.5 mg once daily due to 40-60% increase in drug exposure from decreased clearance 1
• Titrate cautiously with increased monitoring for orthostatic hypotension, falls, and syncope 3

Hepatic Impairment

• Start at 2.5 mg once daily due to 40-60% increase in AUC from decreased hepatic clearance 1
• For chronic stable or vasospastic angina in hepatic insufficiency, use the lower end of the 5-10 mg dose range 1

Renal Impairment

• No dose adjustment required regardless of severity of renal impairment 2, 1
• Amlodipine has minimal renal clearance (7 mL/min/mg) and demonstrates renoprotective effects 2

Coronary Artery Disease

• The recommended dose range is 5-10 mg once daily, with most patients requiring 10 mg for adequate effect 1
• Long-acting calcium channel blockers like amlodipine are preferred for vasospastic angina 3

Common Side Effects

The most common dose-dependent side effect is peripheral edema, occurring in 1.8% at 2.5 mg, 3.0% at 5 mg, and 10.8% at 10 mg daily. 1

Dose-Related Side Effects (incidence increases with higher doses):

• Peripheral edema: 1.8% (2.5 mg) → 3.0% (5 mg) → 10.8% (10 mg) 1
• Palpitations: 0.7% (2.5 mg) → 1.4% (5 mg) → 4.5% (10 mg) 1
• Flushing: 0.7% (2.5 mg) → 1.4% (5 mg) → 2.6% (10 mg) 1
• Dizziness: 1.1% (2.5 mg) → 3.4% (5 mg) → 3.4% (10 mg) 1

Non-Dose-Related Side Effects (>1% incidence):

• Fatigue: 4.5% 1
• Nausea: 2.9% 1
• Abdominal pain: 1.6% 1
• Somnolence: 1.4% 1
• Headache, constipation 4, 1

Gender Differences in Side Effects

Women experience significantly higher rates of edema (14.6% vs 5.6% in men), flushing (4.5% vs 1.5%), and palpitations (3.3% vs 1.4%). 1

Serious but Rare Side Effects (<1%):

• Arrhythmias (including ventricular tachycardia and atrial fibrillation) 1
• Bradycardia, syncope 1
• Angioedema, erythema multiforme 1
• Gingival hyperplasia 1
• Gynecomastia (postmarketing) 1

Important Drug Interactions

CYP3A4 Inhibitors

• Strong CYP3A4 inhibitors (itraconazole, clarithromycin) may significantly increase amlodipine levels 1
• Diltiazem 180 mg daily increases amlodipine exposure by 60% 1

Drugs Affected by Amlodipine

• Simvastatin: 77% increase in exposure when co-administered with amlodipine 10 mg; consider lower simvastatin doses 1
• Cyclosporine: Average 40% increase in trough levels 1
• Tacrolimus: 2.5-4 fold increase in exposure in CYP3A5 expressers; monitor levels closely regardless of genotype 1

Clinical Pearls

• Amlodipine has a long half-life of 30-50 hours, providing true 24-hour blood pressure control with once-daily dosing 1, 5
• Steady-state plasma levels are reached after 7-8 days of consecutive daily dosing 1
• Discontinuation due to adverse effects occurs in only 1.5% of patients, similar to placebo 1
• The ALLHAT trial demonstrated that amlodipine was equally effective as chlorthalidone for primary cardiovascular outcomes, though it showed a 38% increase in heart failure compared to diuretic therapy 3
• Schedule monthly visits until blood pressure target is achieved, then transition to 90-day refills when possible 2