What are the administration guidelines and potential interactions for amlodipine (calcium channel blocker)?

Amlodipine Administration and Clinical Considerations

Amlodipine is dosed at 2.5-10 mg once daily for adults, with 5 mg as the typical starting dose, and should be avoided in patients with heart failure with reduced ejection fraction (HFrEF) unless specifically required. 1

Dosing Guidelines

Standard Adult Dosing

• Starting dose: 5 mg once daily 1, 2
• Dose range: 2.5-10 mg once daily 1, 3
• Titration: Double the dose after 2-4 weeks if blood pressure target not achieved 4
• Administration timing: Can be taken at any time of day to optimize adherence 2

Pediatric Dosing (Ages 6-17 years)

• Starting dose: 2.5 mg once daily 2
• Maximum dose: 5 mg once daily 2
• Extemporaneous suspensions can be compounded for children who cannot swallow tablets 2

Special Populations

• Elderly patients: Consider starting at 2.5 mg due to 40-60% increase in drug exposure from decreased clearance 5
• Hepatic insufficiency: Start at 2.5 mg due to 40-60% increase in AUC 5
• Renal impairment: No dose adjustment required; standard dosing can be used 5

Pharmacokinetic Properties Supporting Once-Daily Dosing

• Half-life: 30-50 hours, allowing true once-daily administration 3, 5, 6
• Time to peak concentration: 6-12 hours after dosing 5
• Steady state: Achieved after 7-8 days of consecutive dosing 5, 6
• Bioavailability: 64-90%, not affected by food 5
• Plasma fluctuation: Only 20-25% between doses with once-daily dosing 6

Critical Contraindications and Warnings

Heart Failure

• Avoid in HFrEF; if required, amlodipine or felodipine may be used cautiously 1
• In the PRAISE-2 trial, amlodipine showed no mortality benefit and was associated with more reports of pulmonary edema in NYHA Class III/IV heart failure patients 5
• No negative inotropic effects at therapeutic doses, but caution still warranted 5

Pregnancy

• Avoid in pregnancy 1

Angioedema

• Unlike ACE inhibitors and ARBs, amlodipine does not carry specific angioedema warnings in the guidelines reviewed 1

Common Adverse Effects

• Peripheral edema: Dose-related, more common in women than men 1, 3
• Headache 2, 3
• Flushing 2, 3
• Dizziness 3
• Constipation 2

The pedal edema is due to arterial vasodilation rather than fluid retention, which explains why diuretics are typically ineffective for this side effect 1

Drug Interactions

CYP3A4 Interactions

• Strong CYP3A4 inhibitors (itraconazole, clarithromycin) may significantly increase amlodipine levels 5
• Diltiazem 180 mg daily increases amlodipine exposure by 60% 5
• Erythromycin does not significantly affect amlodipine exposure 5
• Grapefruit juice has no impact on amlodipine exposure 5

Amlodipine as CYP3A Inhibitor

Amlodipine is a weak CYP3A inhibitor and increases exposure to:

• Simvastatin: 77% increase in exposure with amlodipine 10 mg 5
• Cyclosporine: Average 40% increase in trough levels 5
• Tacrolimus: 2.5-4 fold increase in CYP3A5 expressers; 3-fold increase reported in non-expressers 5

Other Drug Interactions

• Sildenafil: Each agent independently exerts blood pressure lowering effects 5
• No significant interactions with: digoxin, phenytoin, warfarin, indomethacin, atorvastatin, ethanol, cimetidine, or antacids 5

Combination with Beta-Blockers

• Safe to combine; no adverse electrocardiographic effects observed 5
• Unlike non-dihydropyridine calcium channel blockers (diltiazem, verapamil), amlodipine does not increase risk of bradycardia or heart block when combined with beta-blockers 1

Combination Therapy Strategies

• Most adults with hypertension require two or more agents to achieve BP <130/80 mmHg 2
• In Black adults without heart failure or CKD: Combine with thiazide-type diuretic as first-line 2
• Fixed-dose single-pill combinations are recommended when using combination therapy 2
• Effective combinations include: ACE inhibitors, ARBs, beta-blockers, or thiazide diuretics 7, 8

Monitoring and Follow-Up

• Monthly visits until blood pressure target achieved 2
• Switch to 90-day refills once stable 2
• Telehealth strategies can augment office-based management 2
• No tolerance develops with long-term use 7, 8

Clinical Efficacy Profile

Blood Pressure Control

• 24-hour blood pressure control with once-daily dosing 9
• Mean reductions: 23/13 mmHg supine, 24/12 upright 8
• Target BP achieved in 56% with 5 mg and 73% with 10 mg daily 4
• No orthostatic hypotension 8
• No rebound hypertension upon discontinuation 6

Cardiovascular Outcomes

In the CAMELOT trial, amlodipine demonstrated:

• 31% reduction in composite cardiovascular endpoints (p=0.003) 5
• 42% reduction in hospitalization for angina (p=0.002) 5
• 27% reduction in coronary revascularization (p=0.033) 5

Angina Management

• Effective for chronic stable angina at 5-10 mg daily 5
• Increases exercise time by 12.8% (63 seconds) at 10 mg dose 5
• Reduces angina attacks by approximately 4 per week in vasospastic angina 5

Special Clinical Scenarios

Pulmonary Arterial Hypertension

• High-dose amlodipine (up to 20 mg daily) used only in vasoreactivity-positive idiopathic PAH patients 1
• Never use in PAH without documented positive vasoreactivity testing 1
• Requires close follow-up with repeat right heart catheterization at 3-4 months 1

Breastfeeding

• Considered safe with relative infant dose of 1.7-4.3% 3