Is S-amlodipine (calcium channel blocker) safe?

Is S-Amlodipine Safe?

Yes, S-amlodipine is safe and well-tolerated, with a notably lower incidence of peripheral edema compared to racemic amlodipine while maintaining equivalent antihypertensive and anti-anginal efficacy at half the dose. 1

Safety Profile and Tolerability

S-amlodipine represents the pharmacologically active enantiomer of racemic amlodipine, demonstrating excellent safety across multiple clinical contexts:

General Safety Data

• Postmarketing surveillance of over 4,000 patients confirmed negligible peripheral edema incidence with S-amlodipine compared to the racemic formulation, which is the most common adverse effect of dihydropyridine calcium channel blockers 1

• Patients who switched from racemic amlodipine to S-amlodipine due to peripheral edema experienced resolution of this side effect while maintaining blood pressure control 1

• The gradual onset of action and long half-life (40-60 hours) contribute to superior tolerability compared to other dihydropyridines, with minimal vasodilatory side effects like headache, flushing, and dizziness 2, 3

Cardiovascular Safety

Amlodipine (including S-amlodipine) has been extensively validated as safe in patients with coronary artery disease, well-compensated heart failure, and chronic stable angina 4, 5

• The PRAISE trial demonstrated that amlodipine administration in heart failure patients was not accompanied by adverse effects on morbidity or mortality, with favorable effects specifically in nonischemic dilated cardiomyopathy 6

• Long-term safety data indicate a neutral effect on survival in heart failure patients when added to ACE inhibitors and diuretics, making it appropriate for concomitant hypertension or angina 6

• Unlike diltiazem and verapamil, dihydropyridines like amlodipine do not cause cardiac conduction disturbances and can be safely combined with beta-blockers 7, 3

Metabolic and Laboratory Safety

• No clinically significant changes occur in routine laboratory parameters including serum potassium, glucose, lipids, uric acid, or renal function markers 4

• Unlike some antihypertensives, amlodipine does not adversely affect serum lipid patterns 7, 3

• No postural hypotension or significant heart rate changes occur with chronic dosing 2, 7

Special Population Safety

Renal Disease

Amlodipine is explicitly safe in end-stage renal disease and dialysis patients, with renoprotective properties demonstrated in chronic kidney disease 8

• Studies show better preservation of renal function (less decline in creatinine clearance) compared to other antihypertensives 8

• Unlike renally-excreted medications, amlodipine's hepatic metabolism means therapy remains stable regardless of dialysis schedule 8

• Critical caveat: Do not administer to patients on polyacrylonitrile dialysis membranes due to potential anaphylactoid reactions 8

Elderly and Isolated Systolic Hypertension

• Subgroup analyses confirmed S-amlodipine is effective and safe in elderly hypertensives and isolated systolic hypertension patients 1

• Plasma concentrations correlate with effect in both young and elderly patients 4

Combination Therapy Safety

S-amlodipine is well-tolerated when combined with other cardiovascular agents:

• Fixed-dose combinations with atenolol and hydrochlorothiazide are effective and well-tolerated in clinical practice 1

• Safe combination with ACE inhibitors, diuretics, and nitrates has been demonstrated 3

• Can be used with nitroglycerin for angina without contraindication 4

Common Adverse Effects (Mild to Moderate)

The FDA-approved labeling identifies these dose-related effects, more common in women 4:

• Peripheral edema (5.6% men, 14.6% women vs. 1.4% and 5.1% placebo) - significantly reduced with S-amlodipine formulation 4, 1
• Flushing (1.5% men, 4.5% women) 4
• Dizziness and fatigue 4
• Palpitations (1.4% men, 3.3% women) 4

Rare but Serious Considerations

• Postmarketing reports of jaundice and hepatic enzyme elevations (mostly cholestasis/hepatitis) requiring hospitalization in rare cases 4
• Possible association with extrapyramidal disorder reported postmarketing 4
• Rare allergic reactions including angioedema and erythema multiforme 4

Monitoring Recommendations

• Watch for peripheral edema as the primary tolerability concern; consider dose reduction if it develops 8
• Monitor for orthostatic hypotension when initiating therapy, particularly in dialysis patients 8
• No routine laboratory monitoring required given neutral metabolic profile 4

Clinical Bottom Line

S-amlodipine at half the dose of racemic amlodipine provides equivalent efficacy with superior tolerability, particularly regarding peripheral edema. It is safe across diverse patient populations including those with coronary disease, heart failure, renal disease, and elderly patients, with an established track record spanning decades of clinical use 1, 9, 7.