S-Amlodipine

DRUG NAME: S-Amlodipine

Therapeutic Class: Calcium Channel Blocker

Subclass: Dihydropyridine

Schedule (India): H

Route(s): Oral

Formulations Available in India:

• Tablets: 2.5 mg, 5 mg

---

ADULT INDICATIONS + DOSING

Primary Indications (Approved / Standard in India)

Hypertension

• S-Amlodipine is the therapeutically active S(-) enantiomer of racemic amlodipine. Approximately 2.5 mg of S-amlodipine delivers antihypertensive efficacy comparable to 5 mg of racemic amlodipine, as the R(+) enantiomer contributes negligibly to blood pressure lowering but may contribute to adverse effects such as peripheral oedema.
• Can be administered at any time of day, with or without food. However, once a time is chosen, patients should maintain consistency for stable plasma levels.
• Due to its prolonged half-life (approximately 40–50 hours for the active enantiomer), steady state is reached in 7–8 days. Premature dose escalation before this period is a common prescribing error leading to over-treatment and hypotension.
• Suitable as monotherapy or in combination with ACE inhibitors, ARBs, thiazide/thiazide-like diuretics, or beta-blockers. Fixed-dose combinations with telmisartan, atenolol, chlorthalidone, and hydrochlorothiazide are available in India.
• No reflex tachycardia at therapeutic doses due to gradual onset of action, unlike short-acting dihydropyridines.
• Particularly effective in elderly patients with isolated systolic hypertension and in patients with low-renin hypertension.
• If a patient is already on racemic amlodipine 5 mg, they can be switched to S-amlodipine 2.5 mg; if on racemic amlodipine 10 mg, switch to S-amlodipine 5 mg.
• Patients frequently ask if they need to take this medicine lifelong — advise that hypertension is a chronic condition requiring long-term treatment; discontinuation without medical advice risks rebound elevation of blood pressure, although unlike beta-blockers or clonidine, abrupt cessation does not typically cause a hypertensive crisis.
• Patients may ask about the best time to take the tablet — morning or evening dosing are both acceptable; chronotherapy (evening dosing) may be considered in patients with non-dipping nocturnal hypertension based on ambulatory BP monitoring, though this is not universally recommended.

Chronic Stable Angina

• Reduces myocardial oxygen demand by decreasing systemic vascular resistance and afterload, and increases myocardial oxygen supply by dilating coronary arteries.
• Can be combined with beta-blockers and/or long-acting nitrates for synergistic anti-anginal effect. When combined with beta-blockers, the reflex tachycardia risk (already minimal with amlodipine) is further mitigated.
• Particularly useful in patients who have both hypertension and angina, allowing a single agent to address both conditions.
• Avoid abrupt withdrawal in patients with angina — while not as risky as beta-blocker withdrawal, gradual dose reduction is prudent.
• Patients should be counselled that this drug reduces the frequency of angina episodes but is not a rescue medication — sublingual GTN should still be carried for acute episodes.
• In patients who develop dose-limiting peripheral oedema, consider switching to a non-dihydropyridine CCB (e.g., diltiazem) or adding an ACE inhibitor/ARB to reduce oedema while maintaining anti-anginal benefit.

Vasospastic (Prinzmetal’s) Angina

• Dihydropyridine CCBs are the cornerstone of treatment for vasospastic angina, as per standard Indian cardiology practice and international consensus.
• Acts by directly relaxing coronary vascular smooth muscle and preventing coronary vasospasm.
• Effective in reducing both frequency and severity of vasospastic episodes. Some patients may require combination with long-acting nitrates for refractory cases.
• Beta-blockers should generally be avoided in isolated vasospastic angina (can worsen spasm via unopposed alpha-adrenergic activity), making CCBs especially important in this condition.
• Duration of therapy is typically long-term; attempts at withdrawal should be gradual and under specialist supervision, as spasm may recur.

---

Secondary Indications — Adults Only (Off-label, if any)

Raynaud’s Phenomenon

• OFF-LABEL
• Dose: 2.5 mg once daily; may increase to 5 mg once daily based on response
• Duration: Long-term during symptomatic periods; may be used seasonally in milder cases
• Specialist only: Preferably initiated by a rheumatologist or physician experienced in managing vasospastic disorders
• Evidence basis: Racemic amlodipine and other dihydropyridine CCBs (particularly nifedipine) have evidence from multiple RCTs and meta-analyses for reducing the frequency and severity of Raynaud’s attacks. Indian rheumatology practice commonly uses amlodipine when nifedipine is poorly tolerated. S-amlodipine-specific trial data is limited, but pharmacological equivalence with the active enantiomer supports extrapolation.
• Clinical note: Nifedipine extended-release remains the first-choice CCB for Raynaud’s in most guidelines. S-amlodipine is an alternative when nifedipine causes excessive headache, flushing, or hypotension.

---

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Secondary Indications — Paediatric Doses (Off-label, if any)

---

RENAL ADJUSTMENT

• No dose adjustment required regardless of degree of renal impairment (CKD stages 1–5)
• S-Amlodipine is highly protein-bound and primarily hepatically metabolised; renal clearance of unchanged drug is negligible
• Not significantly removed by haemodialysis or peritoneal dialysis; supplemental dosing after dialysis is not required
• Blood pressure monitoring around dialysis sessions is advisable due to haemodynamic fluctuations inherent to dialysis, not specific to this drug
• Safe to use in patients with diabetic nephropathy and hypertensive nephrosclerosis; may offer renal-protective benefit when combined with ACE inhibitors or ARBs (based on ACCOMPLISH trial data for racemic amlodipine)
• Patients and doctors should note: unlike ACE inhibitors/ARBs, S-amlodipine does not cause hyperkalaemia and does not require potassium monitoring, making it a preferred add-on antihypertensive in CKD patients at risk of hyperkalaemia

---

HEPATIC ADJUSTMENT

---

CONTRAINDICATIONS

• Known hypersensitivity to S-amlodipine, racemic amlodipine, or any other dihydropyridine CCB (e.g., nifedipine, felodipine, cilnidipine)
• Severe hypotension (systolic BP <90 mmHg)
• Cardiogenic shock
• Haemodynamically significant aortic stenosis (severe aortic stenosis with symptoms or significant gradient — vasodilation can critically reduce coronary perfusion pressure)
• Unstable angina (as sole agent without beta-blocker coverage — not an absolute contraindication to CCB use in combination, but monotherapy with a dihydropyridine in unstable angina is contraindicated)

---

CAUTIONS

• Mild to moderate aortic stenosis — monitor closely for symptomatic hypotension; reassess haemodynamic status before dose escalation
• Heart failure with reduced ejection fraction (HFrEF) — amlodipine is one of the few CCBs demonstrated not to worsen outcomes in heart failure (PRAISE trial), but cautious initiation and monitoring remain warranted; not a first-line heart failure agent
• Decompensated heart failure — avoid initiation during acute decompensation; may be started or continued once patient is stabilised
• Hepatic impairment — reduced clearance, prolonged half-life, risk of drug accumulation (see Hepatic Adjustment section)
• Elderly patients — increased susceptibility to hypotension, orthostatic drops, falls, and peripheral oedema
• Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin) or strong CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine) — may significantly alter drug levels
• Hypertrophic obstructive cardiomyopathy (HOCM) — vasodilators can worsen outflow tract obstruction
• Patients with severe obstructive coronary artery disease — rare reports of worsening angina or acute MI on initiation or dose increase, possibly due to coronary steal or excessive BP reduction; start at lowest dose and titrate cautiously

---

PREGNANCY

---

LACTATION

---

ELDERLY

• Recommended starting dose: 2.5 mg once daily
• Need for slower titration: Yes; reassess blood pressure after 2–4 weeks (rather than the usual 1–2 weeks) before considering dose escalation. Many elderly patients achieve adequate BP control on 2.5 mg and do not require 5 mg.
• Extra risks:
• • Orthostatic hypotension — always measure sitting and standing blood pressure at each visit in elderly patients on S-amlodipine
  • Increased fall risk — particularly in those on multiple antihypertensives, sedatives, or diuretics; falls in the elderly carry risk of hip fractures and intracranial haemorrhage
  • Peripheral oedema — more common and more troublesome in elderly; may be mistaken for heart failure; evaluate with echocardiography if new oedema develops
  • Dizziness and lightheadedness — counsel about rising slowly from sitting/lying positions
  • Drug accumulation — elderly patients often have subclinical hepatic impairment even without overt liver disease; effective half-life may be prolonged
• Clinical note: S-amlodipine at 2.5 mg is particularly well-suited for elderly patients as it provides the therapeutic benefit of the active enantiomer at a lower total drug load. In the very elderly (>80 years), a target systolic BP of <150 mmHg (rather than <140 mmHg) is often appropriate as per Indian and international geriatric hypertension guidance (API Textbook, HYVET trial data). Over-aggressive BP lowering in the elderly increases risk of falls, syncope, and ischaemic events.

---

MAJOR DRUG INTERACTIONS

---

MODERATE DRUG INTERACTIONS

---

COMMON ADVERSE EFFECTS

• Peripheral oedema — dose-related; more common at 5 mg than 2.5 mg; results from precapillary arteriolar dilatation without venous dilatation, leading to increased capillary hydrostatic pressure; not a sign of heart failure; does not respond well to diuretics. Some Indian comparative studies suggest lower incidence with S-amlodipine compared to racemic amlodipine at equipotent doses.
• Headache — usually transient; more common in the first 1–2 weeks of therapy; generally resolves with continued use
• Dizziness — dose-related; may indicate excessive BP reduction; check standing BP
• Flushing — due to arteriolar vasodilation; more common in fair-skinned individuals; usually subsides with continued therapy
• Fatigue
• Palpitations — usually sinus tachycardia; generally mild and self-limiting
• Nausea
• Somnolence
• Abdominal discomfort

---

SERIOUS ADVERSE EFFECTS

• Angioedema (rare) — swelling of face, lips, tongue, or throat; discontinue immediately, do not re-challenge with any dihydropyridine CCB; manage as per angioedema protocol (adrenaline if airway compromise, antihistamines, corticosteroids)
• Severe hypotension (rare) — more likely in volume-depleted patients, those on multiple antihypertensives, or those with severe aortic stenosis; may require IV normal saline and vasopressor support in ICU setting
• Hepatitis or significant transaminase elevation (rare) — discontinue and evaluate; may present as jaundice, nausea, right upper quadrant pain; check LFTs; refer to hepatologist if persistent
• Worsening angina or acute myocardial infarction (very rare) — reported on initiation or dose escalation in patients with severe obstructive coronary artery disease; mechanism may involve coronary steal or excessive BP lowering; requires immediate cardiology evaluation
• Erythema multiforme (very rare) — discontinue and provide supportive care
• Gingival hyperplasia (uncommon but clinically relevant) — more commonly reported with long-term use; advise good oral hygiene; may require dental evaluation and drug substitution if severe

---

MONITORING REQUIREMENTS

---

BRANDS AVAILABLE IN INDIA

• Asomex (Emcure) — 2.5 mg, 5 mg
• Espin (Micro Labs) — 2.5 mg, 5 mg
• S-Numlo (Glenmark) — 2.5 mg, 5 mg
• Safepres (J B Chemicals) — 2.5 mg, 5 mg
• Stamlo-S (Dr. Reddy’s) — 2.5 mg

• S-Amlodipine + Telmisartan (e.g., Asomex-TM, Telsartan-S)
• S-Amlodipine + Atenolol (e.g., Asomex-AT)
• S-Amlodipine + Hydrochlorothiazide
• S-Amlodipine + Chlorthalidone
• S-Amlodipine + Metoprolol succinate

---

PRICE RANGE (INR)

• 2.5 mg tablet: Approximately ₹2–₹8 per tablet (depending on brand)
• 5 mg tablet: Approximately ₹4–₹12 per tablet (depending on brand)
• S-Amlodipine as a specific chirally pure enantiomer is NOT separately listed on NLEM 2022; racemic amlodipine besylate (2.5 mg, 5 mg, 10 mg tablets) is included on NLEM 2022 and is under NPPA price control
• S-Amlodipine tablets are generally priced marginally higher than generic racemic amlodipine but lower than some branded racemic amlodipine formulations
• Government supply: Racemic amlodipine is widely available through Jan Aushadhi and government hospital supply; S-amlodipine may not be uniformly available in government supply channels

---

CLINICAL PEARLS

• Dose equivalence: 2.5 mg S-amlodipine ≈ 5 mg racemic amlodipine; 5 mg S-amlodipine ≈ 10 mg racemic amlodipine. When switching patients, use this equivalence. The R-enantiomer in racemic amlodipine is pharmacologically inert for blood pressure lowering but may contribute to adverse effects (some Indian studies report lower peripheral oedema incidence with S-amlodipine, though large definitive RCTs are lacking).
• Managing peripheral oedema: This is the most common reason for patient dissatisfaction and non-adherence. The oedema is due to precapillary vasodilation (not fluid overload), so thiazide diuretics are largely ineffective. Combining with an ACE inhibitor or ARB produces postcapillary venodilation that counterbalances the effect and reduces oedema. Leg elevation and compression stockings provide symptomatic relief. If oedema persists despite these measures, switch to cilnidipine or a non-dihydropyridine CCB.
• Timing of action: Allow a minimum of 7–14 days for full antihypertensive effect. One of the most common prescribing errors is escalating the dose too soon. In the elderly, wait 3–4 weeks.
• Heart failure safety: Among all CCBs, amlodipine (and by extension S-amlodipine) is one of the few that has been shown not to increase mortality in heart failure (PRAISE trial). It is NOT a heart failure treatment, but can be safely added for co-existing hypertension or angina in compensated HF patients. Diltiazem and verapamil are contraindicated in HFrEF.
• Statin interaction alert: The simvastatin dose cap at 20 mg when co-prescribed with amlodipine is frequently overlooked. Given that many Indian hypertensive patients also require statins, use atorvastatin or rosuvastatin instead to avoid this interaction entirely.
• Patient counselling point: Patients frequently worry about lifelong medication. Explain that hypertension is a chronic condition and that S-amlodipine is well-tolerated for long-term use. Unlike some antihypertensives, it does not cause metabolic disturbances (no worsening of glucose tolerance, no dyslipidaemia, no hypokalaemia), making it suitable for diabetic and metabolic syndrome patients.

---

VERSION

---

REFERENCES

• CDSCO (approved product information for S-Amlodipine tablets)
• Indian Pharmacopoeia
• NLEM 2022 (racemic amlodipine listing)
• AIIMS Treatment Guidelines
• API Textbook of Medicine
• Goodman & Gilman’s The Pharmacological Basis of Therapeutics (amlodipine pharmacology, enantiomer pharmacokinetics)
• Harrison’s Principles of Internal Medicine (hypertension and angina management)
• Indian comparative studies on S-amlodipine vs racemic amlodipine (for adverse effect profile data; referenced as supportive Indian clinical evidence)