Schedule H

Oral

• Tablets: 2.5 mg, 5 mg, 10 mg

Fixed-Dose Combinations (FDCs) Available:

• Amlodipine + Atenolol

• Amlodipine + Metoprolol

• Amlodipine + Losartan

• Amlodipine + Telmisartan

• Amlodipine + Olmesartan

• Amlodipine + Ramipril

• Amlodipine + Lisinopril

• Amlodipine + Atorvastatin

• Amlodipine + Hydrochlorothiazide

• Amlodipine + Cilnidipine (dual CCB)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertension

Parameter Dose

Starting dose 5 mg orally once daily

Titration Increase to 10 mg after 1–2 weeks if BP target not achieved

Usual maintenance dose 5–10 mg once daily

Maximum dose 10 mg once daily

Clinical Notes:

• First-line antihypertensive option per ICMR Hypertension Guidelines 2020

• Can be taken at any time of day (morning or evening); once-daily dosing due to long half-life (~35–50 hours)

• Start at 2.5 mg in elderly, low body weight patients, or those with hepatic impairment

• Effective as monotherapy or in combination with ACE inhibitors, ARBs, thiazides, or beta-blockers

• Particularly useful in patients with concurrent diabetes, CKD (no dose adjustment needed), or isolated systolic hypertension in elderly

1. Chronic Stable Angina Pectoris

Parameter Dose

Starting dose 5 mg orally once daily

Titration Increase to 10 mg after 7–14 days based on anginal frequency and BP response

Usual maintenance dose 5–10 mg once daily

Maximum dose 10 mg once daily

Clinical Notes:

• Reduces myocardial oxygen demand by decreasing afterload (peripheral vasodilation)

• Can be used as monotherapy or added to beta-blockers/nitrates

• Do not discontinue abruptly — may precipitate rebound angina

• Preferred CCB in angina patients with LV dysfunction (compared to non-dihydropyridines)

1. Vasospastic (Prinzmetal's/Variant) Angina

Parameter Dose

Starting dose 5 mg orally once daily

Titration Increase to 10 mg after 7–14 days if spasm frequency not controlled

Usual maintenance dose 5–10 mg once daily

Maximum dose 10 mg once daily

Clinical Notes:

• Calcium channel blockers are first-line treatment for vasospastic angina

• Long-acting dihydropyridines (amlodipine, nifedipine ER) preferred over short-acting agents

• May be combined with nitrates for refractory cases

• Avoid beta-blockers as monotherapy in vasospastic angina (may worsen spasm)

Secondary Indications – Adults (Off-label)

Indication Dose Duration Supervision Evidence Basis

Raynaud's Phenomenon (OFF-LABEL) Starting: 2.5–5 mg once daily; Maintenance: 5–10 mg once daily Long-term; seasonal use in some patients Specialist recommended (Rheumatology) Case series; international guidelines; Indian specialist practice

Hypertension in Pregnancy (2nd–3rd Trimester) (OFF-LABEL) Starting: 2.5 mg once daily; Maintenance: 2.5–5 mg once or twice daily; Maximum: 10 mg/day During pregnancy as needed Specialist only (Obstetrics) Increasing Indian obstetric practice; limited RCT data; not first-line

Chronic Kidney Disease with Hypertension (as add-on to ACEI/ARB) (OFF-LABEL as specific indication) 5–10 mg once daily Long-term Not required ACCOMPLISH trial; ICMR guidelines support CCB + ACEI/ARB combination; protects renal function

PAEDIATRIC DOSING (Specialist Only)

⚠️ Limited data in children below 6 years of age. Use only under paediatric cardiology or nephrology supervision in younger children.

Primary Indication: Hypertension in Children

Weight-Based Dosing (Children ≥6 years):

Weight / Age Starting Dose Titration Maximum Dose

6–17 years, <20 kg 0.05–0.1 mg/kg once daily Increase based on BP response after 2–4 weeks 0.3 mg/kg/day (maximum 5 mg/day)

6–17 years, ≥20 kg 2.5 mg once daily Increase to 5 mg after 2–4 weeks if needed 5 mg/day (up to 10 mg/day in adolescents under specialist guidance)

Parameter Dose

Starting dose 0.05–0.1 mg/kg/day OR 2.5 mg once daily (whichever appropriate)

Titration Increase after 2–4 weeks based on BP response

Usual maintenance dose 2.5–5 mg once daily

Maximum dose 5 mg/day (10 mg/day in adolescents ≥30 kg under specialist care)

Safety Monitoring:

• Blood pressure (seated and standing if age-appropriate)

• Heart rate

• Peripheral oedema

• Growth parameters

Clinical Notes:

• Once-daily dosing improves adherence in children

• Tablets may need to be compounded for accurate low-dose administration in small children

• Monitor for reflex tachycardia and peripheral oedema

Secondary Indications – Paediatrics (Off-label)

Indication Age Dose Duration Supervision Evidence Basis

Post-operative Hypertension (Cardiac Surgery) (OFF-LABEL) ≥1 year 0.05–0.1 mg/kg once daily; Maximum 0.3 mg/kg/day or 5 mg Short-term Specialist only (Paediatric Cardiology/PICU) Case series; paediatric cardiac surgery protocols

Hypertensive Crisis (Oral Step-down) (OFF-LABEL) ≥6 years 0.1–0.2 mg/kg once daily After IV stabilisation Specialist only (PICU/Nephrology) Hospital protocols; IAP guidance

Age Restrictions:

• Not recommended below 6 years of age except under specialist supervision

• Use in infants (below 1 year) only in exceptional circumstances with paediatric cardiology input

Note: Amlodipine is extensively hepatically metabolised; elimination half-life increases to ~60 hours in hepatic impairment.

• Known hypersensitivity to amlodipine or other dihydropyridine CCBs

• Severe hypotension (SBP <90 mmHg)

• Cardiogenic shock

• Haemodynamically significant aortic stenosis (risk of worsening coronary perfusion)

• Unstable angina (as monotherapy without beta-blocker)

• Acute myocardial infarction with haemodynamic instability or pulmonary oedema

• Heart failure (NYHA Class III–IV) — may use with caution in stable compensated HF; avoid in decompensated HF

• Severe left ventricular dysfunction (LVEF <40%) — initiate at low dose with close monitoring

• Elderly patients — increased sensitivity to hypotensive effects; start low

• Low body weight patients — consider starting at 2.5 mg

• Hepatic impairment — reduced clearance; start low

• Concurrent use with strong CYP3A4 inhibitors — may increase amlodipine levels

• Aortic stenosis (non-severe) — use with caution

• Hypertrophic cardiomyopathy with outflow obstruction

• Sick sinus syndrome (without pacemaker) — use with caution

• Patients prone to peripheral oedema

Parameter Information

Overall Safety Limited human data; not officially approved for pregnancy; classified as Category C equivalent

Risk Theoretical risk of reduced uterine blood flow with hypotension; no confirmed teratogenicity

Preferred Alternatives Labetalol (first-line for chronic hypertension in pregnancy); Nifedipine ER (most commonly used CCB in pregnancy); Methyldopa

When Use May Be Justified Second/third trimester when labetalol or nifedipine not tolerated; postpartum hypertension; obstetric specialist supervision required

Monitoring Maternal blood pressure; fetal growth (if prolonged use); signs of maternal hypotension

Parameter Information

Compatibility Likely compatible; limited human data but expected low infant exposure based on pharmacokinetic properties

Expected Drug Level in Milk Low (highly protein-bound; large volume of distribution)

Preferred Alternatives Nifedipine ER (more breastfeeding safety data); Labetalol; Methyldopa

Infant Monitoring Drowsiness, feeding difficulties, hypotension (theoretical; rarely observed)

Recommendation May continue if already established on amlodipine with good BP control and no infant effects observed

Parameter Recommendation

Starting dose 2.5 mg orally once daily

Titration Increase gradually (every 2–4 weeks) based on BP response and tolerability

Maximum recommended 10 mg once daily

Increased Risks Postural hypotension, falls, peripheral oedema (often prominent), cognitive fluctuations in frail individuals

Additional Precautions Monitor standing BP in first few weeks; assess for oedema at each visit; consider bedtime dosing if postural symptoms occur; excellent choice for isolated systolic hypertension common in elderly

Interacting Drug Mechanism Effect Management

Strong CYP3A4 Inhibitors (ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir) Inhibit amlodipine metabolism Significantly increased amlodipine levels; enhanced hypotensive effect Monitor BP closely; consider dose reduction to 2.5–5 mg; avoid if possible or use alternatives

Simvastatin (>20 mg/day) CYP3A4 inhibition by amlodipine increases simvastatin exposure Increased risk of simvastatin-induced myopathy and rhabdomyolysis Limit simvastatin to ≤20 mg/day when combined with amlodipine; consider alternative statin (atorvastatin, rosuvastatin)

Cyclosporine Reduced CYP3A4 metabolism Increased cyclosporine levels and nephrotoxicity risk Monitor cyclosporine levels; may need dose adjustment

Tacrolimus Reduced CYP3A4 metabolism Increased tacrolimus levels Monitor tacrolimus levels when initiating or adjusting amlodipine

Dantrolene (IV) Unknown mechanism Risk of cardiovascular collapse reported with CCBs Avoid IV dantrolene with amlodipine if possible

Interacting Drug Effect Management

Strong CYP3A4 Inducers (rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) Reduced amlodipine levels and efficacy Monitor BP; may need to increase amlodipine dose or use alternative antihypertensive

Beta-blockers Additive effects on heart rate and BP Commonly used combination; monitor for excessive bradycardia or hypotension

Other Antihypertensives (ACE inhibitors, ARBs, diuretics) Additive hypotensive effect Often intentional combination; monitor BP; adjust doses as needed

Sildenafil, Tadalafil (PDE5 inhibitors) Additive hypotensive effect Use with caution; counsel patient on potential hypotension; avoid if SBP <90 mmHg

Lithium Potential for lithium toxicity (mechanism unclear; possibly volume-related) Monitor lithium levels if used concurrently

Grapefruit Juice CYP3A4 inhibition in gut wall May increase amlodipine levels modestly; advise moderation

NSAIDs May reduce antihypertensive efficacy; fluid retention Monitor BP; use lowest NSAID dose for shortest duration

Digoxin No significant pharmacokinetic interaction No adjustment needed; safe combination

• Peripheral oedema (dose-related; most common; up to 10% at 10 mg)

• Headache

• Flushing

• Dizziness

• Fatigue, asthenia

• Palpitations

• Nausea

• Abdominal pain

• Somnolence/drowsiness

Note: Peripheral oedema is caused by precapillary arteriolar vasodilation (not fluid retention); it is dose-related and often improves with addition of ACE inhibitor/ARB or by lowering the dose.

Adverse Effect Clinical Action

Severe Hypotension Reduce dose or discontinue; supportive care with IV fluids; patient should lie down with legs elevated

Worsening Heart Failure (in predisposed patients) Discontinue; cardiology evaluation; diuretics and standard HF management

Angioedema (rare) Discontinue permanently; emergency management if airway compromise

Hepatotoxicity (rare; usually cholestatic pattern) Monitor LFTs if symptoms (jaundice, pruritus, fatigue); discontinue if significant elevation

Severe Bradycardia (rare; usually with concurrent beta-blocker or non-DHP CCB) Reduce dose or discontinue offending agent; assess for conduction disease

Gingival Hyperplasia (rare; with prolonged use) Maintain oral hygiene; may require drug discontinuation if severe

Erythema Multiforme / Exfoliative Dermatitis (very rare) Discontinue immediately; dermatology consultation

Long-term (every 3–6 months) Blood pressure; heart rate; peripheral oedema; LFTs if symptoms of hepatic dysfunction; adherence assessment

Special Situations Monitor more frequently in elderly, hepatic impairment, or when initiating/stopping interacting drugs

Monotherapy:

• Amlong™ (Micro Labs) — 2.5 mg, 5 mg, 10 mg

• Amlodac™ (Zydus) — 2.5 mg, 5 mg, 10 mg

• Stamlo™ (Dr. Reddy's) — 2.5 mg, 5 mg, 10 mg

• Amlopin™ (USV) — 2.5 mg, 5 mg, 10 mg

• Amlokind™ (Mankind) — 5 mg, 10 mg

• Amlopres™ (Cipla) — 2.5 mg, 5 mg, 10 mg

• Amlod™ (Lupin) — 5 mg, 10 mg

Fixed-Dose Combinations (Examples):

• Amlong-A™ (Amlodipine + Atenolol)

• Stamlo-Beta™ (Amlodipine + Metoprolol)

• Amlopress-AT™ (Amlodipine + Atenolol)

• Amlodac-L™ (Amlodipine + Losartan)

• Telma-AM™ (Amlodipine + Telmisartan)

• Olmy-AM™ (Amlodipine + Olmesartan)

• Cardace-AM™ (Amlodipine + Ramipril)

• Amlostat™ (Amlodipine + Atorvastatin)

• Cilacar-A™ (Amlodipine + Cilnidipine)

2.5 mg tablet ₹0.50–₹2.00 per tablet —

Regulatory: Listed under NLEM 2022 (5 mg tablet); NPPA price controlled for scheduled strengths; widely available in government supply

1. First-line choice in many settings — Amlodipine is one of the most widely prescribed antihypertensives in India due to once-daily dosing, effectiveness, low cost, and safety across diverse populations including diabetics, elderly, and CKD patients

1. Peripheral oedema management — Oedema is dose-related and due to precapillary vasodilation (not fluid overload); it often improves with addition of ACE inhibitor/ARB (causes venodilation and reduces capillary hydrostatic pressure); diuretics are not effective for this indication

1. Long half-life advantage — Half-life of ~35–50 hours provides smooth 24-hour BP control and forgiving pharmacokinetics if a dose is missed; steady state achieved in 7–8 days

1. Simvastatin dose cap — Always limit simvastatin to ≤20 mg/day when combined with amlodipine; consider switching to atorvastatin or rosuvastatin (no dose restriction) if higher statin intensity needed

1. Do not abruptly discontinue in angina — Sudden withdrawal may precipitate rebound angina or ischaemia; taper gradually if discontinuation required

1. Hepatic impairment dosing — Start at 2.5 mg in patients with liver disease; half-life significantly prolonged; titrate slowly

hypertension; calcium-channel-blocker; CCB; dihydropyridine; angina; vasospastic-angina; renal-safe; NLEM-India; elderly-suitable; diabetic-hypertension; peripheral-oedema; Schedule-H

RxIndia v1.0 — 26 May 2025

• CDSCO Product Information

• Indian Pharmacopoeia (IP)

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine

• ICMR Guidelines for Management of Hypertension 2020

• AIIMS Drug Formulary and Treatment Protocols

• IAP Guidelines for Paediatric Hypertension

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• ACCOMPLISH Trial (CCB + ACEi combination evidence)

• Indian hospital protocols (AIIMS, CMC Vellore)