Amlodipine

Generic Name

Amlodipine

Brand Names

Norvasc

Istin

Various generics available globally

Drug Class

Dihydropyridine calcium channel blocker (CCB)

Antihypertensive agent

Antianginal agent

Mechanism of Action

Amlodipine inhibits the influx of calcium ions through L-type calcium channels in vascular smooth muscle and myocardium during depolarization

This action leads to vasodilation of peripheral arteries and coronary arteries

By reducing peripheral vascular resistance, it lowers systemic blood pressure

In the coronary circulation, amlodipine increases myocardial oxygen delivery in patients with vasospastic angina and prevents coronary artery spasm

Unlike non-dihydropyridine CCBs (e.g. verapamil), amlodipine has minimal effects on cardiac conduction and contractility

Therapeutic Indications

Hypertension

First-line or adjunctive treatment to lower blood pressure in adults and children (age ≥6)

Reduces the risk of fatal and non-fatal cardiovascular events such as stroke and myocardial infarction

Chronic Stable Angina

Prevents angina episodes by reducing myocardial oxygen demand via afterload reduction and increasing oxygen supply by coronary vasodilation

Vasospastic Angina (Prinzmetal's)

Relieves and prevents coronary spasm, improving oxygen delivery to myocardium

Off-label and Additional Uses

Raynaud’s phenomenon

Prevention of high-altitude pulmonary edema

Hypertension in pregnancy (after specialist consultation)

Pulmonary hypertension (selected cases)

Hypertension in chronic kidney disease

Migraine prophylaxis (limited data)

Hypertrophic cardiomyopathy with outflow tract obstruction (in select cases)

Dosage and Administration

Adults

Initial dose: 5 mg orally once daily

Elderly, hepatic impairment, or frail patients: consider starting at 2.5 mg once daily

Maximum dose: 10 mg once daily

Children (age ≥6 years)

Initial dose: 2.5 mg once daily

Maximum: 5 mg once daily

Titration

Titrate upward after 7–14 days based on blood pressure response and tolerability

Administration Notes

May be taken with or without food

Administer at the same time each day

Extended half-life allows for once-daily dosing

Pharmacokinetics

Absorption: Slow, peak plasma concentration in 6–12 hours

Bioavailability: ~60–65%

Protein binding: ~97.5%

Half-life: 30–50 hours (enables once-daily dosing)

Metabolism: Hepatic via CYP3A4 to inactive metabolites

Elimination: Primarily via urine (60%), feces (20%)

Contraindications

Known hypersensitivity to amlodipine or any component

Severe hypotension (systolic <90 mmHg)

Cardiogenic shock

Unstable angina (excluding vasospastic)

Severe aortic stenosis (relative – may worsen symptoms)

Heart failure with reduced ejection fraction (HFrEF) – use caution though amlodipine is considered safer than other CCBs

Precautions and Warnings

Use with caution in patients with hepatic impairment due to decreased clearance

Avoid abrupt withdrawal in patients with angina – taper may be preferred

May cause symptomatic hypotension especially in volume-depleted or elderly patients

Use with caution in patients with severe heart failure or impaired left ventricular function

Adverse Effects

Common (≥1%)

Peripheral edema (dose-related, due to precapillary vasodilation)

Headache

Flushing

Dizziness

Palpitations

Fatigue

Nausea

Abdominal pain

Less Common (<1%)

Hypotension

Somnolence

Myalgia

Constipation

Dry mouth

Rash

Visual disturbances

Rare/Serious

Angioedema

Hepatic enzyme elevations

Jaundice/hepatitis

Gingival hyperplasia

Arrhythmias (especially in patients with severe heart disease)

Stevens-Johnson syndrome (extremely rare)

Pregnancy and Lactation

Pregnancy

Category C (based on older FDA system)

Animal studies showed delayed delivery and fetal mortality at high doses

Human data limited but no confirmed teratogenic risk

Used with caution when benefits outweigh risks

Lactation

Excreted in small amounts in breast milk

Considered compatible with breastfeeding by some guidelines

Monitor infant for hypotension, poor feeding

Use in Special Populations

Elderly

Increased sensitivity due to decreased metabolism

Start at lower doses to avoid hypotension

Hepatic Impairment

Clearance is reduced

Start with lower dose (2.5 mg) and titrate slowly

Renal Impairment

No dose adjustment required

Not dialyzable – long half-life protects against fluctuations

Drug Interactions

CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, grapefruit juice)

May increase plasma levels of amlodipine

Monitor for hypotension and side effects

CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin)

May reduce amlodipine plasma levels and effectiveness

Simvastatin

Limit simvastatin dose to 20 mg when co-administered

Increased risk of statin-associated myopathy due to CYP3A4 competition

Beta-blockers

Additive hypotensive effect

May be beneficial in angina or hypertension

Monitor for bradycardia in non-dihydropyridine combinations

Other Antihypertensives

Synergistic BP-lowering effects

Monitor for hypotension when combined with ACE inhibitors, ARBs, or diuretics

Sildenafil and PDE5 inhibitors

Risk of excessive hypotension

Caution especially in elderly

NSAIDs

May blunt antihypertensive effect

Monitor BP in patients on chronic NSAIDs

Monitoring Parameters

Blood pressure and heart rate at baseline and periodically

Monitor for peripheral edema

Liver function tests if hepatotoxicity suspected

Electrolytes in patients with multiple antihypertensives

Signs of dizziness or postural hypotension in elderly

Advantages

Once-daily dosing improves adherence

Long half-life provides stable 24-hour BP control

No need for dose adjustment in renal dysfunction

Well tolerated in elderly and diabetic patients

Does not affect serum lipids or glucose metabolism

Disadvantages

Peripheral edema is a common reason for discontinuation

Slow onset of action compared to some other antihypertensives

No proven benefit in reducing proteinuria (unlike ACE inhibitors or ARBs)

May not be sufficient as monotherapy in severe hypertension

Formulations

Tablets: 2.5 mg, 5 mg, 10 mg

Available in fixed-dose combinations with:

Perindopril (Coveram)

Valsartan (Exforge)

Olmesartan (Sevikar)

Atorvastatin (Caduet)

Telmisartan (Twynsta)

Storage

Store at room temperature

Protect from moisture and light

Keep in original container

Patient Counseling Points

Take at the same time each day

May be taken with or without food

Do not stop suddenly without consulting your doctor

Report swelling of legs, dizziness, or chest pain

Avoid grapefruit juice unless approved by provider

Monitor blood pressure at home regularly

Inform dentist or surgeon if taking amlodipine