Everything about Amlodipine 5mg tablet
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Amlodipine 5 mg Tablet - Complete Drug Profile
Drug Classification
Amlodipine is a long-acting dihydropyridine calcium channel blocker (CCB) - the most peripherally selective class of CCBs. It is marketed under the brand name Norvasc (and Katerzia as an oral suspension). The 5 mg tablet is the most common starting/maintenance dose in adults.
Mechanism of Action
Amlodipine inhibits the transmembrane influx of extracellular calcium ions through L-type voltage-gated calcium channels in:
- Vascular smooth muscle cells - producing arterial vasodilation
- Myocardial cells - with minimal direct cardiac effect (unlike verapamil or diltiazem)
This selective peripheral vasodilation reduces systemic vascular resistance, lowers blood pressure, and reduces myocardial oxygen demand. In vasospastic angina, it directly dilates coronary arteries and relieves spasm.
Unlike verapamil (most cardiac depressant) and diltiazem (intermediate), amlodipine acts primarily as a vasodilator with minimal negative inotropic or chronotropic effects. Reflex sympathetic activation may cause slight tachycardia, but cardiac output is generally maintained or increased. - Katzung's Basic and Clinical Pharmacology, 16th Ed.
Indications (FDA-Approved)
| Indication | Adults | Pediatric |
|---|---|---|
| Hypertension | Yes | Yes (age ≥6 years) |
| Chronic stable angina | Yes | No |
| Vasospastic angina (Prinzmetal's) | Yes | No |
| Angiographically documented CAD (without HF or EF <40%) | Yes | No |
Dosing
Hypertension
| Population | Starting Dose | Titration | Maximum |
|---|---|---|---|
| Adults | 2.5–5 mg once daily | Increase by 2.5 mg every 7–14 days | 10 mg/day |
| Elderly / hepatic impairment | 2.5 mg once daily | Titrate slowly | 10 mg/day |
| Children (6–17 yrs) | 2.5–5 mg once daily | - | 5 mg/day |
Angina / CAD
- Adults: 2.5–10 mg once daily; maintenance typically 10 mg/day
Key note: Steady-state plasma levels are reached after 7–8 days of consecutive dosing. The 5 mg tablet can be given with or without food, at any time of day (consistent timing preferred).
Pharmacokinetics
| Parameter | Value |
|---|---|
| Bioavailability | 64–90% |
| Peak plasma time | 6–12 hours |
| Onset (antihypertensive) | 24–96 hours |
| Duration of effect | 24 hours (once daily dosing) |
| Protein binding | 93–98% |
| Volume of distribution | 21 L/kg |
| Metabolism | Extensive hepatic - CYP3A4; inactive pyridine metabolite |
| Half-life (normal) | 30–50 hours |
| Half-life (hepatic impairment) | Up to 56 hours |
| Elimination | Urine (~60% as metabolites) |
The prolonged half-life makes amlodipine ideal for once-daily dosing and produces a smooth, gradual onset - avoiding the acute hypotension associated with short-acting dihydropyridines like immediate-release nifedipine. - Medscape Drug Reference
Adverse Effects
Common (>1%)
| Effect | Frequency |
|---|---|
| Peripheral edema (ankles, feet) | 1.8–10.8% - most common |
| Headache | 7.3% |
| Fatigue / asthenia | 4.5% |
| Palpitations | 0.7–4.5% |
| Flushing | 0.7–2.6% |
| Dizziness | 1.1–3.4% |
| Nausea | 2.9% |
| Abdominal pain | 1.6% |
| Somnolence | 1.4% |
| Skin rash, pruritus | 1–2% |
| Muscle cramps | 1–2% |
| Male sexual dysfunction | 1–2% |
Less Common (<1%)
- Cardiovascular: arrhythmias (VT, AF), bradycardia, syncope, vasculitis
- GI: constipation, gingival hyperplasia, pancreatitis (rare)
- Neurological: peripheral neuropathy, tremor, vertigo
- Skin: angioedema, erythema multiforme
- Metabolic: hyperglycemia
- Hematologic: leukopenia, thrombocytopenia
Postmarketing
- Extrapyramidal disorder
- Jaundice / hepatic enzyme elevation (cholestasis or hepatitis)
- Gynecomastia
Drug Interactions
CYP3A4 Inhibitors (increase amlodipine levels)
Strong inhibitors - clarithromycin, itraconazole, ketoconazole, ritonavir - can significantly raise amlodipine plasma concentrations. Monitor for enhanced hypotension and edema.
CYP3A4 Inducers (decrease amlodipine levels)
Rifampicin, carbamazepine, phenytoin, St. John's Wort - may reduce efficacy.
Simvastatin
Amlodipine raises simvastatin exposure by ~77% via CYP3A4 inhibition. Simvastatin dose should not exceed 20 mg/day in amlodipine-treated patients. Rosuvastatin (not CYP3A4-metabolized) is preferred if high-dose statin therapy is needed. - Goldman-Cecil Medicine
Cyclosporine / Tacrolimus
Amlodipine may increase blood levels of these immunosuppressants - monitor levels.
Other antihypertensives
Additive blood pressure lowering - particularly with ACE inhibitors, ARBs, beta-blockers, diuretics. Often intentional and beneficial in combination therapy.
Sildenafil / PDE5 inhibitors
Additive hypotensive effect; use with caution and at lowest PDE5 inhibitor dose.
Contraindications
- Known hypersensitivity to amlodipine or any dihydropyridine
Cautions / Special Populations
| Situation | Guidance |
|---|---|
| Severe aortic stenosis | Risk of symptomatic hypotension; use with caution |
| Severe obstructive CAD | Worsening angina or MI possible when dose initiated/increased |
| Severe hepatic impairment | Start at 2.5 mg/day; titrate slowly (extended t½ ~56 hrs) |
| Renal impairment | No dose adjustment needed (hepatic metabolism) |
| Elderly (≥65 years) | Start at 2.5 mg/day due to increased sensitivity |
| Heart failure | Not recommended for HF with EF <40%; may worsen outcomes. Peripheral edema can complicate fluid management |
| Pregnancy (Cat C) | Avoid unless benefit outweighs risk; limited human data |
| Breastfeeding | Excreted in breast milk; generally avoided |
| Pediatric (<6 years) | Not established |
Comparison: Amlodipine vs Other CCBs
| Feature | Amlodipine | Diltiazem | Verapamil |
|---|---|---|---|
| Class | Dihydropyridine | Benzothiazepine | Phenylalkylamine |
| Selectivity | Peripheral (vascular) | Intermediate | Cardiac |
| Negative inotropy | Minimal | Moderate | Significant |
| Heart rate effect | Slight reflex increase | Decrease | Decrease |
| Use in HFrEF | Avoid | Avoid | Avoid |
| Use after MI | Avoid (no mortality benefit) | Avoid | Avoid |
| Dosing frequency | Once daily | TID/BID (SR: daily) | TID/BID (SR: daily) |
| Half-life | 30–50 hrs | 3–9 hrs | 6–12 hrs |
- Lippincott Pharmacology (2024): Amlodipine is the most peripherally active CCB, followed by diltiazem (intermediate), then verapamil (most cardiac).
Clinical Notes
When to prefer amlodipine:
- Hypertension in elderly (once-daily, no CNS side effects)
- Angina + hypertension (dual benefit)
- Hypertension in patients intolerant to ACE inhibitors/ARBs
- Raynaud's phenomenon (vasodilatory effect)
- Isolated systolic hypertension
- Add-on therapy for angina when beta-blockers are maximized but heart rate is already low (amlodipine does not lower heart rate further, unlike diltiazem/verapamil)
When NOT to use:
- Acute decompensated heart failure (can worsen pulmonary edema)
- HFrEF (EF <40%) - no benefit, possible harm
- Unstable angina as monotherapy
- After MI - no mortality benefit, beta-blockers are preferred
ALLHAT Trial significance: Amlodipine demonstrated equivalent cardiovascular outcomes to lisinopril and chlorthalidone for hypertension in high-risk patients, establishing CCBs as first-line antihypertensive agents.
Recent Evidence
A 2025 network meta-analysis (PMID: 39995131) on dihydropyridine CCBs for primary hypertension confirmed the efficacy and safety of long-acting agents including amlodipine, supporting its continued first-line status. No major safety signals challenging current use have emerged.
Practical Tips for Patients
- Take at the same time each day; can be taken with or without food
- Do NOT crush if extended-release formulation (plain amlodipine tablets can be crushed)
- Ankle swelling is the most common side effect - elevating legs helps; does not indicate cardiac problems
- Do not stop suddenly (though no rebound hypertension as with some other agents)
- Avoid grapefruit juice in large quantities (weak CYP3A4 inhibitor, may modestly increase levels)
- Blood pressure response may take 1–2 weeks to fully manifest
- Report chest pain that worsens after starting or increasing dose
Sources: Katzung's Basic and Clinical Pharmacology 16th Ed. | Goldman-Cecil Medicine | Lippincott Illustrated Reviews: Pharmacology | Braunwald's Heart Disease | Medscape Drug Reference (amlodipine) | Medical News Today (updated July 2024)
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