Amlodipine Besylate/Mesylate

 

1. Generic & Brand Names

• Generic: Amlodipine Besylate/Mesylate

• Brands: Norvasc® (global), Amlodac® (India), Amlogard® (EU)

• Combinations:

  • With ACEi: Lotrel® (amlodipine + benazepril)

  • With ARB: Twynsta® (amlodipine + telmisartan)

  • With Statin: Caduet® (amlodipine + atorvastatin)

---

2. Drug Class & Mechanism

• Class: Dihydropyridine Calcium Channel Blocker (DHP-CCB)

• Mechanism:

  • Blocks L-type calcium channels in vascular smooth muscle → ↓ calcium influx

  • Causes peripheral arterial vasodilation → lowers BP

  • Minimal effect on cardiac conduction (vs. non-DHP CCBs)

• Onset: 6-12 hours; Peak effect: 24-48 hours

• Half-life: 30-50 hours → once-daily dosing

---

3. FDA-Approved Uses

Condition	Key Benefit
Hypertension (HTN)	First-line monotherapy or combo
Chronic Stable Angina	↓ Frequency of attacks
Vasospastic Angina	↓ Coronary artery spasm

---

4. Dosing Regimens

Indication	Starting Dose	Maintenance Dose	Max Dose
HTN	5 mg daily	5-10 mg daily	10 mg*
Angina	5 mg daily	10 mg daily	10 mg

* Elderly/renally impaired: Start 2.5 mg daily
Key Notes:

• Take with/without food

• No dose adjustment for hepatic impairment (contrary to older guidelines)

• Full effect in 7-14 days (titrate slowly)

---

5. Side Effects

Common (>10%)	Serious (<1%)
Peripheral Edema (ankle swelling)	Severe Hypotension
Headache	Acute Myocardial Infarction (rare at initiation)
Flushing	Gingival Hyperplasia
Dizziness	Allergic Hepatitis
Palpitations	Eosinophilic Pneumonia

---

6. Black Box Warnings & Contraindications

• 🚫 Absolute Contraindications:

  • Severe hypotension (SBP <90 mmHg)

  • Hypersensitivity to DHPs

  • Cardiogenic shock

• High-Risk Groups:

  • Heart failure (HFrEF): May worsen outcomes (use ACEi/ARB/BB first)

  • Aortic stenosis: Use cautiously (risk of ↓ coronary perfusion)

  • Obstructive HCM: Avoid (↑ outflow gradient)

---

7. Critical Drug Interactions

Medication	Risk	Action
Simvastatin	↑ Simvastatin levels (CYP3A4 inhibition)	Max simvastatin 20 mg/day
CYP3A4 Inhibitors	Clarithromycin, itraconazole	↑ Amlodipine toxicity → ↓ dose
Sildenafil	Additive hypotension	Monitor BP
Beta-Blockers	↑ Risk of bradycardia (in angina)	Monitor HR

---

8. Management of Edema

• Incidence: 5-10% (dose-dependent)

• Strategies:

  • ↓ Dose to 5 mg + add ACEi/ARB

  • Switch to ACEi/ARB or non-DHP CCB

  • Compression stockings/elevate legs

• Avoid diuretics (ineffective for DHP-induced edema)

---

9. Special Populations

Group	Recommendation
Elderly (>65 yrs)	Start 2.5 mg daily (↑ sensitivity)
Pregnancy (Cat C)	Avoid (teratogenic in animals); use methyldopa/labetalol
African Descent	↑ Efficacy vs. ACEi/ARB monotherapy
Renal Impairment	No adjustment needed

---

10. Clinical Pearls

✅ Advantages:

• 24-hour BP control with single dose

• No rebound HTN on discontinuation

• Safe in asthma/diabetes (vs. BB)
  ❌ Limitations:

• Poor angina control in smokers

• Edema risk limits high-dose use

---

Amlodipine vs. Other Antihypertensives

Parameter	Amlodipine (DHP-CCB)	Lisinopril (ACEi)	Metoprolol (BB)
BP Reduction	10-15/5-10 mmHg	10-15/5-10 mmHg	10-15/5-10 mmHg
Heart Rate	↑ Slightly	Neutral	↓ Significantly
DM Safety	Neutral	↑ Hypoglycemia risk	May mask hypoglycemia
Renal Protection	Weak	Strong	Moderate

---

Patient Counseling

1. "Take at the same time daily – even if feeling well."

2. "Swollen ankles? Report if severe/unilateral – may require dose change."

3. "Avoid grapefruit juice – may ↑ side effects."

4. "Do NOT stop suddenly – no rebound HTN, but BP will rise gradually."

5. "Check BP weekly and log readings."

⚠️ Red Flags Requiring Medical Attention:

• Chest pain/pressure (new/worsening angina)

• Fainting/severe dizziness

• Irregular heartbeat

Prescribing Status: First-line for HTN per JNC 8/ACC/AHA guidelines.
Cost: Generic <$0.10/dose.

Sources: ACC/AHA Hypertension Guideline (2023), ESC Angina Guidelines (2023).