Amlodipine

For the majority of adult patients with hypertension, the standard starting dose of amlodipine is 5 mg once daily. Depending on the patient's blood pressure response and clinical goals, the healthcare provider may increase the dose to a maximum of 10 mg once daily. Most of the antihypertensive effect is usually observed within 7 to 14 days of starting a specific dose.

For the treatment of chronic stable or vasospastic angina, the recommended dose for adults is 5 mg to 10 mg once daily. Clinical trials have shown that most patients with coronary artery disease require the 10 mg dose for adequate symptom control. According to the ALLHAT trial (2002), amlodipine is highly effective at preventing cardiovascular complications when dosed appropriately.

Amlodipine is FDA-approved for use in children and adolescents aged 6 to 17 years for the treatment of hypertension. The typical effective dose in this population is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been extensively studied in pediatric patients and are generally not recommended. The safety and efficacy of amlodipine in children younger than 6 years of age have not been established.

Renal Impairment

The pharmacokinetics of amlodipine are not significantly influenced by renal impairment (kidney dysfunction). Therefore, patients with renal failure may usually start at the standard adult dose. Amlodipine is not dialyzable, meaning it is not removed from the blood during dialysis sessions.

Hepatic Impairment

Because amlodipine is extensively metabolized by the liver, the plasma half-life is prolonged in patients with hepatic insufficiency (liver failure). For these individuals, healthcare providers typically recommend a lower starting dose of 2.5 mg once daily. Titration (adjusting the dose) should proceed slowly and with close monitoring.

Elderly Patients

In patients aged 65 and older, the clearance of amlodipine is decreased, resulting in an increase in the area under the curve (AUC) of approximately 40% to 60%. Consequently, the recommended starting dose for elderly patients is 2.5 mg once daily. This 'start low and go slow' approach helps minimize the risk of hypotension and edema (swelling).

• Consistency: Take amlodipine at the same time every day to maintain a steady level of the medication in your bloodstream. Most patients find it easiest to take it in the morning.
• Food: Amlodipine can be taken with or without food. Its absorption is not affected by meals.
• Administration: Swallow the tablet whole with a glass of water. If you are using the 2.5 mg dose and only have 5 mg tablets, ensure they are scored (marked for splitting) and use a pill cutter for accuracy.
• Storage: Store the medication at room temperature (68°F to 77°F or 20°C to 25°C), away from moisture, heat, and direct light. Keep the container tightly closed.

If you miss a dose of amlodipine, take it as soon as you remember. However, if it has been more than 12 hours since your scheduled time, skip the missed dose and take your next dose at the regular time. Do not double the dose to catch up, as this significantly increases the risk of severe hypotension (dangerously low blood pressure).

An overdose of amlodipine can cause excessive peripheral vasodilation and potential reflex tachycardia. Symptoms of a significant overdose include:

• Severe hypotension (fainting, extreme dizziness)
• Rapid or irregular heartbeat
• Feeling very warm or flushed
• Confusion or extreme lethargy

In the event of an overdose, seek emergency medical attention immediately. Clinical management typically involves gastric lavage (stomach pumping) if caught early, followed by cardiovascular support, including elevation of the extremities and administration of intravenous fluids and vasopressors (medications to raise blood pressure). Calcium gluconate may be administered intravenously to reverse the effects of calcium channel blockade.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking this medication without medical guidance, as sudden discontinuation can cause a rebound increase in blood pressure.

The most frequently reported side effect of amlodipine is peripheral edema (swelling of the ankles or feet). This occurs because amlodipine dilates the small arteries (pre-capillary) more than the veins (post-capillary), causing fluid to leak into the surrounding tissues. This effect is dose-dependent; it is more common at the 10 mg dose (approximately 10.8%) than at the 5 mg dose (3.0%).

Other common side effects include:

• Dizziness: Often described as a lightheaded feeling, particularly when standing up quickly.
• Flushing: A feeling of warmth and redness in the face and neck.
• Palpitations: A sensation that the heart is racing or skipping a beat.
• Fatigue: General tiredness or lack of energy.

Some patients may experience the following, though they are less frequent:

• Nausea and Abdominal Pain: Mild digestive upset shortly after taking the medication.
• Somnolence: Excessive sleepiness during the day.
• Visual Disturbances: Blurred vision or double vision.
• Muscle Cramps: Occasional cramping in the legs or back.

Rare but documented side effects include:

• Gingival Hyperplasia: Swelling or overgrowth of the gum tissue around the teeth. Maintaining good oral hygiene can help mitigate this.
• Erythema Multiforme: A skin reaction that can look like targets or 'bullseyes.'
• Gynecomastia: Enlargement of breast tissue in males.
• Leukopenia/Thrombocytopenia: A decrease in white blood cells or platelets, which may be found during routine blood tests.

While amlodipine is generally well-tolerated, some reactions require emergency intervention.

> Warning: Stop taking Amlodipine and call your doctor or emergency services immediately if you experience any of the following:

1. 1Worsening Angina or Myocardial Infarction: Paradoxically, some patients—particularly those with severe obstructive coronary artery disease—may experience increased frequency, duration, or severity of chest pain when starting amlodipine or increasing the dose. This can lead to a heart attack.
2. 2Severe Hypotension: Symptoms include profound dizziness, fainting (syncope), or a cold, clammy feeling. This is more likely to occur in patients who are already taking other blood pressure medications.
3. 3Hypersensitivity/Anaphylaxis: Signs include hives, difficulty breathing, or swelling of the face, lips, tongue, or throat (angioedema).
4. 4Liver Dysfunction: Symptoms include yellowing of the skin or eyes (jaundice), dark urine, and severe upper right abdominal pain.

When taken over many years, amlodipine remains effective and generally safe. The most persistent long-term issue is chronic peripheral edema, which some patients find bothersome. In some cases, healthcare providers may add an ACE inhibitor to the regimen, as these drugs can help 'balance' the pressure in the capillaries and reduce the swelling caused by amlodipine. There is no evidence that long-term use of amlodipine causes damage to the kidneys or increases the risk of cancer.

There are currently no FDA Black Box Warnings for Amlodipine. It is considered to have a high safety profile when used as directed. However, this does not mean the drug is without risk. It must be used with caution in patients with severe aortic stenosis (narrowing of the heart's aortic valve) and those with severe hepatic impairment.

Report any unusual symptoms, especially new or worsening chest pain, to your healthcare provider immediately. Regular follow-ups are necessary to monitor the drug's effectiveness and to check for side effects like edema or changes in heart rhythm.

Amlodipine is a potent vasodilator. While it is highly effective at lowering blood pressure, patients must be aware that its effects are gradual. It is not intended for the immediate relief of an acute hypertensive crisis (extremely high blood pressure requiring instant reduction). Patients should be monitored for 'orthostatic hypotension'—a sudden drop in blood pressure when standing up—which can lead to falls and injuries, particularly in the elderly.

As of 2026, there are no FDA black box warnings for Amlodipine. It is widely recognized for its safety and efficacy in the general population.

• Hypotension Risk: While rare, symptomatic hypotension (low blood pressure) is possible, particularly in patients with severe aortic stenosis. Because the vasodilation produced by amlodipine is gradual in onset, acute hypotension has rarely been reported.
• Increased Angina or Myocardial Infarction: In rare instances, patients with severe obstructive coronary artery disease have developed documented increased frequency, duration, or severity of angina or acute myocardial infarction upon starting calcium channel blocker therapy or at the time of dosage increase. The mechanism for this is not fully understood but may involve reflex sympathetic activation.
• Hepatic Impairment: Since amlodipine is cleared slowly by the liver, patients with pre-existing liver disease should be started on the lowest possible dose (2.5 mg) and monitored closely for toxicity.
• Heart Failure: Although amlodipine does not generally worsen heart failure, it should be used with caution in patients with congestive heart failure. In the PRAISE-2 study, amlodipine did not increase mortality in patients with non-ischemic heart failure, but it may contribute to fluid retention (edema).

Patients taking amlodipine should undergo regular monitoring to ensure the medication is working safely and effectively. This typically includes:

• Blood Pressure Monitoring: Regular checks (both at home and in the clinic) to ensure blood pressure is within the target range.
• Liver Function Tests (LFTs): Periodic blood tests to check enzyme levels (ALT, AST, Bilirubin), especially if the patient has known liver issues.
• Physical Exams: To check for signs of peripheral edema (swelling) or gingival hyperplasia (gum overgrowth).
• Heart Rate: Monitoring for palpitations or tachycardia.

Amlodipine may cause dizziness or fatigue, especially during the first few days of treatment or after a dose increase. Patients should observe how the medication affects them before driving, operating heavy machinery, or performing tasks that require alertness. If you feel dizzy or lightheaded, sit or lie down immediately.

Alcohol can have an additive effect with amlodipine in lowering blood pressure. Consuming alcohol while taking this medication may increase the risk of dizziness, fainting, and headaches. It is generally advised to limit alcohol intake while on antihypertensive therapy. Discuss your alcohol consumption habits with your doctor.

Do not stop taking amlodipine abruptly. While it does not typically cause a 'withdrawal syndrome' like beta-blockers, stopping it suddenly will cause your blood pressure to rise again, potentially increasing the risk of stroke or heart attack. If the medication must be stopped, your doctor will likely provide a tapering schedule or transition you to another medication.

> Important: Discuss all your medical conditions, especially liver disease or heart valve problems, with your healthcare provider before starting Amlodipine.

There are few absolute contraindications for drug combinations with amlodipine, but certain drugs should be avoided if possible:

• Strong CYP3A4 Inducers (e.g., Rifampin, St. John’s Wort): These substances can significantly decrease the plasma concentration of amlodipine, rendering it ineffective. If these must be used, blood pressure should be monitored very closely.

• Simvastatin (Zocor): Co-administration of amlodipine with simvastatin increases the exposure of simvastatin (up to 77%). This increases the risk of myopathy and rhabdomyolysis (muscle breakdown). The dose of simvastatin should be limited to 20 mg daily in patients receiving amlodipine.
• Immunosuppressants (Cyclosporine, Tacrolimus): Amlodipine may increase the blood levels of these drugs, potentially leading to kidney toxicity. Frequent monitoring of immunosuppressant blood levels is required when starting or changing the dose of amlodipine.
• Clopidogrel (Plavix): Some studies suggest that calcium channel blockers might slightly reduce the antiplatelet effect of clopidogrel, though the clinical significance is debated. Monitor for signs of reduced efficacy.

• Other Antihypertensives: Taking amlodipine with ACE inhibitors, ARBs, or beta-blockers has an additive effect. While often therapeutic, it increases the risk of hypotension.
• Sildenafil (Viagra) and other PDE5 Inhibitors: These medications also lower blood pressure. When used with amlodipine, there is a risk of additive blood-pressure-lowering effects. Use with caution.
• NSAIDs (e.g., Ibuprofen, Naproxen): Nonsteroidal anti-inflammatory drugs can cause fluid retention and may slightly decrease the blood-pressure-lowering effects of amlodipine.

• Grapefruit and Grapefruit Juice: Grapefruit inhibits the CYP3A4 enzyme in the gut. While the effect on amlodipine is generally considered modest compared to other CCBs (like nifedipine), it can still increase amlodipine levels in some patients, potentially leading to increased side effects. It is generally recommended to avoid large amounts of grapefruit juice.
• High-Sodium Diet: Excessive salt intake can counteract the blood-pressure-lowering effects of amlodipine.

• St. John’s Wort: As a potent inducer of CYP3A4, it can lower the levels of amlodipine in the blood, making it less effective at controlling blood pressure.
• Melatonin: Some evidence suggests melatonin may interfere with the blood-pressure-lowering effects of calcium channel blockers.
• Calcium Supplements: While it seems counterintuitive, taking calcium supplements does not usually interfere with the action of calcium channel blockers, as the drug works on the 'channels' rather than the calcium levels in the blood.

Amlodipine is not known to significantly interfere with most common clinical laboratory tests. It does not affect blood sugar, cholesterol, or uric acid levels.

For each major interaction, the mechanism usually involves the CYP3A4 enzyme pathway. Inhibition of this enzyme leads to higher drug levels and toxicity, while induction leads to lower levels and treatment failure. Always provide a complete list of your medications to your pharmacist to check for potential interactions.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers.

Amlodipine must NEVER be used in the following circumstances:

• Known Hypersensitivity: If you have had an allergic reaction to amlodipine besylate or any other dihydropyridine calcium channel blocker (such as nifedipine, felodipine, or nicardipine), you must not take this drug. Reactions can range from mild rashes to life-threatening anaphylaxis.
• Severe Hypotension: Because amlodipine lowers blood pressure, it is contraindicated in patients who are already in a state of shock or have clinically significant low blood pressure (e.g., systolic BP < 90 mmHg).

Conditions requiring careful risk-benefit analysis include:

• Severe Aortic Stenosis: In patients with narrowing of the aortic valve, the peripheral vasodilation caused by amlodipine can reduce the blood flow to the coronary arteries, potentially leading to a collapse or worsened heart function.
• Severe Hepatic Impairment: Due to the extensive liver metabolism of amlodipine, the drug will accumulate in the body of patients with liver failure. It is not strictly contraindicated, but the risk of toxicity is much higher.
• Obstructive Hypertrophic Cardiomyopathy (HOCM): Like other vasodilators, amlodipine should be used with caution in patients with outflow tract obstruction.
• Acute Myocardial Infarction: Amlodipine should be used with extreme caution in the period immediately following a heart attack, especially if heart failure is present.

There is a potential for cross-sensitivity among members of the dihydropyridine class. If you have had a severe skin reaction (like Stevens-Johnson Syndrome) to one dihydropyridine, your doctor will likely avoid the entire class. However, there is no cross-sensitivity between amlodipine and non-dihydropyridines like verapamil or diltiazem.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of heart valve disease or liver problems, before prescribing Amlodipine.

Amlodipine is currently classified under the older FDA Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Animal studies have shown some developmental toxicity at doses many times higher than the human dose. According to the American College of Obstetricians and Gynecologists (ACOG), other agents like nifedipine (another CCB) or labetalol are often preferred for managing hypertension in pregnancy due to more extensive data. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Limited data from published clinical studies indicate that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on nursing infants have been observed. While generally considered compatible with breastfeeding by the World Health Organization (WHO), nursing mothers should monitor their infants for signs of low blood pressure or lethargy.

Amlodipine is approved for children aged 6 to 17 years. The primary use in this population is for essential hypertension. It has been shown to be effective and well-tolerated in this age group. It is NOT approved for children under the age of 6. There is no evidence that amlodipine affects growth or development in children, but long-term studies are limited.

Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. however, other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range (2.5 mg), reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Amlodipine is not significantly cleared by the kidneys. Approximately 10% of the drug is excreted unchanged in the urine. Therefore, no initial dose adjustment is required for patients with renal impairment. However, these patients should still be monitored for systemic effects as they may be more sensitive to changes in blood pressure.

As the liver is the primary site of metabolism, hepatic impairment significantly increases the half-life of amlodipine (from ~35 hours to ~56 hours). Patients with any degree of liver dysfunction must be started on the 2.5 mg dose. Failure to adjust the dose in these patients can lead to drug accumulation and severe side effects.

> Important: Special populations require individualized medical assessment. Always inform your doctor if you are planning to become pregnant or have a history of liver disease.

Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. It is a member of the dihydropyridine class of calcium channel blockers. Specifically, it inhibits the influx of calcium ions through L-type (long-lasting) voltage-gated channels. By binding to the alpha-1 subunit of the channel, amlodipine keeps the channel in its inactive or 'closed' state, preventing the surge of calcium into the cell that is necessary for muscle contraction. Unlike non-dihydropyridines, amlodipine has minimal effect on the sinoatrial (SA) and atrioventricular (AV) nodes of the heart at therapeutic doses.

The onset of action for amlodipine is slow (6-12 hours for peak effect), which prevents the 'reflex tachycardia' (fast heart rate) that occurs when blood pressure drops too rapidly. The duration of effect is at least 24 hours, making once-daily dosing effective. There is a linear relationship between the dose and the reduction in blood pressure. Long-term use does not typically lead to tolerance (loss of effectiveness).

| Parameter | Value |

|---|---|

| Bioavailability | 64% - 90% |

| Protein Binding | 93% - 98% |

| Half-life | 30 - 50 hours (up to 56h in hepatic impairment) |

| Tmax (Time to Peak) | 6 - 12 hours |

| Metabolism | Hepatic (Extensive via CYP3A4) |

| Excretion | Renal 60% (as metabolites), Fecal 20-25% |

• Molecular Formula: C20H25ClN2O5 (as amlodipine) / C20H25ClN2O5 • C6H6O3S (as besylate salt)
• Molecular Weight: 408.9 g/mol (base) / 567.1 g/mol (besylate)
• Solubility: Slightly soluble in water; sparingly soluble in ethanol.
• Structure: Amlodipine is a 1,4-dihydropyridine derivative. It contains a chiral center and is marketed as a racemic mixture of (R)- and (S)-isomers, though the (S)-isomer is responsible for the calcium channel blocking activity.

Amlodipine is classified as a Dihydropyridine Calcium Channel Blocker. It is distinct from other classes of antihypertensives like ACE inhibitors (which affect the renin-angiotensin system) or Beta-blockers (which affect the sympathetic nervous system). Within its class, it is grouped with medications like Nifedipine, Felodipine, and Lercanidipine.