Usage
- Amlodipine is prescribed for the treatment of hypertension (high blood pressure), chronic stable angina (chest pain due to reduced blood flow to the heart), and vasospastic angina (chest pain due to spasms in the coronary arteries).
- Pharmacological Classification: Calcium Channel Blocker, Dihydropyridine type.
- Mechanism of Action: Amlodipine inhibits the influx of calcium ions into vascular smooth muscle cells and cardiac muscle cells, leading to vasodilation (widening of blood vessels) and a decrease in myocardial oxygen demand.
Alternate Names
- International/Regional Variations: Amlodipine besylate (the besylate salt form).
- Brand Names: Norvasc, Amvaz, Katerzia, Norliqva.
How It Works
- Pharmacodynamics: Amlodipine primarily affects the cardiovascular system by causing vasodilation, reducing peripheral vascular resistance, and lowering blood pressure. It also decreases myocardial contractility and oxygen demand, relieving angina symptoms.
- Pharmacokinetics:
- Absorption: Well-absorbed orally, reaching peak plasma concentrations in 6-12 hours. Bioavailability is around 60-80%.
- Metabolism: Extensively metabolized in the liver by CYP3A4 enzymes to inactive metabolites.
- Elimination: Primarily eliminated via hepatic metabolism, with a small portion excreted unchanged in the urine. Elimination half-life is around 30-50 hours, allowing for once-daily dosing.
- Mode of Action: Amlodipine selectively blocks L-type calcium channels in vascular smooth muscle and cardiac muscle. This inhibition prevents calcium influx, leading to relaxation of the vascular smooth muscle and vasodilation.
- Receptor Binding/Enzyme Inhibition: Amlodipine binds to the alpha-1 subunit of L-type calcium channels, inhibiting calcium influx.
- Elimination Pathways: Primarily hepatic metabolism via CYP3A4 enzymes, followed by biliary and renal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose is 5 mg orally once daily. May be increased to a maximum of 10 mg once daily as needed.
- Angina: Initial dose is 5 mg orally once daily. The usual maintenance dose is 5-10 mg orally once daily. Maximum dose 10 mg per day.
Children (6-17 years old):
- Hypertension: Initial dose is 2.5 mg orally once daily. May be increased to 5 mg orally once daily if blood pressure goal is not achieved after 4 weeks.
- Pediatric Safety: Doses above 5 mg/day have not been studied in children.
Special Cases:
- Elderly Patients: Initial dose is typically 2.5 mg orally once daily, with careful titration as needed.
- Patients with Renal Impairment: No dosage adjustment is usually necessary as amlodipine is not significantly affected by renal function.
- Patients with Hepatic Dysfunction: Start with a lower initial dose (2.5 mg/day) and titrate cautiously.
- Patients with Comorbid Conditions: Dose adjustment may be required depending on the specific comorbidity.
Clinical Use Cases
- Amlodipine is not typically administered via intubation.
- Amlodipine is not indicated for use during surgical procedures, mechanical ventilation, in the intensive care unit, or in emergency situations like status epilepticus or cardiac arrest. It is used for the management of chronic conditions like hypertension and angina.
Dosage Adjustments
- Dose adjustments may be necessary for patients with hepatic impairment, severe heart failure, or those taking CYP3A4 inhibitors or inducers.
Side Effects
Common Side Effects:
- Peripheral edema (swelling of ankles and feet), headache, dizziness, flushing, fatigue, palpitations.
Rare but Serious Side Effects:
- Severe hypotension, reflex tachycardia, pulmonary edema, hepatic dysfunction.
Long-Term Effects:
- Peripheral edema can be persistent with long-term use.
Adverse Drug Reactions (ADR):
- Angioedema, hepatitis, severe hypotension.
Contraindications
- Hypersensitivity to amlodipine or other dihydropyridines.
- Severe hypotension.
- Cardiogenic shock.
- Left ventricular outflow tract obstruction (e.g., severe aortic stenosis).
- Hemodynamically unstable heart failure after acute myocardial infarction.
Drug Interactions
- CYP3A4 Inhibitors: (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin, ritonavir) can increase amlodipine levels, requiring dose reduction.
- CYP3A4 Inducers: (e.g., rifampin, phenytoin, St. John’s wort) may decrease amlodipine levels, potentially reducing efficacy.
- Other Antihypertensives: Additive effects can occur, potentially causing excessive hypotension.
- Grapefruit juice: Can increase amlodipine levels, potentially leading to side effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.)
- Fetal Risks: Potential for prolonged gestation and labor.
- Breastfeeding: Amlodipine is present in breast milk. While generally considered safe, caution is advised and it is recommended not to be used during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Calcium channel blocker inhibiting calcium influx into vascular smooth muscle and cardiac muscle, causing vasodilation.
- Side Effects: Peripheral edema, headache, dizziness, flushing.
- Contraindications: Hypersensitivity, severe hypotension, shock, LVOT obstruction, unstable heart failure post-MI.
- Drug Interactions: CYP3A4 inhibitors/inducers, other antihypertensives, grapefruit juice.
- Pregnancy & Breastfeeding: Category C, use with caution; present in breast milk, avoid if possible.
- Dosage: 5-10 mg once daily for adults; 2.5-5 mg once daily for children (6-17 years).
- Monitoring Parameters: Blood pressure, heart rate, signs of peripheral edema, liver function tests.
Popular Combinations
- Amlodipine is often combined with other antihypertensive agents, such as ACE inhibitors (e.g., benazepril), ARBs (e.g., valsartan, olmesartan), or thiazide diuretics. These combinations can provide synergistic blood pressure lowering effects.
Precautions
- General Precautions: Monitor blood pressure, assess for hepatic/renal function, and consider drug interactions.
- Specific Populations: Use with caution in patients with heart failure. Avoid during breastfeeding if possible.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine?
A: Adults: 5-10 mg once daily; Children (6-17 years): 2.5-5 mg once daily; Elderly: Initial dose 2.5 mg once daily, titrate with caution.
Q2: What are the common side effects of Amlodipine?
A: Peripheral edema, headache, dizziness, flushing, and palpitations.
Q3: How does Amlodipine work?
A: It blocks calcium channels, leading to vasodilation and reduced blood pressure.
Q4: Can Amlodipine be used during pregnancy?
A: Pregnancy Category C. Use only if the potential benefit outweighs the potential risk.
Q5: What are the contraindications for Amlodipine?
A: Hypersensitivity, severe hypotension, shock, LVOT obstruction, and hemodynamically unstable heart failure post-MI.
Q6: Does Amlodipine interact with other medications?
A: Yes, it interacts with CYP3A4 inhibitors and inducers, other antihypertensives, and grapefruit juice.
Q7: Can Amlodipine be used in patients with renal impairment?
A: Yes, usually no dosage adjustment is necessary.
Q8: What should I monitor in patients taking Amlodipine?
A: Blood pressure, heart rate, signs of peripheral edema, and liver function tests.
Q9: Can Amlodipine be crushed?
A: While some tablets can be crushed, it is generally recommended to administer the tablet whole as directed. Consult the specific product information for details on crushability.
Q10: How long does it take for amlodipine to work?
A: The blood pressure lowering effect of amlodipine is usually observed within 1-2 weeks of starting treatment. The peak effect might take longer.
