Usage
- S-Amlodipine is primarily prescribed for hypertension (high blood pressure) and chronic stable angina (chest pain due to reduced blood flow to the heart). It can also be used for vasospastic angina (Prinzmetal’s angina) and angiographically documented coronary artery disease (CAD) in patients without heart failure or an ejection fraction less than 40%.
- Pharmacological classification: Dihydropyridine calcium channel blocker, antihypertensive, antianginal agent.
- Mechanism of Action: S-Amlodipine inhibits the influx of calcium ions into vascular smooth muscle cells and cardiac myocytes by blocking L-type calcium channels. This leads to vasodilation (widening of blood vessels), reducing blood pressure and improving myocardial oxygen delivery.
Alternate Names
- S-(-)-Amlodipine
- Levamlodipine
- Brand names: Norvasc, Katerzia, Norliqva, Mylovasc, Asomex (and others, which can vary regionally).
How It Works
- Pharmacodynamics: S-Amlodipine’s primary effect is the relaxation of vascular smooth muscle, leading to peripheral vasodilation and a decrease in systemic vascular resistance, thereby lowering blood pressure. It also dilates coronary arteries, improving blood flow to the heart muscle.
- Pharmacokinetics:
- Absorption: Well-absorbed orally, with peak plasma concentrations reached in 6-12 hours. Food does not significantly affect absorption. Absolute bioavailability is 64-90%.
- Metabolism: Extensively metabolized by the liver, primarily via CYP3A4.
- Elimination: Primarily eliminated through the kidneys (renal excretion), with a half-life of 30-50 hours, allowing for once-daily dosing.
- Mode of Action: Binds to the dihydropyridine binding site on L-type calcium channels, inhibiting calcium influx into cells. This leads to decreased vascular tone and vasodilation.
- Elimination Pathways: Primarily hepatic metabolism followed by renal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension: Initial dose: 2.5-5 mg orally once daily. May be increased to a maximum of 10 mg once daily, titrated over 7-14 days as needed based on blood pressure response. Smaller or frail individuals and geriatric patients: 2.5mg initially.
- Angina/CAD: 5-10 mg orally once daily, with most patients requiring 10 mg daily.
Children (6-17 years):
- Hypertension: 2.5-5 mg orally once daily. Doses above 5 mg daily have not been studied in pediatric patients.
- Safety and efficacy not established in children younger than 6 years of age.
Special Cases:
- Elderly Patients: Initial dose of 2.5 mg is recommended. Titrate cautiously as needed.
- Patients with Renal Impairment: No dosage adjustment is typically necessary.
- Patients with Hepatic Dysfunction: Start with a lower initial dose (e.g., 1.25 mg or 2.5 mg) and titrate slowly.
- Patients with Comorbid Conditions: Monitor closely, especially those with heart failure.
Clinical Use Cases
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Dosage adjustments may be necessary depending on the specific clinical scenario and patient’s hemodynamic status. Continuous blood pressure monitoring is crucial. Information on use during specific emergency situations (e.g., status epilepticus, cardiac arrest) is limited and adjustments must be made based on the patient’s condition and response.
Dosage Adjustments
- Adjust dose based on blood pressure response and tolerance. Consider lower initial doses and slower titration in patients with hepatic impairment. Monitor for adverse events, especially peripheral edema. No specific dosage adjustment based on creatinine clearance (renal function).
Side Effects
Common Side Effects:
- Peripheral edema (swelling of ankles and feet)
- Headache
- Dizziness
- Flushing
- Fatigue
Rare but Serious Side Effects:
- Hypotension
- Reflex tachycardia
- Angioedema
- Hepatotoxicity (liver damage)
Long-Term Effects:
- Potential for worsening of pre-existing heart failure in susceptible individuals.
Adverse Drug Reactions (ADR):
- Severe hypotension
- Angioedema requiring urgent treatment.
Contraindications
- Hypersensitivity to dihydropyridines or amlodipine
- Cardiogenic shock
- Severe aortic stenosis
- Unstable angina (excluding Prinzmetal’s angina)
Drug Interactions
- CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, clarithromycin): May increase amlodipine levels, increasing the risk of side effects.
- CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine): May decrease amlodipine levels, reducing efficacy.
- Other antihypertensives: Additive hypotensive effects.
- Grapefruit juice: Can increase amlodipine levels.
- Simvastatin: Can increase simvastatin levels.
- Immunosuppressants (e.g., cyclosporine, tacrolimus): May increase levels of these drugs.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Use only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Excreted in breast milk. Not recommended during breastfeeding or, if it is deemed absolutely necessary to use during breastfeeding, an alternative method of infant feeding should be considered.
Drug Profile Summary
- Mechanism of Action: Calcium channel blocker, inhibits calcium influx into vascular smooth muscle and cardiac myocytes.
- Side Effects: Peripheral edema, headache, dizziness, flushing, fatigue. Rarely, hypotension, reflex tachycardia.
- Contraindications: Hypersensitivity, cardiogenic shock, severe aortic stenosis, unstable angina.
- Drug Interactions: CYP3A4 inhibitors/inducers, other antihypertensives, grapefruit juice.
- Pregnancy & Breastfeeding: Category C; not recommended during breastfeeding.
- Dosage: Hypertension: 2.5-10 mg/day; Angina: 5-10 mg/day. Adjust for hepatic impairment.
- Monitoring Parameters: Blood pressure, heart rate, signs of edema, liver function tests.
Popular Combinations
- Amlodipine/atorvastatin (for hypertension and hyperlipidemia)
- Amlodipine/valsartan or amlodipine/olmesartan (for hypertension)
- Amlodipine/telmisartan
- Amlodipine/perindopril
- Amlodipine/aliskiren or amlodipine/aliskiren/hydrochlorothiazide
- Nebivolol/S-amlodipine
- S-amlodipine/losartan
Precautions
- General Precautions: Monitor blood pressure and heart rate. Assess for peripheral edema. Monitor liver function tests in patients with hepatic impairment.
- Specific Populations: See “Dosage - Special Cases.” Careful consideration needed in patients with severe obstructive coronary artery disease.
- Lifestyle Considerations: Limiting alcohol intake, smoking cessation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for S-Amlodipine?
A: Adults: 2.5-10 mg once daily for hypertension, 5-10 mg once daily for angina. Children (6-17 years): 2.5-5 mg once daily for hypertension. Elderly and patients with hepatic impairment: Start with a lower dose.
Q2: How does S-Amlodipine differ from racemic amlodipine?
A: S-Amlodipine is the single active enantiomer of amlodipine. It may offer similar efficacy at lower doses than the racemic mixture.
Q3: What are the most common side effects?
A: Peripheral edema, headache, dizziness, and flushing are the most frequently reported side effects.
Q4: Can S-Amlodipine be used in patients with renal impairment?
A: Generally, no dosage adjustment is necessary in patients with renal impairment, as amlodipine’s pharmacokinetics are not significantly affected.
Q5: Are there any significant drug interactions I should be aware of?
A: Yes. CYP3A4 inhibitors and inducers can alter amlodipine levels. Concomitant use with other antihypertensives can potentiate the hypotensive effect. Grapefruit juice can increase amlodipine levels. It is essential to review the patient’s medication list for potential interactions.
Q6: Can S-Amlodipine be used during pregnancy or breastfeeding?
A: S-Amlodipine is Pregnancy Category C, meaning it should only be used if the potential benefit outweighs the potential risk to the fetus. It is excreted in breast milk and not generally recommended during breastfeeding.
Q7: What should I monitor in patients taking S-Amlodipine?
A: Monitor blood pressure, heart rate, and signs of edema. Monitor liver function tests in patients with hepatic impairment.
Q8: Is there a maximum daily dose for S-Amlodipine?
A: Yes, the maximum recommended dose for adults is 10 mg per day.
Q9: How should I manage an S-amlodipine overdose?
A: Supportive care is the mainstay of treatment, including cardiovascular support (fluids, vasopressors if needed), and monitoring vital signs and electrolyte levels. Activated charcoal might be beneficial early after ingestion. Calcium gluconate administration can mitigate cardiovascular effects.
Q10: Can S-amlodipine be abruptly discontinued?
A: Abrupt discontinuation is not recommended, especially in patients with angina, as it can potentially lead to rebound hypertension or angina. The medication should be gradually tapered down under medical supervision.
