Usage
Amlodipine + Atorvastatin is prescribed for the concomitant treatment of hypertension and hyperlipidemia in patients who require both medications. It is also indicated for angina and coronary artery disease.
Pharmacological Classification:
- Amlodipine: Dihydropyridine calcium channel blocker, antihypertensive, antianginal
- Atorvastatin: HMG-CoA reductase inhibitor (statin), lipid-lowering agent
Mechanism of Action:
This combination drug works through two distinct mechanisms:
- Amlodipine: Relaxes vascular smooth muscle by blocking calcium influx, leading to vasodilation and reduced blood pressure. Also improves myocardial oxygen delivery in angina.
- Atorvastatin: Inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, reducing LDL cholesterol and triglycerides while increasing HDL cholesterol.
Alternate Names
The combination of amlodipine and atorvastatin itself does not have an international nonproprietary name (INN).
Brand Names: Caduet
How It Works
Pharmacodynamics:
- Amlodipine: Decreases systemic vascular resistance and blood pressure. Improves coronary blood flow and reduces myocardial oxygen demand.
- Atorvastatin: Lowers LDL cholesterol, total cholesterol, and triglycerides. Increases HDL cholesterol. Reduces inflammation and improves endothelial function.
Pharmacokinetics:
- Amlodipine: Well absorbed orally, peak plasma concentration in 6-12 hours. Extensive hepatic metabolism, primarily by CYP3A4. Eliminated via renal and fecal routes. Half-life of approximately 30-50 hours.
- Atorvastatin: Well absorbed orally, peak plasma concentration in 1-2 hours. Extensive hepatic metabolism, primarily by CYP3A4. Excreted mainly in bile. Half-life of approximately 14 hours.
Mode of Action:
- Amlodipine: Blocks L-type calcium channels in vascular smooth muscle and cardiac myocytes, reducing calcium influx.
- Atorvastatin: Competitively inhibits HMG-CoA reductase, blocking the conversion of HMG-CoA to mevalonate.
Elimination Pathways:
- Amlodipine: Hepatic metabolism (CYP3A4), renal and fecal excretion.
- Atorvastatin: Hepatic metabolism (CYP3A4), biliary excretion.
Dosage
Standard Dosage
Adults:
The starting dose is typically Amlodipine 5mg/Atorvastatin 10mg once daily. The dose may be titrated based on individual response and tolerability up to a maximum of Amlodipine 10mg/Atorvastatin 80mg once daily.
Children:
Amlodipine/Atorvastatin combination is not recommended for use in children under 10 years old. For children over 10 years old, the typical starting dose is Amlodipine 2.5mg/Atorvastatin 10mg, adjustable up to 5mg/20mg. Safety and efficacy have not been established in children younger than 10 years.
Special Cases:
- Elderly Patients: Initiate amlodipine at the lower end of the dosage range (2.5 mg) due to potential for decreased clearance. Titrate carefully.
- Patients with Renal Impairment: Amlodipine dosage adjustment is generally not necessary. Atorvastatin should be used with caution and may require a dose reduction.
- Patients with Hepatic Dysfunction: Amlodipine/Atorvastatin combination is contraindicated in patients with active liver disease. Amlodipine should be initiated at 2.5mg in patients with mild to moderate hepatic impairment and titrated carefully. Atorvastatin is contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminases.
- Patients with Comorbid Conditions: Use with caution in patients with heart failure, severe aortic stenosis, and hypothyroidism. Monitor blood glucose in patients with diabetes.
Clinical Use Cases
The specific use cases outlined below (Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations) relate to the individual components of the combination product and not the fixed-dose combination itself. The use of Amlodipine/Atorvastatin in these settings is based on the clinical judgment of the treating physician.
Dosage Adjustments
Dosage adjustments are based on individual patient response and tolerability. Consider renal and hepatic function, concomitant medications, and comorbid conditions. Dosage adjustments may be required for patients taking drugs that inhibit or induce CYP3A4.
Side Effects
Common Side Effects
Peripheral edema, headache, flushing, dizziness, fatigue, muscle pain, joint pain, diarrhea, nausea, abdominal pain.
Rare but Serious Side Effects
Myopathy, rhabdomyolysis, hepatotoxicity, angioedema, allergic reactions, hypotension.
Long-Term Effects
Increased risk of myopathy with long-term use, especially at higher doses. Monitor liver function regularly.
Adverse Drug Reactions (ADR)
Severe allergic reactions, rhabdomyolysis, significant hypotension, liver injury.
Contraindications
Hypersensitivity to amlodipine or atorvastatin, active liver disease, unexplained persistent elevations of hepatic transaminases, pregnancy, breastfeeding.
Drug Interactions
CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, HIV protease inhibitors) can increase plasma concentrations of both amlodipine and atorvastatin. CYP3A4 inducers (e.g., rifampin, phenytoin) may decrease plasma levels. Avoid grapefruit juice. Other interactions may occur with certain antivirals, azole antifungals, and macrolide antibiotics.
Pregnancy and Breastfeeding
Contraindicated in pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Amlodipine: Calcium channel blocker, vasodilator. Atorvastatin: HMG-CoA reductase inhibitor, lowers cholesterol.
- Side Effects: Peripheral edema, headache, muscle pain, myopathy (rare), hepatotoxicity (rare).
- Contraindications: Hypersensitivity, active liver disease, pregnancy, breastfeeding.
- Drug Interactions: CYP3A4 inhibitors and inducers, grapefruit juice.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 5/10mg to 10/80mg once daily, adjusted based on response.
- Monitoring Parameters: Blood pressure, lipid profile, liver function tests, creatine kinase (if muscle symptoms develop).
Popular Combinations
Amlodipine is often combined with other antihypertensives like ACE inhibitors, ARBs, or thiazide diuretics. Atorvastatin may be combined with other lipid-lowering therapies like ezetimibe in cases of severe hypercholesterolemia.
Precautions
Use with caution in patients with heart failure, severe aortic stenosis, hepatic impairment, and hypothyroidism. Monitor liver function and creatine kinase if muscle symptoms occur. Limit alcohol consumption.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amlodipine + Atorvastatin?
A: The starting dose is typically 5mg/10mg once daily, titratable up to a maximum of 10mg/80mg daily based on patient response and tolerability.
Q2: What are the common side effects of Amlodipine + Atorvastatin?
A: Common side effects include peripheral edema, headache, flushing, dizziness, fatigue, muscle and joint pain, diarrhea, nausea, and abdominal pain.
Q3: What are the contraindications for this combination?
A: Contraindications include hypersensitivity to amlodipine or atorvastatin, active liver disease, pregnancy, and breastfeeding.
Q4: Are there any significant drug interactions?
A: Yes, significant interactions can occur with CYP3A4 inhibitors (e.g., clarithromycin, azole antifungals) and inducers (e.g., rifampin), as well as grapefruit juice.
Q5: How should I monitor patients on this medication?
A: Monitor blood pressure, lipid panel, liver function tests, and creatine kinase (if muscle symptoms arise).
Q6: Can this medication be used in patients with renal impairment?
A: Amlodipine can generally be used without dosage adjustment. Atorvastatin should be used cautiously and may require a dose reduction.
Q7: Can this medication be used in pregnancy?
A: No, it is contraindicated in pregnancy.
Q8: What should patients avoid while taking Amlodipine + Atorvastatin?
A: Patients should avoid grapefruit juice and excessive alcohol consumption. They should also follow a low-fat, low-cholesterol diet.
Q9: What should I do if a patient develops muscle pain while taking this drug?
A: Evaluate the patient for myopathy. Check creatine kinase levels. Consider discontinuing the medication if myopathy is suspected.
Q10: How does hepatic impairment affect dosing?
A: This combination is contraindicated in patients with active liver disease. Amlodipine should be started at a low dose and titrated carefully. Atorvastatin is contraindicated with active liver disease or unexplained transaminase elevations.
