Introduction
Caduet is a fixed-dose combination medication containing amlodipine besylate (a calcium channel blocker) and atorvastatin calcium (an HMG-CoA reductase inhibitor). This unique combination therapy addresses both hypertension and dyslipidemia simultaneously, providing a convenient treatment option for patients requiring management of both cardiovascular risk factors.
Mechanism of Action
Caduet exerts its effects through two distinct mechanisms:
- Amlodipine component: Inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle, producing peripheral arterial vasodilation and reducing coronary vascular resistance
- Atorvastatin component: Competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, resulting in increased hepatic LDL receptor expression and accelerated clearance of circulating LDL
Indications
- Hypertension (amlodipine component)
- Chronic stable angina, vasospastic angina (amlodipine component)
- Hyperlipidemia (atorvastatin component)
- Primary prevention of cardiovascular disease in patients with multiple risk factors
- Secondary prevention in patients with established cardiovascular disease
Dosage and Administration
Available strengths: Combinations of amlodipine/atorvastatin: 2.5/10 mg, 2.5/20 mg, 2.5/40 mg, 5/10 mg, 5/20 mg, 5/40 mg, 5/80 mg, 10/10 mg, 10/20 mg, 10/40 mg, 10/80 mg Standard dosing: Once daily, with or without food Dose titration: Based on individual patient response and tolerability Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution; contraindicated in active liver disease
- Geriatric patients: Consider starting at lower doses
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Both components well absorbed orally; bioavailability: amlodipine 64-90%, atorvastatin ~30% Distribution: Extensive tissue distribution; high protein binding (>90% for both components) Metabolism: Hepatic metabolism via CYP3A4 (both components) Elimination: Amlodipine elimination half-life 30-50 hours; atorvastatin elimination half-life 14 hours Excretion: Primarily hepatic elimination; <10% renal excretion of unchanged drugContraindications
- Hypersensitivity to any component
- Active liver disease or unexplained persistent elevations of serum transaminases
- Pregnancy and breastfeeding
- Women of childbearing potential not using adequate contraception
Warnings and Precautions
Boxed Warning: Risk of myopathy/rhabdomyolysis with statin therapy- Hepatotoxicity: Monitor liver enzymes before initiation and periodically thereafter
- Myopathy: Monitor for muscle pain, tenderness, or weakness; assess CK levels if symptoms occur
- Hypotension: Particularly in patients with severe aortic stenosis
- Increased HbA1c: Small increases in blood glucose levels reported
- Cognitive effects: Memory loss, confusion reported rarely
Drug Interactions
Strong CYP3A4 inhibitors: Clarithromycin, itraconazole, HIV protease inhibitors - increased risk of myopathy Cyclosporine: Significantly increases atorvastatin exposure Gemfibrozil: Avoid concomitant use due to increased myopathy risk Colchicine: Increased risk of myopathy Digoxin: Amlodipine may increase digoxin levels Grapefruit juice: May increase atorvastatin exposureAdverse Effects
Common (≥2%):- Edema (amlodipine-related)
- Headache
- Dizziness
- Flushing
- Myalgia
- Arthralgia
- Diarrhea
- Nausea
- Rhabdomyolysis with renal failure
- Hepatotoxicity
- Severe hypotension
- Angioedema
- Stevens-Johnson syndrome
Monitoring Parameters
- Blood pressure regularly
- Lipid panel at baseline, 4-12 weeks after initiation/changes, and periodically
- Liver enzymes at baseline, 12 weeks, and periodically
- CPK levels if muscle symptoms develop
- Renal function periodically
- Signs/symptoms of heart failure in patients with cardiac dysfunction
- Blood glucose monitoring in diabetic patients
Patient Education
- Take medication exactly as prescribed, once daily
- Report any unexplained muscle pain, tenderness, or weakness immediately
- Avoid grapefruit products while taking this medication
- Regular blood tests are necessary to monitor therapy
- Do not stop taking without consulting your healthcare provider
- Use effective contraception if of childbearing potential
- Maintain heart-healthy lifestyle including diet and exercise
- Rise slowly from sitting/lying position to prevent dizziness
- Report any signs of liver problems (yellowing skin/eyes, dark urine)
References
1. FDA Prescribing Information: Caduet (amlodipine besylate/atorvastatin calcium) 2. Grundy SM, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350 3. Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018;71(19):e127-e248 4. Sica DA. Calcium channel blocker-related peripheral edema: can it be resolved? J Clin Hypertens. 2003;5(4):291-295 5. Thompson PD, et al. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395-2410 6. Product monograph: Caduet (amlodipine/atorvastatin). Pfizer Canada Inc. 2022