General Information

Caduet  is a combination of amlodipine besylate, a calcium channel blocker, and atorvastatin calcium, a HMG CoA-reductase inhibitor.

Caduet is specifically indicated for:

• the treatment of hypertension, to lower blood pressure
• the treatment of Coronary Artery Disease 
• as an adjunct therapy to diet for prevention of cardiovascular disease and hyperlipidemia

The recommended dose is:

Amlodipine: Usual starting dose is 5mg/day. Maximum dose is 10 mg/day. Start small adults or children, fragile, or elderly patients, or patients with hepatic insufficiency on 2.5 mg once daily.

Atorvastatin: Usual starting dose is 10-20 mg/day. Maximum dose is 80 mg/day. Start patients requiring large LDL-C reduction (> 45%) at 40 mg once daily.

Mechanism of Action

Amlodipine, a long acting calcium ion antagonist, is the active ingredient in Norvasc (Pfizer) and Lotrel (Novartis). Amlodipine inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. The drug binds to dihydropyridine and nondihydropyridine binding sites. In addition, 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.

Atorvastatin, a HMGCoA reductase inhibitor indicated for lowering cholesterol, is the active ingredient in Lipitor (Pfizer). Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a precursor of sterols, including cholesterol. Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMGCoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL.

Side Effects

Adverse events associated with the use of Caduet may include (but are not limited to) the following:

• Headache
• Abdominal Pain
• Rash
• Chest pain,
• Nausea
• Insomnia
• Dizziness

Clinical Trial Results

FDA approval of Caduet was based on a double-blind, placebo-controlled study enrolling 1,600 subjects with co-morbid hypertension and dyslipidemia. Results showed that all combination-treatment groups of amlodipine and atorvastatin demonstrated statistically significant dose-related reductions in systolic blood pressure (SBP), Diastolic Blood pressure (DBP) and LDL-C compared to placebo.

Subjects received once daily treatment with eight dose combinations of amlodipine and atorvastatin (5/10, 10/10, 5/20, 10/20, 5/40, 10/40, 5/80, or 10/80mg), amlodipine alone (5 mg or 10 mg), atorvastatin alone (10 mg, 20 mg, 40 mg, or 80 mg) or placebo.