RxPRODUCT NEWS PROFILE: Caduet

Pfizer's Caduet (amlodipine besylate and atorvastatin calcium) received FDA approval January 30, 2004, as the first dual-therapy product to be marketed for hypertension and dyslipidemia and the first cross-risk-factor single-pill combination. Whereas Pfizer currently markets both of Caduet's individual ingredients? Norvasc (amlodipine besylate) and Lipitor (atorvastatin calcium)? the combination of the 2 drugs is new. Approximately 30 million Americans suffer from both hypertension and hyperlipidemia, yet only 10% are appropriately treated for both. Patients with both disease states are at a higher risk for cardiovascular events than patients with only 1 ailment.¹

Additionally, the results of a recent study suggest that lipid-lowering agents may be cardioprotective in patients with normal to mildly elevated cholesterol levels. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), a European prospective, randomized, controlled clinical trial, showed that hypertensive patients with normal to slightly elevated cholesterol levels who took atorvastatin had 36% fewer fatal coronary events and nonfatal heart attacks than patients in the control group.² As a result, Pfizer is targeting both conditions with 1 pill to optimize the management of comorbid hypertension and dyslipidemia. In addition, a combination product may improve patient compliance, because the patient will need to take only 1 pill and pay for only 1 product.

Pharmacology of Atorvastatin

Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the enzyme involved in cholesterol formation. In addition to preventing cholesterol formation in the liver, atorvastatin increases the number of hepatic low-density lipoprotein (LDL) receptors, which increases LDL uptake and catabolism. In vitro studies have shown that atorvastatin is metabolized by cytochrome P-450 3A4, and caution should be used when administering atorvastatin and inhibitors of this enzyme. Atorvastatin is primarily hepatically metabolized; clinicians should consider dosage adjustments in patients with hepatic insufficiency. No dosage adjustment is required in renal insufficiency. Atorvastatin's mean plasma half-life is 14 hours, but, due to active metabolites, its HMG-CoA reductase inhibition can last 20 to 30 hours.³

Pharmacology of Amlodipine

Amlodipine is a dihydropyridine calcium channel blocker. It inhibits the influx of calcium ions into vascular smooth muscle and cardiac muscle, resulting in reduced peripheral vascular resistance and reduced blood pressure. Amlodipine is metabolized hepatically. Dosing adjustments are necessary for patients with hepatic insufficiency. No dosing adjustment is needed in renal insufficiency.

Amlodipine's terminal half-life is 30 to 50 hours. Steady-state plasma levels are reached after 7 to 8 days of daily dosing.4

Clinical Trials

Although the results of Caduet's clinical trials have not yet been released, preliminary reports show that many of the 3700 patients taking Caduet have successfully reached optimal control of their hypertension and dyslipidemia.¹

Safety

The most commonly reported adverse drug reactions with Caduet were described as mild to moderate. They included headache, dizziness, fluid retention, weakness, and abdominal pain. As with other HMG-CoA reductase inhibitors, patients experiencing muscle pain, tenderness, or weakness should contact their physician immediately, because these symptoms may be signs of a serious statinrelated adverse reaction.

Caduet has been used in conjunction with thiazide diuretics, betablockers, and angiotensin-converting enzyme inhibitors. It is contraindicated in patients with active liver disease or unexplained elevation of serum transaminase. Caduet should not be used in women who are pregnant or breast-feeding.¹

Availability

Pfizer plans to market several strengths of Caduet. At this time, the strengths are not available. Caduet's introduction heralds a new era, in which drug companies may create combination dosage forms to address common comorbidities.

Dr. Holmberg is a pharmacist with Phoenix Indian Medical Center, Phoenix, Ariz. Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health. The opinions expressed herein are those of the authors and not necessarily of any government agency.

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