Pharmacology Update

Amlodipine/Atorvastatin Tablets (Caduet)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The FDA has approved a combination product of amlodipine and atrovastatin for the treatment of patients with comorbid hypertension and hypercholesterolemia. Both ingredients are widely used in clinical practice; the calcium channel blocker amlodipine (Norvasc) for the treatment of hypertension and the statin atorvastatin (Lipitor) for the treatment of hypercholesterolemia. The single product is approved for the simultaneous treatment of both conditions and is available in multiple strengths. It is marketed by Pfizer as Caduet.

Indications

Amlodipine/atorvastatin is indicated for the treatment of hypertension, angina, and hyperlipidemia in patients for whom treatment with both agents is appropriate.1

Dosage

The dose should be determined based on titration of individual components. The combination product is available as 5 mg or 10 mg of amlodipine with 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin.

Potential Advantages

The combination provides a convenient product for the administration of amlodipine and atorvastatin.

Potential Disadvantages

The combination limits flexibility in selection of agents and dosage adjustment.

Comments

The approval of Caduet was based on a double-blind placebo-controlled study of 1660 patients with hypertension and dyslipidemia. Subjects were randomized to the 8 dose combinations of amlodipine/atorvastatin, amlodipine alone, atorvastatin alone, or placebo.1 The effects on blood pressure or cholesterol reduction did not differ among the groups on the combination or each agent alone. In a large study (n = 19,342) hypertensive subjects with average or lower-than-average total cholesterol levels (250 mg/dL or less), but with 3 or more risk factors, were randomized to receive atorvastatin or placebo in addition to their antihypertensive regimen.2 Patients were randomized to amlodipine with or without perindopril or atenolol with or without bendroflumethiazide.3 Treatment was stopped after a median follow-up of 3.3 years due to significant reduction in fatal and nonfatal strokes, total cardiovascular events and total coronary events. Overall mortality, however, was not significantly different. In a small study (n = 21) the combination of amilodipine and atorvastatin appear to have an additive effect on the reduction of arterial elasticity in patients with hypertension and hypercholesterolemia.4

The wholesale costs of Caduet ranged from $3 to $4 depending on the strength and are expected to be less then the costs of the drugs prescribed separately.

Clinical Implications

Recent studies have suggested that aggressive lowering of cholesterol appears to lead to better outcomes. Aggressive lowering of cholesterol reduced death and major cardiovascular events following acute coronary syndrome.5 Similarly, aggressive treatment appears to reduce the progression of coronary atherosclerosis.6

Finally, the addition of a statin to an antihypertensive regimen also appears to reduce cardiovascular events in patients with 3 or more cardiovascular risk factors. While Caduet offer convenience for patients with both risks factors, the combination is less useful for initial therapy because calcium channel blockers are not considered first line therapy for hypertension.

Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Asst. Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.

References

1. Cadets Product Information. Pfizer Labs. January 2004.

2. Sever PS, et al. Lancet. 2003;361:1149-1158.

3. Sever PS, et al. J Hypertens. 2001;6:1139-1147.

4. Leibovitz E, et al. Am J Hypertens. 2003;16(9 pt 1):715-718.

5. Cannon CP, et al. N Eng J Med. 2004;350:1495-1504.

6. Nissen SE, et al. JAMA. 2004;291:1071-1080.