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Amlodipine/Atorvastatin (Caduet) for Preventing Heart Disease



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Am Fam Physician. 2006 Mar 15;73(6):1067-1068.

Synopsis

Amlodipine/atorvastatin (Caduet) is a combination of two drugs, amlodipine (Norvasc) and atorvastatin (Lipitor). Amlodipine is a long-acting dihydropyridine calcium-channel blocker indicated for the treatment of hypertension, chronic stable angina, and vasospastic angina. Atorvastatin is a synthetic HMG-CoA reductase inhibitor (statin) indicated for the prevention of cardiovascular disease in persons with multiple risk factors for coronary heart disease, heterozygous familial and nonfamilial hypercholesterolemia, and elevated serum triglycerides. Amlodipine/atorvastatin, which is not a first-line drug, is indicated for patients who require simultaneous treatment with both drugs.

Name Dosage Dose form Approximate monthly cost*

Amlodipine/atorvastatin (Caduet)

Individualized based on effectiveness and tolerance

2.5/10-, 2.5/20-, 2.5/40-, 5/10-, 5/20-, 5/40-, 5/80-, 10/10-, 10/20-, 10/40-, and 10/80-mg tablets

$104 (2.5/10, 5/10, and 10/10 mg)

10/80 mg per day maximum

$142 (2.5/20, 2.5/40, 5/20, 5/40, 5/80, 10/20, 10/40, and 10/80 mg)


*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2005.

Name Dosage Dose form Approximate monthly cost*

Amlodipine/atorvastatin (Caduet)

Individualized based on effectiveness and tolerance

2.5/10-, 2.5/20-, 2.5/40-, 5/10-, 5/20-, 5/40-, 5/80-, 10/10-, 10/20-, 10/40-, and 10/80-mg tablets

$104 (2.5/10, 5/10, and 10/10 mg)

10/80 mg per day maximum

$142 (2.5/20, 2.5/40, 5/20, 5/40, 5/80, 10/20, 10/40, and 10/80 mg)


*—Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2005.

Safety

Amlodipine/atorvastatin has the same safety profile as its individual components and can be administered safely across the dosage range.1 Serious but rare side effects include hepatotoxicity and rhabdomyolysis, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and cardiac failure. Amlodipine/atorvastatin is contraindicated in women who are pregnant (U.S. Food and Drug Administration pregnancy category X) or breastfeeding, and in persons with active liver disease, unexplained persistent elevation of serum transaminase, or a history of hypersensitivity to either component.1

Tolerability

The side effects of amlodipine/atorvastatin are similar to those for each component, most commonly abdominal pain, constipation, dyspepsia, edema, flatulence, and headache. Five percent of patients discontinue therapy because of side effects.2

Effectiveness

The goal of treating hypertension and hyperlipidemia is to reduce cardiovascular morbidity and mortality. Diuretics are the first-line agents for hypertension because they are safe and inexpensive and have been shown to decrease all-cause morbidity and mortality.3

The angiotensin-converting enzyme (ACE) inhibitor ramipril (Altace) was shown to prevent progressive renal disease more effectively than amlodipine in black patients with hypertension.4 Amlodipine, although effective at lowering blood pressure and treating anginal symptoms, has not been shown to reduce the risks of myocardial infarction, stroke, or death.57 Amlodipine also has been associated with worse cardiovascular outcomes than ACE inhibitors despite similar effects on blood-pressure lowering.7

Atorvastatin has been shown to be effective as primary prevention in patients with diabetes.8 It also has been shown to prevent rehospitalization as a result of a current ischemic episode in those who have experienced acute coronary syndrome.9 However, atorvastatin has not been shown to decrease all-cause mortality in patients with or without coronary heart disease.8 There are no data that suggest taking combination therapy provides different outcomes than taking the individual products.

Price

A one-month supply of amlodipine/atorvastatin tablets costs approximately $104 (2.5/10, 5/10, and 10/10 mg) or $142 (2.5/20, 2.5/40, 5/20, 5/40, 5/80, 10/20, 10/40, and 10/80 mg), slightly lower than the cost of the drugs individually—amlodipine $50 (2.5 and 5 mg) to $69 (10 mg) and atorvastatin $78 (10 mg) to $113 (20, 40, and 80 mg). When generic versions of the individual drugs become available, the cost difference will reverse to favor the individual drugs. The patent for Norvasc is due to expire in 2007, and that for Lipitor in 2010. For some patients, however, one insurance co-pay for the combination product may be favorable compared with two separate co-pays.

Simplicity

For patients, taking one tablet can be simpler than taking two products, but no research has been performed to evaluate the difference in compliance. For physicians developing an appropriate treatment plan for these patients, titrating the doses of the individual drugs using separate products might be easier than using the combination product. Amlodipine/atorvastatin can be used in patients as young as six years; 2.5 mg amlodipine usually is appropriate for older persons and children.1 The maximum recommended atorvastatin dosage for children six to 17 years of age is 20 mg daily.1

Bottom Line

Amlodipine/atorvastatin offers no added benefit in safety, tolerability, or effectiveness over amlodipine and atorvastatin taken separately. It has not been shown to improve mortality or morbidity in patients who have hypertension with or without dyslipidemia. The only potential advantages to amlodipine/atorvastatin therapy are convenience and a single insurance co-pay. Calcium-channel blockers, including amlodipine, are not the drugs of choice for treating hypertension; they are for patients who cannot tolerate or who do not experience adequate control with diuretics, beta blockers, or ACE inhibitors. Amlodipine/atorvastatin should not be used as initial therapy but may be useful once the dosages have been titrated.

The Authors

STEPHEN A. WILSON, M.D., M.P.H., is assistant director at the University of Pittsburgh Medical Center, St. Margaret Family Medicine Residency, Pittsburgh, Pa.

ANNETTE SANFORD, PHARM.D., is family medicine specialty pharmacy resident in the Department of Medical Education at the University of Pittsburgh Medical Center, St. Margaret Family Medicine Residency.

REFERENCES

1. Caduet (amlodipine/atorvastatin) tablets. Product information. New York: Pfizer Labs, 2004. Accessed online November 29, 2005, at: http://www.pfizer.com/pfizer/download/uspi_caduet.pdf.

2. Blank R, LaSalle J, Reeves R, Maroni J, Tarasenko L, Sun F. Single-pill therapy in the treatment of concomitant hypertension and dyslipidemia (the amlodipine/atorvastatin gemini study). J Clin Hypertens. 2005;7:264–73.

3. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. . Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs. usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288:2998–007.

4. Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, et al., African American Study of Kidney Disease and Hypertension Study Group. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002;288:2421–1.

5. Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292:2217–5.

6. Opie LH, Schall R. Evidence-based evaluation of calcium channel blockers for hypertension: equality of mortality and cardiovascular risk relative to conventional therapy [published correction appears in J Am Coll Cardiol 2002;39:1409–10]. J Am Coll Cardiol. 2002;39:315–2.

7. Tatti P, Pahor M, Byington RP, Di Mauro P, Guarisco R, Strollo G, et al. Outcome results of the Fosinopril versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998;21:597–603.

8. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial. Lancet. 2004;364:685–96.

9. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al., Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285:1711–8.

STEPS drug updates cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each update provides an independent review of a new medication by authors who have no financial association with the drug manufacturer.

The series coordinator is Allen F. Shaughnessy, Pharm.D., Tufts University Family Medicine Residency Program, Boston, Mass.


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