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Prescribing Information
CADUET® (amlodipine besylate/atorvastatin calcium) Tablets
Dosage and Administration
Return to the CADUET Product Center

Dosage of CADUET must be individualized on the basis of both effectiveness and tolerance for each individual component in the treatment of hypertension/angina and hyperlipidemia.

Amlodipine (Hypertension or angina)

Adults: The usual initial antihypertensive oral dose of amlodipine is 5 mg once daily with a maximum dose of 10 mg once daily. Small, fragile, or elderly individuals, or patients with hepatic insufficiency may be started on 2.5 mg once daily and this dose may be used when adding amlodipine to other antihypertensive therapy.

Dosage should be adjusted according to each patient's need. In general, titration should proceed over 7 to 14 days so that the physician can fully assess the patient's response to each dose level. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently.

The recommended dose of amlodipine for chronic stable or vasospastic angina is 5-10 mg, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg for adequate effect. See ADVERSE REACTIONS section for information related to dosage and side effects.

The recommended dose range of amlodipine for patients with coronary artery disease is 5-10 mg once daily. In clinical studies the majority of patients required 10 mg (see CLINICAL PHARMACOLOGY, Clinical studies).

Children: The effective antihypertensive oral dose of amlodipine in pediatric patients ages 6-17 years is 2.5 mg to 5 mg once daily. Doses in excess of 5 mg daily have not been studied in pediatric patients. (see CLINICAL PHARMACOLOGY).

Atorvastatin (Hyperlipidemia)

Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)
The recommended starting dose of atorvastatin is 10 or 20 mg once daily. Patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg once daily. The dosage range of atorvastatin is 10 to 80 mg once daily. Atorvastatin can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of atorvastatin should be individualized according to patient characteristics such as goal of therapy and response (see current NCEP Guidelines). After initiation and/or upon titration of atorvastatin, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10-17 years of age)
The recommended starting dose of atorvastatin is 10 mg/day; the maximum recommended dose is 20 mg/day (doses greater than 20 mg have not been studied in this patient population). Doses should be individualized according to the recommended goal of therapy (see current NCEP Pediatric Panel Guidelines1, CLINICAL PHARMACOLOGY, and INDICATIONS AND USAGE.)  Adjustments should be made at intervals of 4 weeks or more.

Homozygous Familial Hypercholesterolemia
The dosage of atorvastatin in patients with homozygous FH is 10 to 80 mg daily.  Atorvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable. Note: a 2.5/80 mg CADUET tablet is not available. Management of patients needing a 2.5/80 mg combination requires individual assessments of dyslipidemia and therapy with the individual components as a 2.5/80 mg CADUET tablet is not available.

Concomitant Lipid Lowering Therapy
Atorvastatin may be used with bile acid resins. The combination of statins and fibrates should generally be used with caution (see WARNINGS, Skeletal Muscle, and PRECAUTIONS, Drug Interactions).

Dosage in Patients With Renal Impairment
Renal disease does not affect the plasma concentrations nor LDL-C reduction of atorvastatin; thus, dosage adjustment in patients with renal dysfunction is not necessary (see WARNINGS, Skeletal Muscle, and CLINICAL PHARMACOLOGY, Specific Populations).

Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or a Combination of Ritonavir plus Saquinavir or Lopinavir plus Ritonavir

In patients taking cyclosporine, therapy should be limited to LIPITOR 10 mg once daily. In patients taking clarithromycin, itraconazole or in patients with HIV taking a combination of ritonavir plus saquinavir or lopinavir plus ritonavir, for doses of atorvastatin exceeding 20 mg, appropriate clinical assessment is recommended to ensure that the lowest dose necessary of atorvastatin is employed (see WARNINGS, Skeletal Muscle, and PRECAUTIONS, Drug Interactions).

CADUET

CADUET may be substituted for its individually titrated components. Patients may be given the equivalent dose of CADUET or a dose of CADUET with increased amounts of amlodipine, atorvastatin or both for additional antianginal effects, blood pressure lowering, or lipid lowering effect.

CADUET may be used to provide additional therapy for patients already on one of its components. As initial therapy for one indication and continuation of treatment of the other, the recommended starting dose of CADUET should be selected based on the continuation of the component being used and the recommended starting dose for the added monotherapy.

CADUET may be used to initiate treatment in patients with hyperlipidemia and either hypertension or angina. The recommended starting dose of CADUET should be based on the appropriate combination of recommendations for the monotherapies. The maximum dose of the amlodipine component of CADUET is 10 mg once daily. The maximum dose of the atorvastatin component of CADUET is 80 mg once daily.

See above for detailed information related to the dosing and administration of amlodipine and atorvastatin.

  1. National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children Adolescents. Pediatrics. 89(3):495-501. 1992.

CADUET Safety Information
 

CADUET is a combination of two medications, Norvasc® (amlodipine besylate) and Lipitor® (atorvastatin calcium), and is indicated in patients for whom treatment with both Norvasc and Lipitor is appropriate.

Norvasc is indicated for the treatment of hypertension; treatment of chronic stable or vasospastic angina; and to reduce the risk of a coronary revascularization procedure and hospitalization due to angina in patients with recently angiographically documented CAD and without heart failure.

Lipitor is indicated as an adjunct to diet to reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adult patients with multiple risk factors but without clinically evident coronary heart disease (CHD); to reduce the risk of MI and stroke in patients with type 2 diabetes and without clinically evident CHD, but with multiple risk factors; to reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adult patients with clinically evident CHD; as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels; and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia.

Important Safety Information

CADUET is contraindicated in patients with active liver disease or unexplained persistent elevations of hepatic transaminases; in women who are or may become pregnant or who are nursing; in patients with hypersensitivity to any component of this medication.

Rare cases of rhabdomyolysis have been reported with the atorvastatin component of CADUET and with other statins. Tell patients to promptly report muscle pain, tenderness, or weakness. Predisposing factors include advanced age (≥65), uncontrolled hypothyroidism, and renal impairment. Patients with a history of renal impairment merit closer monitoring. In cases of myopathy or rhabdomyolysis, therapy should be temporarily withheld or discontinued.

The concomitant use of higher doses of atorvastatin with certain drugs such as cyclosporine and strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, and HIV protease inhibitors) increased the risk of myopathy/rhabdomyolysis. Lower doses of the atorvastatin component of CADUET should be considered. Physicians should carefully monitor patients for signs or symptoms of myopathy early during therapy and when titrating the dose of either drug.

It is recommended that liver function tests be performed prior to and at 12 weeks following both the initiation of CADUET therapy and any elevation in dose of the atorvastatin component, and periodically thereafter. If ALT or AST values >3 x ULN persist, dose reduction or withdrawal of CADUET is recommended.

Generally CCBs should be used with caution in patients with heart failure. In studies with amlodipine, there has been no evidence of worsened heart failure.

In a controlled clinical trial, the most common adverse events were edema, headache, and dizziness. These were similar to those reported previously with amlodipine and/or atorvastatin.

In a post hoc analysis of the SPARCL study in patients without CHD who had a stroke or TIA within the preceding 6 months, a higher incidence of hemorrhagic stroke was seen in the atorvastatin 80-mg group compared with placebo (2.3% vs. 1.4%). Some baseline characteristics, including hemorrhagic and lacunar stroke on study entry, were associated with a higher incidence of hemorrhagic stroke in the atorvastatin group.

 

Please see full prescribing information.

CADUET® (amlodipine besylate/atorvastatin calcium)

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