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Caduet (Amlodipine Besylate / Atorvastatin Calcium) - Indications and Dosage

 
 



TABLE 5. Overview of Efficacy Results in TNT
Endpoint


Atorvastatin 10
mg
(N=5006)

Atorvastatin 80
mg
(N=4995)


HR * (95%CI)

PRIMARY ENDPOINT
n
(%)
n
(%)

First major cardiovascular endpoint
548
(10.9)
434
(8.7)
0.78 (0.69, 0.89)
Components of the Primary Endpoint





CHD death
127
(2.5)
101
(2.0)
0.80 (0.61, 103)
Non-fatal, non-procedure related MI
308
(6.2)
243
(4.9)
0.78 (0.66, 0.93)
Resuscitated cardiac arrest
26
(0.5)
25
(0.5)
0.96 (0.56, 1.67)
Stroke (fatal and non-fatal)
155
(3.1)
117
(2.3)
0.75 (0.59, 0.96)
SECONDARY ENDPOINTS




First CHF with hospitalization
164
(3.3)
122
(2.4)
0.74 (0.59, 0.94)
First PVD endpoint
282
(5.6)
275
(5.5)
0.97 (0.83, 1.15)
First CABG or other coronary
revascularization procedure ‡
904
(18.1)
667
(13.4)
0.72 (0.65, 0.80)
First documented angina endpoint ‡ 615
12.3)
545
(10.9)
0.88 (0.79, 0.99)
All cause mortality
282
(5.6)
284
(5.7)
1.01 (0.85, 1.19)
Components of all cause mortality





Cardiovascular death
155
(3.1)
126
(2.5)
0.81 (0.64, 1.03)
Noncardiovascular death
127
(2.5)
158
(3.2)
1.25 (0.99, 1.57)
Cancer death
75
(1.5)
85
(1.7)
1.13 (0.83, 1.55)
Other non-CV death
43
(0.9)
58
(1.2)
1.35 (0.91, 2.00)
Suicide, homicide and other traumatic
non-CV death
9
(0.2)
15
(0.3)
1.67 (0.73, 3.82)
HR=hazard ratio, CHD =coronary heart disease; CI=confidence interval; MI=myocardial infarction; CHF=congestive heart failure;
CV=cardiovascular; PVD=peripheral vascular disease; CABG=coronary artery bypass graft
Confidence intervals for the Secondary Endpoints were not adjusted for multiple comparisons.
*      Atorvastatin 80 mg: atorvastatin 10 mg
†      Secondary endpoints not included in primary endpoint
‡      Component of other secondary endpoints


Of the events that comprised the primary efficacy endpoint, treatment with LIPITOR 80 mg/day significantly reduced the rate of non-fatal, non-procedure related MI and fatal and non-fatal stroke, but not CHD death or resuscitated cardiac arrest (Table 5). Of the predefined secondary endpoints, treatment with LIPITOR 80 mg/day significantly reduced the rate of coronary revascularization, angina, and hospitalization for heart failure, but not peripheral vascular disease. The reduction in the rate of CHF with hospitalization was only observed in the 8% of patients with a prior history of CHF.

There was no significant difference between the treatment groups for all-cause mortality (Table 5). The proportions of subjects who experienced cardiovascular death, including the components of CHD death and fatal stroke, were numerically smaller in the LIPITOR 80 mg group than in the LIPITOR 10 mg treatment group. The proportions of subjects who experienced noncardiovascular death were numerically larger in the LIPITOR 80 mg group than in the LIPITOR 10 mg treatment group.

In the Incremental Decrease in Endpoints Through Aggressive Lipid Lowering Study (IDEAL), treatment with LIPITOR 80 mg/day was compared to treatment with simvastatin 20–40 mg/day in 8,888 subjects up to 80 years of age with a history of CHD to assess whether reduction in CV risk could be achieved. Patients were mainly male (81%), white (99%) with an average age of 61.7 years, and an average LDL-C of 121.5 mg/dL at randomization; 76% were on statin therapy. In this prospective, randomized, open-label, blinded endpoint (PROBE) trial with no run-in period, subjects were followed for a median duration of 4.8 years. The mean LDL-C, TC, TG, HDL, and non-HDL cholesterol levels at Week 12 were 78, 145, 115, 45, and 100 mg/dL during treatment with 80 mg of LIPITOR and 105, 179, 142, 47, and 132 mg/dL during treatment with 20–40 mg of simvastatin.

There was no significant difference between the treatment groups for the primary endpoint, the rate of first major coronary event (fatal CHD, nonfatal MI and resuscitated cardiac arrest): 411 (9.3%) in the LIPITOR 80 mg/day group vs. 463 (10.4%) in the simvastatin 20–40 mg/day group, HR 0.89, 95% CI (0.78, 1.01), p=0.07.

There were no significant differences between the treatment groups for all-cause mortality: 366 (8.2%) in the LIPITOR 80 mg/day group vs. 374 (8.4%) in the simvastatin 20–40 mg/day group. The proportions of subjects who experienced CV or non-CV death were similar for the LIPITOR 80 mg group and the simvastatin 20–40 mg group.

Atorvastatin Studies in Hyperlipidemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Fredrickson Types IIa and IIb)

Atorvastatin reduces total-C, LDL-C, VLDL-C, apo B, and TG, and increases HDL-C in patients with hyperlipidemia and mixed dyslipidemia. Therapeutic response is seen within 2 weeks, and maximum response is usually achieved within 4 weeks and maintained during chronic therapy.

Atorvastatin is effective in a wide variety of patient populations with hyperlipidemia, with and without hypertriglyceridemia, in men and women, and in the elderly.

In two multicenter, placebo-controlled, dose-response studies in patients with hyperlipidemia, atorvastatin given as a single dose over 6 weeks, significantly reduced total-C, LDL-C, apo B, and TG (pooled results are provided in Table 6).

Table 6. Dose-Response in Patients With Primary Hyperlipidemia (Adjusted Mean Percent Change From Baseline)*
Dose
N     
TC
LDL-C
Apo B
TG
HDL-C
Non-HDL-C/ HDL-C
Placebo    
21     
4
4
3
10
-3
7
10
22     
-29
-39
-32
-19
6
-34
20
20     
-33
-43
-35
-26
9
-41
40
21    
-37
-50
-42
-29
6
-45
80
23     
-45
-60
-50
-37
5
-53
*      Results are pooled from 2 dose-response studies.


In patients with Fredrickson Types IIa and IIb hyperlipoproteinemia pooled from 24 controlled trials, the median (25th and 75th percentile) percent changes from baseline in HDL-C for atorvastatin 10, 20, 40, and 80 mg were 6.4 (-1.4, 14), 8.7 (0, 17), 7.8 (0, 16), and 5.1 (-2.7, 15), respectively. Additionally, analysis of the pooled data demonstrated consistent and significant decreases in total-C, LDL-C, TG, total-C/HDL-C, and LDL-C/HDL-C.

In three multicenter, double-blind studies in patients with hyperlipidemia, atorvastatin was compared to other statins. After randomization, patients were treated for 16 weeks with either atorvastatin 10 mg per day or a fixed dose of the comparative agent (Table 7).

Table 7. Mean Percent Change From Baseline at Endpoint (Double-Blind, Randomized, Active-Controlled Trials)
Treatment
(Daily Dose)

N

Total-C

LDL-C

Apo B

TG

HDL-C
Non-HDL-C/
HDL-C
Study 1







Atorvastatin 10 mg 707
-27 * -36 * -28 * -17 * +7
-37 *
Lovastatin 20 mg
191
-19
-27
-20
-6
+7
-28
95% CI for Diff †
-9.2, -6.5
-10.7, -7.1
-10.0, -6.5
-15.2, -7.1
-1.7, 2.0
-11.1, -7.1
Study 2







Atorvastatin 10 mg 222
-25 ‡ -35 ‡ -27 ‡ -17 ‡ +6
-36 ‡
Pravastatin 20 mg
77
-17
-23
-17
-9
+8
-28
95% CI for Diff †
-10.8, -6.1
-14.5, -8.2
-13.4, -7.4
-14.1, -0.7
-4.9, 1.6
-11.5, -4.1
Study 3







Atorvastatin 10 mg 132
-29 § -37 § -34 § -23 § +7
-39 §
Simvastatin 10 mg
45
-24
-30
-30
-15
+7
-33
95% CI for Diff †
-8.7, -2.7
-10.1, -2.6
-8.0, -1.1
-15.1, -0.7
-4.3, 3.9
-9.6, -1.9
*      Significantly different from lovastatin, ANCOVA, p less than or equal to 0.05
†      A negative value for the 95% CI for the difference between treatments favors atorvastatin for all except HDL-C, for which a positive value favors atorvastatin. If the range does not include 0, this indicates a statistically significant difference.
‡      Significantly different from pravastatin, ANCOVA, p less than or equal to 0.05
§     
   Significantly different from simvastatin, ANCOVA, p less than or equal to 0.05

The impact on clinical outcomes of the differences in lipid-altering effects between treatments shown in Table 7 is not known. Table 7 does not contain data comparing the effects of atorvastatin 10 mg and higher doses of lovastatin, pravastatin, and simvastatin. The drugs compared in the studies summarized in the table are not necessarily interchangeable.

Atorvastatin Effects in Hypertriglyceridemia (Fredrickson Type IV)

The response to atorvastatin in 64 patients with isolated hypertriglyceridemia treated across several clinical trials is shown in the table below (Table 8). For the atorvastatin-treated patients, median (min, max) baseline TG level was 565 (267–1502).

Table 8. Combined Patients With Isolated Elevated TG: Median (min, max) Percent Changes From Baseline

Placebo
(N=12)
Atorvastatin 10 mg
(N=37)
Atorvastatin 20 mg
(N=13)
Atorvastatin 80 mg
(N=14)
Triglycerides -12.4 (-36.6, 82.7) -41.0 (-76.2, 49.4) -38.7 (-62.7, 29.5) -51.8 (-82.8, 41.3)
Total-C -2.3 (-15.5, 24.4) -28.2 (-44.9, -6.8) -34.9 (-49.6, -15.2) -44.4 (-63.5, -3.8)
LDL-C 3.6 (-31.3, 31.6) -26.5 (-57.7, 9.8) -30.4 (-53.9, 0.3) -40.5 (-60.6, -13.8)
HDL-C 3.8 (-18.6, 13.4) 13.8 (-9.7, 61.5) 11.0 (-3.2, 25.2) 7.5 (-10.8, 37.2)
VLDL-C -1.0 (-31.9, 53.2) -48.8 (-85.8, 57.3) -44.6 (-62.2, -10.8) -62.0 (-88.2, 37.6)
non-HDL-C -2.8 (-17.6, 30.0) -33.0 (-52.1, -13.3) -42.7 (-53.7, -17.4) -51.5 (-72.9, -4.3)
Atorvastatin Effects in Dysbetalipoproteinemia (Fredrickson Type III)

The results of an open-label crossover study of atorvastatin in 16 patients (genotypes: 14 apo E2/E2 and 2 apo E3/E2) with dysbetalipoproteinemia (Fredrickson Type III) are shown in the table below (Table 9).

Table 9. Open-Label Crossover Study of 16 Patients With Dysbetalipoproteinemia (Fredrickson Type III)


Median % Change (min, max)

Median (min, max) at
Baseline (mg/dL)
Atorvastatin 10 mg Atorvastatin 80 mg
Total-C 442 (225, 1320) -37 (-85, 17) -58 (-90, -31)
Triglycerides 678 (273, 5990) -39 (-92, -8) -53 (-95, -30)
IDL-C + VLDL-C 215 (111, 613) -32 (-76, 9) -63 (-90, -8)
non-HDL-C 411 (218, 1272) -43 (-87, -19) -64 (-92, -36)
Atorvastatin Effects in Homozygous Familial Hypercholesterolemia

In a study without a concurrent control group, 29 patients ages 6 to 37 years with homozygous FH received maximum daily doses of 20 to 80 mg of atorvastatin. The mean LDL-C reduction in this study was 18%. Twenty-five patients with a reduction in LDL-C had a mean response of 20% (range of 7% to 53%, median of 24%); the remaining 4 patients had 7% to 24% increases in LDL-C. Five of the 29 patients had absent LDL-receptor function. Of these, 2 patients also had a portacaval shunt and had no significant reduction in LDL-C. The remaining 3 receptor-negative patients had a mean LDL-C reduction of 22%.

Atorvastatin Effects in Heterozygous Familial Hypercholesterolemic Pediatric Patients

In a double-blind, placebo-controlled study followed by an open-label phase, 187 boys and postmenarchal girls 10–17 years of age (mean age 14.1 years) with heterozygous FH or severe hypercholesterolemia, were randomized to atorvastatin (n=140) or placebo (n=47) for 26 weeks and then all received atorvastatin for 26 weeks. Inclusion in the study required 1) a baseline LDL-C level ≥ 190 mg/dL or 2) a baseline LDL-C level ≥ 160 mg/dL and positive family history of FH or documented premature cardiovascular disease in a first- or second-degree relative. The mean baseline LDL-C value was 218.6 mg/dL (range: 138.5–385.0 mg/dL) in the atorvastatin group compared to 230.0 mg/dL (range: 160.0–324.5 mg/dL) in placebo group. The dosage of atorvastatin (once daily) was 10 mg for the first 4 weeks and up-titrated to 20 mg if the LDL-C level was > 130 mg/dL. The number of atorvastatin-treated patients who required up-titration to 20 mg after Week 4 during the double-blind phase was 80 (57.1%).

Atorvastatin significantly decreased plasma levels of total-C, LDL-C, triglycerides, and apolipoprotein B during the 26 week double-blind phase (see Table 10).

Table 10. Lipid-altering Effects of Atorvastatin in Adolescent Boys and Girls with Heterozygous Familial Hypercholesterolemia or Severe Hypercholesterolemia (Mean Percent Change From Baseline at Endpoint in Intention-to-Treat Population)
DOSAGE N Total-C LDL-C HDL-C TG Apolipoprotein B
Placebo 47 -1.5 -0.4 -1.9 1.0 0.7
Atorvastatin 140 -31.4 -39.6 2.8 -12.0 -34.0

The mean achieved LDL-C value was 130.7 mg/dL (range: 70.0–242.0 mg/dL) in the atorvastatin group compared to 228.5 mg/dL (range: 152.0–385.0 mg/dL) in the placebo group during the 26 week double-blind phase.

The safety and efficacy of atorvastatin doses above 20 mg have not been studied in controlled trials in children. The long-term efficacy of atorvastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.

Clinical Study of Combined Amlodipine and Atorvastatin in Patients with Hypertension and Dyslipidemia

In a double-blind, placebo-controlled study, a total of 1660 patients with co-morbid hypertension and dyslipidemia 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 10/80 mg), amlodipine alone (5 mg or 10 mg), atorvastatin alone (10 mg, 20 mg, 40 mg, or 80 mg) or placebo. In addition to concomitant hypertension and dyslipidemia, 15% of the patients had diabetes mellitus, 22% were smokers and 14% had a positive family history of cardiovascular disease. At eight weeks, all eight 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, with no overall modification of effect of either component on SBP, DBP and LDL-C (Table 11).

Table 11. Efficacy in Terms of Reduction in Blood Pressure and LDL-C
Efficacy of the Combined Treatments in Reducing Systolic BP
Parameter / Analysis ATO 0 mg ATO 10 mg ATO 20 mg ATO 40 mg ATO 80 mg

Mean change
(mmHg)
-3.0 -4.5 -6.2 -6.2 -6.4
AML 0 mg






Difference versus
placebo (mmHg)
- -1.5 -3.2 -3.2 -3.4

Mean change
(mmHg)
-12.8 -13.7 -15.3 -12.7 -12.2
AML 5 mg






Difference versus
placebo (mmHg)
-9.8 -10.7 -12.3 -9.7 -9.2

Mean change
(mmHg)
-16.2 -15.9 -16.1 -16.3 -17.6
AML 10 mg






Difference versus
placebo (mmHg)
-13.2 -12.9 -13.1 -13.3 -14.6

Efficacy of the Combined Treatments in Reducing Diastolic BP
Parameter / Analysis ATO 0 mg ATO 10 mg ATO 20 mg ATO 40 mg ATO 80 mg

Mean change
(mmHg)
-3.3 -4.1 -3.9 -5.1 -4.1
AML 0 mg






Difference versus
placebo (mmHg)
- -0.8 -0.6 -1.8 -0.8

Mean change
(mmHg)
-7.6 -8.2 -9.4 -7.3 -8.4
AML 5 mg






Difference versus
placebo (mmHg)
-4.3 -4.9 -6.1 -4.0 -5.1

Mean change
(mmHg)
-10.4 -9.1 -10.6 -9.8 -11.1
AML 10 mg






Difference versus
placebo (mmHg)
-7.1 -5.8 -7.3 -6.5 -7.8

Efficacy of the Combined Treatments in Reducing LDL-C (% change)
Parameter / Analysis ATO 0 mg ATO 10 mg ATO 20 mg ATO 40 mg ATO 80 mg







AML 0 mg Mean % change -1.1 -33.4 -39.5 -43.1 -47.2














AML 5 mg Mean % change -0.1 -38.7 -42.3 -44.9 -48.4














AML 10 mg Mean % change -2.5 -36.6 -38.6 -43.2 -49.1




INDICATIONS AND USAGE

CADUET (amlodipine and atorvastatin) is indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate.

Amlodipine1. Hypertension : Amlodipine is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents; 2. Coronary Artery Disease (CAD)
Chronic Stable Angina: Amlodipine is indicated for the treatment of chronic stable angina. Amlodipine may be used alone or in combination with other antianginal or antihypertensive agents;
Vasospastic Angina (Prinzmetal's or Variant Angina): Amlodipine is indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine may be used as monotherapy or in combination with other antianginal drugs.
Angiographically Documented CAD: In patients with recently documented CAD by angiography and without heart failure or an ejection fraction less than 40%, amlodipine is indicated to reduce the risk of hospitalization due to angina and to reduce the risk of a coronary revascularization procedure.

AND

Atorvastatin

Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is recommended as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with CHD or multiple risk factors for CHD, the atorvastatin component of CADUET can be started simultaneously with diet restriction.

1. Prevention of Cardiovascular Disease: In adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low HDL-C, or a family history of early coronary heart disease, atorvastatin is indicated to:

  • Reduce the risk of myocardial infarction
  • Reduce the risk of stroke
  • Reduce the risk for revascularization procedures and angina

In patients with type 2 diabetes, and without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as retinopathy, albuminuria, smoking, or hypertension, LIPITOR is indicated to:
  • Reduce the risk of myocardial infarction
  • Reduce the risk of stroke;

In patients with clinically evident coronary heart disease, LIPITOR is indicated to:
  • Reduce the risk of non-fatal myocardial infarction
  • Reduce the risk of fatal and non-fatal stroke
  • Reduce the risk for revascularization procedures
  • Reduce the risk of hospitalization for CHF
  • Reduce the risk of angina

2. Heterozygous Familial and Nonfamilial Hyperlipidemia : Atorvastatin is indicated 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 (Fredrickson Types IIa and IIb); 3. Elevated Serum TG Levels : Atorvastatin is indicated as an adjunct to diet for the treatment of patients with elevated serum TG levels (Fredrickson Type IV); 4. Primary Dysbetalipoproteinemia : Atorvastatin is indicated for the treatment of patients with primary dysbetalipoproteinemia (Fredrickson Type III) who do not respond adequately to diet; 5. Homozygous Familial Hypercholesterolemia : Atorvastatin is indicated to reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable; 6. Pediatric Patients : Atorvastatin is indicated as an adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present:
  • LDL-C remains greater than or equal to 190 mg/dL or
  • LDL-C remains greater than or equal to 160 mg/dL and:
      there is a positive family history of premature cardiovascular disease or
    • two or more other CVD risk factors are present in the pediatric patients.

The antidyslipidemic component of CADUET has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons (Fredrickson Types I and V).

DOSAGE AND ADMINISTRATION

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 Guidelines 3, CLINICAL PHARMACOLOGY, and INDICATIONS AND USAGE). Adjustments should be made at intervals of 4 weeks or more.

3 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. 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. Monitor for signs of myopathy in patients receiving the combination of statins and fibrates (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.

HOW SUPPLIED

CADUET tablets contain amlodipine besylate and atorvastatin calcium equivalent to amlodipine and atorvastatin in the dose strengths described below.

CADUET tablets are differentiated by tablet color/size and are engraved with "Pfizer" on one side and a unique number on the other side. CADUET tablets are supplied for oral administration in the following strengths and package configurations:

Table 14. CADUET Packaging Configurations
CADUET
Package
Configuration
Tablet Strength
(amlodipine besylate/
atorvastatin calcium) mg
NDC # Engraving Tablet Color





Bottle of 30
2.5/20 54868-5672-0 CDT 252 White
Bottle of 30 2.5/40 54868-5699-0
CDT 254 White
Bottle of 30
Bottle of 90
5/10 54868-3287-0
54868-3287-1
CDT 051 White
Bottle of 30
Bottle of 90
5/20 54868-1207-0
54868-1207-1
CDT 052 White
Bottle of 30 5/40 54868-5179-0 CDT 054 White
Bottle of 30 5/80 54868-5420-0
CDT 058 White
Bottle of 30 10/10 54868-5567-0 CDT 101 Blue
Bottle of 30
Bottle of 90
10/20 54868-5209-0
54868-5209-1
CDT 102 Blue
Bottle of 30
Bottle of 90
10/40 54868-5200-0
54868-5200-1
CDT 104 Blue
Bottle of 30
Bottle of 90
10/80 54868-5523-0
54868-5523-1
CDT 108 Blue

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

Rx only

Manufactured by:
Pfizer Ireland Pharmaceuticals
Dublin, Ireland

LAB-0276-15.0

January 2010

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