Caduet Indications and Usage
CADUET (amlodipine and atorvastatin) is indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate.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.
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.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
- 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).
CADUET contains atorvastatin and is therefore contraindicated in patients with active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.
CADUET is contraindicated in patients with known hypersensitivity to any component of this medication.
Pregnancy and Lactation
CADUET contains atorvastatin and is therefore contraindicated in women who are pregnant or may become pregnant. The atorvastatin component of CADUET may cause fetal harm when administered to a pregnant woman. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia.
There are no adequate and well-controlled studies of atorvastatin use during pregnancy; however in rare reports congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, atorvastatin revealed no evidence of teratogenicity. CADUET, WHICH INCLUDES ATORVASTATIN, SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING AGE ONLY WHEN SUCH PATIENTS ARE HIGHLY UNLIKELY TO CONCEIVE AND HAVE BEEN INFORMED OF THE POTENTIAL HAZARDS. If the patient becomes pregnant while taking this drug, therapy should be discontinued immediately and the patient apprised of the potential hazard to the fetus (see PRECAUTIONS, Pregnancy).
It is not known whether atorvastatin or amlodipine are excreted into human milk; however a small amount of another statin does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women taking CADUET should not breastfeed their infants (see PRECAUTIONS, Nursing Mothers).
Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with the atorvastatin component of CADUET and with other statins. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Such patients merit closer monitoring for skeletal muscle effects.
The atorvastatin component of CADUET, like other statins, occasionally causes myopathy, defined as muscle aches or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values >10 times ULN. 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) increases the risk of myopathy/rhabdomyolysis.
Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, or marked elevation of CPK. Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. CADUET therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.
The risk of myopathy during treatment with statins is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, clarithromycin, combination of ritonavir plus saquinavir or lopinavir plus ritonavir, niacin, or azole antifungals. Physicians considering combined therapy with CADUET and fibric acid derivatives, erythromycin, clarithromycin, a combination of ritonavir plus saquinavir or lopinavir plus ritonavir, immunosuppressive drugs, azole antifungals, or lipid-modifying doses of niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs or symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Lower starting and maintenance doses of atorvastatin should be considered when taken concomitantly with the aforementioned drugs (see PRECAUTIONS, Drug Interactions). Periodic creatine phosphokinase (CPK) determinations may be considered in such situations, but there is no assurance that such monitoring will prevent the occurrence of severe myopathy.
Prescribing recommendations for atorvastatin, a component of CADUET, and interacting agents are summarized in Table 12 (see DOSAGE AND ADMINISTRATION, PRECAUTIONS, Drug Interactions, and CLINICAL PHARMACOLOGY).
|Interacting Agents||Prescribing Recommendations|
|Cyclosporine||Do not exceed 10 mg atorvastatin daily|
|Clarithromycin, Itraconazole, HIV protease inhibitors (ritonavir plus saquinavir or lopinavir plus ritonavir,)||Caution when exceeding doses > 20mg atorvastatin daily. The lowest dose necessary should be used.|
In patients taking CADUET, therapy should be temporarily withheld or discontinued in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).
Statins, like the atorvastatin component of CADUET and like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. Persistent elevations (>3 times the upper limit of normal [ULN] occurring on 2 or more occasions) in serum transaminases occurred in 0.7% of patients who received atorvastatin in clinical trials. The incidence of these abnormalities was 0.2%, 0.2%, 0.6%, and 2.3% for 10, 20, 40, and 80 mg, respectively.
In clinical trials in patients taking the atorvastatin component of CADUET, the following has been observed. One patient in clinical trials developed jaundice. Increases in liver function tests (LFT) in other patients were not associated with jaundice or other clinical signs or symptoms. Upon dose reduction, drug interruption, or discontinuation, transaminase levels returned to or near pretreatment levels without sequelae. Eighteen of 30 patients, with persistent LFT elevations continued treatment with a reduced dose of atorvastatin.
It is recommended that liver function tests be performed prior to and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter. Liver enzyme changes generally occur in the first 3 months of treatment with the atorvastatin component of CADUET. Patients who develop increased transaminase levels should be monitored until the abnormalities resolve. Should an increase in ALT or AST of >3 times ULN persist, reduction of dose or withdrawal of CADUET is recommended.
Active liver disease or unexplained persistent transaminase elevations are contraindications to the use of CADUET (see CONTRAINDICATIONS).
Increased Angina and/or Myocardial Infarction
Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
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