Caduet

Dosage Forms & Strengths

amlodipine/atorvastatin

tablet

• 2.5/10mg
• 2.5/20mg
• 2.5/40mg
• 5/10mg
• 5/20mg
• 5/40mg
• 5/80mg
• 10/10mg
• 10/20mg
• 10/40mg
• 10/80mg

Hypertension/Angina & Hyperlipidemia

Dosage must be individualized for each individual component for treatment of hypertension, angina, and/or hyperlipidemia; amlodipine dose may be titrated after 1-2 weeks and the atorvastatin dose after 2-4 weeks; not to exceed 10 mg amlodipine or 80 mg atorvastatin

2.5-10 mg amlodipine; 10-80 mg atorvastatin PO qDay

Renal Impairment

Dose adjustment not necessary

Hepatic Impairment

Contraindicated in active liver disease

Dosage Forms & Strengths

amlodipine/atorvastatin

tablet

• 2.5/10mg
• 2.5/20mg
• 5/10mg
• 5/20mg

Hypertension & Hyperlipidemia

Dosage must be individualized for each individual component for treatment of hypertension/hyperlipidemia; amlodipine dose may be titrated after 1-2 weeks and the atorvastatin dose after 2-4 weeks; not to exceed 5 mg amlodipine or 20 mg atorvastatin

<6 years: Safety and efficacy not established

>6 years: 2.5-5 mg amlodipine; 10-20 mg atorvastatin PO qDay

Consider initiating amlodipine dose at lower end of the spectrum due to possible decrease in renal or hepatic clearance

Contraindications

Hypersensitivity to amlodipine or atorvastatin

Active liver disease, or unexplained elevated transminases

Pregnancy, lactation

Cautions

Hypotension with or without syncope is possible (particularly with severe aortic stenosis)

CHF

Persistent progressive dermatologic reactions

Exacerbation of angina and/or MI (during initiation of treatment, after dose increase, or withdrawal of beta blocker)

Caution in liver impairment

Heavy alcohol use, history of liver disease, renal failure

Rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with the atorvastatin

Myopathy, risk of myopathy increased by coadministration with CYP3A4 inhibiors (eg, fibrates, niacin, cyclosporine, macrolides, azole antifungals); therapy should be discontinued if myopathy diagnosed or suspected

Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction; monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment

Rare reports of immune-mediated necrotizing myopathy (IMNM), characterized by increased serum creatine kinase that persist despite discontinuing statin

Adverse reactions associated with atorvastatin therapy reported including anaphylaxis, angioneurotic edema, bullous rashes (including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), rhabdomyolysis, myositis, fatigue, tendon rupture, fatal and non-fatal hepatic failure, dizziness, depression, peripheral neuropathy, pancreatitis and interstitial lung disease

Withhold or discontinue if myopathy, renal failure, or transaminase levels >3x ULN develops

Use in patients with recent stroke or TIA: SPARCL study observed higher incidence of hemorrhagic stroke with atorvastatin 80 mg (compared with placebo)

Increased HbA1c and fasting serum glucose levels reported with HMG-CoA reductase inhibitors

Clarithromycin, itraconazole, HIV protease inhibitors (saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir) may increase risk of myopathy/rhabdomyolysis; do not exceed 20 mg atorvastatin

Amlodipine may increase systemic exposure of cyclosporine or tacrolimus when co-administered; frequent monitoring of trough blood levels of cyclosporine and tacrolimus recommended; adjust dose when appropriate

Caduet is part of the drug class:

• HMG CoA reductase inhibitors, other combinations

Some medicines may interact with Caduet. Tell your doctor if you are taking any other prescription or non-prescription medicines, vitamins, or herbal supplements. Especially tell your doctor if you are taking any of the following:

• amiodarone
• antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), and voriconazole (Vfend)
• colchicine (Colcrys)
• cyclosporine (Neoral, Sandimmune)
• daptomycin (Cubicin)
• diltiazem (Cardizem)
• dronedarone (Multaq)
• clofibrate
• gemfibrozil (Lopid)
• indinavir (Crixivan)
• ritonavir (Norvir)
• simvastatin (Zocor)
• imatinib (Gleevec)
• telithromycin (Ketek)
• clarithromycin (Biaxin)
• erythromycin
• mibefradil
• nefazodone (Serzone)
• niacin
• delavirdine (Rescriptor)
• quinine (Qualaquin)
• dalfopristin
• verapamil (Calan, Covera-HS,  Verelan, Verelan PM)
• sildenafil (Revatio, Viagra)
• St. John's Wort
• cimetidine (Tagamet)
• digoxin (Lanoxin)
• birth control pills
• tacrolimus (Prograf, Protopic)
• spironolactone (Aldactone)

There may be other medicines that interact with Caduet. This is not a complete list of Caduet drug interactions. Check with your doctor before you start, stop, or change the dose of any medicine.

Amlodipine and atorvastatin is a combination of a calcium channel blocker and HMG-CoA reductase inhibitor (statin). Amlodipine is used alone or together with other medicines to treat angina (chest pain) or high blood pressure. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. Maintaining a lower blood pressure can reduce the risk of strokes and heart attacks.

Atorvastatin is used together with a proper diet to lower cholesterol and triglyceride (fats) levels in the blood. This medicine may help prevent medical problems (e.g., chest pain, heart attack, or stroke) that are caused by fats clogging the blood vessels. It may also be used to prevent certain types of heart and blood vessel problems in patients with risk factors for heart problems.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of amlodipine and atorvastatin combination in the pediatric population. Safety and efficacy have not been established.

Appropriate studies have not been performed on the relationship of age to the effects of amlodipine to treat high blood pressure in children younger than 6 years of age. Safety and efficacy have not been established.

Atorvastatin alone is safe to use in boys and some girls 10 to 17 years of age for treating certain types of high cholesterol.

Teenage girls taking atorvastatin should be counseled on appropriate birth control methods to prevent pregnancy.

Geriatric

Appropriate studies have not been performed on the relationship of age to the effects of amlodipine and atorvastatin combination in the geriatric population. Safety and efficacy have not been established.

Pregnancy

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Posaconazole
• Ritonavir

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amiodarone
• Atazanavir
• Bezafibrate
• Ceritinib
• Ciprofibrate
• Clarithromycin
• Clofibrate
• Clopidogrel
• Colchicine
• Conivaptan
• Cyclosporine
• Dalfopristin
• Danazol
• Dantrolene
• Daptomycin
• Darunavir
• Digoxin
• Diltiazem
• Domperidone
• Droperidol
• Elbasvir
• Eliglustat
• Erythromycin
• Fenofibrate
• Fenofibric Acid
• Fluconazole
• Fosamprenavir
• Fusidic Acid
• Gemfibrozil
• Grazoprevir
• Idelalisib
• Indinavir
• Isavuconazonium Sulfate
• Itraconazole
• Ketoconazole
• Lacosamide
• Lopinavir
• Mibefradil
• Nefazodone
• Nelfinavir
• Netupitant
• Niacin
• Piperaquine
• Quinupristin
• Saquinavir
• Simeprevir
• Simvastatin
• Tacrolimus
• Tegafur
• Telaprevir
• Telithromycin
• Tipranavir
• Troleandomycin
• Verapamil

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amiodarone
• Amprenavir
• Azithromycin
• Bexarotene
• Black Cohosh
• Boceprevir
• Bosentan
• Clopidogrel
• Efavirenz
• Eltrombopag
• Etravirine
• Fosphenytoin
• Indinavir
• Interferon Beta
• Oat Bran
• Pectin
• Phenytoin
• Pioglitazone
• Quinine
• Rifampin
• St John's Wort
• Voriconazole

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Liver disease, history of—Use with caution. May cause side effects to become worse.

• Convulsions (seizures), not well-controlled or
• Electrolyte or metabolic enzyme deficiencies or disorders or
• Hypotension (low blood pressure) or
• Infection, severe or
• Kidney disease, severe or
• Major surgery or trauma, recent—Patients with these conditions may be at risk of developing muscle and kidney problems.

• Coronary artery disease, severe, obstructive—Use of this medicine may result in other heart problems.

• Diabetes or
• Thyroid problems—Use with caution. May make these conditions worse.

• Heart disease (e.g., aortic stenosis)—Use with caution. The blood pressure-lowering effects of this medicine may be increased.

• Liver disease, active or
• Liver enzymes, elevated—Should not be used in patients with these conditions.

• Stroke, recent or
• Transient ischemic attack (TIA), recent—Atorvastatin may increase chance of having hemorrhagic stroke (stroke caused by bleeding in the brain).

• If you have an allergy to amlodipine, atorvastatin, or any other part of Caduet (amlodipine and atorvastatin).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Active liver disease or a rise in liver enzymes.
• If you are pregnant or may be pregnant. Do not take this medicine if you are pregnant.
• If you are breast-feeding. Do not breast-feed while you take Caduet.
• If you are taking any of these drugs: Cyclosporine, gemfibrozil, telaprevir, or tipranavir plus ritonavir.
• If you are taking any of these drugs: Cimetidine, ketoconazole, or spironolactone.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Caduet with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how Caduet affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Have your blood pressure checked often. Talk with your doctor.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• If you are taking this medicine and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• Avoid or limit drinking alcohol to less than 3 drinks a day. Drinking too much alcohol may raise your chance of liver disease.
• If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
• Follow the diet plan that your doctor told you about.
• If you are taking Caduet for chest pain, it will not treat chest pain as it happens. This medicine is only used to prevent or lower the number of chest pain attacks.
• It is rare, but worse chest pain and heart attack can happen after this medicine is first started or after the dose is raised. The risk may be greater in people who have very bad heart blood vessel disease. Talk with the doctor.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Caduet with your other drugs.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• Use birth control that you can trust to prevent pregnancy while taking Caduet.
• If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

Use Caduet (amlodipine and atorvastatin) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Swallow whole. Do not chew, break, or crush.
• If you have trouble swallowing, talk with your doctor.
• Take this medicine at the same time of day.
• To gain the most benefit, do not miss doses.
• Keep taking Caduet as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is less than 12 hours until the next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Active Liver Disease

Atorvastatin is contraindicated in patients with active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels [see Warnings and Precautions 5.2 and Clinical Pharmacology 12.3].

Pregnancy

Atorvastatin is contraindicated in women who are pregnant or may become pregnant. Atorvastatin 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 should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazard. 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 Specific Populations (8.1)].

Nursing Mothers

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 Specific Populations (8.3)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

Amlodipine

Rats and mice treated with amlodipine maleate in the diet for up to two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 mg amlodipine/kg/day, showed no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was, on a mg/m2 basis, similar to the maximum recommended human dose of 10 mg amlodipine/day.4 For the rat, the highest dose level was, on a mg/m2 basis, about twice the maximum recommended human dose. 4

Mutagenicity studies conducted with amlodipine maleate revealed no drug related effects at either the gene or chromosome levels.

There was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and females for 14 days prior to mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose 4 of 10 mg/day on a mg/m2 basis).

4 Based on patient weight of 50 kg.

Atorvastatin

In a 2-year carcinogenicity study with atorvastatin calcium in rats at dose levels equivalent to 10, 30, and 100 mg atorvastatin/kg/day, 2 rare tumors were found in muscle in high-dose females: in one, there was a rhabdomyosarcoma and, in another, there was a fibrosarcoma. This dose represents a plasma AUC (0–24) value of approximately 16 times the mean human plasma drug exposure after an 80 mg oral dose.

A 2-year carcinogenicity study in mice given atorvastatin calcium at dose levels equivalent to 100, 200, or 400 mg atorvastatin/kg/day resulted in a significant increase in liver adenomas in high-dose males and liver carcinomas in high-dose females. These findings occurred at plasma AUC (0–24) values of approximately 6 times the mean human plasma drug exposure after an 80 mg oral dose.

In vitro, atorvastatin was not mutagenic or clastogenic in the following tests with and without metabolic activation: the Ames test with Salmonella typhimurium and Escherichia coli, the HGPRT forward mutation assay in Chinese hamster lung cells, and the chromosomal aberration assay in Chinese hamster lung cells. Atorvastatin was negative in the in vivo mouse micronucleus test.

There were no effects on fertility when rats were given atorvastatin calcium at doses equivalent to up to 175 mg atorvastatin/kg/day (15 times the human exposure). There was aplasia and aspermia in the epididymides of 2 of 10 rats treated with atorvastatin calcium at a dose equivalent to 100 mg atorvastatin/kg/day for 3 months (16 times the human AUC at the 80 mg dose); testis weights were significantly lower at 30 and 100 mg/kg/day and epididymal weight was lower at 100 mg/kg/day. Male rats given the equivalent of 100 mg atorvastatin/kg/day for 11 weeks prior to mating had decreased sperm motility, spermatid head concentration, and increased abnormal sperm. Atorvastatin caused no adverse effects on semen parameters, or reproductive organ histopathology in dogs given doses of atorvastatin calcium equivalent to 10, 40, or 120 mg atorvastatin/kg/day for two years.

Many drugs can interact with amlodpine and atorvastatin. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

• other cholesterol medications;

• birth control pills;

• an antibiotic or antifungal medicine;

• antiviral medicine to treat HIV or hepatitis C;

• heart medication; or

• medicine to prevent organ transplant rejection.

This list is not complete and many other drugs can interact with amlodipine and atorvastatin. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

More frequent side effects include: edema, fatigue, and headache. See below for a comprehensive list of adverse effects.