Amlodipine And Atorvastatin
FDA Drug Information • Also known as: Amlodipine And Atorvastatin, Caduet
- Brand Names
- Amlodipine And Atorvastatin, Caduet
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Amlodipine and atorvastatin tablets, USP combine the calcium channel blocker amlodipine besylate with the HMG CoA-reductase inhibitor atorvastatin calcium. Amlodipine besylate, USP is chemically described as 3-ethyl-5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(o-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulphonate. Its molecular formula is C 20 H 25 ClN 2 O 5
What Is Amlodipine And Atorvastatin Used For?
1 INDICATIONS AND USAGE Amlodipine and atorvastatin tablets are indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate. Amlodipine Hypertension Amlodipine is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including amlodipine. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Amlodipine may be used alone or in combination with other antihypertensive agents. Coronary Artery Disease (CAD) Chronic Stable Angina Amlodipine is indicated for the symptomatic treatment of chronic stable angina. Amlodipine may be used alone or in combination with other antianginal agents. Vasospastic Angina (Prinzmetal’s or Variant Angina) Amlodipine is indicated for the...
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Amlodipine and Atorvastatin Tablets Dosage of amlodipine and atorvastatin tablets must be individualized on the basis of both effectiveness and tolerance for each individual component in the treatment of hypertension/angina and hyperlipidemia. Select doses of amlodipine and atorvastatin independently. Amlodipine and atorvastatin tablets may be substituted for its individually titrated components. Patients may be given the equivalent dose of amlodipine and atorvastatin or a dose of amlodipine and atorvastatin with increased amounts of amlodipine, atorvastatin, or both for additional antianginal effects, blood pressure lowering, or lipid-lowering effect. Amlodipine and atorvastatin tablets may be used to provide additional therapy for patients already on one of its components. Amlodipine and atorvastatin tablets may be used to initiate treatment in patients with hyperlipidemia and either hypertension or angina. Important Dosage Information Take amlod ipine and atorvastatin tablets orally once daily at any time of the day, with or without food. Amlodipine The usual initial antihypertensive oral dosage of amlodipine is 5 mg once daily, and the maximum dose is 10 mg once daily. Pediatric (age > 6 years), small adult, fragile, or elderly patients, 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. Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titration may proceed more rapidly, however, if clinically warranted, provided the patient is assessed frequently. Angina The recommended dosage of amlodipine for chronic stable or vasospastic angina is 5 to 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. Coronary Artery Disease The recommended dosage range of amlodipine for patients with CAD is 5 to 10 mg once daily. In clinical studies, the majority of patients required 10 mg [see Clinical Studies ( 14.4 )] . Pediatrics The effective antihypertensive oral dose of amlodipine in pediatric patients ages 6 to 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 (12.3) and Clinical Studies (14.1)] . Atorvastatin Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating atorvastatin, and adjust the dosage if necessary. Recommended Dosage in Adult Patients The recommended starting dosage of atorvastatin is 10 mg to 20 mg once daily. The dosage range is 10 mg to 80 mg once daily. Patients who require reduction in LDL-C greater than 45% may be started at 40 mg once daily. Recommended Dosage in Pediatric Patients 10 Years of Age and Older with HeFH The recommended starting dosage of atorvastatin is 10 mg once daily. The dosage range is 10 mg to 20 mg once daily. Recommended...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.1 )] Immune-Mediated Necrotizing Myopathy [see Warnings and Precautions ( 5.2 )] Hepatic Dysfunction [see Warnings and Precautions ( 5.3 )] Increases in HbA1c and Fasting Serum Glucose Levels [see Warnings and Precautions ( 5.6 )] Most common adverse reaction to amlodipine is edema which occurred in a dose related manner ( 6.1 ). Most common adverse reactions (incidence ≥5%) are nasopharyngitis, arthralgia, diarrhea, pain in extremity, and urinary tract infection to atorvastatin ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800- 706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Amlodipine and Atorvastatin Amlodipine and atorvastatin has been evaluated for safety in 1,092 patients in double-blind placebo-controlled studies treated for co-morbid hypertension and dyslipidemia. In general, treatment with amlodipine and atorvastatin was well tolerated. For the most part, adverse reactions have been mild or moderate in severity. In clinical trials with amlodipine and atorvastatin, no adverse reactions peculiar to this combination have been observed. Adverse reactions are similar in terms of nature, severity, and frequency to those reported previously with amlodipine and atorvastatin. The following information is based on the clinical experience with amlodipine and atorvastatin. Amlodipine Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. In general, treatment with amlodipine was well tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with amlodipine were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine (N=1,730) at doses up to 10 mg to placebo (N=1,250), discontinuation of amlodipine because of adverse reactions was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). The most commonly reported side effects more frequent than placebo are dizziness and edema. The incidence (%) of side effects that occurred in a doserelated manner are as follows: Amlodpine 2.5 mg N=275 5 mg N=296 10 mg N=268 Placebo N=520 Edema 1.8 3 10.8 0.6 Dizziness 1.1 3.4 3.4 1.5 Flushing 0.7 1.4 2.6 0 Palpitations 0.7 1.4 4.5 0.6 Other adverse reactions that were not clearly dose related but were reported at an incidence greater than 1.0% in placebo-controlled clinical trials include the following: Amlodipine (%) (N=1,730) Placebo (%) (N=1,250) Fatigue 4.5 2.8 Nausea 2.9 1.9 Abdominal Pain 1.6 0.3 Somnolece 1.4 0.6 Edema, flushing, palpitations, and somnolence appear to be more common in women than in men. The following events occurred in < 1% but > 0.1% of patients treated with amlodipine in controlled clinical trials or under conditions of open trials or marketing experience where a causal relationship is uncertain; they are listed to alert the physician to a possible relationship: Cardiovascular : arrhythmia (including ventricular tachycardia and atrial fibrillation), bradycardia, chest pain, peripheral ischemia, syncope, tachycardia, vasculitis. Central and Peripheral Nervous System : hypoesthesia, neuropathy peripheral, paresthesia, tremor, vertigo. Gastrointestinal : anorexia, constipation, dysphagia, diarrhea, flatulence, pancreatitis, vomiting, gingival hyperplasia. General : allergic reaction, asthenia, 2 back pain, hot flushes, malaise, pain, rigors, weight gain, weight decrease. Musculoskeletal System : arthralgia, arthrosis, muscle cramps, 2 myalgia. Psychiatric : sexual...
Drug Interactions
7 DRUG INTERACTIONS Data from a drug-drug interaction study involving 10 mg of amlodipine and 80 mg of atorvastatin in healthy subjects indicate that the pharmacokinetics of amlodipine are not altered when the drugs are co-administered. The effect of amlodipine on the pharmacokinetics of atorvastatin showed no effect on the C max : 91% (90% confidence interval: 80 to 103%), but the AUC of atorvastatin increased by 18% (90% confidence interval: 109 to 127%) in the presence of amlodipine, which is not clinically meaningful. No drug interaction studies have been conducted with amlodipine and atorvastatin and other drugs, although studies have been conducted in the individual amlodipine and atorvastatin components, as described below: Amlodipine See full prescribing information for details regarding concomitant use of amlodipine and atorvastatin tablets with other drugs or grapefruit juice that increase the risk of myopathy and rhabdomyolysis (2.5, 7.3 ). Rifampin: May reduce atorvastatin plasma concentrations. Administer simultaneously with atorvastatin ( 7.4 ) Oral Contraceptives: May increase plasma levels of norethindrone and ethinyl estradiol; consider this effect when selecting an oral contraceptive ( 7.5 ). Digoxin: May increase digoxin plasma levels; monitor patients appropriately ( 7.5 ). 7.1 Impact of Other Drugs on Amlodipine CYP3A Inhibitors 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 [see Clinical Pharmacology ( 12.3 )] . CYP3A Inducers No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. Sildenafil Monitor for hypotension when sildenafil is co-administered with amlodipine [see Clinical Pharmacology ( 12.2 )] . 7.2 Impact of Amlodipine on Other Drugs Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate [see Clinical Pharmacology ( 12.3 )] . Atorvastatin 7.3 Drug Interactions that may Increase the Risk of Myopathy and Rhabdomyolysis with Atorvastatin Atorvastatin is a substrate of CYP3A4 and transporters (e.g., OATP1B1/1B3, P-gp, or BCRP). Atorvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters. Table 3 includes a list of drugs that may increase exposure to atorvastatin and may increase the risk of myopathy and rhabdomyolysis when used concomitantly and instructions for preventing or managing them [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )] . Table 3. Drug Interactions...
Contraindications
4 CONTRAINDICATIONS Acute liver failure or decompensated cirrhosis [see Warnings and Precautions ( 5.3 )]. Hypersensitivity to amlodipine, atorvastatin or any excipients in amlodipine and atorvastatin tablets. Hypersensitivity reactions, including anaphylaxis, angioneurotic edema, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported [see Adverse Reactions ( 6.2 )]. Acute liver failure or decompensated cirrhosis (4). Hypersensitivity to amlodipine, atorvastatin or any excipient in amlodipine and atorvastatin tablets (4).
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Atorvastatin Discontinue atorvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Atorvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, atorvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology ( 12.1 )]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with atorvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data). In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered atorvastatin at doses that resulted in up to 30 and 20 times, respectively, the human exposure at the maximum recommended human dose (MRHD) of 80 mg, based on body surface area (mg/m 2 ). In rats administered atorvastatin during gestation and lactation, decreased postnatal growth and development delay were observed at doses ≥ 6 times the MRHD (see Data). Amlodipine The limited available data based on post marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with porrly controlled hypertension in pregnancy (see Clinical...
Overdosage
10 OVERDOSAGE There is no information on overdosage with amlodipine and atorvastatin in humans. Amlodipine Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited. Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the MRHD on a mg/m 2 basis) caused a marked peripheral vasodilation and hypotension. If overdose should occur with amlodipine, initiate active cardiac and respiratory monitoring. Perform frequent blood pressure measurements. Should hypotension occur, provide cardiovascular support including elevation of the extremities and administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with specific attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit. Atorvastatin No specific antidotes for atorvastatin are known. Contact Poison Control (1-800-222-1222) for latest recommendations. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin clearance.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Amlodipine and atorvastatin tablets, USP contain amlodipine besylate and atorvastatin calcium, in the form of propylene glycol solvate, equivalent to amlodipine and atorvastatin in the dose strengths described below. Amlodipine and atorvastatin tablets, USP 5 mg/10 mg are white to off-white, oval, biconvex, film-coated tablets, engraved "5/10" on one side, "APO" on the other side. NDC 72162-2092-3: 30 Tablets in a BOTTLE. Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Repackaged/Relabeled by: Bryant Ranch Prepack Burbank, CA 91504
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.