AMLODIPINE BESYLATE- amlodipine besylate tablet
Unit Dose Services
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use amlodipine besylate tablets safely and effectively. See full prescribing information for amlodipine besylate tablets. Amlodipine Besylate Tablets Initial U.S. Approval: 1987
INDICATIONS AND USAGEAmlodipine besylate tablets are a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: DOSAGE AND ADMINISTRATION
: Doses in excess of 5 mg daily have not been studied in pediatric patients. ( ) Important Limitation2.2 DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
ADVERSE REACTIONSMost common adverse reactions are headache and edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1% are headache, fatigue, nausea, abdominal pain, and somnolence. ( ) 6 To report SUSPECTED ADVERSE REACTIONS, contact Qualitest Pharmaceuticals at 1-800-444-4011 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONS
See 17 for FDA-approved patient labeling. Revised: 5/2010 |
FULL PRESCRIBING INFORMATION: CONTENTS*3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS7 DRUG INTERACTIONS7.10 Drug/Laboratory Test Interactions8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.3 Pharmacokinetics and Metabolism12.4 Pediatric Patients13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
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FULL PRESCRIBING INFORMATION
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
No evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day (respectively, 8 times and 23 times the maximum recommended human dose of 10 mg on a mg/m basis) during their respective periods of major organogenesis. However, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. Amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose. 112
- 1
- Based on patient weight of 50 kg.
8.3 Nursing Mothers
It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while amlodipine is administered.
8.4 Pediatric Use
Effect of amlodipine on blood pressure in patients less than 6 years of age is not known.
8.5 Geriatric Use
Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required . [see ] Dosage and Administration (2.1)
10 OVERDOSAGE
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 maximum recommended human dose on a mg/m basis) caused a marked peripheral vasodilation and hypotension. 2
If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
11 DESCRIPTION
Amlodinpine besylate is the besylate salt of amlodipine, a long-acting calcium channel blocker.
Amlodipine besylate is chemically described as 3-Ethyl-5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulphonate. Its molecular formula is C H ClN O •C H O S, and its structural formula is: 202525663
Amlodipine besylate is a white crystalline powder with a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate tablets are formulated as white tablets equivalent to 2.5, 5, and 10 mg of amlodipine for oral administration. In addition to the active ingredient, amlodipine besylate, each tablet contains the following inactive ingredients: dibasic calcium phosphate anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. in vitro
Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include the following:
12.3 Pharmacokinetics and Metabolism
After oral administration of therapeutic doses of amlodipine, absorption produces peak plasma concentrations between 6 and 12 hours. Absolute bioavailability has been estimated to be between 64 and 90%. The bioavailability of amlodipine is not altered by the presence of food.
Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. studies have shown that approximately 93% of the circulating drug is bound to plasma proteins in hypertensive patients. Elimination from the plasma is biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7 to 8 days of consecutive daily dosing. Ex vivo
The pharmacokinetics of amlodipine are not significantly influenced by renal impairment. Patients with renal failure may therefore receive the usual initial dose.
Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40–60%, and a lower initial dose may be required. A similar increase in AUC was observed in patients with moderate to severe heart failure.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
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 amlodipine mg/kg/day, showed no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was, on a mg/m basis, similar to the maximum recommended human dose of 10 mg amlodipine/day. For the rat, the highest dose was, on a mg/m basis, about twice the maximum recommended human dose. 2222
Mutagenicity studies conducted with amlodipine maleate revealed no drug related effects at either the gene or chromosome level.
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 of 10 mg/day on a mg/m basis). 22
- 2
- Based on patient weight of 50 kg
PATIENT INFORMATION AMLODIPINE BESYLATE TABLETS
Read this information carefully before you start taking and each time you refill your prescription. There may be new information. This information does not replace talking with your doctor. If you have any questions about , ask your doctor. Your doctor will know if is right for you. amlodipineamlodipineamlodipine
is a type of medicine known as a calcium channel blocker (CCB). It is used to treat high blood pressure (hypertension) and a type of chest pain called angina. It can be used by itself or with other medicines to treat these conditions.
What is ?
amlodipine
Amlodipine
High blood pressure comes from blood pushing too hard against your blood vessels. relaxes your blood vessels, which lets your blood flow more easily and helps lower your blood pressure. Drugs that lower blood pressure lower your risk of having a stroke or heart attack.
High Blood Pressure (hypertension)
Amlodipine
Angina is a pain or discomfort that keeps coming back when part of your heart does not get enough blood. Angina feels like a pressing or squeezing pain, usually in your chest under the breastbone. Sometimes you can feel it in your shoulders, arms, neck, jaws, or back. can relieve this pain.
Angina
Amlodipine
Do not use if you are allergic to amlodipine (the active ingredient in ), or to the inactive ingredients. Your doctor or pharmacist can give you a list of these ingredients.
Who should not use amlodipine?
amlodipine besylate tablets amlodipine besylate tablets
Tell your doctor about any prescription and non-prescription medicines you are taking, including natural or herbal remedies. Tell your doctor if you:
What should I tell my doctor before taking ?
amlodipine
- ever had heart disease
- ever had liver problems
- are pregnant, or plan to become pregnant. Your doctor will decide if is the best treatment for you. amlodipine
- are breastfeeding. Do not breastfeed while taking . You can stop breastfeeding or take a different medicine. amlodipine
How should I take ? amlodipine
- Take once a day, with or without food. You can take with most drinks, including grapefruit juice. amlodipineamlodipine
- It may be easier to take your dose if you do it at the same time every day, such as with breakfast or dinner, or at bedtime. Do not take more than one dose of at a time. amlodipine
- If you miss a dose, take it as soon as you remember. Do not take if it has been more than 12 hours since you missed your last dose. Wait and take the next dose at your regular time. amlodipine
- You can use nitroglycerin and together. If you take nitroglycerin for angina, don't stop taking it while you are taking Other medicines:amlodipineamlodipine.
- While you are taking , do not stop taking your other prescription medicines, including any other blood pressure medicines, without talking to your doctor. amlodipine
- If you took too much , call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away. amlodipine
What should I avoid while taking ? amlodipine
- breastfeed. It is not known if will pass through your milk. Do notamlodipine
- start any new prescription or non-prescription medicines or supplements, unless you check with your doctor first. Do not
may cause the following side effects. Most side effects are mild or moderate:
What are the possible side effects of ?
amlodipine
Amlodipine
- headache
- swelling of your legs or ankles
- tiredness, extreme sleepiness
- stomach pain, nausea
- dizziness
- flushing (hot or warm feeling in your face)
- arrhythmia (irregular heartbeat)
- heart palpitations (very fast heartbeat)
It is rare, but when you first start taking or increase your dose, you may have a heart attack or your angina may get worse. If that happens, call your doctor right away or go directly to a hospital emergency room. amlodipine
Tell your doctor if you are concerned about any side effects you experience. These are not all the possible side effects of . For a complete list, ask your doctor or pharmacist. amlodipine
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or by visitingwww.fda.gov/medwatch.
Keep away from children. Store at 20° to 25°C (between 68° and 77°F) [see USP Controlled Room Temperature]. Keep out of the light. Do not store in the bathroom. Keep in a dry place.
How do I store ?
amlodipine
amlodipineamlodipinebesylate tabletsamlodipineamlodipine
Sometimes, doctors will prescribe a medicine for a condition that is not written in the patient information leaflets. Only use the way your doctor told you to. Do not give to other people, even if they have the same symptoms you have. It may harm them.
General advice about
amlodipine
amlodipineamlodipine
You can ask your pharmacist or doctor for information about . amlodipine
Manufactured for: Huntsville, AL 35811
QUALITEST PHARMACEUTICALS
8182524 Revised: 5/2010 R3
| AMLODIPINE BESYLATE
amlodipine besylate tablet |
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| Labeler - Unit Dose Services (831995316) |
| Registrant - Unit Dose Services (831995316) |
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| Unit Dose Services | 831995316 | REPACK | |