16 How Supplied/storage And Handling

Amlodipine besylate tablet, USP is a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: •   Hypertension (1.1)    o  Amlodipine besylate tablets are indicated for the treatment of hypertension, to  lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. •   Coronary Artery Disease (1.2)     o   Chronic Stable Angina     o   Vasospastic Angina (Prinzmetal's or Variant Angina)     o   Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40%

• Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. ( 2.1 )         o  Small, fragile, or elderly patients or patients with hepatic insufficiency may be started on 2.5 mg once daily.    ( 2.1 ) • Pediatric starting dose: 2.5 mg to 5 mg once daily. ( 2.2 ) Important Limitation: Doses in excess of 5 mg daily have not been studied in pediatric patients. ( 2.2 )

10 mg Tablets Amlodipine Besylate Tablets, USP - 10 mg (Amlodipine besylate USP equivalent to 10 mg of Amlodipine per tablet) are supplied as white to off white round tablets with "128" debossed on one side and "C" on other side and supplied as follows:   NDC 68788-6386-3 Bottle of 30   NDC 68788-6386-6 Bottle of 60   NDC 68788-6386-9 Bottle of 90   NDC 68788-6386-1 Bottle of 100 Storage Store at 20°C to 25°C (68°F to 77°F). [See USP controlled room temperature.] Protect from light and moisture. Manufactured by: Cipla, Ltd., Verna, Goa India Manufactured for: Cipla USA, Inc. 10 Independence Boulevard, Suite 300 Warren, NJ 07059 Revised: 2/2020 Repackaged By: Preferred Pharmaceuticals Inc.

•  Known sensitivity to amlodipine ( 4 )

Amlodipine 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 20 H 25 CIN 2 O 5 •C 6 H 6 O 3 S, and its structural formula is:

•    Do not exceed doses greater than 20 mg daily of simvastatin. ( 7.2 )

Amlodipine besylate (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years [see Clinical Studies (14.1) ] . Effect of amlodipine besylate on blood pressure in patients less than 6 years of age is not known.

Clinical studies of amlodipine besylate 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) ] .

Most common adverse reaction to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence > 1.0% are fatigue, nausea, abdominal pain, and somnolence. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipla Limited, India at 1- 866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 besylate 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 2 basis) caused a marked peripheral vasodilation and hypotension. 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 besylate is highly protein bound, hemodialysis is not likely to be of benefit.

Risk Summary The limited available data based on post-marketing reports with NORVASC 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 poorly controlled hypertension in pregnancy [see Clinical Considerations] . In animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times the maximum recommended human dose (MRHD), respectively. However for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Data Animal Data 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 (approximately 10 and 20 times the MRHD based on body surface area, respectively) during their respective periods of major organogenesis. However for rats, 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.

Amlodipine besylate tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal 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 besylate tablet, USP. 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 besylate tablets may be used alone or in combination with other antihypertensive agents.

PATIENT INFORMATION Amlodipine besylate tablets, USP (am loe' di peen bes' i late) Read this information carefully before you start taking Amlodipine besylate tablets 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 Amlodipine besylate tablets, ask your doctor. Your doctor will know if Amlodipine besylate tablets is right for you. What is amlodipine besylate tablets? Amlodipine besylate tablets 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. High Blood Pressure (hypertension) High blood pressure comes from blood pushing too hard against your blood vessels. Amlodipine besylate tablets 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. Angina 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. Amlodipine besylate tablets can relieve this pain. Who should not use amlodipine besylate tablets? Do not use amlodipine besylate tablets if you are allergic to amlodipine (the active ingredient in amlodipine besylate tablets ) , or to the inactive ingredients. Your doctor or pharmacist can give you a list of these ingredients. What should I tell my doctor before taking 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: •     ever had heart disease •     ever had liver problems •    are pregnant, or plan to become pregnant. Your doctor will decide if amlodipine besylate tablets is the best treatment for you. • are breast-feeding. Amlodipine besylate passes into your milk. How should I take amlodipine besylate tablets? •    Take amlodipine besylate tablets once a day, with or without food. •   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 amlodipine besylate tablets at a time. •   If you miss a dose, take it as soon as you remember. Do not take amlodipine besylate tablets if it has been more than 12 hours since you missed your last dose. Wait and take the next dose at your regular time. •  Other medicines: You can use nitroglycerin and amlodipine besylate tablets together. If you take nitroglycerin for angina, don't stop taking it while you are taking amlodipine besylate tablets . •    While you are taking amlodipine besylate tablets, do not stop taking your other prescription medicines, including any other blood pressure medicines, without talking to your doctor. •   If you took too much amlodipine besylate tablets, call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away. What should I avoid while taking amlodipine besylate tablets? •   Do not start any new prescription or non-prescription medicines or supplements, unless you check with your doctor first. What are the possible side effects of amlodipine besylate tablets? Amlodipine besylate tablets may cause the following side effects. Most side effects are mild or moderate: •    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) •    muscle rigidity, tremor and/or abnormal muscle movement It is rare, but when you first start taking amlodipine besylate tablets 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. Tell your doctor if you are concerned about any side effects you experience. These are not all the possible side effects of amlodipine besylate tablets. For a complete list, ask your doctor or pharmacist . How do I store amlodipine besylate tablets? Keep Amlodipine besylate tablets, USP away from children. Store at 20°C to 25°C (68°F to 77°F). [See USP controlled room temperature.] Protect from light and moisture. General advice about amlodipine besylate tablets Sometimes, doctors will prescribe a medicine for a condition that is not written in the patient information leaflets. Only use amlodipine besylate tablets the way your doctor told you to. Do not give amlodipine besylate tablets to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or doctor for information about Amlodipine besylate tablets, USP. Manufactured by: Cipla, Ltd., Verna, Goa India Manufactured for: Cipla USA, Inc. 10 Independence Boulevard, Suite 300 Warren, NJ 07059        Revised: 2/2020 Repackaged By: Preferred Pharmaceuticals Inc.

•  2.5 mg, 5 mg, and 10 mg Tablets ( 3 )

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 in vitro 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. 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: Exertional Angina: In patients with exertional angina, amlodipine  besylate reduces the total peripheral resistance (after load) against which the heart works and reduces the rate pressure product, and thus myocardial oxygen demand, at any given level of exercise. Vasospastic Angina: Amlodipine besylate has been demonstrated to block constriction and restore blood flow in coronary arteries and arterioles in response to calcium, potassium epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro . This inhibition of coronary spasm is responsible for the effectiveness of amlodipine besylate in vasospastic (Prinzmetal's or variant) angina.

Hemodynamics: Following administration of therapeutic doses to patients with hypertension, amlodipine besylate produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels with chronic dosing. Although the acute intravenous administration of amlodipine besylate decreases arterial blood pressure and increases heart rate in hemodynamic studies of patients with chronic stable angina, chronic oral administration of amlodipine in clinical trials did not lead to clinically significant changes in heart rate or blood pressures in normotensive patients with angina. With chronic once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with amlodipine besylate is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (Diastolic pressure 105–114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90–104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressures (+1/–2 mmHg). In hypertensive patients with normal renal function, therapeutic doses of amlodipine besylate resulted in a decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria. As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine besylate have generally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure or volume. In hemodynamic studies, amlodipine besylate has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when coadministered with beta-blockers to man. Similar findings, however, have been observed in normal or well-compensated patients with heart failure with agents possessing significant negative inotropic effects. Electrophysiologic Effects: Amlodipine besylate does not change sinoatrial nodal function or atrioventricular conduction in intact animals or man. In patients with chronic stable angina, intravenous administration of 10 mg did not significantly alter A-H and H-V conduction and sinus node recovery time after pacing. Similar results were obtained in patients receiving amlodipine besylate and concomitant beta-blockers. In clinical studies in which amlodipine besylate was administered in combination with beta-blockers to patients with either hypertension or angina, no adverse effects on electrocardiographic parameters were observed. In clinical trials with angina patients alone, amlodipine besylate therapy did not alter electrocardiographic intervals or produce higher degrees of AV blocks. Drug interactions Sildenafil : When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect [see Drug Interactions ( 7.1 )].

•   Pediatric: Effect on patients less than 6 years old is not known. ( 8.4 ) •   Geriatric: Start dosing at the low end of the dose range. ( 8.5 )

•   Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely. ( 5.1 ) •   Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of Amlodipine besylate tablet, USP, particularly in patients with severe obstructive coronary artery disease. ( 5.2 ) •   Titrate slowly in patients with severe hepatic impairment. ( 5.3 )

Principle Display Panel- Label NDC 68788-6386     Rx ONLY Amlodipine Besylate Tablets, USP 10 mg PHARMACIST : Please dispense with Patient Leaflet Cipla Repackaged By: Preferred Pharmaceuticals Inc.

Amlodipine besylate tablet, USP is a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: •   Hypertension (1.1)    o  Amlodipine besylate tablets are indicated for the treatment of hypertension, to  lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. •   Coronary Artery Disease (1.2)     o   Chronic Stable Angina     o   Vasospastic Angina (Prinzmetal's or Variant Angina)     o   Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40%

• Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. ( 2.1 )         o  Small, fragile, or elderly patients or patients with hepatic insufficiency may be started on 2.5 mg once daily.    ( 2.1 ) • Pediatric starting dose: 2.5 mg to 5 mg once daily. ( 2.2 ) Important Limitation: Doses in excess of 5 mg daily have not been studied in pediatric patients. ( 2.2 )

10 mg Tablets Amlodipine Besylate Tablets, USP - 10 mg (Amlodipine besylate USP equivalent to 10 mg of Amlodipine per tablet) are supplied as white to off white round tablets with "128" debossed on one side and "C" on other side and supplied as follows:   NDC 68788-6386-3 Bottle of 30   NDC 68788-6386-6 Bottle of 60   NDC 68788-6386-9 Bottle of 90   NDC 68788-6386-1 Bottle of 100 Storage Store at 20°C to 25°C (68°F to 77°F). [See USP controlled room temperature.] Protect from light and moisture. Manufactured by: Cipla, Ltd., Verna, Goa India Manufactured for: Cipla USA, Inc. 10 Independence Boulevard, Suite 300 Warren, NJ 07059 Revised: 2/2020 Repackaged By: Preferred Pharmaceuticals Inc.

•  Known sensitivity to amlodipine ( 4 )

•    Do not exceed doses greater than 20 mg daily of simvastatin. ( 7.2 )

Amlodipine besylate (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years [see Clinical Studies (14.1) ] . Effect of amlodipine besylate on blood pressure in patients less than 6 years of age is not known.

Clinical studies of amlodipine besylate 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) ] .

Most common adverse reaction to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence > 1.0% are fatigue, nausea, abdominal pain, and somnolence. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cipla Limited, India at 1- 866-604-3268 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 besylate 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 2 basis) caused a marked peripheral vasodilation and hypotension. 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 besylate is highly protein bound, hemodialysis is not likely to be of benefit.

Amlodipine 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 20 H 25 CIN 2 O 5 •C 6 H 6 O 3 S, and its structural formula is:

Risk Summary The limited available data based on post-marketing reports with NORVASC 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 poorly controlled hypertension in pregnancy [see Clinical Considerations] . In animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times the maximum recommended human dose (MRHD), respectively. However for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Data Animal Data 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 (approximately 10 and 20 times the MRHD based on body surface area, respectively) during their respective periods of major organogenesis. However for rats, 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.

Amlodipine besylate tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal 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 besylate tablet, USP. 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 besylate tablets may be used alone or in combination with other antihypertensive agents.

PATIENT INFORMATION Amlodipine besylate tablets, USP (am loe' di peen bes' i late) Read this information carefully before you start taking Amlodipine besylate tablets 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 Amlodipine besylate tablets, ask your doctor. Your doctor will know if Amlodipine besylate tablets is right for you. What is amlodipine besylate tablets? Amlodipine besylate tablets 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. High Blood Pressure (hypertension) High blood pressure comes from blood pushing too hard against your blood vessels. Amlodipine besylate tablets 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. Angina 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. Amlodipine besylate tablets can relieve this pain. Who should not use amlodipine besylate tablets? Do not use amlodipine besylate tablets if you are allergic to amlodipine (the active ingredient in amlodipine besylate tablets ) , or to the inactive ingredients. Your doctor or pharmacist can give you a list of these ingredients. What should I tell my doctor before taking 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: •     ever had heart disease •     ever had liver problems •    are pregnant, or plan to become pregnant. Your doctor will decide if amlodipine besylate tablets is the best treatment for you. • are breast-feeding. Amlodipine besylate passes into your milk. How should I take amlodipine besylate tablets? •    Take amlodipine besylate tablets once a day, with or without food. •   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 amlodipine besylate tablets at a time. •   If you miss a dose, take it as soon as you remember. Do not take amlodipine besylate tablets if it has been more than 12 hours since you missed your last dose. Wait and take the next dose at your regular time. •  Other medicines: You can use nitroglycerin and amlodipine besylate tablets together. If you take nitroglycerin for angina, don't stop taking it while you are taking amlodipine besylate tablets . •    While you are taking amlodipine besylate tablets, do not stop taking your other prescription medicines, including any other blood pressure medicines, without talking to your doctor. •   If you took too much amlodipine besylate tablets, call your doctor or Poison Control Center, or go to the nearest hospital emergency room right away. What should I avoid while taking amlodipine besylate tablets? •   Do not start any new prescription or non-prescription medicines or supplements, unless you check with your doctor first. What are the possible side effects of amlodipine besylate tablets? Amlodipine besylate tablets may cause the following side effects. Most side effects are mild or moderate: •    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) •    muscle rigidity, tremor and/or abnormal muscle movement It is rare, but when you first start taking amlodipine besylate tablets 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. Tell your doctor if you are concerned about any side effects you experience. These are not all the possible side effects of amlodipine besylate tablets. For a complete list, ask your doctor or pharmacist . How do I store amlodipine besylate tablets? Keep Amlodipine besylate tablets, USP away from children. Store at 20°C to 25°C (68°F to 77°F). [See USP controlled room temperature.] Protect from light and moisture. General advice about amlodipine besylate tablets Sometimes, doctors will prescribe a medicine for a condition that is not written in the patient information leaflets. Only use amlodipine besylate tablets the way your doctor told you to. Do not give amlodipine besylate tablets to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or doctor for information about Amlodipine besylate tablets, USP. Manufactured by: Cipla, Ltd., Verna, Goa India Manufactured for: Cipla USA, Inc. 10 Independence Boulevard, Suite 300 Warren, NJ 07059        Revised: 2/2020 Repackaged By: Preferred Pharmaceuticals Inc.

•  2.5 mg, 5 mg, and 10 mg Tablets ( 3 )

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 in vitro 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. 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: Exertional Angina: In patients with exertional angina, amlodipine  besylate reduces the total peripheral resistance (after load) against which the heart works and reduces the rate pressure product, and thus myocardial oxygen demand, at any given level of exercise. Vasospastic Angina: Amlodipine besylate has been demonstrated to block constriction and restore blood flow in coronary arteries and arterioles in response to calcium, potassium epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro . This inhibition of coronary spasm is responsible for the effectiveness of amlodipine besylate in vasospastic (Prinzmetal's or variant) angina.

Hemodynamics: Following administration of therapeutic doses to patients with hypertension, amlodipine besylate produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by a significant change in heart rate or plasma catecholamine levels with chronic dosing. Although the acute intravenous administration of amlodipine besylate decreases arterial blood pressure and increases heart rate in hemodynamic studies of patients with chronic stable angina, chronic oral administration of amlodipine in clinical trials did not lead to clinically significant changes in heart rate or blood pressures in normotensive patients with angina. With chronic once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with amlodipine besylate is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (Diastolic pressure 105–114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90–104 mmHg). Normotensive subjects experienced no clinically significant change in blood pressures (+1/–2 mmHg). In hypertensive patients with normal renal function, therapeutic doses of amlodipine besylate resulted in a decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria. As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with amlodipine besylate have generally demonstrated a small increase in cardiac index without significant influence on dP/dt or on left ventricular end diastolic pressure or volume. In hemodynamic studies, amlodipine besylate has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when coadministered with beta-blockers to man. Similar findings, however, have been observed in normal or well-compensated patients with heart failure with agents possessing significant negative inotropic effects. Electrophysiologic Effects: Amlodipine besylate does not change sinoatrial nodal function or atrioventricular conduction in intact animals or man. In patients with chronic stable angina, intravenous administration of 10 mg did not significantly alter A-H and H-V conduction and sinus node recovery time after pacing. Similar results were obtained in patients receiving amlodipine besylate and concomitant beta-blockers. In clinical studies in which amlodipine besylate was administered in combination with beta-blockers to patients with either hypertension or angina, no adverse effects on electrocardiographic parameters were observed. In clinical trials with angina patients alone, amlodipine besylate therapy did not alter electrocardiographic intervals or produce higher degrees of AV blocks. Drug interactions Sildenafil : When amlodipine and sildenafil were used in combination, each agent independently exerted its own blood pressure lowering effect [see Drug Interactions ( 7.1 )].

•   Pediatric: Effect on patients less than 6 years old is not known. ( 8.4 ) •   Geriatric: Start dosing at the low end of the dose range. ( 8.5 )

•   Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely. ( 5.1 ) •   Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of Amlodipine besylate tablet, USP, particularly in patients with severe obstructive coronary artery disease. ( 5.2 ) •   Titrate slowly in patients with severe hepatic impairment. ( 5.3 )

Principle Display Panel- Label NDC 68788-6386     Rx ONLY Amlodipine Besylate Tablets, USP 10 mg PHARMACIST : Please dispense with Patient Leaflet Cipla Repackaged By: Preferred Pharmaceuticals Inc.