Amlodipine Besylate: Package Insert and Label Information (Page 3 of 4)

14.1 Effects in Hypertension

Adult Patients

The antihypertensive efficacy of amlodipine has been demonstrated in a total of 15 double-blind, placebo-controlled, randomized studies involving 800 patients on amlodipine and 538 on placebo. Once daily administration produced statistically significant placebo-corrected reductions in supine and standing blood pressures at 24 hours postdose, averaging about

12/6 mmHg in the standing position and 13/7 mmHg in the supine position in patients with mild to moderate hypertension. Maintenance of the blood pressure effect over the 24-hour dosing interval was observed, with little difference in peak and trough effect. Tolerance was not demonstrated in patients studied for up to 1 year. The 3 parallel, fixed dose, dose response studies showed that the reduction in supine and standing blood pressures was dose-related within the recommended dosing range. Effects on diastolic pressure were similar in young and older patients. The effect on systolic pressure was greater in older patients, perhaps because of greater baseline systolic pressure. Effects were similar in black patients and in white patients.

Pediatric Patients

Two hundred sixty-eight hypertensive patients aged 6 to 17 years were randomized first to amlodipine 2.5 or 5 mg once daily for 4 weeks and then randomized again to the same dose or to placebo for another 4 weeks. Patients receiving 2.5 mg or 5 mg at the end of 8 weeks had significantly lower systolic blood pressure than those secondarily randomized to placebo. The magnitude of the treatment effect is difficult to interpret, but it is probably less than 5 mmHg systolic on the 5 mg dose and 3.3 mmHg systolic on the 2.5 mg dose. Adverse events were similar to those seen in adults.

14.2 Effects in Chronic Stable Angina

The effectiveness of 5 to 10 mg/day of amlodipine in exercise-induced angina has been evaluated in 8 placebo-controlled, double-blind clinical trials of up to 6 weeks duration involving 1038 patients (684 amlodipine, 354 placebo) with chronic stable angina. In 5 of the 8 studies, significant increases in exercise time (bicycle or treadmill) were seen with the 10 mg dose. Increases in symptom-limited exercise time averaged 12.8% (63 sec) for amlodipine 10 mg, and averaged 7.9% (38 sec) for amlodipine 5 mg. Amlodipine 10 mg also increased time to 1 mm ST segment deviation in several studies and decreased angina attack rate. The sustained efficacy of amlodipine in angina patients has been demonstrated over long-term dosing. In patients with angina, there were no clinically significant reductions in blood pressures (4/1 mmHg) or changes in heart rate (+0.3 bpm).

14.3 Effects in Vasospastic Angina

In a double-blind, placebo-controlled clinical trial of 4 weeks duration in 50 patients, amlodipine therapy decreased attacks by approximately 4/week compared with a placebo decrease of approximately 1/week (p<0.01). Two of 23 amlodipine and 7 of 27 placebo patients discontinued from the study due to lack of clinical improvement.

14.4 Effects in Documented Coronary Artery Disease

In PREVENT, 825 patients with angiographically documented coronary artery disease were randomized to amlodipine (5 to 10 mg once daily) or placebo and followed for 3 years. Although the study did not show significance on the primary objective of change in coronary luminal diameter as assessed by quantitative coronary angiography, the data suggested a favorable outcome with respect to fewer hospitalizations for angina and revascularization procedures in patients with CAD.

CAMELOT enrolled 1318 patients with CAD recently documented by angiography, without left main coronary disease and without heart failure or an ejection fraction <40%. Patients (76% males, 89% Caucasian, 93% enrolled at US sites, 89% with a history of angina, 52% without PCI, 4% with PCI and no stent, and 44% with a stent) were randomized to double-blind treatment with either amlodipine (5 to 10 mg once daily) or placebo in addition to standard care that included aspirin (89%), statins (83%), beta-blockers (74%), nitroglycerin (50%), anti-coagulants (40%), and diuretics (32%), but excluded other calcium channel blockers. The mean duration of follow-up was 19 months. The primary endpoint was the time to first occurrence of one of the following events: hospitalization for angina pectoris, coronary revascularization, myocardial infarction, cardiovascular death, resuscitated cardiac arrest, hospitalization for heart failure, stroke/TIA, or peripheral vascular disease. A total of 110 (16.6%) and 151 (23.1%) first events occurred in the amlodipine and placebo groups, respectively, for a hazard ratio of 0.691 (95% CI: 0.540 to 0.884, p = 0.003). The primary endpoint is summarized in Figure 1 below. The outcome of this study was largely derived from the prevention of hospitalizations for angina and the prevention of revascularization procedures (see Table 1). Effects in various subgroups are shown in Figure 2.

In an angiographic substudy (n=274) conducted within CAMELOT, there was no significant difference between amlodipine and placebo on the change of atheroma volume in the coronary artery as assessed by intravascular ultrasound.

Figure 1 — Kaplan-Meier Analysis of Composite Clinical Outcomes for Amlodipine versus Placebo

Figure 1 -- Kaplan-Meier Analysis of Composite Clinical Outcomes for Amlodipine versus Placebo
(click image for full-size original)

Figure 2 — Effects on Primary Endpoint of Amlodipine versus Placebo across Sub-Groups

Figure 2 -- Effects on Primary Endpoint of Amlodipine versus Placebo across Sub-Groups
(click image for full-size original)

Table 1 below summarizes the significant composite endpoint and clinical outcomes from the composites of the primary endpoint. The other components of the primary endpoint including cardiovascular death, resuscitated cardiac arrest, myocardial infarction, hospitalization for heart failure, stroke/TIA, or peripheral vascular disease did not demonstrate a significant difference between amlodipine and placebo.

Table 1. Incidence of Significant Clinical Outcomes for CAMELOT
Clinical Outcomes N (%) Amlodipine ( N = 663 ) Placebo ( N = 655 ) Risk Reduction ( p value )
*
Total patients with these events
Composite CV Endpoint 110 ( 16 . 6 ) 151 ( 23 . 1 ) 31 % ( 0 . 003 )
Hospitalization for Angina *51(7.7)84(12.8)42%(0.002)
Coronary Revascularization *78(11.8)103(15.7)27%(0.033)

14.5 Studies in Patients with Heart Failure

Amlodipine has been compared to placebo in four 8 to 12 week studies of patients with NYHA Class II/III heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or left ventricular ejection fraction. In a long-term (follow-up at least 6 months, mean 13.8 months) placebo- controlled mortality/morbidity study of amlodipine 5 to 10 mg in 1153 patients with NYHA Classes III (n=931) or IV (n=222) heart failure on stable doses of diuretics, digoxin, and ACE inhibitors, amlodipine had no effect on the primary endpoint of the study which was the combined endpoint of all-cause mortality and cardiac morbidity (as defined by life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure), or on NYHA classification, or symptoms of heart failure. Total combined all-cause mortality and cardiac morbidity events were 222/571 (39%) for patients on amlodipine and 246/583 (42%) for patients on placebo; the cardiac morbid events represented about 25% of the endpoints in the study.

Another study (PRAISE-2) randomized patients with NYHA Class III (80%) or IV (20%) heart failure without clinical symptoms or objective evidence of underlying ischemic disease, on stable doses of ACE inhibitors (99%), digitalis (99%), and diuretics (99%), to placebo (n=827) or amlodipine (n=827) and followed them for a mean of 33 months. There was no statistically significant difference between amlodipine and placebo in the primary endpoint of all-cause mortality (95% confidence limits from 8% reduction to 29% increase on amlodipine). With amlodipine there were more reports of pulmonary edema.

16 HOW SUPPLIED/STORAGE AND HANDLING

2.5 mg Tablets

Amlodipine Besylate Tablets USP, 2.5 mg – (amlodipine besylate equivalent to 2.5 mg of amlodipine per tablet) are supplied as pink color mottled, round, flat-faced, beveled edged tablets debossed with “L” on one side and “28” on the other side and supplied as follows:

NDC 68180-719-09 Bottles of 90

5 mg Tablets

Amlodipine Besylate Tablets USP, 5 mg – (amlodipine besylate equivalent to 5 mg of amlodipine per tablet) are supplied as white to off white capsule shaped tablets debossed with “L” on one side and “29” on the other side and supplied as follows:

NDC 68180-720-09 Bottles of 90

NDC 68180-720-03 Bottles of 1000

10 mg Tablets

Amlodipine Besylate Tablets USP, 10 mg – (amlodipine besylate equivalent to 10 mg of amlodipine per tablet) are supplied as white to off white round, flat faced, beveled edged tablet debossed with “L” on one side and “32” on the other side and supplied as follows:

NDC 68180-721-09 Bottles of 90

NDC 68180-721-03 Bottles of 1000

Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] and dispense in tight, light-resistant containers (USP).

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

MADE IN INDIA.

Revised: May 2021

Amlodipine Besylate (am-LOE-di-peen BES-i-late)

Tablets USP

Rx Only

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 an amlodipine besylate tablet is right for you.

What is Amlodipine Besylate Tablet?

Amlodipine besylate tablet 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 tablet 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 tablet is the best treatment for you.
  • are breast-feeding. Amlodipine besylate tablet passes into your milk.

How should I take Amlodipine Besylate Tablets?

  • Takeamlodipine besylate tablet 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 ofamlodipine besylate tablets at a time.
  • If you miss a dose, take it as soon as you remember. Do not takeamlodipine 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 andamlodipine besylate tablets together. If you take nitroglycerin for angina, don’t stop taking it while you are takingamlodipine besylate tablets.
  • While you are takingamlodipine 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 muchamlodipine 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.

To report side effects, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

How do I store Amlodipine Besylate Tablets?

Keep amlodipine besylate tablets away from children. Store amlodipine besylate tablets at 20° to 25°C (68° to 77°F). Keep amlodipine besylate tablets out of the light. Do not store in the bathroom. Keep amlodipine besylate tablets in a dry place.

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 , or you can visit the Lupin website at www.lupinpharmaceuticals.com or call 1-800-399-2561.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

MADE IN INDIA.

Revised: May 2021 ID#: 267375

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