Amlodipine Besylate

Lake Erie Medical DBA Quality Care Products LLC

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use amlodipine besylate safely and effectively. See full prescribing information for amlodipine besylate tablets. Amlodipine besylate tablets for oral administrationInitial U.S. Approval: 1987INDICATIONS AND USAGE Hypertension (1.1) Coronary Artery Disease (1.2) Chronic Stable Angina Vasospastic Angina (Prinzmetal's or Variant Angina) Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40% DOSAGE AND ADMINISTRATION Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. (2.1) 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: 2.2DOSAGE FORMS AND STRENGTHS 2.5 mg, 5 mg, and 10 mg Tablets (3) CONTRAINDICATIONS Known sensitivity to amlodipine (4) WARNINGS AND PRECAUTIONS Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, because of the gradual onset of action, acute hypotension is unlikely. (5.1) Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease. (5.2) Titrate slowly when administering calcium channel blockers to patients with severe hepatic impairment. (5.4) Side Effects6To report SUSPECTED ADVERSE REACTIONS, contact at or FDA at 1-800-FDA-1088 or www.fda.gov/medwatchUSE IN SPECIFIC POPULATIONS Pregnancy: Use only if the potential benefit justifies the potential risk. (8.1) Nursing: Discontinue when administering amlodipine besylate. (8.3) 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, due to the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. (8.5)

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 INDICATIONS & USAGE
  • 1.1 Hypertension
  • 1.2 Coronary Artery Disease (CAD)
• 2 DOSAGE & ADMINISTRATION
  • 2.1 Adults
  • 2.2 Children
• 3 DOSAGE FORMS & STRENGTHS
• 4 AMLODIPINE BESYLATE CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Hypotension
  • 5.2 Increased Angina or Myocardial Infarction
  • 5.3 Beta-Blocker Withdrawal
  • 5.4 Patients with Hepatic Failure
• 6 AMLODIPINE BESYLATE ADVERSE REACTIONS
  • 6.1 Clinical Trials Experience
  • 6.2 Postmarketing Experience
• 7 DRUG INTERACTIONS
  • 7.1 In Vitro Data
  • 7.2 Cimetidine
  • 7.3 Grapefruit Juice
  • 7.4 Magnesium and Aluminum Hydroxide Antacid
  • 7.5 Sildenafil
  • 7.6 Atorvastatin
  • 7.7 Digoxin
  • 7.8 Ethanol (Alcohol)
  • 7.9 Warfarin
  • 7.10 Drug/Laboratory Test Interactions
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 10 OVERDOSAGE
• 11 AMLODIPINE BESYLATE DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics and Metabolism
  • 12.4 Pediatric Patients
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 14 CLINICAL STUDIES
  • 14.1 Effects in Hypertension
  • 14.2 Effects in Chronic Stable Angina
  • 14.3 Effects in Vasospastic Angina
  • 14.4 Effects in Documented Coronary Artery Disease
  • 14.5 Studies in Patients with Heart Failure
• 16 HOW SUPPLIED/STORAGE AND HANDLING
  • 16.1 2.5 mg Tablets
  • 16.2 5 mg Tablets
  • 16.3 10 mg Tablets
  • 16.4 Storage
• PATIENT PACKAGE INSERT
• PRINCIPAL DISPLAY PANEL - 5 mg Tablets

FULL PRESCRIBING INFORMATION

1 INDICATIONS & USAGE

1.1 Hypertension

1.2 Coronary Artery Disease (CAD)

2 DOSAGE & ADMINISTRATION

2.1 Adults

[see Clinical Studies (14.4)]

2.2 Children

[see Clinical Pharmacology (12.4), Clinical Studies (14.1)]

3 DOSAGE FORMS & STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Hypotension

5.2 Increased Angina or Myocardial Infarction

5.3 Beta-Blocker Withdrawal

5.4 Patients with Hepatic Failure

_1/2

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Adverse Event	2.5 mg	5.0 mg	10.0 mg	Placebo
	N=275	N=296	N=268	N=520
Edema	1.8	3.0	10.8	0.6
Dizziness	1.1	3.4	3.4	1.5
Flushing	0.7	1.4	2.6	0.0
Palpitation	0.7	1.4	4.5	0.6

Placebo-Controlled Studies

Adverse Event	Amlodipine (%)	Placebo (%)
	(N=1730)	(N=1250)
Headache	7.3	7.8
Fatigue	4.5	2.8
Nausea	2.9	1.9
Abdominal Pain	1.6	0.3
Somnolence	1.4	0.6

	Amlodipine		Placebo
Adverse Event	Male=%	Female=%	Male=%	Female=%
	(N=1218)	(N=512)	(N=914)	(N=336)
Edema	5.6	14.6	1.4	5.1
Flushing	1.5	4.5	0.3	0.9
Palpitations	1.4	3.3	0.9	0.9
Somnolence	1.3	1.6	0.8	0.3

Cardiovascular:

Central and Peripheral Nervous System:

Gastrointestinal:¹

General:¹

Musculoskeletal System:¹

Psychiatric:¹

Respiratory System:¹

Skin and Appendages:^{1 1}

Special Senses:

Urinary System:

Autonomic Nervous System:

Metabolic and Nutritional:

Hemopoietic:

¹







[see Clinical Studies (14.4)]

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 In Vitro Data

In vitro

7.2 Cimetidine

7.3 Grapefruit Juice

7.4 Magnesium and Aluminum Hydroxide Antacid

7.5 Sildenafil

7.6 Atorvastatin

7.7 Digoxin

7.8 Ethanol (Alcohol)

7.9 Warfarin

7.10 Drug/Laboratory Test Interactions

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

<sup>2 2 2

2</sup>

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

[see Dosage and Administration (2.1)]

10 OVERDOSAGE

²

11 DESCRIPTION

_202525663

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

in vitro







in vitro

12.2 Pharmacodynamics

12.3 Pharmacokinetics and Metabolism

Ex vivo

12.4 Pediatric Patients

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

<sup>2 3 2 3



32

3</sup>

14 CLINICAL STUDIES

14.1 Effects in Hypertension

Adult Patients


Pediatric Patients

14.2 Effects in Chronic Stable Angina

14.3 Effects in Vasospastic Angina

14.4 Effects in Documented Coronary Artery Disease

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

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

Table 1. Incidence of Significant Clinical Outcomes for CAMELOT

Clinical Outcomes N (%)	Amlodipine (N=663)	Placebo (N=655)	Risk Reduction (p-value)
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)
*Total patients with these events

14.5 Studies in Patients with Heart Failure

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 2.5 mg Tablets

16.2 5 mg Tablets

16.3 10 mg Tablets

16.4 Storage

ALKEM LABORATORIES LTD.

PATIENT PACKAGE INSERT

AMLODIPINE BESYLATE TABLETS 2.5 mg, 5 mg, and 10 mg


What is amlodipine besylate?


High Blood Pressure (hypertension)


Angina


Who should not use amlodipine besylate?


What should I tell my doctor before taking amlodipine besylate?

• ever had heart disease
• ever had liver problems
• are pregnant, or plan to become pregnant. Your doctor will decide if amlodipine besylate is the best treatment for you.
• are breast-feeding. Do not breast-feed while taking amlodipine besylate. You can stop breast-feeding or take a different medicine.

How should I take amlodipine besylate?

• Take amlodipine besylate tablets once a day, with or without food. You can take amlodipine besylate with most drinks, including grapefruit juice.
• 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 at a time.
• If you miss a dose, take it as soon as you remember. Do not take amlodipine besylate 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 together. If you take nitroglycerin for angina, don't stop taking it while you are taking amlodipine besylate.
• While you are taking amlodipine besylate, 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, 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?

• Do not breast-feed. It is not known if amlodipine besylate will pass through your milk.
• 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?

• 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)

How do I store amlodipine besylate tablets?


General advice about amlodipine besylate





ALKEM LABORATORIES LTD.

PRINCIPAL DISPLAY PANEL - 5 mg Tablets

Amlodipine Besylate AMLODIPINE BESYLATE TABLET Product Information Product Type Human prescription drug label Item Code (Source) NDC:35356-059(NDC:51991-667) Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength amlodipine besylate AMLODIPINE 5 mg Inactive Ingredients Ingredient Name Strength cellulose, microcrystalline ANHYDROUS DIBASIC CALCIUM PHOSPHATE SODIUM STARCH GLYCOLATE TYPE A POTATO SILICON DIOXIDE MAGNESIUM STEARATE Product Characteristics Color Size Imprint Code Shape white (off-white) 8 mm 210 ROUND Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:35356-059-10 10 in 1 BOTTLE, PLASTIC Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA078925 2011-02-21