METOPROLOL SUCCINATE tablet, extended release

United States - English - NLM (National Library of Medicine)

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Active ingredient:
METOPROLOL SUCCINATE (UNII: TH25PD4CCB) (METOPROLOL - UNII:GEB06NHM23)
Available from:
Bryant Ranch Prepack
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Metoprolol succinate extended-release tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure lowers 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 metoprolol. 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 1 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
Product summary:
Product: 63629-8100 NDC: 63629-8100-1 30 TABLET, EXTENDED RELEASE in a BOTTLE
Authorization status:
Abbreviated New Drug Application
Authorization number:
63629-8100-1

METOPROLOL SUCCINATE- metoprolol succinate tablet, extended release

Bryant Ranch Prepack

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use METOPROLOL SUCCINATE EXTENDED-

RELEASE TABLETS safely and effectively. See full prescribing information for METOPROLOL SUCCINATE

EXTENDED-RELEASE TABLETS

METOPROLOL SUCCINATE extended-release TABLETS for oral use.

Initial U.S. Approval:1992

WARNING: ISCHEMIC HEART DISEASE

See full prescribing information for complete boxed warning.

Following abrupt cessation of therapy with beta-blocking agents, exacerbations of angina pectoris and

myocardial infarction have occurred. Warn patients against interruption or discontinuation of therapy

without the physician's advice. (5.1)

INDICATIONS AND USAGE

Metoprolol succinate, is a beta -selective adrenoceptor blocking agent.

Metoprolol succinate extended-release tablets, USP are 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. (1.1)

Angina Pectoris. (1.2)

Heart Failure - for the treatment of stable, symptomatic (NYHA Class II or III) heart failure of ischemic, hypertensive,

or cardiomyopathic origin. (1.3)

DOSAGE AND ADMINISTRATION

Administer once daily. Dosing of metoprolol succinate extended-release tablets, USP should be individualized. (2)

Heart Failure: Recommended starting dose is 12.5 mg or 25 mg doubled every two weeks to the highest dose tolerated

or up to 200 mg. (2.3)

Hypertension: Usual initial dosage is 25 to 100 mg once daily. The dosage may be increased at weekly (or longer)

intervals until optimum blood pressure reduction is achieved. Dosages above 400 mg per day have not been studied.

(2.1)

Angina Pectoris: Usual initial dosage is 100 mg once daily. Gradually increase the dosage at weekly intervals until

optimum clinical response has been obtained or there is an unacceptable bradycardia. Dosages above 400 mg per day

have not been studied. (2.2)

Switching from immediate-release metoprolol to metoprolol succinate extended-release tablets: use the same total

daily dose of metoprolol succinate extended-release tablets. (2)

DOSAGE FORMS AND STRENGTHS

Metoprolol succinate extended-release tablets, USP: 25 mg, 50 mg, 100 mg and 200 mg. (3)

CONTRAINDICATIONS

Known hypersensitivity to product components. (4)

Severe bradycardia. (4)

Heart block greater than first degree. (4)

Cardiogenic shock. (4)

Decompensated cardiac failure. (4)

Sick sinus syndrome without a pacemaker. (4)

WARNINGS AND PRECAUTIONS

Heart Failure: Worsening cardiac failure may occur. (5.2)

Bronchospastic Disease: Avoid beta blockers. (5.3)

Pheochromocytoma: If required, first initiate therapy with an alpha blocker. (5.4)

Major Surgery: Avoid initiation of high-dose extended-release metoprolol in patients undergoing non-cardiac surgery

because it has been associated with bradycardia, hypotension, stroke and death. Do not routinely withdraw chronic beta

blocker therapy prior to surgery. (5.5, 6.1)

Diabetes and Hypoglycemia: May mask tachycardia occurring with hypoglycemia. (5.6)

Patients with Hepatic Impairment: (5.7)

Thyrotoxicosis: Abrupt withdrawal in patients with thyrotoxicosis might precipitate a thyroid storm. (5.8)

Anaphylactic Reactions: Patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

(5.9)

Peripheral Vascular Disease: Can aggravate symptoms of arterial insufficiency. (5.10)

Calcium Channel Blockers: Because of significant inotropic and chronotropic effects in patients treated with beta-

blockers and calcium channel blockers of the verapamil and diltiazem type, caution should be exercised in patients

treated with these agents concomitantly. (5.11)

ADVERSE REACTIONS

Most common adverse reactions: tiredness, dizziness, depression, shortness of breath, bradycardia, hypotension,

diarrhea, pruritus, rash. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Ingenus Pharmaceuticals LLC Toll-Free at 1-877-748-

1970 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Catecholamine-depleting drugs may have an additive effect when given with beta-blocking agents. (7.1)

CYP2D6 Inhibitors are likely to increase metoprolol concentration. (7.2)

Concomitant use of glycosides, clonidine, and diltiazem and verapamil with beta-blockers can increase the risk of

bradycardia. (7.3)

Beta-blockers including metoprolol, may exacerbate the rebound hypertension that can follow the withdrawal of

clonidine. (7.3)

USE IN SPECIFIC POPULATIONS

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Use this drug during pregnancy only

if clearly needed. (8.1)

Nursing Mothers: Consider possible infant exposure. (8.3)

Pediatrics: Safety and effectiveness have not been established in patients < 6 years of age. (8.4)

Geriatrics: No notable difference in efficacy or safety vs. younger patients. (8.5)

Hepatic Impairment: Consider initiating metoprolol succinate extended-release tablet therapy at low doses and

gradually increase dosage to optimize therapy, while monitoring closely for adverse events. (8.6)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 8/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: ISCHEMIC HEART DISEASE:

1 INDICATIONS AND USAGE

1.1 Hypertension

1.2 Angina Pectoris

1.3 Heart Failure

2 DOSAGE AND ADMINISTRATION

2.1 Hypertension

2.2 Angina Pectoris

2.3 Heart Failure

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Ischemic Heart Disease

5.2 Heart Failure

5.3 Bronchospastic Disease

5.4 Pheochromocytoma

5.5 Major Surgery

5.6 Diabetes and Hypoglycemia

5.7 Hepatic Impairment

5.8 Thyrotoxicosis

5.9 Anaphylactic Reaction

5.10 Peripheral Vascular Disease

5.11 Calcium Channel Blockers

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Post-Marketing Experience

6.3 Laboratory Test Findings

7 DRUG INTERACTIONS

7.1 Catecholamine Depleting Drugs

7.2 CYP2D6 Inhibitors

7.3 Digitalis, Clonidine, and Calcium Channel Blockers

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Hepatic Impairment

8.7 Renal Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY

14 CLINICAL STUDIES

14.1 Angina Pectoris

14.2 Heart Failure

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

WARNING: ISCHEMIC HEART DISEASE:

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of

angina pectoris and, in some cases, myocardial infarction have occurred. When

discontinuing chronically administered metoprolol succinate extended-release tablets,

particularly in patients with ischemic heart disease, the dosage should be gradually reduced

over a period of 1 - 2 weeks and the patient should be carefully monitored. If angina

markedly worsens or acute coronary insufficiency develops, metoprolol succinate

extended-release tablet administration should be reinstated promptly, at least temporarily,

and other measures appropriate for the management of unstable angina should be taken.

Warn patients against interruption or discontinuation of therapy without the physician's

advice. Because coronary artery disease is common and may be unrecognized, it may be

prudent not to discontinue metoprolol succinate extended-release tablet therapy abruptly

even in patients treated only for hypertension (5.1).

1 INDICATIONS AND USAGE

1.1 Hypertension

Metoprolol succinate extended-release tablets are indicated for the treatment of hypertension, to lower

blood pressure. Lowering blood pressure lowers 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 metoprolol.

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 1 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.

Metoprolol succinate extended-release tablets may be administered with other antihypertensive agents.

1.2 Angina Pectoris

Metoprolol succinate extended-release tablets are indicated in the long-term treatment of angina

pectoris, to reduce angina attacks and to improve exercise tolerance.

1.3 Heart Failure

Metoprolol succinate extended-release tablets are indicated for the treatment of stable, symptomatic

(NYHA Class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin. It was

studied in patients already receiving ACE inhibitors, diuretics, and, in the majority of cases, digitalis. In

this population, metoprolol succinate extended-release tablets decreased the rate of mortality plus

hospitalization, largely through a reduction in cardiovascular mortality and hospitalizations for heart

failure.

2 DOSAGE AND ADMINISTRATION

Metoprolol succinate extended-release tablets are an extended-release tablet intended for once daily

administration. For treatment of hypertension and angina, when switching from immediate-release

metoprolol to metoprolol succinate extended-release tablets, use the same total daily dose of

metoprolol succinate extended-release tablets. Individualize the dosage of metoprolol succinate

extended- release tablets. Titration may be needed in some patients.

Metoprolol succinate extended-release tablets are scored on both sides and can be divided; however,

do not crush or chew the whole or half tablet.

2.1 Hypertension

Adults: The usual initial dosage is 25 to 100 mg daily in a single dose. The dosage may be increased at

weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the

maximum effect of any given dosage level will be apparent after 1 week of therapy. Dosages above 400

mg per day have not been studied.

Pediatric Hypertensive Patients 6 Years of age: A pediatric clinical hypertension study in patients 6 to 16

years of age did not meet its primary endpoint (dose response for reduction in SBP); however, some

other endpoints demonstrated effectiveness [see Use in Specific Populations (8.4)]. If selected for

treatment, the recommended starting dose of metoprolol succinate extended-release tablets is 1.0 mg/kg

once daily, but the maximum initial dose should not exceed 50 mg once daily. Dosage should be

adjusted according to blood pressure response. Doses above 2.0 mg/kg (or in excess of 200 mg) once

daily have not been studied in pediatric patients [see Clinical Pharmacology (12.3)].

Metoprolol succinate extended-release tablets are not recommended in pediatric patients < 6 years of

age [see Use in Specific Populations (8.4)].

2.2 Angina Pectoris

Individualize the dosage of metoprolol succinate extended-release tablets. The usual initial dosage is

100 mg daily, given in a single dose. Gradually increase the dosage at weekly intervals until optimum

clinical response has been obtained or there is a pronounced slowing of the heart rate. Dosages above

400 mg per day have not been studied. If treatment is to be discontinued, reduce the dosage gradually

over a period of 1 - 2 weeks [see Warnings and Precautions (5)].

2.3 Heart Failure

Dosage must be individualized and closely monitored during up-titration. Prior to initiation of

metoprolol succinate extended-release tablets, stabilize the dose of other heart failure drug therapy.

The recommended starting dose of metoprolol succinate extended-release tablets is 25 mg once daily

for two weeks in patients with NYHA Class II heart failure and 12.5 mg once daily in patients with more

severe heart failure. Double the dose every two weeks to the highest dosage level tolerated by the

patient or up to 200 mg of metoprolol succinate extended-release tablets. Initial difficulty with titration

should not preclude later attempts to introduce metoprolol succinate extended-release tablets. If patients

experience symptomatic bradycardia, reduce the dose of metoprolol succinate extended-release tablets.

If transient worsening of heart failure occurs, consider treating with increased doses of diuretics,

If transient worsening of heart failure occurs, consider treating with increased doses of diuretics,

lowering the dose of metoprolol succinate extended-release tablets or temporarily discontinuing it. The

dose of metoprolol succinate extended-release tablets should not be increased until symptoms of

worsening heart failure have been stabilized.

3 DOSAGE FORMS AND STRENGTHS

25 mg tablets white, oval, biconvex, scored on both sides, film-coated tablet engraved with "N / 25".

50 mg tablets white, round, biconvex, scored on both sides, film-coated tablet engraved with "N / 50".

100 mg tablets white, round, biconvex, scored on both sides, film-coated tablet engraved with "N /

100".

200 mg tablets white, oval, biconvex, scored on both sides, film-coated tablet engraved with "N / 200".

4 CONTRAINDICATIONS

Metoprolol succinate extended-release tablets are contraindicated in severe bradycardia, second or

third degree heart block, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome

(unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of

this product.

5 WARNINGS AND PRECAUTIONS

5.1 Ischemic Heart Disease

Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina

pectoris and, in some cases, myocardial infarction have occurred. When discontinuing chronically

administered metoprolol succinate extended-release tablets, particularly in patients with ischemic heart

disease, gradually reduce the dosage over a period of 1 - 2 weeks and monitor the patient. If angina

markedly worsens or acute coronary ischemia develops, promptly reinstate metoprolol succinate

extended-release tablets, and take measures appropriate for the management of unstable angina. Warn

patients not to interrupt therapy without their physician's advice. Because coronary artery disease is

common and may be unrecognized, avoid abruptly discontinuing metoprolol succinate extended-release

tablets in patients treated only for hypertension.

5.2 Heart Failure

Worsening cardiac failure may occur during up-titration of metoprolol succinate extended-release

tablets. If such symptoms occur, increase diuretics and restore clinical stability before advancing the

dose of metoprolol succinate extended-release tablets [see Dosage and Administration (2)]. It may be

necessary to lower the dose of metoprolol succinate extended-release tablets or temporarily

discontinue it. Such episodes do not preclude subsequent successful titration of metoprolol succinate

extended-release tablets.

5.3 Bronchospastic Disease

PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE

BETA-BLOCKERS. Because of its relative beta cardio-selectivity, however, metoprolol succinate

extended-release tablets may be used in patients with bronchospastic disease who do not respond to, or

cannot tolerate, other antihypertensive treatment. Because beta -selectivity is not absolute, use the

lowest possible dose of metoprolol succinate extended-release tablets. Bronchodilators, including

beta -agonists, should be readily available or administered concomitantly [see Dosage and

Administration (2)].

5.4 Pheochromocytoma

If metoprolol succinate extended-release tablets are used in the setting of pheochromocytoma, it should

be given in combination with an alpha blocker, and only after the alpha blocker has been initiated.

Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a

paradoxical increase in blood pressure due to the attenuation of beta-mediated vasodilatation in skeletal

muscle.

5.5 Major Surgery

Avoid initiation of a high-dose regimen of extended-release metoprolol in patients undergoing non-

cardiac surgery, since such use in patients with cardiovascular risk factors has been associated with

bradycardia, hypotension, stroke and death.

Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major

surgery, however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment

the risks of general anesthesia and surgical procedures.

5.6 Diabetes and Hypoglycemia

Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as

dizziness and sweating may not be significantly affected.

5.7 Hepatic Impairment

Consider initiating metoprolol succinate extended-release tablets therapy at doses lower than those

recommended for a given indication; gradually increase dosage to optimize therapy, while monitoring

closely for adverse events.

5.8 Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism, such as tachycardia.

Abrupt withdrawal of beta-blockade may precipitate a thyroid storm.

5.9 Anaphylactic Reaction

While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of

allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of

epinephrine used to treat an allergic reaction.

5.10 Peripheral Vascular Disease

Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral

vascular disease.

5.11 Calcium Channel Blockers

Because of significant inotropic and chronotropic effects in patients treated with beta-blockers and

calcium channel blockers of the verapamil and diltiazem type, caution should be exercised in patients

treated with these agents concomitantly.

6 ADVERSE REACTIONS

The following adverse reactions are described elsewhere in labeling:

Worsening angina or myocardial infarction[see Warnings and Precautions (5)].

Worsening heart failure[see Warnings and Precautions (5)].

Worsening AV block[see Contraindications (4)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, 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. The adverse reaction information from clinical trials

does, however, provide a basis for identifying the adverse events that appear to be related to drug use

and for approximating rates.

Hypertension and Angina: Most adverse reactions have been mild and transient. The most common

(>2%) adverse reactions are tiredness, dizziness, depression, diarrhea, shortness of breath, bradycardia,

and rash.

Heart Failure: In the MERIT-HF study comparing metoprolol succinate extended-release tablets in

daily doses up to 200 mg (mean dose 159 mg once-daily; n=1990) to placebo (n=2001), 10.3% of

metoprolol succinate extended-release tablets patients discontinued for adverse reactions vs. 12.2% of

placebo patients.

The table below lists adverse reactions in the MERIT-HF study that occurred at an incidence of 1% in

the metoprolol succinate extended-release tablets group and greater than placebo by more than 0.5%,

regardless of the assessment of causality.

Adverse Reactions Occurring in the MERIT-HF Study at an Incidence ≥1% in the metoprolol

succinate extended-release tablets Group and Greater Than Placebo by More Than 0.5%

Metoprolol succinate extended-

release tablet group; n=1990

% of patients

Placebo; n=2001

% of patients

Dizziness/vertigo

Bradycardia

Accident and/or injury

Post-operative Adverse Events: In a randomized, double-blind, placebo-controlled trial of 8351

patients with or at risk for atherosclerotic disease undergoing non-vascular surgery and who were not

taking beta–blocker therapy, metoprolol succinate extended-release tablets 100 mg was started 2 to 4

hours prior to surgery then continued for 30 days at 200 mg per day. Metoprolol succinate extended-

release tablets use was associated with a higher incidence of bradycardia (6.6% vs. 2.4%; HR, 2.74;

95% CI 2.19, 3.43), hypotension (15% vs. 9.7%; HR 1.55; 95% CI 1.37, 1.74), stroke (1.0% vs. 0.5%;

HR 2.17; 95% CI 1.26, 3.74) and death (3.1% vs. 2.3%; HR 1.33; 95% CI 1.03, 1.74) compared to

placebo.

6.2 Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of metoprolol succinate

extended-release tablets or immediate-release metoprolol. Because these reactions are reported

voluntarily from a population of uncertain size, it is not always possible to reliably estimate their

frequency or establish a causal relationship to drug exposure.

Cardiovascular: Cold extremities, arterial insufficiency (usually of the Raynaud type), palpitations,

peripheral edema, syncope, chest pain and hypotension.

Respiratory: Wheezing (bronchospasm), dyspnea.

Central Nervous System: Confusion, short-term memory loss, headache, somnolence, nightmares,

insomnia, anxiety/nervousness, hallucinations, paresthesia.

Gastrointestinal: Nausea, dry mouth, constipation, flatulence, heartburn, hepatitis, vomiting.

Hypersensitive Reactions: Pruritus.

Miscellaneous: Musculoskeletal pain, arthralgia, blurred vision, decreased libido, male impotence,

tinnitus, reversible alopecia, agranulocytosis, dry eyes, worsening of psoriasis, Peyronie's disease,

sweating, photosensitivity, taste disturbance.

Potential Adverse Reactions: In addition, there are adverse reactions not listed above that have been

reported with other beta-adrenergic blocking agents and should be considered potential adverse

reactions to metoprolol succinate extended-release tablets.

Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible

syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability,

clouded sensorium, and decreased performance on neuropsychometrics.

Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.

Hypersensitive Reactions: Laryngospasm, respiratory distress.

6.3 Laboratory Test Findings

Clinical laboratory findings may include elevated levels of serum transaminase, alkaline phosphatase,

and lactate dehydrogenase.

7 DRUG INTERACTIONS

7.1 Catecholamine Depleting Drugs

Catecholamine depleting drugs (e.g., reserpine, monoamine oxidase (MAO) inhibitors) may have an

additive effect when given with beta-blocking agents. Observe patients treated with metoprolol

succinate extended-release tablets plus a catecholamine depletor for evidence of hypotension or marked

bradycardia, which may produce vertigo, syncope, or postural hypotension.

7.2 CYP2D6 Inhibitors

Drugs that inhibit CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone are likely to

increase metoprolol concentration. In healthy subjects with CYP2D6 extensive metabolizer phenotype,

coadministration of quinidine 100 mg and immediate-release metoprolol 200 mg tripled the

concentration of S-metoprolol and doubled the metoprolol elimination half-life. In four patients with

cardiovascular disease, coadministration of propafenone 150 mg t.i.d. with immediate-release

metoprolol 50 mg t.i.d. resulted in two- to five-fold increases in the steady-state concentration of

metoprolol. These increases in plasma concentration would decrease the cardioselectivity of

metoprolol.

7.3 Digitalis, Clonidine, and Calcium Channel Blockers

Digitalis glycosides, clonidine, diltiazem and verapamil slow atrioventricular conduction and decrease

heart rate. Concomitant use with beta blockers can increase the risk of bradycardia.

If clonidine and a beta blocker, such as metoprolol are coadministered, withdraw the beta-blocker

several days before the gradual withdrawal of clonidine because beta-blockers may exacerbate the

rebound hypertension that can follow the withdrawal of clonidine. If replacing clonidine by beta-

blocker therapy, delay the introduction of beta-blockers for several days after clonidine administration

has stopped [see Warnings and Precautions (5.11)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

Metoprolol tartrate has been shown to increase post-implantation loss and decrease neonatal survival in

rats at doses up to 22 times, on a mg/m basis, the daily dose of 200 mg in a 60-kg patient. Distribution

studies in mice confirm exposure of the fetus when metoprolol tartrate is administered to the pregnant

animal. These studies have revealed no evidence of impaired fertility or teratogenicity. There are no

adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not

always predictive of human response, use this drug during pregnancy only if clearly needed.

8.3 Nursing Mothers

Metoprolol is excreted in breast milk in very small quantities. An infant consuming 1 liter of breast milk

daily would receive a dose of less than 1 mg of the drug. Consider possible infant exposure when

metoprolol succinate extended-release tablets are administered to a nursing woman.

8.4 Pediatric Use

One hundred forty-four hypertensive pediatric patients aged 6 to 16 years were randomized to placebo

or to one of three dose levels of metoprolol succinate extended-release tablets. (0.2, 1.0 or 2.0 mg/kg

once daily) and followed for 4 weeks. The study did not meet its primary endpoint (dose response for

reduction in SBP). Some pre-specified secondary endpoints demonstrated effectiveness including:

Dose-response for reduction in DBP,

1 mg/kg vs. placebo for change in SBP, and

2 mg/kg vs. placebo for change in SBP and DBP.

The mean placebo corrected reductions in SBP ranged from 3 to 6 mmHg, and DBP from 1 to 5 mmHg.

Mean reduction in heart rate ranged from 5 to 7 bpm but considerably greater reductions were seen in

some individuals [see Dosage and Administration (2.1)].

No clinically relevant differences in the adverse event profile were observed for pediatric patients

aged 6 to 16 years as compared with adult patients.

Safety and effectiveness of metoprolol succinate extended-release tablets have not been established in

patients < 6 years of age.

8.5 Geriatric Use

Clinical studies of metoprolol succinate extended-release tablets in hypertension did not include

sufficient numbers of subjects aged 65 and over to determine whether they respond differently from

younger subjects. Other reported clinical experience in hypertensive patients has not identified

differences in responses between elderly and younger patients.

Of the 1,990 patients with heart failure randomized to metoprolol succinate extended-release tablets in

the MERIT-HF trial, 50% (990) were 65 years of age and older and 12% (238) were 75 years of age

and older. There were no notable differences in efficacy or the rate of adverse reactions between older

and younger patients.

In general, use a low initial starting dose in elderly patients given their greater frequency of decreased

hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Hepatic Impairment

No studies have been performed with metoprolol succinate extended-release tablets in patients with

hepatic impairment. Because metoprolol succinate extended-release tablets is metabolized by the liver,

metoprolol blood levels are likely to increase substantially with poor hepatic function. Therefore,

initiate therapy at doses lower than those recommended for a given indication; and increase doses

gradually in patients with impaired hepatic function.

8.7 Renal Impairment

The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a

clinically significant degree from those in normal subjects. No reduction in dosage is needed in patients

with chronic renal failure [see Clinical Pharmacology (12.3)].

10 OVERDOSAGE

Signs and Symptoms - Overdosage of metoprolol succinate extended-release tablets may lead to severe

bradycardia, hypotension, and cardiogenic shock. Clinical presentation can also include: atrioventricular

block, heart failure, bronchospasm, hypoxia, impairment of consciousness/coma, nausea and vomiting.

Treatment – Consider treating the patient with intensive care. Patients with myocardial infarction or heart

failure may be prone to significant hemodynamic instability. Seek consultation with a regional poison

control center and a medical toxicologist as needed. Beta-blocker overdose may result in significant

resistance to resuscitation with adrenergic agents, including beta-agonists. On the basis of the

pharmacologic actions of metoprolol, employ the following measures.

There is very limited experience with the use of hemodialysis to remove metoprolol, however

metoprolol is not highly protein bound.

Bradycardia: Evaluate the need for atropine, adrenergic-stimulating drugs or pacemaker to treat

bradycardia and conduction disorders.

Hypotension: Treat underlying bradycardia. Consider intravenous vasopressor infusion, such as

dopamine or norepinephrine.

Heart failure and shock: May be treated when appropriate with suitable volume expansion, injection of

glucagon (if necessary, followed by an intravenous infusion of glucagon), intravenous administration of

adrenergic drugs such as dobutamine, with

receptor agonistic drugs added in presence of

vasodilation.

Bronchospasm: Can usually be reversed by bronchodilators.

11 DESCRIPTION

Metoprolol succinate, is a beta -selective (cardioselective) adrenoceptor blocking agent, for oral

administration, available as extended-release tablets. Metoprolol succinate extended-release tablets,

USP have been formulated to provide a controlled and predictable release of metoprolol for once-daily

administration. The tablets comprise a multiple unit system containing metoprolol succinate in a

multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed

to deliver metoprolol continuously over the dosage interval. The tablets contain 23.75, 47.5, 95 and 190

mg of metoprolol succinate equivalent to 25, 50, 100 and 200 mg of metoprolol tartrate, USP,

respectively. Its chemical name is (±)1- (isopropylamino)-3-[p-(2-methoxyethyl) phenoxy]-2-propanol

succinate (2:1) (salt). Its structural formula is:

Metoprolol succinate, USP is a white crystalline powder with a molecular weight of 652.8. It is freely

soluble in water; soluble in methanol; sparingly soluble in ethanol; slightly soluble in dichloromethane

and 2-propanol; practically insoluble in ethyl-acetate, acetone, diethylether and heptane. Inactive

ingredients: sugar spheres, povidone, ethyl cellulose, polyethylene glycol, hydroxypropyl cellulose,

triethyl citrate, magnesium stearate, microcrystalline cellulose, titanium dioxide, polydextrose,

hypromellose, and triacetin.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Hypertension: The mechanism of the antihypertensive effects of beta-blocking agents has not been

elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of

catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac

output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression

of renin activity.

Heart Failure: The precise mechanism for the beneficial effects of beta-blockers in heart failure has not

been elucidated.

12.2 Pharmacodynamics

Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as

shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of

systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4)

reduction of reflex orthostatic tachycardia.

Metoprolol is a beta -selective (cardioselective) adrenergic receptor blocking agent. This preferential

effect is not absolute, however, and at higher plasma concentrations, metoprolol also inhibits beta -

adrenoreceptors, chiefly located in the bronchial and vascular musculature. Metoprolol has no intrinsic

sympathomimetic activity, and membrane-stabilizing activity is detectable only at plasma concentrations

much greater than required for beta-blockade. Animal and human experiments indicate that metoprolol

slows the sinus rate and decreases AV nodal conduction.

The relative beta -selectivity of metoprolol has been confirmed by the following: (1) In normal

subjects, metoprolol is unable to reverse the beta -mediated vasodilating effects of epinephrine. This

contrasts with the effect of nonselective beta-blockers, which completely reverse the vasodilating

effects of epinephrine. (2) In asthmatic patients, metoprolol reduces FEV and FVC significantly less

than a nonselective beta-blocker, propranolol, at equivalent beta -receptor blocking doses.

The relationship between plasma metoprolol levels and reduction in exercise heart rate is independent

of the pharmaceutical formulation. Using an E

model, the maximum effect is a 30% reduction in

exercise heart rate, which is attributed to beta -blockade. Beta -blocking effects in the range of 30-

80% of the maximal effect (approximately 8-23% reduction in exercise heart rate) correspond to

metoprolol plasma concentrations from 30-540 nmol/L. The relative beta -selectivity of metoprolol

diminishes and blockade of beta -adrenoceptors increases at plasma concentration above 300 nmol/L.

Although beta-adrenergic receptor blockade is useful in the treatment of angina, hypertension, and heart

failure there are situations in which sympathetic stimulation is vital. In patients with severely damaged

hearts, adequate ventricular function may depend on sympathetic drive. In the presence of AV block,

beta-blockade may prevent the necessary facilitating effect of sympathetic activity on conduction.

Beta -adrenergic blockade results in passive bronchial constriction by interfering with endogenous

adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with

exogenous bronchodilators in such patients.

In other studies, treatment with metoprolol succinate extended-release tablets produced an improvement

in left ventricular ejection fraction. Metoprolol succinate extended-release tablets was also shown to

delay the increase in left ventricular end-systolic and end-diastolic volumes after 6 months of treatment.

12.3 Pharmacokinetics

Adults: In man, absorption of metoprolol is rapid and complete. Plasma levels following oral

administration of conventional metoprolol tablets, however, approximate 50% of levels following

intravenous administration, indicating about 50% first-pass metabolism. Metoprolol crosses the blood-

brain barrier and has been reported in the CSF in a concentration 78% of the simultaneous plasma

concentration.

Plasma levels achieved are highly variable after oral administration. Only a small fraction of the drug

(about 12%) is bound to human serum albumin. Metoprolol is a racemic mixture of R- and S-

enantiomers, and is primarily metabolized by CYP2D6. When administered orally, it exhibits

stereoselective metabolism that is dependent on oxidation phenotype. Elimination is mainly by

biotransformation in the liver, and the plasma half-life ranges from approximately 3 to 7 hours. Less than

5% of an oral dose of metoprolol is recovered unchanged in the urine; the rest is excreted by the

kidneys as metabolites that appear to have no beta-blocking activity.

Following intravenous administration of metoprolol, the urinary recovery of unchanged drug is

approximately 10%. The systemic availability and half-life of metoprolol in patients with renal failure

do not differ to a clinically significant degree from those in normal subjects. Consequently, no

reduction in metoprolol succinate dosage is usually needed in patients with chronic renal failure.

Metoprolol is metabolized predominantly by CYP2D6, an enzyme that is absent in about 8% of

Caucasians (poor metabolizers) and about 2% of most other populations. CYP2D6 can be inhibited by a

number of drugs. Poor metabolizers and extensive metabolizers who concomitantly use CYP2D6

inhibiting drugs will have increased (several-fold) metoprolol blood levels, decreasing metoprolol's

cardioselectivity [see Drug Interactions (7.2)].

In comparison to conventional metoprolol, the plasma metoprolol levels following administration of

metoprolol succinate extended-release tablets are characterized by lower peaks, longer time to peak and

significantly lower peak to trough variation. The peak plasma levels following once-daily

administration of metoprolol succinate extended-release tablets average one-fourth to one-half the peak

plasma levels obtained following a corresponding dose of conventional metoprolol, administered once

daily or in divided doses. At steady state the average bioavailability of metoprolol following

administration of metoprolol succinate extended-release tablets, across the dosage range of 50 to 400

mg once daily, was 77% relative to the corresponding single or divided doses of conventional

metoprolol. Nevertheless, over the 24-hour dosing interval,

-blockade is comparable and dose-related

[see Clinical Pharmacology (12)]. The bioavailability of metoprolol shows a dose-related, although not

directly proportional, increase with dose and is not significantly affected by food following metoprolol

succinate extended-release tablets administration.

Pediatrics: The pharmacokinetic profile of metoprolol succinate extended-release tablets was studied in

120 pediatric hypertensive patients (6-17 years of age) receiving doses ranging from 12.5 to 200 mg

once daily. The pharmacokinetics of metoprolol were similar to those described previously in adults.

Age, gender, race, and ideal body weight had no significant effects on metoprolol pharmacokinetics.

Metoprolol apparent oral clearance (CL/F) increased linearly with body weight. Metoprolol

pharmacokinetics have not been investigated in patients < 6 years of age.

13 NONCLINICAL TOXICOLOGY

13.1 CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY

Long-term studies in animals have been conducted to evaluate the carcinogenic potential of metoprolol

tartrate. In 2-year studies in rats at three oral dosage levels of up to 800 mg/kg/day (41 times, on a

mg/m basis, the daily dose of 200 mg for a 60-kg patient), there was no increase in the development of

spontaneously occurring benign or malignant neoplasms of any type. The only histologic changes that

appeared to be drug related were an increased incidence of generally mild focal accumulation of foamy

macrophages in pulmonary alveoli and a slight increase in biliary hyperplasia. In a 21-month study in

Swiss albino mice at three oral dosage levels of up to 750 mg/kg/day (18 times, on a mg/m basis, the

daily dose of 200 mg for a 60-kg patient), benign lung tumors (small adenomas) occurred more

frequently in female mice receiving the highest dose than in untreated control animals. There was no

increase in malignant or total (benign plus malignant) lung tumors, nor in the overall incidence of tumors

or malignant tumors. This 21-month study was repeated in CD-1 mice, and no statistically or

biologically significant differences were observed between treated and control mice of either sex for

any type of tumor.

All genotoxicity tests performed on metoprolol tartrate (a dominant lethal study in mice, chromosome

studies in somatic cells, a Salmonella/mammalian-microsome mutagenicity test, and a nucleus anomaly

test in somatic interphase nuclei) and metoprolol succinate (a Salmonella/mammalian-microsome

mutagenicity test) were negative.

No evidence of impaired fertility due to metoprolol tartrate was observed in a study performed in rats at

doses up to 22 times, on a mg/m basis, the daily dose of 200 mg in a 60-kg patient.

14 CLINICAL STUDIES

In five controlled studies in normal healthy subjects, the same daily doses of metoprolol succinate

extended-release tablets and immediate-release metoprolol were compared in terms of the extent and

duration of beta - blockade produced. Both formulations were given in a dose range equivalent to 100-

400 mg of immediate-release metoprolol per day. In these studies, metoprolol succinate extended-

release tablets was administered once a day and immediate-release metoprolol was administered once to

four times a day. A sixth controlled study compared the beta -blocking effects of a 50 mg daily dose of

the two formulations. In each study, beta -blockade was expressed as the percent change from baseline

in exercise heart rate following standardized submaximal exercise tolerance tests at steady state.

Metoprolol succinate extended-release tablets administered once a day, and immediate-release

metoprolol administered once to four times a day, provided comparable total beta -blockade over 24

hours (area under the beta -blockade versus time curve) in the dose range 100-400 mg. At a dosage of

50 mg once daily, metoprolol succinate extended-release tablets produced significantly higher total

beta -blockade over 24 hours than immediate-release metoprolol. For metoprolol succinate extended-

release tablets, the percent reduction in exercise heart rate was relatively stable throughout the entire

dosage interval and the level of beta -blockade increased with increasing doses from 50 to 300 mg

daily. The effects at peak/trough (i.e., at 24-hours post-dosing) were: 14/9, 16/10, 24/14, 27/22 and

27/20% reduction in exercise heart rate for doses of 50, 100, 200, 300 and 400 mg metoprolol

succinate extended-release tablets once a day, respectively. In contrast to metoprolol succinate

extended-release tablets, immediate-release metoprolol given at a dose of 50-100 mg once a day

produced a significantly larger peak effect on exercise tachycardia, but the effect was not evident at 24

hours. To match the peak to trough ratio obtained with metoprolol succinate extended-release tablets

over the dosing range of 200 to 400 mg, a t.i.d. to q.i.d. divided dosing regimen was required for

immediate-release metoprolol. A controlled cross-over study in heart failure patients compared the

plasma concentrations and beta -blocking effects of 50 mg immediate-release metoprolol administered

t.i.d., 100 mg and 200 mg metoprolol succinate extended-release tablets once daily. A 50 mg dose of

immediate-release metoprolol t.i.d. produced a peak plasma level of metoprolol similar to the peak

level observed with 200 mg of metoprolol succinate extended-release tablets. A 200 mg dose of

metoprolol succinate extended-release tablets produced a larger effect on suppression of exercise-

induced and Holter-monitored heart rate over 24 hours compared to 50 mg t.i.d. of immediate-release

metoprolol.

In a double-blind study, 1092 patients with mild-to-moderate hypertension were randomized to once

daily metoprolol succinate extended-release tablets (25, 100, or 400 mg), felodipine extended-release

tablets, the combination, or placebo. After 9 weeks, metoprolol succinate extended-release tablets alone

decreased sitting blood pressure by 6-8/4-7 mmHg (placebo-corrected change from baseline) at 24

hours post-dose. The combination of metoprolol succinate extended-release tablets with felodipine

extended-release tablets has greater effects on blood pressure.

In controlled clinical studies, an immediate-release dosage form of metoprolol was an effective

antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics at

dosages of 100-450 mg daily. Metoprolol succinate extended-release tablets, in dosages of 100 to 400

mg once daily, produces similar

-blockade as conventional metoprolol tablets administered two to four

times daily. In addition, metoprolol succinate extended-release tablets administered at a dose of 50 mg

once daily lowered blood pressure 24-hours post-dosing in placebo-controlled studies. In controlled,

comparative, clinical studies, immediate-release metoprolol appeared comparable as an antihypertensive

agent to propranolol, methyldopa, and thiazide-type diuretics, and affected both supine and standing

blood pressure. Because of variable plasma levels attained with a given dose and lack of a consistent

relationship of antihypertensive activity to drug plasma concentration, selection of proper dosage

requires individual titration.

14.1 Angina Pectoris

By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial

contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any

given level of effort, thus making it useful in the long-term management of angina pectoris.

In controlled clinical trials, an immediate-release formulation of metoprolol has been shown to be an

effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance.

The dosage used in these studies ranged from 100 to 400 mg daily. Metoprolol succinate extended-

release tablets, in dosages of 100 to 400 mg once daily, has been shown to possess beta-blockade

similar to conventional metoprolol tablets administered two to four times daily.

14.2 Heart Failure

MERIT-HF was a double-blind, placebo-controlled study of metoprolol succinate extended-release

tablets conducted in 14 countries including the US. It randomized 3991 patients (1990 to metoprolol

succinate extended-release tablets) with ejection fraction 0.40 and NYHA Class II-IV heart failure

attributable to ischemia, hypertension, or cardiomyopathy. The protocol excluded patients with

contraindications to beta-blocker use, those expected to undergo heart surgery, and those within 28

days of myocardial infarction or unstable angina. The primary endpoints of the trial were (1) all-cause

mortality plus all-cause hospitalization (time to first event) and (2) all-cause mortality. Patients were

stabilized on optimal concomitant therapy for heart failure, including diuretics, ACE inhibitors, cardiac

glycosides, and nitrates. At randomization, 41% of patients were NYHA Class II; 55% NYHA Class III;

65% of patients had heart failure attributed to ischemic heart disease; 44% had a history of

hypertension; 25% had diabetes mellitus; 48% had a history of myocardial infarction. Among patients in

the trial, 90% were on diuretics, 89% were on ACE inhibitors, 64% were on digitalis, 27% were on a

lipid-lowering agent, 37% were on an oral anticoagulant, and the mean ejection fraction was 0.28. The

mean duration of follow-up was one year. At the end of the study, the mean daily dose of metoprolol

succinate extended-release tablets was 159 mg.

The trial was terminated early for a statistically significant reduction in all-cause mortality (34%,

nominal p= 0.00009). The risk of all-cause mortality plus all-cause hospitalization was reduced by 19%

(p= 0.00012). The trial also showed improvements in heart failure-related mortality and heart failure-

related hospitalizations, and NYHA functional class.

The table below shows the principal results for the overall study population. The figure below

illustrates principal results for a wide variety of subgroup comparisons, including US vs. non-US

populations (the latter of which was not pre-specified). The combined endpoints of all-cause mortality

plus all-cause hospitalization and of mortality plus heart failure hospitalization showed consistent

effects in the overall study population and the subgroups, including women and the US population.

However, in the US subgroup (n=1071) and women (n=898), overall mortality and cardiovascular

mortality appeared less affected. Analyses of female and US patients were carried out because they

each represented about 25% of the overall population. Nonetheless, subgroup analyses can be difficult

to interpret and it is not known whether these represent true differences or chance effects.

Clinical Endpoints in the MERIT-HF Study

Clinical Endpoint

Number of Patients

Relative Risk

(95% Cl)

Risk Reduction With

Metoprolol

Succinate

Extended-

Release

tablets

Nominal

value

Placebo

n=2001

Metoprolol

Succinate Extended-

Release

tablets n=1990

All-cause

mortality

plus

all-caused

hospitalization

0.81(0.73-

0.90)

0.00012

All-cause mortality

0.66(0.53-

0.81)

0.00009

All-cause

mortality

plus

heart

failure

hospitalization

0.69(0.60-

0.80)

0.0000008

Cardiovascular

mortality

0.62(0.50-

0.78)

0.000022

Sudden death

0.59(0.45-

0.78)

0.0002

Death

worsening

heart

failure

0.51(0.33-

0.79)

0.0023

Hospitalizations

worsening

heart

failure

0.0000076

Cardiovascular

hospitalization

0.00028

Time to first event

Comparison of treatment groups examines the number of hospitalizations (Wilcoxon test); relative risk and risk

reduction are not applicable.

15 REFERENCES

1. Devereaux PJ, Yang H, Yusuf S, Guyatt G, Leslie K, Villar JC et al. Effects of extended-release

metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled

trial. Lancet. 2008; 371:1839-47.

16 HOW SUPPLIED/STORAGE AND HANDLING

Product: 63629-8100

NDC: 63629-8100-1 30 TABLET, EXTENDED RELEASE in a BOTTLE

17 PATIENT COUNSELING INFORMATION

Advise patients to take metoprolol succinate extended-release tablets regularly and continuously, as

directed, preferably with or immediately following meals. If a dose is missed, the patient should take

only the next scheduled dose (without doubling it). Patients should not interrupt or discontinue

metoprolol succinate extended-release tablets without consulting the physician.

Advise patients (1) to avoid operating automobiles and machinery or engaging in other tasks requiring

alertness until the patient's response to therapy with metoprolol succinate extended-release tablets has

been determined; (2) to contact the physician if any difficulty in breathing occurs; (3) to inform the

physician or dentist before any type of surgery that he or she is taking metoprolol succinate extended-

release tablets.

Heart failure patients should be advised to consult their physician if they experience signs or symptoms

of worsening heart failure such as weight gain or increasing shortness of breath.

SPL UNCLASSIFIED

Manufactured for: Ingenus Pharmaceuticals LLC

Orlando, FL 32839-6408

Customer toll-free number: 1-877-748-1970

Manufactured by: Novast Laboratories Ltd.

Nantong, China 226009

Rx Only

I0080

Iss. 07/2017

Rev. A

METOPROLOL SUCCINATE 100MG TABLET

METOPROLOL SUCCINATE

metoprolol succinate tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 36 29 -8 10 0 (NDC:50 742-6 17)

Bryant Ranch Prepack

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

METO PRO LO L SUCCINATE (UNII: TH25PD4CCB) (METOPROLOL - UNII:GEB0 6 NHM23)

METOPROLOL TARTRATE 10 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

PO VIDO NE, UNSPECIFIED (UNII: FZ9 8 9 GH9 4E)

ETHYLCELLULO SE, UNSPECIFIED (UNII: 7Z8 S9 VYZ4B)

PO LYETHYLENE GLYCO L 3 3 50 (UNII: G2M7P15E5P)

HYDRO XYPRO PYL CELLULO SE ( 16 0 0 0 0 0 WAMW) (UNII: RFW2ET6 71P)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

PO LYDEXTRO SE (UNII: VH2XOU12IE)

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

TRIACETIN (UNII: XHX3C3X6 73)

Product Characteristics

Color

WHITE

S core

2 pieces

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

N;10 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 36 29 -8 10 0 -1

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 7/18 /20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 410 6

0 2/0 6 /20 18

Labeler -

Bryant Ranch Prepack (171714327)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Bryant Ranch Prepack

171714327

REPACK(6 36 29 -8 10 0 ) , RELABEL(6 36 29 -8 10 0 )

Revised: 8/2019

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