METOPROLOL SUCCINATE tablet, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

METOPROLOL SUCCINATE (UNII: TH25PD4CCB) (METOPROLOL - UNII:GEB06NHM23)

Available from:

Legacy Pharmaceutical Packaging, LLC

INN (International Name):

METOPROLOL SUCCINATE

Composition:

METOPROLOL TARTRATE 100 mg

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 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 (eg, 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. Metoprolol succinate extended-release tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. Metoprolol succinate extended-release tablets are indicated to reduce the risk of cardiovascular mortality and heart-failure hospitalizations in patients with heart failure. 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. Risk Summary Untreated hypertension and heart failure during pregnancy can lead to adverse outcomes for the mother and the fetus (see Clinical Considerations). Available data from published observational studies have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with metoprolol use during pregnancy. However, there are inconsistent reports of intrauterine growth restriction, preterm birth, and perinatal mortality with maternal use of beta blockers, including metoprolol, during pregnancy (see Data). In animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, approximately 24 times the daily dose of 200 mg in a 60-kg patient on a mg/m 2 basis. 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 to 4% and 15 to 20%, respectively. Clinical consideration 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. Stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. There is a risk for preterm birth with pregnant women with chronic heart failure in 3rd trimester of pregnancy. Fetal/Neonatal adverse reactions Metoprolol crosses the placenta. Neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. Observe neonates and manage accordingly. Data Human Data Data from published observational studies did not demonstrate an association of major congenital malformations and use of metoprolol in pregnancy. The published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. Methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. These observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. Animal Data Metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, i.e., 24 times, on a mg/m basis, the daily dose of 200 mg in a 60 kg patient. No fetal abnormalities were observed when pregnant rats received metoprolol orally up to a dose of 200 mg/kg/day, i.e., 10 times, the daily dose of 200 mg in a 60 kg patient. Risk Summary Limited available data from published literature report that metoprolol is present in human milk. The estimated daily infant dose of metoprolol received from breastmilk ranges from 0.05 mg to less than 1 mg. The estimated relative infant dosage was 0.5% to 2% of the mother's weight‑adjusted dosage (see Data). No adverse reactions of metoprolol on the breastfed infant have been identified. There is no information regarding the effects of metoprolol on milk production. Clinical consideration Monitoring for adverse reactions Monitor the breastfed infant for bradycardia and other symptoms of beta blockade such as listlessness (hypoglycemia). Data Based on published case reports, the estimated infant daily dose of metoprolol received from breast milk range from 0.05 mg to less than 1 mg. The estimated relative infant dosage was 0.5% to 2% of the mother’s weight-adjusted dosage. In two women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. The estimated amount of metoprolol and alphahydroxy metoprolol in breast milk is reported to be less than 2% of the mother's weightadjusted dosage. In a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. The average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17.0 to 158.7). The average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. Risk Summary Based on the published literature, beta blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. No evidence of impaired fertility due to metoprolol was observed in rats [see Nonclinical Toxicology (13.1)]. 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 (0.2, 1 or 2 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 have not been established in patients <6 years of age. Clinical studies of metoprolol succinate extended-release 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 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. No studies have been performed with metoprolol succinate extended-release in patients with hepatic impairment. Because metoprolol succinate extended-release 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. 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) ].

Product summary:

Metoprolol succinate extended-release tablets USP, 100 mg are white to off-white, round shaped, film-coated tablets, debossed with “M” and “3” separated by breakline on one side and plain on other side. They are supplied in bottles of 30 tablets. Unit of Use bottles of 30                                          NDC 68645-479-54 Store at 20°-25°C (68°-77°F); [See USP Controlled Room Temperature.]

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

METOPROLOL SUCCINATE- METOPROLOL SUCCINATE TABLET, EXTENDED RELEASE
LEGACY PHARMACEUTICAL PACKAGING, LLC
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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
INDICATIONS AND USAGE
Metoprolol succinate extended-release tablets, metoprolol succinate,
is a beta-adrenergic blocker
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, to reduce the risk of cardiovascular mortality and
heart failure hospitalizations in patients
with heart failure.(1.3)
DOSAGE AND ADMINISTRATION
Administer once daily. Titrate at weekly or longer intervals as needed
and tolerated. (2)
Hypertension: Starting dose is 25 to 100 mg. (2.1)
Angina Pectoris: Starting dose is 100 mg. (2.2)
Heart Failure: Starting dose is 12.5 mg or 25 mg. (2.3)
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 : 100 mg (3)
CONTRAINDICATIONS
Known hypersensitivity to product components. (4)
Severe bradycardia. Greater than first degree heart block, or sick
sinus syndrome without a pacemaker.
(4)
Cardiogenic shock or decompensated heart failure. (4)
WARNINGS AND PRECAUTIONS
Abrupt cessation may exacerbate myocardial ischemia. (5)
Heart Failure: Worsening cardiac failure may occur. (5.2)
Bronchospastic Disease: Avoid beta-blockers. (5.3)
Concomitant use of glycosides, clonidine, and diltiazem and verapamil
with beta-blockers can increase
the risk of bradycardia. (5.4)
Pheochro