METOPROLOL SUCCINATE
METOPROLOL SUCCINATE
Manufacturer: Redpharm Drug
Clinical information
Indications & Usage
1 INDICATIONS AND USAGE 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) 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 is indicated to reduce the risk of cardiovascular mortality and heart-failure hospitalization in patients with heart failure.
Dosage & Administration
2 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 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) 2.1 Hypertension Adults: The usual initial dosage is 25 to 100 mg daily in a single dose. Adjust dosage 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 is 1 mg/kg once daily, but the maximum initial dose should not exceed 50 mg once daily. Adjust dosage according to blood pressure response. Doses above 2 mg/kg (or in excess of 200 mg) once daily have not been studied in pediatric patients [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3) ]. Metoprolol succinate has not been studied in pediatric patients < 6 years of age [see Use in Specific Populations (8.4)]. 2.2 Angina Pectoris Individualize the dosage of metoprolol succinate. 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 to 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, stabilize the dose of other heart failure drug therapy. The recommended starting dose of metoprolol succinate 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. Initial difficulty with titration should not preclude later attempts to introduce metoprolol succinate. If patients experience symptomatic bradycardia, reduce the dose of metoprolol succinate. If transient worsening of heart failure occurs, consider treating with increased doses of diuretics, lowering the dose of metoprolol succinate or temporarily discontinuing it. The dose of metoprolol succinate should not be increased until symptoms of worsening heart failure have been stabilized. 2.4 Administration Metoprolol succinate extended-release tablets are scored and can be divided; however, do not crush or chew the whole or half tablet.
Contraindications
4 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) Metoprolol succinate extended-release tablets are contraindicated in severe bradycardia, second or third-degree heart block, cardiogenic shock, decompensated heart failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product.
Safety
Adverse Reactions
6 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 Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 in daily doses up to 200 mg (mean dose 159 mg once-daily; n=1990) to placebo (n=2001), 10.3% of metoprolol succinate 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 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 Group and Greater Than Placebo by More Than 0.5 % Metoprolol Succinate n=1990 % of patients Placebo n=2001 % of patients Dizziness/vertigo 1.8 1 Bradycardia 1.5 0.4 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 100 mg was started 2 to 4 hours prior to surgery then continued for 30 days at 200 mg per day. Metoprolol succinate 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% 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. 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.
Drug Interactions
7 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) Beta-blockers including metoprolol, may exacerbate the rebound hypertension that can follow the withdrawal of clonidine. (7.3) 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 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 are strong inhibitors of CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone were shown to double metoprolol concentrations. While there is no information about moderate or weak inhibitors, these too are likely to increase metoprolol concentration. Increases in plasma concentration decrease the cardioselectivity of metoprolol [see Clinical Pharmacology (12.3) ]. Monitor patients closely, when the combination cannot be avoided. 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 co-administered, 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.
Additional information
Description
11 DESCRIPTION Metoprolol succinate, is a beta 1 -selective (cardioselective) adrenoceptor blocking agent, for oral administration, available as extended release tablets. Metoprolol succinate has 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, respectively. Its chemical name is (±)1- (isopropyl amino)-3-[p-(2-methoxyethyl) phenoxy]-2-propanol succinate (2:1) (salt). Its structural formula is: Metoprolol succinate, USP is a white to off white powder with a molecular weight of 652.8. It is freely soluble in water; soluble in methanol; sparingly soluble in alcohol and slightly soluble in isopropyl alcohol. Each metoprolol succinate extended-release tablet intended for oral administration contains metoprolol succinate equivalent to 25 mg, 50 mg, 100 mg or 200 mg of metoprolol tartrate. In addition, each tablet contains the following inactive ingredients: Colloidal silicon dioxide, croscarmellose sodium, ethyl cellulose, glycerin, hypromellose, magnesium stearate, methyl cellulose, microcrystalline cellulose, polyethylene glycol, povidone and talc. Additionally, each metoprolol succinate extended-release tablets contain opadry II white 03B28796 which contains hypromellose, polyethylene glycol and titanium dioxide. Meets USP Dissolution Test 4. figure
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Metoprolol Succinate Extended-release Tablets USP, 25 mg are white to off-white color, oval shaped, biconvex coated tablets, debossed with "564" on one side and break line on the other side and are supplied as follows: NDC 68382-564-01 in bottles of 100 tablets with child-resistant closure NDC 68382-564-05 in bottles of 500 tablets NDC 68382-564-10 in bottles of 1000 tablets Metoprolol Succinate Extended-release Tablets USP, 50 mg are white to off-white color, round shaped, biconvex coated tablets, debossed with "565" on one side and break line on the other side and are supplied as follows: NDC 68382-565-01 in bottles of 100 tablets with child-resistant closure NDC 68382-565-05 in bottles of 500 tablets NDC 68382-565-10 in bottles of 1000 tablets Metoprolol Succinate Extended-release Tablets USP, 100 mg are white to off-white color, round shaped, biconvex coated tablets, debossed with "566" on one side and break line on other side and are supplied as follows: NDC 68382-566-01 in bottles of 100 tablets with child-resistant closure NDC 68382-566-05 in bottles of 500 tablets NDC 68382-566-10 in bottles of 1000 tablets Metoprolol Succinate Extended-release Tablets USP, 200 mg are white to off-white color, oval shaped, biconvex coated tablets, debossed with "5" and "67" on either side of break line and plain on the other side and are supplied as follows: NDC 68382-567-01 in bottles of 100 tablets with child-resistant closure NDC 68382-567-05 in bottles of 500 tablets NDC 68382-567-10 in bottles of 1000 tablets Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight container (USP).
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Frequently Asked Questions
What is metoprolol succinate used for?+
Metoprolol succinate is used to treat high blood pressure, which can reduce the risk of heart-related problems. It works by blocking the effects of certain natural chemicals in your body, such as epinephrine, on the heart and blood vessels. Consult a doctor to discuss the benefits and risks of taking metoprolol succinate for your specific condition.
How long does it take for metoprolol succinate to start working?+
Metoprolol succinate may take a few weeks to start working, and it's essential to take it as directed by your doctor. You may not feel any different when taking this medication, but it's crucial to continue taking it to control your blood pressure. Consult a doctor to monitor your progress and adjust your treatment plan if necessary.
Can I stop taking metoprolol succinate if my blood pressure is under control?+
It's not recommended to stop taking metoprolol succinate without consulting your doctor, even if your blood pressure is under control. Stopping the medication suddenly can cause your blood pressure to rise, which may lead to serious health problems. Consult a doctor to discuss the best course of treatment for your specific condition.
What are the common side effects of metoprolol succinate?+
Common side effects of metoprolol succinate include dizziness, fatigue, and shortness of breath. These side effects are usually mild and temporary, but if they persist or worsen, you should consult a doctor. Consult a doctor to discuss any concerns you have about the potential side effects of metoprolol succinate.
Can I take metoprolol succinate with other medications?+
It's essential to inform your doctor about all the medications you're taking, including prescription and over-the-counter medications, before starting metoprolol succinate. Some medications may interact with metoprolol succinate, which can increase the risk of side effects. Consult a doctor to discuss potential interactions and ensure safe treatment.
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