What is the recommended dosing and management for extended release metoprolol (beta-blocker) in patients with hypertension, angina, or heart failure?

From the Guidelines

Extended-release metoprolol should be initiated at a dose of 12.5-25 mg once daily for heart failure, with careful upward titration every two weeks as tolerated, targeting 200 mg daily, as recommended by the 2013 ACCF/AHA guideline for the management of heart failure 1. For hypertension and angina, the dose can be initiated at 25-100 mg once daily, with dose adjustments every 1-2 weeks based on blood pressure response, up to a maximum of 400 mg daily. The medication should be taken consistently with or without food, and tablets should be swallowed whole, not crushed or chewed. Dose adjustments are necessary for patients with hepatic impairment. When discontinuing metoprolol, gradual tapering over 1-2 weeks is essential to prevent rebound hypertension or worsening angina. Patients should monitor for common side effects including fatigue, dizziness, and bradycardia, and seek medical attention for shortness of breath or significant heart rate changes. Metoprolol works by blocking beta-1 adrenergic receptors, reducing heart rate and contractility, which decreases cardiac output and oxygen demand while lowering blood pressure and improving symptoms in heart failure patients through reduced sympathetic stimulation. The use of extended-release metoprolol has been shown to reduce morbidity and mortality in patients with heart failure, as demonstrated in the MERIT-HF trial, which found a 34% decrease in all-cause mortality and a 41% decrease in sudden death 1. Key points to consider when managing patients on extended-release metoprolol include:

• Monitoring blood pressure and heart rate regularly
• Adjusting the dose as needed to achieve optimal blood pressure control
• Being aware of potential side effects, such as fatigue and dizziness
• Gradually tapering the dose when discontinuing the medication
• Considering the patient's overall clinical status and medical history when making treatment decisions. The 2013 ACCF/AHA guideline for the management of heart failure recommends the use of beta blockers, including extended-release metoprolol, for all patients with current or prior symptoms of HFrEF, unless contraindicated, to reduce morbidity and mortality 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION Myocardial Infarction Early Treatment During the early phase of definite or suspected acute myocardial infarction, initiate treatment with metoprolol tartrate as soon as possible after the patient’s arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized Begin treatment in this early phase with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate injection each; give the injections at approximately 2-minute intervals. During the intravenous administration of metoprolol tartrate injection, monitor blood pressure, heart rate, and electrocardiogram In patients who tolerate the full intravenous dose (15 mg), initiate metoprolol tartrate tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose and continued for 48 hours. Thereafter, the maintenance dosage is 100 mg orally twice daily Start patients who appear not to tolerate the full intravenous on metoprolol tartrate tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows. In patients with severe intolerance, discontinue metoprolol tartrate (see WARNINGS)

The recommended dosing for extended release metoprolol in patients with hypertension, angina, or heart failure is not explicitly stated in the provided drug labels. However, the labels provide information on the dosing for myocardial infarction and other conditions.

• For myocardial infarction, the initial dose is 5 mg intravenously every 2 minutes for 3 doses, followed by 50 mg orally every 6 hours for 48 hours, and then 100 mg orally twice daily for maintenance.
• The labels also provide guidance on dose adjustment for certain patient populations, such as those with renal impairment (no dose adjustment needed) and hepatic impairment (initiate at low doses with cautious gradual dose titration).
• Additionally, the labels warn against abrupt discontinuation of metoprolol therapy in patients with coronary artery disease, and recommend gradual reduction of the dose over 1 to 2 weeks if discontinuation is necessary 2 2.

From the Research

Recommended Dosing for Extended Release Metoprolol

• The recommended initial dosage of extended release metoprolol is 12.5 to 25 mg once daily, with gradual increases at 2-weekly intervals until the target dosage of 200 mg once daily or maximal tolerated dosage is attained 3, 4.
• The dosage may vary depending on the patient's condition, such as New York Heart Association (NYHA) functional class II, III, or IV, and ejection fraction 4, 5.

Management of Extended Release Metoprolol in Patients with Hypertension, Angina, or Heart Failure

• Extended release metoprolol is effective in reducing mortality and improving clinical status in patients with stable mild to moderate chronic heart failure due to left ventricular systolic dysfunction 3, 6.
• The drug is also effective in reducing the incidence of sudden death and death due to progressive heart failure in patients with heart failure 3, 4.
• In patients with severe heart failure, extended release metoprolol has been shown to reduce mortality, hospitalizations, and improve NYHA functional class 5.
• The pharmacokinetics and pharmacodynamics of extended release metoprolol have been compared to immediate-release metoprolol, with similar peak plasma levels and a more pronounced suppression of heart rate observed with the extended release formulation 7.

Key Considerations

• Extended release metoprolol should be initiated at a low dosage and gradually increased to minimize the risk of adverse effects 3, 4.
• Patients should be monitored closely for signs of worsening heart failure, and the dosage should be adjusted accordingly 4, 5.
• The drug is generally well tolerated, with a low incidence of adverse effects and withdrawals due to adverse effects 3, 5.