What is the difference between oral metoprolol (beta blocker) and intravenous (IV) metoprolol (beta blocker)?

From the Guidelines

There are significant differences between oral and intravenous (IV) metoprolol, primarily in their pharmacokinetics, onset of action, and dosing, which impact their use in different clinical scenarios. Oral metoprolol is available in immediate-release tablets (typically dosed twice daily) and extended-release formulations (taken once daily), while IV metoprolol comes as a solution for injection. The key difference lies in their pharmacokinetics: IV metoprolol has an immediate onset of action (within minutes) compared to oral metoprolol, which takes 1-2 hours to reach therapeutic effect 1. IV metoprolol bypasses first-pass metabolism in the liver, resulting in higher bioavailability and more predictable blood levels.

Key Differences and Clinical Implications

• Onset of Action: IV metoprolol acts rapidly, making it suitable for emergency situations like hypertensive emergencies or acute coronary syndromes, whereas oral metoprolol is more suited for long-term management of conditions like hypertension, angina, and heart failure.
• Dosing: IV metoprolol is typically given as 5 mg boluses every 5 minutes (up to 3 doses) in acute settings, as outlined in the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction 1.
• Indications: The decision to use IV versus oral metoprolol should be based on the clinical scenario, with IV administration reserved for situations requiring rapid beta-blockade or when oral administration isn't possible, and oral metoprolol used for chronic conditions.
• Safety and Efficacy: The early routine use of intravenous beta blockers, including metoprolol, was examined in COMMIT/CCS-2, showing a neutral effect on the combined endpoint of death, recurrent MI, or cardiac arrest, but with lower rates of recurrent MI and VF balanced by a higher rate of cardiogenic shock, especially in certain subgroups like patients over 70 years 1.

Clinical Decision Making

When deciding between oral and IV metoprolol, clinicians must consider the urgency of the situation, the patient's ability to take oral medications, and the potential risks and benefits of each formulation. The choice between oral and IV metoprolol should prioritize the patient's immediate needs and long-term outcomes, considering factors such as the presence of contraindications, the risk of cardiogenic shock, and the need for rapid beta-blockade. Given the potential for cardiogenic shock, especially in vulnerable populations, the use of IV metoprolol should be approached with caution and careful patient selection, as recommended by guidelines 1.

From the FDA Drug Label

In a large (1,395 patients randomized), double-blind, placebo-controlled clinical study, metoprolol was shown to reduce 3-month mortality by 36% in patients with suspected or definite myocardial infarction Patients were randomized and treated as soon as possible after their arrival in the hospital, once their clinical condition had stabilized and their hemodynamic status had been carefully evaluated. Initial treatment consisted of intravenous followed by oral administration of metoprolol or placebo, given in a coronary care or comparable unit. The study thus was able to show a benefit from the overall metoprolol regimen but cannot separate the benefit of very early intravenous treatment from the benefit of later beta-blocker therapy

The main difference between oral metoprolol and IV metoprolol is the route of administration.

• IV metoprolol is used for initial treatment in certain situations, such as in patients with suspected or definite myocardial infarction, where rapid administration is necessary.
• Oral metoprolol is used for maintenance therapy and can be administered at a later time. The FDA label does not provide a direct comparison of the efficacy of oral versus IV metoprolol, but it does suggest that both routes of administration can be effective in certain clinical situations 2.

From the Research

Difference between Oral Metoprolol and IV Metoprolol

• The difference between oral metoprolol and IV metoprolol lies in their pharmacokinetics and pharmacodynamics, as reported in various studies 3, 4, 5.
• Oral metoprolol is suitable for twice daily administration, with a duration of effect longer than expected from its half-life, and may be possible for once daily administration in treating hypertension 5.
• IV metoprolol, on the other hand, has been studied in various clinical trials, including those in patients with acute myocardial infarction, where it has been shown to reduce mortality rates 4.
• The pharmacokinetic parameters of metoprolol, such as maximum plasma concentration (Cmax), time to reach maximum plasma concentration (Tmax), and area under the concentration-time curve (AUC), vary between oral and IV administration, with oral administration showing a dose-dependent increase in these parameters 4.
• Additionally, the effects of metoprolol on heart failure have been evaluated in several studies, including the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) trial, which showed a 34% reduction in relative risk of all-cause mortality in patients with chronic heart failure due to ischaemic or dilated cardiomyopathy 6.

Pharmacokinetic Parameters

• The pharmacokinetic parameters of metoprolol after oral and IV administration have been summarized in a systematic review, which included data from 41 articles, including 6 after IV and 12 after oral administration in healthy individuals 4.
• The review reported that the oral studies depicted a dose-dependent increase in Cmax, Tmax, and AUC, while the IV studies showed an increase in clearance (CL) in patients with renal impairment and a decrease in CL in patients with hepatic cirrhosis 4.

Clinical Implications

• The differences between oral and IV metoprolol have important clinical implications, particularly in the treatment of hypertension, angina pectoris, and heart failure 3, 5, 6.
• The choice of administration route and dosage regimen should be based on individual patient needs and response to treatment, as well as the presence of any comorbidities or concomitant medications 4, 7.