Toprol‐XL® (metoprolol succinate)
Description
Toprol‐XL® (metoprolol succinate, AstraZeneca) is a selective β1‐adrenergic receptor blocking agent formulated in extended release for once‐a‐day administration. It has a new indication for stable, symptomatic heart failure secondary to ischemia, hypertension, or cardiomyopathy.
Clinical Pharmacology
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At lower plasma concentrations, metoprolol succinate is cardioselective, while at higher concentrations it exhibits β2‐adrenergic receptor blocking activity in vascular and bronchial musculature.
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At higher plasma concentrations, the β1 selectivity diminishes and the β2 receptor blocking activity increases.
Pharmacodynamics
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Heart rate and cardiac output are reduced during exercise and at rest.
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Systolic blood pressure is also reduced during exercise and reflex orthostatic tachycardia.
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In asthmatic patients, metoprolol does not reduce the forced expiratory volume in 1 second or the forced vital capacity to the same extent as noncardioselective β blockers.
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At maximal effect, heart rate is reduced by 28%.
Pharmacokinetics
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Metoprolol is rapidly and completely absorbed from the gastrointestinal tract.
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This agent crosses the blood‐brain barrier.
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About 12% is bound to serum albumin.
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The drug is eliminated by biotransformation in the liver.
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The plasma half‐life ranges from 3–7 hours, with less than 5% of the initial dose recovered unchanged in the urine.
Clinical Indications
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The initial indication for the drug was in treating hypertension and angina pectoris.
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The new indication is for the treatment of stable, symptomatic heart failure (New York Heart Association [NYHA] class II or III) of ischemic, hypertensive, or cardiomyopathic origin.
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Metoprolol can be used either alone or in combination with other medications typically used to treat hypertension, angina pectoris, and congestive heart failure.
Warnings and Precautions
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The drug should be given with caution to patients with known bronchospastic disease.
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Abrupt cessation of treatment can cause reflex tachycardia, which exacerbates angina pectoris or hypertension.
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Diabetic patients should be watched because of the ability of β blockers to mask the effects of hypoglycemia.
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β Blockers can also mask the clinical effects of thyrotoxicosis.
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The drug should be used with caution in patients with impaired hepatic function.
Adverse Reactions
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Fatigue and dizziness have been reported in 10% of patients receiving the drug.
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Depression has been reported in 5% of patients.
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Dyspnea and symptomatic bradycardia have been reported in 1% and 3%, respectively.
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Rash and gastrointestinal complaints have been reported in approximately 5% of patients.
Dosage and Administration
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The 25‐mg tablets are scored.
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The recommended starting dose for treatment of heart failure is 25 mg/day for patients with NYHA class II heart failure and 12.5 mg/day for patients with more severe heart failure.
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The dose can then be doubled every 2 weeks, as tolerated, to a maximal dose of 200 mg/day.
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The usual initial dosage for patients with angina pectoris is 100 mg/day, and it can be increased to achieve the desired effect, to a maximum of 400 mg/day.
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The initial dosage for the treatment of hypertension is 50–100 mg/day, either alone or in combination with a diuretic. The dose can be increased at weekly intervals, up to 400 mg/day.
Summary
Toprol‐XL® (metoprolol succinate) is a familiar P blocker used in the treatment of hypertension and angina for many years. It is now approved and indicated for the treatment of stable, symptomatic heart failure. The new scored, 25‐mg tablets will make dosing easy and convenient.