Metoprolol Tartrate

Acute Toxicity

Several cases of overdosage have been reported, some leading to death.

Oral LD50's (mg/kg): mice, 1158-2460; rats, 3090-4670.

Signs And Symptoms

Potential signs and symptoms associated with overdosage with Lopressor are bradycardia, hypotension, bronchospasm, myocardial infarction, cardiac failure, and death.

Management

There is no specific antidote.

In general, patients with acute or recent myocardial infarction may be more hemodynamically unstable than other patients and should be treated accordingly (see WARNINGS, Myocardial Infarction).

On the basis of the pharmacologic actions of Lopressor, the following general measures should be employed:

Elimination of the Drug: Gastric lavage should be performed.

Other clinical manifestations of overdose should be managed symptomatically based on modern methods of intensive care.

Hypotension: Administer a vasopressor, e.g., levarterenol or dopamine.

Bronchospasm: Administer a beta2-stimulating agent and/or a theophylline derivative.

Cardiac Failure: Administer digitalis glycoside and diuretic. In shock resulting from inadequate cardiac contractility, consider administration of dobutamine, isoproterenol, or glucagon.

Advise patients (1) to avoid operating automobiles and machinery or engaging in other tasks requiring alertness until the patient’s response to therapy with Lopressor has been determined; (2) to contact the physician if any difficulty in breathing occurs; (3) to inform the physician or dentist before any type of surgery that he or she is taking Lopressor.

Your pharmacist can provide more information about metoprolol.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Hypertension And Angina

These adverse reactions were reported for treatment with oral Lopressor. Most adverse effects have been mild and transient.

Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported.

Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; and hypotension have been reported in about 1 of 100 patients. Gangrene in patients with pre-existing severe peripheral circulatory disorders has also been reported very rarely. (See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS.)

Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients (see WARNINGS). Rhinitis has also been reported.

Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1 of 100 patients. Vomiting was a common occurrence. Postmarketing experience reveals very rare reports of hepatitis, jaundice and nonspecific hepatic dysfunction. Isolated cases of transaminase, alkaline phosphatase, and lactic dehydrogenase elevations have also been reported.

Pruritus or rash have occurred in about 5 of 100 patients. Very rarely, photosensitivity and worsening of psoriasis has been reported.

Peyronie's disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, and tinnitus have also been reported.

There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. There have been very rare reports of weight gain, arthritis, and retroperitoneal fibrosis (relationship to Lopressor has not been definitely established).

The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with Lopressor.

Myocardial Infarction

These adverse reactions were reported from treatment regimens where intravenous Lopressor was administered, when tolerated.

Central Nervous System: Tiredness has been reported in about 1 of 100 patients. Vertigo, sleep disturbances, hallucinations, headache, dizziness, visual disturbances, confusion, and reduced libido have also been reported, but a drug relationship is not clear.

Cardiovascular: In the randomized comparison of Lopressor and placebo described in the CLINICAL PHARMACOLOGY section, the following adverse reactions were reported:

Respiratory: Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients.

Gastrointestinal: Nausea and abdominal pain have been reported in fewer than 1 of 100 patients.

Dermatologic: Rash and worsened psoriasis have been reported, but a drug relationship is not clear.

Miscellaneous: Unstable diabetes and claudication have been reported, but a drug relationship is not clear.

Potential Adverse Reactions

A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to Lopressor.

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, slightly clouded sensorium, and decreased performance on neuropsychometrics.

Cardiovascular: Intensification of AV block (see CONTRAINDICATIONS).

Hematologic: Agranulocytosis, nonthrombocytopenic purpura, and thrombocytopenic purpura.

Hypersensitive Reactions: Fever combined with aching and sore throat, laryngospasm, and respiratory distress.

Postmarketing Experience

The following adverse reactions have been reported during postapproval use of Lopressor: confusional state, an increase in blood triglycerides and a decrease in High Density Lipoprotein (HDL). Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency.

Read the entire FDA prescribing information for Lopressor (Metoprolol Tartrate)

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).157 161 500 501

β-Adrenergic blocking agents (β-blockers) generally not preferred for initial management of hypertension, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).242 501 502 503 504 515 523 524 527

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers.229 230 233 265 266 500 501 504 However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.500

Angina

Management of chronic stable angina pectoris.109 147

A component of the standard therapeutic measures in the management of unstable angina or non-ST-segment elevation/non-Q-wave MI.158 218 219

MI

Secondary prevention following acute MI to reduce the risk of reinfarction and mortality.109 123 124 126 127 144 158

Supraventricular Arrhythmias

Has been used in the treatment of supraventricular tachycardia† (SVT) (e.g., atrial flutter†, junctional tachycardia†, focal atrial tachycardia†, paroxysmal supraventricular tachycardia† [PSVT]).300 301

Vagal maneuvers and/or IV adenosine are considered first-line interventions for acute treatment of SVT when clinically indicated; if such measures are ineffective or not feasible, may consider an IV β-blocker.300 Oral β-blockers may be used for ongoing management.300 Although evidence of efficacy is limited, experts state that overall safety of β-adrenergic blockers warrants use.300

Used to slow ventricular rate in patients with atrial fibrillation or flutter.158 300 301

Ventricular Arrhythmias

β-Blockers have been used in patients with cardiac arrest precipitated by ventricular fibrillation† or pulseless VT†; however, routine administration after cardiac arrest is potentially harmful and not recommended.400

β-Blockers may be useful in the management of certain forms of polymorphic VT† (e.g., associated with acute ischemia).158 401

Heart Failure

Management of mild to moderately severe (NYHA class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin (in conjunction with other heart failure therapies [e.g., ACE inhibitors, diuretics, cardiac glycosides]).147 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 215 216 524 800 Used to increase survival and to reduce the risk of hospitalization.524 800

The American College of Cardiology Foundation (ACCF), AHA, and the Heart Failure Society of America (HFSA) recommend therapy with an ACE inhibitor, angiotensin II receptor antagonist, or angiotensin receptor-neprilysin inhibitor (ARNI) in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality in patients with symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (ACCF/AHA stage C heart failure).800

Initiate a clinical-trial proven β-blocker (carvedilol. bisoprolol, extended-release metoprolol succinate) to reduce the risk of death in patients with chronic heart failure; benefits shown with these β-blockers not considered indicative of a β-blocker class effect.524

Experts recommend that β-blockers be used in conjunction with ACE inhibitors in all patients with asymptomatic heart failure† (i.e., structural heart disease but no signs or symptoms; ACCF/AHA stage B heart failure) with reduced LVEF.524 800

Vascular Headache

Prophylaxis of migraine headache†; not recommended for the treatment of a migraine attack that has already started.231

Absorption

Bioavailability

Metoprolol tartrate is rapidly and almost completely absorbed from the GI tract.109 After an oral dose (as conventional tablets), about 50% of the drug undergoes first-pass metabolism in the liver.109

Peak plasma concentrations are reached in about 90 minutes following a single oral dose as conventional tabletsa or 7 hours following administration as extended-release tablets.148

Steady-state oral bioavailability of extended-release tablets given once daily is about 77% of that of conventional tablets at corresponding dosages.147 148 Following oral administration as extended-release tablets, peak plasma metoprolol concentrations are about 25–50% of those attained after administration of conventional tablets.147

Plasma concentrations attained after IV administration are approximately twice those attained following oral administration.a

Onset

Reduction in systolic BP during exercise reported within 15 minutes after a single oral dose of metoprolol tartrate 50–80 mg; with chronic therapy, effect on systolic BP usually is maximal within 1 week.a

The extended-release tablets, given once daily, produce similar hypotensive effects as conventional tablets at similar dosages.147 148

Maximum β-adrenergic blocking activity occurs at 20 minutes after a 10-minute IV infusion.109

Duration

Reduction in systolic BP during exercise persisted for 6 hours following a single oral dose of metoprolol tartrate 50–80 mg.a Hypotensive effect of extended-release tablets may persist for 24 hours.147 Duration of β-adrenergic blocking effect is dose related.109

Following IV infusion of metoprolol tartrate 5 or 15 mg, β-adrenergic blocking activity persisted for approximately 5 or 8 hours, respectively.109

Food

Food does not affect bioavailability of extended-release tablets.147

When conventional tablets are administered with food, peak plasma concentrations are higher and the extent of absorption is increased.a

Distribution

Extent

Widely distributed into body tissues.a Concentrations in heart, liver, lungs, and saliva exceed plasma concentration.a Crosses the blood-brain barrier;147 concentration in CSF is about 78% of the simultaneous plasma concentration.a

Crosses the placenta.a

Concentration in milk is about 3–4 times the maternal plasma concentrations, but the actual amount distributed into milk appears to be very small.101 102

Plasma Protein Binding

11–12% (albumin).109

Elimination

Metabolism

Undergoes first-pass metabolism in the liver by CYP2D6 to inactive metabolites.109 147

Elimination Route

Excreted in urine, principally as metabolites.109

Half-life

3–4 hours.109

Special Populations

Half-life does not increase appreciably with impaired renal function.109

Half-life is about 7.6 hours in poor metabolizers of the drug.a Concomitant use of CYP2D6 inhibitors (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions) in poor metabolizers will lead to increases in plasma metoprolol concentrations and a decrease in β1-selectivity.147

You should not use this medication if you have a serious heart problem (heart block, sick sinus syndrome, slow heart rate), severe circulation problems, severe heart failure, or a history of slow heart beats that caused fainting.

• Metoprolol tartrate is a heart medication that belongs to a class of drugs known as beta-blockers. Metoprolol tartrate works by blocking the effects of epinephrine on beta-1 receptors within the heart tissue, causing the heart to pump more slowly and with less force. At high doses, metoprolol also blocks beta-2 receptors within the lungs and breathing tubes (which may affect breathing).
• Metoprolol is available as two different salts: metoprolol tartrate and metoprolol succinate. These two salts are not interchangeable because they have different dosages, durations of action, and indications for use.

Metoprolol tartrate

• Lowers blood pressure and relieves symptoms of angina in people with heart disease or who have had a heart attack.
• Immediate-release metoprolol tartrate has been shown to reduce the risk of death or another heart attack when given immediately following a heart attack.
• May also be used to lower the risk of a heart attack in people with heart disease.
• An injectable form is available which may be given by healthcare providers for people with unstable angina or arrhythmia.
• May be used off-label for other conditions such as migraine prevention and to treat certain arrhythmias.
• Classified as a "selective" beta-blocker meaning it is less likely to affect breathing and insulin response than other nonselective beta-blockers.

• Take tablets at the same time each day.
• Food can affect absorption. Take tablets with or immediately following food.
• Report any shortness of breath or facial swelling immediately to your doctor.
• Also talk to your doctor if you develop a very slow heartbeat or cold feeling in your hands or feet.
• If you are diabetic, talk to your doctor about the possibility that metoprolol may reduce symptoms of hypoglycemia.
• Talk to you doctor if you are having any side effects that are interfering with your quality of life. Do not stop taking metoprolol suddenly.
• Do not substitute metoprolol tartrate with metoprolol succinate..
• Always check that your prescription is correct. There have been a number of dosing errors involving metoprolol tablets.
• Your doctor will need to regularly monitor your blood pressure and possibly other markers. Keep your appointments.
• Metoprolol may impair your thinking or reaction time and affect your ability to drive. Drinking alcohol may enhance these effects. Do not drive if you think your driving ability is being compromised by metoprolol.