IMPORTANT SAFETY INFORMATION

INDICATIONS AND USAGE

LOPRESSOR is a beta-adrenergic blocker indicated in adult patients:

• 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.
• In the long-term treatment of angina pectoris.
• In the treatment of hemodynamically stable patients with definite or suspected myocardial infarction, to reduce the risk of cardiovascular mortality when used in conjunction with intravenous metoprolol therapy.

CONTRAINDICATIONS

LOPRESSOR is contraindicated in severe bradycardia, second- or third-degree heart block, cardiogenic shock, systolic blood pressure <100, 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.

WARNINGS AND PRECAUTIONS

Abrupt Cessation of Therapy

Abrupt cessation of LOPRESSOR can cause exacerbations of angina pectoris and in some cases, myocardial infarction. Taper the dose over a period of 1–2 weeks and monitor closely particularly in patients with ischemic heart disease. If angina markedly worsens or acute coronary ischemia develops, promptly reinstate LOPRESSOR, and take measures appropriate for the management of unstable angina. Warn patients not to interrupt therapy without their physician’s advice. Because coronary artery disease is common and may be unrecognized, avoid abruptly discontinuing LOPRESSOR in patients treated only for hypertension.

Heart Failure

LOPRESSOR may temporarily worsen cardiac failure during up-titration. If such symptoms occur, increase diuretics and restore clinical stability before advancing the dose of LOPRESSOR. Dose reduction or temporary discontinuation may be needed, but such episodes do not preclude subsequent successful titration of LOPRESSOR.

Bronchospastic Disease

Patients with bronchospastic disease, in general, should not receive beta-blockers, including LOPRESSOR. Because of its relative beta1 cardio-selectivity, however, LOPRESSOR may be used in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment.

Pheochromocytoma

If LOPRESSOR is used in the setting of pheochromocytoma, it should be given in combination with an alpha blocker, and only after the alpha blocker has been initiated.

Major Surgery

Avoid initiation of a high-dose regimen of beta-blocker therapy in patients undergoing non-cardiac surgery, since such use in patients with cardiovascular risk factors has been associated with bradycardia, hypotension, stroke and death. Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery, however, the impaired ability of the heart to respond to reflex adrenergic stimuli may increase the risks of general anesthesia and surgical procedures.

Hypoglycemia

Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed to seek emergency treatment.

Thyrotoxicosis

Beta adrenergic blockade may mask certain clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta-blockade may precipitate a thyroid storm.

Risk of Anaphylactic Reaction

While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions.

Peripheral Vascular Disease

LOPRESSOR can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease.

See Full Prescribing Information for additional warnings and precautions associated with LOPRESSOR.

ADVERSE REACTIONS

The following adverse reactions are described elsewhere in the labeling:

• Worsening angina or myocardial infarction
• Worsening heart failure
• Worsening AV block

See Full Prescribing Information for additional adverse reactions associated with LOPRESSOR.

DRUG INTERACTIONS

Catecholamine Depleting Drugs

Catecholamine depleting drugs (e.g., reserpine, MAO inhibitors) can increase the risk of bradycardia or hypotension, which may produce vertigo, syncope, or postural hypotension.

Epinephrine

While taking beta-blockers, patients with a history of severe anaphylactic reactions to various allergens may exhibit increased sensitivity to repeated exposure and may not respond adequately to usual doses of epinephrine used for treating allergic reactions.

CYP2D6 Inhibitors

Strong CYP2D6 inhibitors—such as quinidine, fluoxetine, paroxetine, and propafenone—have been shown to double plasma concentrations of metoprolol. Although data on moderate or weak inhibitors are lacking, they may also elevate metoprolol levels. Increased plasma concentrations can reduce the cardioselectivity of metoprolol. If co-administration is unavoidable, patients should be monitored closely.

Negative Chronotropes

Digitalis glycosides, clonidine, diltiazem, and verapamil reduce the heart rate by slowing atrioventricular conduction. When used with beta-blockers, the risk of bradycardia may increase. See Full Prescribing Information for additional potential drug interactions associated with LOPRESSOR.

USE IN SPECIFIC POPULATIONS

Pregnancy

If high blood pressure or a heart attack is not treated during pregnancy, it can be harmful to both the mother and baby. Metoprolol can pass through the placenta, so babies born to mothers taking this medication may be at risk for low blood pressure, low blood sugar, a slow heart rate, and trouble breathing. Babies should be closely monitored after birth if the mother took metoprolol during pregnancy.

Lactation

No adverse reactions of metoprolol on the breastfed infant have been identified. There is no information regarding the effects of metoprolol on milk production.

Females and Males of Reproductive Potential

Based on the published literature, metoprolol may cause erectile dysfunction and inhibit sperm motility.

Pediatric Use

Pediatric use of LOPRESSOR has not been studied.

Geriatric Use

In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Impairment

LOPRESSOR has not been studied in patients with hepatic impairment.

Renal Impairment

The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. No reduction in dosage is needed in patients with chronic renal failure.

OVERDOSAGE

Overdosage of LOPRESSOR may lead to severe bradycardia, hypotension, and cardiogenic shock. Clinical presentation can also include atrioventricular block, heart failure, bronchospasm, hypoxia, impairment of consciousness/coma, nausea and vomiting.

LOPRESSOR is available as a 10 mg/mL oral solution.

To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals LLC at 1-866-982-5438 or the FDA at www.fda.gov/medwatch

Please see Full Prescribing Information at https://liquid.lopressor.us.com/

LOP-003-25