No

Beta Blocker, Beta₁ Selective

Treatment of hypertension and angina pectoris; prevention of myocardial infarction, atrial fibrillation, flutter, symptomatic treatment of hypertrophic subaortic stenosis

C (per manufacturer);D (in 2nd and 3rd trimesters, based on expert analysis)

Clinical effects on the fetus: Crosses the placenta. None; mild IUGR probably secondary to maternal hypertension. Available evidence suggests safe use during pregnancy and breast-feeding. Monitor breast-fed infant for symptoms of beta-blockade.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to metoprolol or any component; sinus bradycardia; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; uncompensated cardiac failure; pregnancy (2nd and 3rd trimesters)

Must use care in compensated heart failure and monitor closely for a worsening of the condition (efficacy has not been established for metoprolol). Avoid abrupt discontinuation in patients with a history of CAD; slowly wean while monitoring for signs and symptoms of ischemia. Use caution in patients with PVD (can aggravate arterial insufficiency). Use caution with concurrent use of beta-blockers and either verapamil or diltiazem; bradycardia or heart block can occur. Avoid concurrent I.V. use of both agents. In general, beta-blockers should be avoided in patients with bronchospastic disease. Metoprolol, with B1 selectivity, should be used cautiously in bronchospastic disease with close monitoring. Use cautiously in diabetics because it can mask prominent hypoglycemic symptoms. Can mask signs of thyrotoxicosis. Can cause fetal harm when administered in pregnancy. Use cautiously in the hepatically impaired. Use care with anesthetic agents which decrease myocardial function.

>10%:

Central nervous system: Drowsiness, insomnia

Endocrine & metabolic: Decreased sexual ability

1% to 10%:

Cardiovascular: Bradycardia, palpitations, edema, congestive heart failure, reduced peripheral circulation

Central nervous system: Mental depression

Gastrointestinal: Diarrhea or constipation, nausea, vomiting, stomach discomfort

Respiratory: Bronchospasm

Miscellaneous: Cold extremities

<1% (Limited to important or life-threatening symptoms): Chest pain, arrhythmias, orthostatic hypotension, nervousness, headache, depression, hallucinations, confusion (especially in the elderly), thrombocytopenia, leukopenia, shortness of breath, hepatitis, hepatic dysfunction, jaundice

Symptoms of intoxication include cardiac disturbances, CNS toxicity, bronchospasm, hypoglycemia and hyperkalemia. The most common cardiac symptoms include hypotension and bradycardia; atrioventricular block, intraventricular conduction disturbances, cardiogenic shock, and asystole may occur with severe overdose, especially with membrane-depressant drugs (eg, propranolol); CNS effects include convulsions, coma, and respiratory arrest.

Treatment includes symptomatic treatment of seizures, hypotension, hyperkalemia and hypoglycemia; bradycardia and hypotension resistant to atropine, isoproterenol or pacing, may respond to glucagon; wide QRS defects caused by the membrane-depressant poisoning may respond to hypertonic sodium bicarbonate; repeat-dose charcoal, hemoperfusion, or hemodialysis may be helpful in removal of only those beta-blockers with a small V_d, long half-life or low intrinsic clearance (acebutolol, atenolol, nadolol, sotalol)

CYP2D6 enzyme substrate

Clonidine: Hypertensive crisis after or during withdrawal of either agent.

Drugs which slow AV conduction (digoxin): effects may be additive with beta-blockers.

Fluoxetine may inhibit the metabolism of metoprolol resulting in cardiac toxicity.

Glucagon: Metoprolol may blunt the hyperglycemic action of glucagon.

Hydralazine may enhance the bioavailability of metoprolol.

Insulin and oral hypoglycemics: Metoprolol may mask tachycardia from hypoglycemia.

Metoprolol reduces antipyrine's clearance by 18%.

NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam) may reduce the antihypertensive effects of beta-blockers.

Oral contraceptives may increase the AUC and C_max of metoprolol.

Salicylates may reduce the antihypertensive effects of beta-blockers.

Sulfonylureas: Beta-blockers may alter response to hypoglycemic agents.

Verapamil or diltiazem may have synergistic or additive pharmacological effects when taken concurrently with beta-blockers; avoid concurrent I.V. use.

Selective inhibitor of beta₁-adrenergic receptors; competitively blocks beta₁-receptors, with little or no effect on beta₂-receptors at doses <100 mg; does not exhibit any membrane stabilizing or intrinsic sympathomimetic activity

Peak antihypertensive effect: Oral: Within 1.5-4 hours

Duration: 10-20 hours

Absorption: 95%

Protein binding: 8%

Metabolism: Significant first-pass metabolism; extensively metabolized in the liver

Bioavailability: Oral: 40% to 50%

Half-life: 3-4 hours; End-stage renal disease: 2.5-4.5 hours

Elimination: In urine (3% to 10% as unchanged drug)

Children: Oral: 1-5 mg/kg/24 hours divided twice daily; allow 3 days between dose adjustments

Adults:

Oral: 100-450 mg/day in 2-3 divided doses, begin with 50 mg twice daily and increase doses at weekly intervals to desired effect

Extended release: Same daily dose administered as a single dose

I.V.: 5 mg every 2 minutes for 3 doses in early treatment of myocardial infarction; thereafter administer 50 mg orally every 6 hours 15 minutes after last I.V. dose and continue for 48 hours; then administer a maintenance dose of 100 mg twice daily

Elderly: Oral: Initial: 25 mg/day; usual range: 25-300 mg/day

Hemodialysis: Administer dose posthemodialysis or administer 50 mg supplemental dose; supplemental dose is not necessary following peritoneal dialysis

Dosing adjustment/comments in hepatic disease: Reduced dose probably necessary

Should be administered with food, as food increases absorption

Administer I.V. push, inject slowly over 1 minute

Blood pressure, apical and radial pulses, fluid I & O, daily weight, respirations, mental status, and circulation in extremities before and during therapy

Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. This class of drug is beneficial for elderly patients with hypertension. A recent UKPDS study showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.

Myocardial infarction: Beta-blockers, in general without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of myocardial infarction and continued long-term. In this setting, therapy should be avoided in patients with hypotension, cardiogenic shock, or heart block.

Surgery: Atenolol has also been shown to improve cardiovascular outcomes when used in the perioperative period in patients with underlying cardiovascular disease who are undergoing noncardiac surgery. Bisoprolol in high-risk patients undergoing vascular surgery reduced the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction.

Atrial fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.

Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.

Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.

Heart failure: There is emerging evidence that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive heart failure (NYHA class II-III). To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration.

Metoprolol has also been used in the treatment of vasovagal (neurogenic) syncope.

Sedation and dizziness are common; may cause depression; may rarely cause insomnia, confusion, amnesia, or nightmares

Barbiturates may decrease the effects of metoprolol; beta-blockers may increase the effects of psychotropics; monitor clinical status for potential changes

No information available to require special precautions

Noncardioselective beta-blockers (ie, propranolol, nadolol) enhance the pressor response to epinephrine, resulting in hypertension and bradycardia. This has not been reported for metoprolol, a cardioselective beta-blocker. Therefore, local anesthetic with vasoconstrictor can be safely used in patients medicated with metoprolol. Many nonsteroidal anti-inflammatory drugs such as ibuprofen and indomethacin can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.

I.V. use in emergency situations - patient information is included in general instructions.

Monitor hemodynamic status carefully after acute MI, monitor orthostatic blood pressures, apical and peripheral pulse and mental status changes (ie, confusion, depression)

Injection, as tartrate: 1 mg/mL (5 mL)

Tablet, as tartrate: 50 mg, 100 mg

Tablet, as succinate [equivalent to tartrate], sustained release: 50 mg, 100 mg, 200 mg

A mixture of metoprolol 10 mg/mL plus hydrochlorothiazide 5 mg/mL was found to be stable for 60 days in a refrigerator in a 1:1 preparation of Ora-Sweet® and Ora-Plus®, in Ora-Sweet® SF and Ora-Plus®, and in cherry syrup

Anthony T, Jastremski J, Elliott W, et al, "Charcoal Hemoperfusion for the Treatment of a Combined Diltiazem and Metoprolol Overdose," Ann Emerg Med, 1986, 15(11):1344-8.

Foster CA and Aston SJ, "Propranolol-Epinephrine Interaction: A Potential Disaster," Plast Reconstr Surg, 1983, 72(1):74-8.

Lee DW and Cohan B, "Refractory Cardiogenic Shock and Complete Heart Block After Verapamil SR and Metoprolol Treatment: A Case Report," Angiology, 1995, 46(6):517-9.

Love JN, "Beta-Blocker Toxicity: A Clinical Diagnosis," Am J Emerg Med, 1994, 12(3):356-7.

Moller BJ, "Massive Intoxication With Metoprolol," Br Med J, 1976, 1(6003):222.

Schallreuter KU, "Beta-Adrenergic Blocking Drugs May Exacerbate Vitiligo," Br J Dermatol, 1995, 132(1):168-9.

Shore ET, Cepin D, and Davidson MJ, "Metoprolol Overdose," Ann Emerg Med, 1981, 10(10):524-7.

Sire S, "Metoprolol Intoxication," Lancet, 1976, 2(7995):1137.

Wallin CJ and Hulting J, "Massive Metoprolol Poisoning Treated With Prenalterol," Acta Med Scand, 1983, 214(3):253-5.

Wong DG, Spence JD, Lamki L, et al, "Effect of Nonsteroidal Anti-inflammatory Drugs on Control of Hypertension of Beta-Blockers and Diuretics," Lancet, 1986, 1(8488):997-1001.

Wynn RL, "Dental Nonsteroidal Anti-inflammatory Drugs and Prostaglandin-Based Drug Interactions, Part Two," Gen Dent, 1992, 40(2):104, 106, 108.

Wynn RL, "Epinephrine Interactions With Beta-Blockers," Gen Dent, 1994, 42(1):16, 18.