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Metoprolol Tartrate

Class: beta-Adrenergic Blocking Agents
Note: This monograph also contains information on Metoprolol Succinate
VA Class: CV100
Molecular Formula: C22H23ClN6O•K ½C4H4 O4
CAS Number: 98418-47-4
Brands: Toprol XL, Lopressor, Lopressor HCT

Introduction

β1-Selective adrenergic blocking agent.109 147 281

Uses for Metoprolol Tartrate

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).100 111 157 160 161

One of several preferred initial therapies in hypertensive patients with ischemic heart disease, heart failure, or diabetes mellitus.232

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.232

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.158 218 219 281

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AMI

Secondary prevention following AMI to reduce the risk of reinfarction and mortality.109 123 124 126 127 144 158 281

Supraventricular Tachyarrhythmias

β-Adrenergic blocking agents, including metoprolol, are one of several preferred antiarrhythmic agents for the treatment of stable, narrow-complex supraventricular tachycardias (e.g., paroxysmal supraventricular tachycardia [reentry supraventricular tachycardia], ectopic or multifocal atrial tachycardia, junctional tachycardia) if the rhythm is not controlled by vagal maneuvers or adenosine in patients with preserved left ventricular function and for rate control in atrial fibrillation or flutter in patients with preserved left ventricular function.281

Ventricular Tachyarrhythmias

Reduction of the incidence of ventricular fibrillation associated with myocardial ischemia or infarction.158 197 281

Treatment of sustained polymorphic ventricular tachycardia following AMI.158 197

CHF

Management of mild to moderately severe (NYHA class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin (in conjunction with ACE inhibitors, diuretics, and cardiac glycosides).147 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 215 216

Vascular Headache

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

Metoprolol Tartrate Dosage and Administration

General

  • β1-Adrenergic blocking selectivity diminishes as dosage is increased.109 147

  • If long-term therapy is discontinued, reduce dosage gradually over a period of 1–2 weeks.109 147 (See Abrupt Withdrawal of Therapy under Cautions.)

Hypertension

  • Metoprolol/hydrochlorothiazide fixed combination is not recommended for initial combination therapy;159 adjust initial and subsequent dosages by administering each drug separately.a

Administration

Administer orally109 147 or by IV injection.109

For ACLS during CPR, may be administered by intraosseous infusion.281

Oral Administration

Conventional Tablets

Administer metoprolol tartrate conventional tablets daily as a single dose or in divided doses, with or immediately following meals.109

Extended-release Tablets

Administer metoprolol succinate extended-release tablets daily as a single dose.147

Extended-release tablets are scored and can be divided.147 However, swallow tablet or half tablet whole; do not chew or crush.147

When switching from conventional tablets to extended-release tablets, administer the same daily dosage.147

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Monitor heart rate, BP, and ECG during IV therapy.158

Discontinue IV therapy when therapeutic efficacy is achieved (e.g., slowing of ventricular rate in atrial fibrillation) or if systolic BP or heart rate declines to <100 mm Hg or 50 bpm, respectively.158 Discontinue therapy in patients with severe intolerance to IV therapy.109

Rate of Administration

Administer as a rapid IV injection.109 Administer over 1–2 minutes for the management of unstable angina or non-ST-segment elevation/non-Q-wave MI.218

Dosage

Available as metoprolol tartrate and metoprolol succinate; dosage expressed in terms of the tartrate.109 147

Pediatric Patients

Hypertension
Oral

Some experts recommend an initial dosage of 1–2 mg/kg daily given in 2 divided doses.260 Increase dosage as necessary up to a maximum dosage of 6 mg/kg (up to 200 mg) daily given in 2 divided doses.260

Adults

Hypertension
Oral

Initially, 50–100 mg given once daily (extended-release tablets) or in single or divided doses daily (conventional tablets).109 147 232 Increase dosage at weekly (or longer) intervals until optimum effect is achieved.109 147

If satisfactory BP response is not maintained throughout the day, larger doses, more frequent administration, or use of extended-release tablets may be required.a

Angina
Long-term Management
Oral

Initially, 100 mg given once daily (extended-release tablets) or in 2 divided doses daily (conventional tablets).109 147 Increase dosage at weekly intervals until optimum response is obtained or pronounced slowing of heart rate occurs.109 147

Usual maintenance dosage is 100–400 mg daily.109

Unstable Angina or Non-ST-Segment Elevation MI
IV, then Oral

Patients at high risk for ischemic events should receive IV loading dose followed by conversion to an oral regimen; oral therapy is recommended for lower risk patients.218 219

5 mg IV every 5 minutes up to a total of 15 mg.218 If IV dose is tolerated, 25–50 mg orally, initiated 15 minutes after the last IV dose and repeated every 6 hours for 48 hours, followed by 100 mg twice daily.218 Target resting heart rate is 50–60 bpm in the absence of dose-limiting adverse effects.218

AMI

As soon as clinical condition allows, administer oral therapy (conventional tablets) to patients who have contraindications to or do not tolerate IV therapy during the early phase of definite or suspected AMI or to patients in whom therapy is delayed.a

Early Treatment.
IV, then Oral

2.5–5 mg IV every 2–5 minutes up to a total of 15 mg over 10–15 minutes.a If total IV dose is tolerated, 50 mg orally, initiated 15 minutes after the last IV dose and repeated every 6 hours for 48 hours, followed by 100 mg twice daily.109 If total IV dose is not tolerated, 25 or 50 mg (depending on the degree of intolerance) orally every 6 hours beginning 15 minutes after the last IV dose or as soon as clinical condition allows.109

Late Treatment
Oral

100 mg twice daily for at least 3 months.109

Supraventricular Tachyarrhythmias
Paroxysmal Supraventricular Tachycardia, Junctional Tachycardia, Ectopic Tachycardia, Multifocal Atrial Tachycardia
IV or Intraosseous

5 mg every 5 minutes, up to a total dose of 15 mg.281

Atrial Fibrillation.
IV, then Oral

2.5–5 mg IV every 2–5 minutes as necessary to control rate, up to a total of 15 mg over 10–15 minutes.158 197 203 281 Then, 25–100 mg orally twice daily for long-term control.203

Intraosseous

5 mg every 5 minutes, up to a total dose of 15 mg.281

CHF
Oral

Initially, 25 mg (extended-release tablets) once daily in adults with NYHA class II heart failure.147 In patients with more severe heart failure, use an initial dosage of 12.5 mg (extended-release tablets) once daily.147 Double the dosage every 2 weeks to a dosage of 200 mg or until highest tolerated dosage is reached.147

Some experts recommend initiation of therapy with 12.5 mg (extended-release tablets) daily or 6.25 mg (conventional tablets) twice daily for 2–4 weeks.163 173 205 If tolerated, increase to 25 mg daily for 2–4 weeks; subsequent dosages can be doubled every 2–4 weeks.163 147

If deterioration occurs during titration, increase dosage of concurrent diuretic147 205 and decrease dosage of metoprolol or temporarily discontinue metoprolol.147 205 Do not continue dosage titration until symptoms of worsening heart failure have stabilized.147 205 Initial difficulty in dosage titration should not preclude subsequent attempts to successfully titrate the dosage.147 205

Reduce dosage in patients with CHF who experience symptomatic bradycardia (e.g., dizziness) or 2nd or 3rd degree heart block.147 205

Vascular Headache
Migraine
Oral

Dosages of 50–300 mg daily have been used in clinical studies; usual effective dosage was 200 mg daily.231

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Maximum 6 mg/kg (up to 200 mg) daily.260

Adults

Hypertension
Oral

Dosages >400 mg (extended-release tablets) and 450 mg (conventional tablets) daily have not been studied.109 147

Angina
Oral

Dosages >400 mg daily have not been studied.109 147

IV

Maximum 15 mg over 15 minutes in patients with unstable angina or non-ST-segment elevation MI.218

AMI
IV

Maximum 15 mg over 10–15 minutes.a

Supraventricular Tachyarrhythmias
Atrial Fibrillation.
Oral

Maximum 100 mg twice daily.203

IV

Maximum 15 mg over 10–15 minutes.158 203 281

CHF
Oral

Up to 200 mg daily.147

Special Populations

Hepatic Impairment

Elimination occurs mainly in the liver; dosage reductions may be necessary.109 a

Renal Impairment

Dosage adjustments are not required.109 147

Geriatric Patients

Cautious dosage selection recommended; initiate therapy at the lower end of the dosage range.147

Cautions for Metoprolol Tartrate

Contraindications

  • Patients with sinus bradycardia, heart block greater than 1st degree, cardiogenic shock, overt or decompensated cardiac failure, or sick sinus syndrome (unless a permanent pacemaker is in place).109 147 159 281

  • Patients with AMI who have a heart rate <45–60 bpm, heart block greater than 1st degree, systolic BP <100 mm Hg, or moderate to severe cardiac failure.109 281

Warnings/Precautions

Warnings

Abrupt Withdrawal of Therapy

Abrupt discontinuance may exacerbate angina symptoms or precipitate MI in patients with CAD.109 147 a Avoid abrupt discontinuance.109 147 Gradually decrease dosage over 1–2 weeks and monitor patients carefully.109 147 If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly, at least temporarily, and initiate appropriate measures for the management of unstable angina.109 147

Cardiac Failure

Possible precipitation of CHF;109 possible decreased exercise tolerance in patients with left ventricular dysfunction.a

Initiate therapy and subsequent dosage adjustments in patients with CHF under close medical supervision.147 163 205 Prior to initiation of metoprolol, stabilize patient on other therapy (e.g., ACE inhibitor, diuretic, and/or cardiac glycoside).147 163 205 Symptomatic improvement may not be evident for 2–3 months after initiating therapy.163 205

Avoid use in patients with decompensated CHF;147 a use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with ACE inhibitors, cardiac glycosides, and/or diuretics);147 a use with extreme caution in patients with substantial cardiomegaly.a

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending cardiac failure occur; if cardiac failure continues, discontinue therapy, gradually if possible.109 147

Bronchospastic Disease

Possible bronchoconstriction, especially at dosages >100 mg daily.109 a

Use with caution in patients with bronchospastic disease; administer lowest effective dosage (initially in 3 divided doses) and with maximal therapy with a β2-adrenergic agonist.109 a

Bradycardia

Possible bradycardia and depressed SA node automaticity.109 147 a

Carefully monitor hemodynamic status of patients with MI; use with caution in patients with sinus node dysfunction.109 147 a

If heart rate < 40 bpm with evidence of decreased cardiac output, administer IV atropine; if bradycardia is refractory to atropine, discontinue metoprolol and consider cautious administration of isoproterenol or use of a cardiac pacemaker.109 281

AV Block

Possible intensification of AV block, AV dissociation, AV conduction delays,281 complete heart block, or cardiac arrest, especially in patients with preexisting heart block caused by digoxin or other factors.109 a

Use with caution, if at all, in patients with AV conduction defects.a

If heart block occurs in patients with MI, discontinue metoprolol and administer IV atropine; if the heart block is refractory to atropine, consider cautious administration of isoproterenol or use of a cardiac pacemaker.109

Hypotension

If hypotension (systolic BP <90 mm Hg) occurs in patients with MI, discontinue metoprolol and assess hemodynamic status and extent of myocardial damage.109 Invasive monitoring of central venous, pulmonary capillary wedge, and arterial pressures may be necessary; appropriate therapy with IV fluids and other treatment modalities recommended.109

If hypotension is associated with severe bradycardia or heart block, provide treatment directed at reversing these.109 (See Bradycardia and also see AV Block under Cautions.)

Major Surgery

Possible increased risks associated with general anesthesia (e.g., severe hypotension, maintenance of heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.109 147

Use with caution in patients undergoing major surgery involving general anesthesia; avoid use of anesthetics that cause myocardial depression (see Specific Drugs under Interactions).a

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, palpitation, BP changes, tremor, feelings of anxiety) and increased insulin-induced hypoglycemia.109 147 a

Use with caution in patients with diabetes mellitus.109 147

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked.109 147 Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.109 147

General Precautions

Ocular Effects

Possible dry eyes and decreased tear production, minimal injection of conjunctivae and/or eyelids, punctate keratitis, keratoconjunctivitis or corneal ulceration.a Close observation recommended.a

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling between Toprol-XL (metoprolol succinate) and Topamax (trade name for topiramate, an anticonvulsant and antimigraine agent) may result in errors.261 262 263 264

Potential also exists for dispensing errors involving confusion between Toprol-XL and Tegretol or Tegretol-XR (trade names for carbamazepine, an anticonvulsant also used for relief of pain associated with trigeminal neuralgia, as well as for various psychiatric disorders).261 263

These medication errors have been associated with serious adverse events sometimes requiring hospitalization as a result of either lack of the intended medication (e.g., seizure recurrence, return of hallucinations, suicide attempt, hypertension recurrence) or exposure to the wrong drug (e.g., bradycardia in a patient erroneously receiving metoprolol).261 262 263 264 261 262 263 264

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.a

Specific Populations

Pregnancy

Category C.109 147

Lactation

Distributed into milk.147 Use with caution.109

Pediatric Use

Safety and efficacy remain to be fully established in children;109 147 however, some experts have recommended dosages for hypertension based on current limited clinical experience.258

Geriatric Use

Among patients with heart failure, safety and efficacy profiles in geriatric individuals are similar to those in younger adults.147

BP determinations recommended in both the seated position and after patient stands quietly for 2–5 minutes (to recognize postural hypotension).160

Hepatic Impairment

Hepatic elimination; use with caution.109 147 a

Common Adverse Effects

Dizziness, tiredness, insomnia, gastric upset.a

Interactions for Metoprolol Tartrate

Metabolized by CYP2D6.147 200 201 202 208 210 211

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 inhibitors: Potential pharmacodynamic (increased β-adrenergic blockade, decreased cardioselectivity of metoprolol) and pharmacokinetic interaction (prolonged half-life and increased plasma concentrations of metoprolol).147 200 201 202 208 210 211

Specific Drugs

Drug

Interaction

Comments

Calcium-channel blocking agents, nondihydropyridine

Possible additive negative effects on SA or AV nodal conductiona

Digoxin

Possible additive negative effects on SA or AV nodal conductiona

Diuretics

Increased hypotensive effecta

Adjust dosage carefullya

Fluoxetine

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

Anesthetics, general (myocardial depressant agents [e.g., diethyl ether])

Increased risk of hypotension and heart failure109

Avoid use of general anesthetics with myocardial depressant effectsa

Hydralazine

Increased risk of pulmonary hypertension in patients with uremia a

Hypotensive agents

Possible increased hypotensive effecta

Adjust dosage carefullya

Paroxetine

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

Use with caution209 211 212

Propafenone

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

Quinidine

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

Reserpine

Additive effects109

Monitor for hypotension and bradycardia109

Sertraline

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

When concomitant sertraline therapy is discontinued, may need to increase metoprolol dosage208

Sympathomimetic agents

Antagonism of β1-adrenergic stimulating effectsa

Verapamil

Increased oral bioavailability105 106

Avoid concomitant use, if possible;105 106 if used concomitantly, adjust metoprolol dosage and monitor patient closely106

Metoprolol Tartrate Pharmacokinetics

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

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.109 Protect from light.109

Extended-Release Tablets

25°C (may be exposed to 15–30°C).147

Parenteral

Injection

30°C or less (preferably 15–30°C).109 Protect from light109 and freezing.a

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility
Y-Site CompatibilityHID

Compatible

Abciximab

Alteplase

Amiodarone HCl

Argatroban

Bivalirudin

Ceftaroline fosamil

Diltiazem HCl

Eptifibatide

Furosemide

Heparin sodium

Meperidine HCl

Milrinone lactate

Morphine sulfate

Procainamide HCl

Sodium nitroprusside

Incompatible

Amphotericin B cholesteryl sulfate complex

Lidocaine HCl

Nitroglycerin

Variable

Nesiritide

Actions

  • Inhibits response to adrenergic stimuli by competitively blocking β1-adrenergic receptors within the myocardium.109 147 Blocks β2-adrenergic receptors within bronchial and vascular smooth muscle only in high doses.109 147

  • Decreases resting heart rate, reflex orthostatic tachycardia, myocardial contractility, and cardiac output at rest and during exercise (without increasing peripheral resistance); inhibits exercise-induced increases in heart rate; increases systolic ejection time and cardiac volume, without changing stroke volume; decreases conduction velocity through the SA and AV nodes; and decreases myocardial automaticity.109 147 a

  • No intrinsic sympathomimetic activity and little or no membrane-stabilizing effect on the heart.109 147

  • Reduces BP by decreasing cardiac output, decreasing sympathetic outflow from the CNS, suppressing renin release, and/or reducing peripheral resistance.109 147 a

  • In patients with MI, reduces heart rate, systolic BP, cardiac output, and ventricular fibrillation.109 a

  • In patients with angina, blocks catecholamine-induced increases in heart rate, velocity and extent of myocardial contraction, and BP, resulting in decreased myocardial oxygen consumption.109 147

  • Increases airway resistance and decreases ventilatory capacity in asthmatic patients.109 147 a

  • Causes little inhibition of glycogenolysis in skeletal and cardiac muscles; inhibits increase in plasma glycerol during exercise; inhibits insulin release less than propranolol.a

Advice to Patients

  • Importance of taking metoprolol exactly as prescribed.214

  • Importance of not interrupting or discontinuing therapy without consulting clinician; patients should temporarily limit their physical activity when discontinuing therapy.109 147

  • If a dose is missed, importance of patient taking only the next scheduled dose (i.e., the next dose should not be doubled).109 147

  • Importance of immediately informing clinician at the first sign or symptom of impending cardiac failure (e.g., weight gain, increased shortness of breath) or if any difficulty in breathing occurs.109

  • In patients with heart failure, importance of informing clinician of signs or symptoms of exacerbation (e.g., weight gain, difficulty in breathing).147

  • Importance of patients informing anesthesiologist or dentist that they are receiving metoprolol therapy prior to undergoing major surgery.109 147

  • Importance of avoiding some activities (e.g., operating machinery, driving a motor vehicle) until effects on individual are known.109 147

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.109 147 159

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.109

  • Importance of informing patients of other important precautionary information.109 147 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Metoprolol Succinate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release, film-coated

23.75 mg (equivalent to 25 mg of metoprolol tartrate)

Toprol XL (scored)

AstraZeneca

47.5 mg (equivalent to 50 mg of metoprolol tartrate)

Toprol XL (scored)

AstraZeneca

95 mg (equivalent to 100 mg of metoprolol tartrate)

Toprol XL (scored)

AstraZeneca

190 mg (equivalent to 200 mg of metoprolol tartrate)

Toprol XL (scored)

AstraZeneca

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Metoprolol Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

50 mg*

Lopressor (scored)

Novartis

Metoprolol Tartrate Tablets

100 mg*

Lopressor (scored)

Novartis

Metoprolol Tartrate Tablets

Parenteral

Injection

1 mg/mL

Lopressor

Novartis

Metoprolol Tartrate Injection

Metoprolol Tartrate and Hydrochlorothiazide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

50 mg Metoprolol Tartrate and Hydrochlorothiazide 25 mg

Lopressor HCT (scored)

Novartis

100 mg Metoprolol Tartrate and Hydrochlorothiazide 25 mg

Lopressor HCT (scored)

Novartis

100 mg Metoprolol Tartrate and Hydrochlorothiazide 50 mg

Lopressor HCT (scored)

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lopressor 100MG Tablets (NOVARTIS): 60/$165.98 or 180/$497.95

Lopressor 50MG Tablets (NOVARTIS): 60/$118.99 or 180/$334.98

Lopressor HCT 100-50MG Tablets (NOVARTIS): 30/$81.99 or 90/$224.97

Lopressor HCT 50-25MG Tablets (NOVARTIS): 60/$120.99 or 180/$349.96

Metoprolol Succinate 100MG 24-hr Tablets (WOCKHARDT USA): 30/$44.99 or 60/$77.97

Metoprolol Succinate 200MG 24-hr Tablets (WOCKHARDT USA): 90/$195.99 or 180/$375.99

Metoprolol Succinate 25MG 24-hr Tablets (WOCKHARDT USA): 30/$29.99 or 90/$79.97

Metoprolol Succinate 50MG 24-hr Tablets (WOCKHARDT USA): 30/$33.99 or 90/$86.97

Metoprolol Tartrate 100MG Tablets (CARACO): 60/$15.99 or 180/$25.97

Metoprolol Tartrate 25MG Tablets (MYLAN): 30/$12.99 or 60/$14.98

Metoprolol Tartrate 50MG Tablets (CARACO): 60/$13.99 or 90/$18.97

Metoprolol-Hydrochlorothiazide 100-25MG Tablets (MYLAN): 30/$50.99 or 90/$132.96

Metoprolol-Hydrochlorothiazide 100-50MG Tablets (MYLAN): 30/$55.99 or 90/$149.97

Metoprolol-Hydrochlorothiazide 50-25MG Tablets (MYLAN): 60/$63.99 or 180/$168.97

Toprol XL 100MG 24-hr Tablets (ASTRAZENECA LP): 30/$60.99 or 90/$159.99

Toprol XL 200MG 24-hr Tablets (ASTRAZENECA LP): 90/$266.98 or 180/$507.97

Toprol XL 25MG 24-hr Tablets (ASTRAZENECA LP): 30/$46.99 or 90/$119.97

Toprol XL 50MG 24-hr Tablets (ASTRAZENECA LP): 30/$44.99 or 90/$110.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 10, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984; 144:1045-57. [IDIS 184763] [PubMed 6143542]

101. Sandström B, Regardh CG. Metoprolol excretion into milk. Br J Clin Pharmacol. 1980; 9:518-9. [IDIS 114928] [PubMed 7397065]

102. Liedholm H, Melander A, Bitzén PO et al. Accumulation of atenolol and metoprolol in human breast milk. Eur J Clin Pharmacol. 1981; 20:229-31. [IDIS 148916] [PubMed 7286041]

103. Searle & Co. Calan SR prescribing information. Chicago; 1986 Nov.

104. Searle & Co. Calan prescribing information. Chicago, IL; 1986 Nov.

105. McLean AJ, Knight R, Harrison PM et al. Clearance-based oral drug interaction between verapamil and metoprolol and comparison with atenolol. Am J Cardiol. 1985; 55:1628-9. [IDIS 201348] [PubMed 4003307]

106. Keech AC, Harper RW, Harrison PM et al. Pharmacokinetic interaction between oral metoprolol and verapamil for angina pectoris. Am J Cardiol. 1986; 58:551-2. [IDIS 222014] [PubMed 3529913]

107. Mangini RJ, ed. Drug interaction facts. St. Louis: JB Lippincott Co; 1986(Jul):122a.

108. Knoll Pharmaceuticals. Isoptin SR prescribing information. Whippany, NJ; 1987 Nov.

109. Novartis. Lopressor (metoprolol tartrate) tablets and injection prescribing information. East Hanover, NJ; 1999 Apr.

110. National Heart, Lung, and Blood Institute Task Force on Blood Pressure Control in Children. Report of the Second Task Force on Blood Pressure Control in Children—1987. Pediatrics. 1987; 79:1-25. [IDIS 224856] [PubMed 3797155]

111. 1988 Joint National Committee. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [IDIS 242588] [PubMed 3365073]

112. Arsura EL, Solar M, Lefkin AS et al. Metoprolol in the treatment of multifocal atrial tachycardia. Crit Care Med. 1987; 15:591-4. [PubMed 3568727]

113. Hazard PB, Burnett CR. Treatment of multifocal atrial tachycardia with metoprolol. Crit Care Med. 1987; 15:20-5. [PubMed 3792010]

114. Arsura E, Lefkin AS, Scher DL et al. A randomized, double-blind, placebo-controlled study of verapamil and metoprolol in treatment of multifocal atrial tachycardia. Am J Med. 1988; 85:519-24. [IDIS 247332] [PubMed 3052051]

115. Scher DL, Arsura EL. Multifocal atrial tachycardia: mechanisms, clinical correlates, and treatment. Am Heart J. 1989; 118:574-80. [PubMed 2570520]

116. Arsura E, Lefkin AS, Scher DL et al. A randomized, double-blind, placebo-controlled study of verapamil and metoprolol in treatment of multifocal atrial tachycardia. Am J Med. 1988; 85:519-24. [IDIS 247332] [PubMed 3052051]

117. Salerno DM, Anderson B, Sharkey PJ et al. Intravenous verapamil for treatment of multifocal atrial tachycardia with and without calcium pretreatment. Ann Intern Med. 1987; 107:623-8. [IDIS 235738] [PubMed 3662276]

118. Lui CY, Franchina JJ. Verapamil and multifocal atrial tachycardia. Ann Intern Med. 1988; 108:486-7. [IDIS 239629] [PubMed 3341685]

119. Arsura EL, Scher DL. Verapamil and multifocal atrial tachycardia. Ann Intern Med. 1988; 108:487.

120. Hazard PB, Burnett CR. Verapamil in multifocal atrial tachycardia: hemodynamic and respiratory changes. Chest. 1987; 91:68-70. [IDIS 225161] [PubMed 3792087]

121. Levine JH, Michael JR, Guarnieri T. Treatment of multifocal atrial tachycardia with verapamil. N Engl J Med. 1985; 312:21-5. [IDIS 194455] [PubMed 3964904]

122. Levine JH, Michael JR, Guarnieri T. Verapamil for multifocal atrial tachycardia. N Engl J Med. 1985; 312:1126-7. [IDIS 198978] [PubMed 3982471]

123. Yusuf S, Wittes J, Friedman L. Overview of results of randomized clinical trials in heart disease. 1. Treatments following myocardial infarction. JAMA. 1988; 260:2088-93. [IDIS 246179] [PubMed 2901501]

124. American College of Cardiology and American Heart Association. ACC/AHA guidelines for the early management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Develop Guidelines for the Early Management of Patients with Acute Myocardial Infarction). Circulation. 1990; 82:664-707. [IDIS 269868] [PubMed 2197021]

125. Roque F, Amuchastegui LM, Lopez Morillos MA et al. The TIARA Study Group. Beneficial effects of timolol on infarct size and late ventricular tachycardia in patients with acute myocardial infarction. Circulation. 1987; 76:610-7. [IDIS 252227] [PubMed 3304706]

126. Goldman L, Sia STB, Cook EF et al. Costs and effectiveness of routine therapy with long-term beta-adrenergic antagonists after acute myocardial infarction. N Engl J Med. 1988; 319:152-7. [IDIS 243813] [PubMed 2898733]

127. Yusuf S, Peto R, Lewis J et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985; 27:335-71. [PubMed 2858114]

128. Yusuf S, Sleight P, Held P et al. Routine medical management of acute myocardial infarction: lessons from overviews of recent randomized controlled trials. Circulation. 1990; 82:(Suppl II)II:117-34.

129. Held P, Yusuf S. Early intravenous beta-blockade in acute myocardial infarction. Cardiology. 1989; 76:132-43. [PubMed 2568179]

130. Pedersen TR for the Norwegian Multicenter Study Group. Six-year follow-up of the Norwegian multicenter study on timolol after acute myocardial infarction. N Engl J Med. 1985; 313:1055-8. [IDIS 206156] [PubMed 2864634]

131. Pedersen TR for the Norwegian Multicenter Study Group. The Norwegian multicenter study of timolol after myocardial infarction. Circulation. 1983; 67:(Suppl I)49-53.

132. The Beta-Blocker Pooling Project Research Group. The Beta-Blocker Pooling Project (BBPP): subgroup findings from randomized trials in post infarction patients. Eur Heart J. 1988; 9:8-16.

133. β-Blocker Heart Attack Trial Research Group. A randomized trial of propranolol in patients with acute myocardial infarction. 1. Mortality results. JAMA. 1982; 247:1707-14. [PubMed 7038157]

134. The Norwegian Multicenter Study Group. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med. 1981; 304:801-7. [IDIS 128981] [PubMed 7010157]

135. Gheorghiade M, Schultz L, Tilley B et al. Effects of propranolol in non-Q-wave acute myocardial infarction in the beta blocker heart attack trial. Am J Cardiol. 1990; 66:129-33. [IDIS 269724] [PubMed 2196771]

136. The MIAMI Trial Research Group. Mortality. Am J Cardiol. 1985; 56:15-22G.

137. The TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial. N Engl J Med. 1989; 320:618-27. [IDIS 251664] [PubMed 2563896]

138. Herlitz J, Waldenstrom J, Hjalmrson A. Infarct size limitation after early intervention with metoprolol in the MIAMI trial. Cardiology. 1988; 75:117-22. [PubMed 3370654]

139. Rehnqvist N, Olsson G, Erhardt L et al. Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event. Int J Cardiol. 1987; 15:301-8. [PubMed 3298080]

140. Snyder S. Metoprolol-induced polymyalgia-like syndrome. Ann Intern Med. 1991; 114:96-7. [IDIS 275442] [PubMed 1983947]

141. Yusuf S, Wittes J, Probstfield J. Evaluating effects of treatment in subgroups of patients within a clinical trial: the case of non-Q-wave myocardial infarction and beta blockers. Am J Cardiol. 1990; 66:220-22. [IDIS 269732] [PubMed 1973589]

142. Griggs TR, Wagner GS, Gettes LS. Beta-adrenergic blocking agents after myocardial infarction: an undocumented need in patients at lowest risk. J Am Coll Cardiol. 1983; 1:1530-3. [PubMed 6133891]

143. Pedersen TR for the Norwegian Multicenter Study Group. Six-year follow-up of the Norwegian multicenter study on timolol after myocardial infarction. N Engl J Med. 1986; 314:1052.

144. Frishman WH, Furberg CD, Friedewald WT. β-Adrenergic blockade for survivors of acute myocardial infarction. N Engl J Med. 1984; 310:830-7. [IDIS 182809] [PubMed 6142420]

145. Roberts R, Rogers WJ, Mueller H et al. Immediate versus deferred β-blockade following thrombolytic therapy in patients with acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) II-B study. Circulation. 1991; 83:422-37. [IDIS 278007] [PubMed 1671346]

146. Reviewers’ comments (personal observations).

147. Astra. Toprol XL (metoprolol succinate) extended-release tablets prescribing information. Wilmington, DE; 2001 Oct.

148. Sandberg A, Blomquist I, Jonsson UE et al. Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: a comparison with conventional tablets. Eur J Clin Pharmacol. 1988; 33(Suppl):S9-14.

149. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. [IDIS 309043] [PubMed 8422206]

150. Weber MA, Laragh JH. Hypertension: steps forward and steps backward: the Joint National Committee fifth report. Arch Intern Med. 1993; 153:149-52. [PubMed 8422205]

151. Collins R, Peto R, MacMahon S et al. Blood pressure, stroke, and coronary heart disease. Part 2, short-term reductions in blood pressure: an overview of randomized drug trials in their epidemiological context. Lancet. 1990; 335:827-38. [IDIS 264836] [PubMed 1969567]

152. Alderman MH. Which antihypertensive drugs first—and why! JAMA. 1992; 267:2786-7. Editorial.

153. MacMahon S, Peto R, Cutler J et al. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990; 335:765-74. [PubMed 1969518]

154. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991; 265:3255-64. [IDIS 282107] [PubMed 2046107]

155. Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-hypertension). Lancet. 1991; 338:1281-5. [IDIS 289158] [PubMed 1682683]

156. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992; 304:405-12. [IDIS 292411] [PubMed 1445513]

157. Psaty BM, Smith NL, Siscovich DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45. [IDIS 380501] [PubMed 9042847]

158. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Managment of Acute Myocardial Infarction). From ACC website.

159. Novartis. Lopressor HCT (metoprolol tartrate and hydrochlorothiazide) tablets prescribing information. East Hanover, NJ; 1999 Nov

160. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

161. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]

162. Whelton PK, Appel LJ, Espeland MA et al. for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998; 279:839-46. [PubMed 9515998]

163. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: apporaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9A-38A.

164. Packer M, Colucci WS, Sackner-Bernstein JD et al, for the PRECISE Study Group. Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure: the PRECISE trial. Circulation. 1996; 94:2793-9.

165. Fisher ML, Gottlieb SS, Plotnick GD et al. Beneficial effects of metoprolol in heart failure associated with coronary artery disease: a randomized trial. J Am Coll Cardiol. 1994; 23:943-50. [IDIS 326479] [PubMed 8106700]

166. Bristow MR, Gilbert EM, Abraham WT et al et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996; 94:2807-16. [IDIS 377689] [PubMed 8941106]

167. Metra M, Nardi M, Raffaele G et al. Effects of short- and long-term carvedilol administration on rest and exercise hemodynamic variables, exercise capacity and clinical conditions in paatients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1994; 24:1678-87. [IDIS 339059] [PubMed 7963115]

168. Olsen SL, Gilbert EM, Renlund DG et al. Carvedilol improves left ventricular function and symptoms in chronic heart failure: a double-blind randomized study. J Am Coll Cardiol. 1995; 25:1225-31. [IDIS 347002] [PubMed 7722114]

169. Krum H, Sackner-Bernstein JD, Goldsmith RL et al. Double-blind placebo controlled study of the long-term efficacy of carvedilol in patients with severe chronic heart failure. Circulation. 1995; 92:1499-506. [IDIS 353924] [PubMed 7664433]

170. Waagstein F, Bristow MR, Swedberg K et al. Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Lancet. 1993; 342:1441-6. [IDIS 322759] [PubMed 7902479]

171. CIBIS Investigators and Committees. A randomized trial of β-blockade in heart failure: the cardiac insufficiency bisoprolol study (CIBIS). Circulation. 1994; 90:1765-73. [IDIS 336973] [PubMed 7923660]

172. 6. Colucci WS, Packer M, Bristow MR et al, for the US Carvedilol Heart Failure Study Group. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. Circulation. 1996; 94:2800-6.

173. The International Steering Committee on behalf of the MERIT-HF study group. Rationale, design, and organization of the metoprolol CR/XL randomized intervention trial in heart failure (MERIT-HF). Am J Cardiol. 1997; 80(Suppl 9B):J54-8.

174. Bristow MR, Gilbert EM, Abraham WT et al. Effect of carvedilol on LV function and mortality in diabetic versus non-diabetic patients with ischemic or nonischemic dilated cardimyopathy. Circulation. 1996; 94(Suppl I):I664.

175. Lechat P, Packer M, Chalon S et al. Clinical effects of β-adrenergic blockade in chronic heart failure: a meta-analysis of double-blind, placebo-controlled, randomized trials. Circulation. 1998; 98:1184-91. [IDIS 414954] [PubMed 9743509]

176. Van Campen LC, Visser FC, Visser CA. Ejection fraction improvement by beta-blocker treatment in patients with heart failure: an analysis of studies published in the literature. J Cardiovasc Pharmacol. 1998; 32(Suppl 1):S31-5. [IDIS 413510] [PubMed 9731693]

177. SmithKline Beecham Pharmaceuticals. Coreg (carvedilol) tablets prescribing information. Philadelphia, PA; 1998 May.

178. Rousseau MF, Chapelle F, Van Eyll C et al. Medium-term effects of beta-blockade on left ventricular mechanics: a double-blind, placebo-controlled comparison of nebivolol and atenolol in patients with ischemic left ventricular dysfunction. J Card Fail. 1996; 2:15-23. [PubMed 8798100]

179. Mattioli AV, Modena MG, Fantini G et al. Atenolol in dilated cardiomyopathy: a clinical instrumental study. Cardiovasc Drugs Ther. 1990; 4:505-7. [PubMed 2285633]

180. American Diabetes Association. Clinical Practice Recommendations 2001. Position Statement. Diabetic nephropathy. Diabetes Care. 2001; 24(Suppl 1):S69-72.

181. Genuth S. United Kingdom prospective diabetes study results are in. J Fam Pract. 1998; 47:(Suppl 5):S27.

182. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2001; 24(Suppl 1):S33-43.

183. Watkins PJ. UKPDS: a message of hope and a need for change. Diabet Med. 1998; 15:895-6. [PubMed 9827842]

184. Bretzel RG, Voit K, Schatz H et al. The United Kingdom Prospective Diabetes Study (UKPDS): implications for the pharmacotherapy of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1998; 106:369-72. [PubMed 9831300]

185. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317:703-13. [IDIS 412064] [PubMed 9732337]

186. American Diabetes Association. The United Kingdom Prospective Diabetes Study (UKPDS) for type 2 diabetes: what you need to know about the results of a long-term study. Washington, DC; 1998 Sep 15 from American Diabetes Association web site.

187. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317:713-20. [IDIS 412065] [PubMed 9732338]

188. Davis TM. United Kingdom Prospective Diabetes Study: the end of the beginning? Med J Aust. 1998; 169:511-2.

189. American Diabetes Association. Clinical Practice Recommendations 1999. Position statement. Implications of the United Kingdom propective Diabetes Study. Diabetes Care. 1999; 22(Suppl 1):S27-31.

190. Lim PO, MacDonald TM. Antianginal and β-adrenergic blocking drugs. In: Dukes MNG, ed. Meyler’s side effects of drugs. 13th ed. New York: Elsevier/North Holland Inc; 1996:488-535.

191. Gress TW, Nieto FJ, Shahar E et al. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med. 2000; 342:905-12. [IDIS 442916] [PubMed 10738048]

192. Sowers JR, Bakris GL. Antihypertensive therapy and the risk of type 2 diabetes mellitus. N Engl J Med. 2000; 342:969-70. [IDIS 442921] [PubMed 10738057]

193. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

194. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

195. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [IDIS 452007] [PubMed 10977801]

196. Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998; 351:1755-62. [IDIS 409003] [PubMed 9635947]

197. American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Part 6: advanced cardiovascular life support. Circulation. 2000;102(Suppl I):I86-171.

198. Andersson B, Aberg J. The effect of heart rate of immediate and slow-release metoprolol in patients with chronic heart failure. J Am Coll Cardiol. 1999; 33(Suppl.A):183A-4A.

199. Hjalmarson A, Goldstein S, Fagerberg B et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). JAMA. 2000; 283:1295-1302. [IDIS 441604] [PubMed 10714728]

200. Walley T, Piromohamed M, Proudlove C et al. Interaction of metoprolol and fluoxetine. Lancet. 1993; 341:967-8. [IDIS 313006] [PubMed 8096308]

201. Hemeryck A, Lefebvre RA, De Vriendt C et al. Paroxetine affects metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers. Clin Pharmacol Ther. 2000; 67:283-91. [IDIS 445309] [PubMed 10741632]

202. Merck & Co. Blocadren (timolol maleate) tablets prescribing information (dated 1997 Nov). In: Physicians’ desk reference. 55nd ed. Montvale, NJ: Medical Economics Company Inc; 2001:1886-8.

203. Fuster V, Ryden LE, Asinger RW et al. ACC/AHA/ESC guidelines for the management of atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients with Atrial Fibrillation). J Am Coll Cardiol. 2001; 38:1266i-lxx.

204. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25:S71-S73.

205. Hunt SA, Baker DW, Chin MH et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). 2001. From ACC website. Accessed July 25, 2002.

206. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl 1):S33-43.

207. American Diabetes Association. Clinical practice recommendations 2002. Position statement. Diabetic nephropathy. Diabetes Care. 2002; 25(Suppl 1):S85-89.

208. Pfizer Roerig. Zoloft (sertraline hydrochloride) tablets prescribing information. New York, NY; 2002 May.

209. Reviewers’ comments (personal observations) on clomipramine hydrochloride 28:16.04.

210. Ozdemir V, Naranjo CA, Shulman RW et al. Determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition by paroxetine and fluvoxamine in vivo. J Clin Psychopharmacol. 1998; 18:198-207. [IDIS 407017] [PubMed 9617978]

211. Belpaire FM, Wijnant P, Temmerman A et al. The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors. Eur J Clin Pharmacol. 1998; 54:261-4. [PubMed 9681670]

212. SmithKline Beecham Pharmaceuticals, Philadelphia, PA: Personal communication on paroxetine 28:16.04.

213. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Chronic Stable Angina). J Am Coll Cardiol. 1999; 33:2092-7.

214. Messerli FH, Grossman E, Goldbourt U. Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review. JAMA 1998;279:1903-7.

215. Califf RM, O’Connor CM. β-Blocker therapy for heart failure. The evidence is in, now the work begins. JAMA. 2000; 283:1335-6. [IDIS 441609] [PubMed 10714735]

216. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999; 353:2001-7. [PubMed 10376614]

217. Novartis. Diovan (valsartan) capsules prescribing information. East Hanover, NJ; 2002.

218. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). 2002. From ACC website. Accessed November 7, 2002.

219. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non&#x0096;ST-segment elevation myocardial infarction: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2002; 40:1366-74. [IDIS 488261] [PubMed 12383588]

220. White H. Unmet therapeutic needs in the management of acute ischemia. Am J Cardiol. 1997; 80(Suppl 4A):2b-10b. [IDIS 392824] [PubMed 9291240]

221. Alexander JH, Harrington RA. Recent antiplatelet drug trials in the acute coronary syndromes. Clinical interpretation of PRISM, PRISM-PLUS, PARAGON A, and PURSUIT. Drugs. 1998; 56:965-76. [PubMed 9878986]

222. Théroux P. Antiplatelet therapy: do the new platelet inhibitors add significantly to the clinical benefits of aspirin? Am Heart J. 1997; 134:S62-70.

223. Catella-Lawson F, Fitzgerald GA. Confusion in reperfusion: problems in the clinical development of antithrombotic drugs. Circulation. 1997; 95: 793-5.

224. Popma JJ, Weitz J, Bittl JA. Antithrombotic therapy in patients undergoing coronary angioplasty. Chest. 1998; 114:728s-41s. [IDIS 416752] [PubMed 9822074]

225. Antman EM, Fox KM et al. Guidelines for the diagnosis and management of unstable angina and non-Q-wave myocardial infarction: proposed revisions. Am Heart J. 2000; 139:461-75. [IDIS 444999] [PubMed 10689261]

226. Cairns JA, Theroux P, Lewis D et al. Antithrombotic agents in coronary artery disease. Chest. 1998; 114(Suppl 5):611S-33S. [IDIS 416745] [PubMed 9822067]

227. Kaul S, Shah PK. Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin? J Am Coll Cardiol. 2000; 35:1699-702.

228. Williams CL, Hayman LL, Daniels SR et al. Cardiovascular health in childhood: a statement for health professional from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2002; 106:143-60. [PubMed 12093785]

229. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-229. [IDIS 490723] [PubMed 12479770]

230. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-riskhypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

231. US Headache Consortium. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. St. Paul, Minnesota; December 10, 2001. From the American Academy of Neurology website.

232. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (Also published in JAMA. 2003; 289.

233. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41.

234. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.

235. The Guidelines Subcommitee of the WHO/ISH Mild Hypertension Liaison Committee. 1999 guidelines for the management of hypertension. J Hypertension. 1999; 17:392-403.

236. Kaplan NM. Initial treatment of adult patients with essential hypertension. Part 2: alternating monotherapy is the preferred treatment. Pharmacotherapy. 1985; 5:195-200. [IDIS 394161] [PubMed 4034407]

237. Bauer JH. Stepped-care approach to the treatment of hypertension: is it obsolete? (unpublished observations)

238. Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs. Lancet. 2000;356:1955-64.

239. Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4:393-404.

240. Black HR, Elliott WJ, Neaton JD et al. Baseline characteristics and elderly blood pressure control in the CONVINCE trial. Hypertension. 2001; 37:12-18. [PubMed 11208750]

241. Black HR, Elliott WJ, Grandits G, et al. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003;289:2073-2082.

242. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE). Lancet. 2002;359:995-1003.

243. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145-153.

244. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033-41.

245. Wing LMH, Reid CM, Ryan P, et al, for Second Australian National Blood Pressure Study Group. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348:583-92.

246. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651-58.

247. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293-302.

248. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993; 342:821-8. [IDIS 320478] [PubMed 8104270]

249. Kober L, Torp-Pedersen C, Carlsen JE, et al, for Trandolapril Cardiac Evaluation (TRACE) Study Group. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1995;333:1670-6.

250. Hager WD, Davis BR, Riba A, et al, for the Survival and Ventricular Enlargement (SAVE) Investigators. Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: the SAVE Study Experience. Am Heart J. 1998;135:406-13.

251. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309-1321.

252. Tepper D. Frontiers in congestive heart failure: effect of metoprolol CR/XL in chronic heart failure: MetoprololCR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Congest Heart Fail. 1999;5:184-5.

253. The Capricorn Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the Capricorn randomized trial. Lancet. 2001; 357:1385-90. [IDIS 465816] [PubMed 11356434]

254. Pfeffer MA, Braunwald E, Moye LA et al for the SAVE Investigators Group. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargment Trial. N Engl J Med. 1992; 327:669. [IDIS 301129] [PubMed 1386652]

255. Cohn JN, Tognoni GA. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001; 345:1667-75. [IDIS 473009] [PubMed 11759645]

256. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999; 341:709-17. [IDIS 431313] [PubMed 10471456]

257. Reviewers’ comments (personal observations) on the Thiazides General Statement 40:28.

258. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.

259. Carter B for the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Personal communication.

260. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76. [PubMed 15286277]

261. Gormley GJ. Dear pharmacist letter: important alert regarding medication errors: Toprol-XL and Topamax; Toprol-XL and Tegretol and Tegretol-XR. Wilmington, DE: AstraZeneca; 2005 Sep. From FDA website.

262. Spivey JM, Hulihan J. Dear pharmacist letter: alert: Topamax (topiramate) and Toprol-XL (metoprolol succinate) dispensing errors. Titusville, NJ: Ortho-McNeil Neurologics Inc; 2005 Sep. From FDA website.

263. Gormley GJ. Dear healthcare professional letter: important alert regarding medication errors: Toprol-XL and Topamax; Toprol-XL and Tegretol and Tegretol-XR. Wilmington, DE: AstraZeneca: 2005 Sep. From FDA website.

264. Hulihan J. Dear healthcare professional letter: alert: Topamax (topiramate) and Toprol-XL (metoprolol succinate) dispensing errors. Titusville, NJ: Ortho-McNeil Neurologics Inc; 2005 Sep. From FDA website.

281. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211.

a. AHFS Drug Information 2003. McEvoy GK, ed. Metoprolol. Bethesda, MD: American Society of Health-System Pharmacists; 2003:1762-70.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc; 2013:784-5.

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