Lopressor

1-10%

Dizziness (10%)

Headache (10%)

Tiredness (10%)

Depression (5%)

Diarrhea (5%)

Pruritus (5%)

Bradycardia (9%)

Rash (5%)

Dyspnea (1-3%)

Cold extremities (1%)

Constipation (1%)

Dyspepsia (1%)

Heart failure (1%)

Hypotension (1%)

Nausea (1%)

Flatulence (1%)

Heartburn (1%)

Xerostomia (1%)

Wheezing (1%)

Bronchospasm (1%)

Frequency Not Defined

Decreased exercise tolerance

Raynaud phenomenon

Increased triglyceride levels and insulin resistance, decreased high-density lipoprotein (HDL) levels

Postmarketing reports

Anxiety/nervousness

Hallusinations

Paresthesia

Hepatitis

Vomiting

Arthralgia

Male impotence

Reversible alopecia

Agranulocytosis

Dry eyes

Worsening of psoriasis

Pyronie’s disease

Sweating

Photosensitivity

Taste disturbance

• Metoprolol should be taken before meals or at bedtime.
• The dose for treating hypertension is 100-450 mg daily in single or divided doses.
• Angina is treated with 100-400 mg daily in two divided doses.
• Heart attack (acute myocardial infarction) is treated with three 5 mg injections administered 2 minutes apart followed by treatment with 50 mg oral metoprolol every 6 hours for 48 hours. After 48 hours, patients should receive 100 mg orally twice daily for at least 3 months.
• The dose for congestive heart failure is 25 mg/daily initially. Then the dose is increased every 2 weeks to reach a target dose of 200 mg/daily orally.
• Hyperthyroidism is treated with 25 to 30 mg by mouth every 6 hours.

• Tablets: 25, 50, and 100 mg.
• Tablets (extended release): 25, 50, 100, and 200 mg.
• Injection: 1 mg/ml

• Tablets should be stored between 15 C and 30 C (59 F and 86 F).
• They should be protected from moisture and dispensed in tight, light-resistant containers.

• Metoprolol blocks the action of the sympathetic nervous system, a portion of the involuntary nervous system, by blocking beta receptors on sympathetic nerves. Since the sympathetic nervous system is responsible for increasing the rate with which the heart beats, by blocking the action of these nerves metoprolol reduces the heart rate and is useful in treating abnormally rapid heart rhythms.
• Metoprolol also reduces the force of contraction of heart muscle and thereby lowers blood pressure. By reducing the heart rate and the force of muscle contraction, metoprolol reduces the need for oxygen by heart muscle. Since heart pain (angina pectoris) occurs when oxygen demand of the heart muscle exceeds the supply of oxygen, metoprolol, by reducing the demand for oxygen, is helpful in treating heart pain.

• The FDA approved metoprolol in August 1978.

Lopressor is part of the drug class:

• Beta blocking agents, selective

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• reserpine (Serpalan, Serpasil)
• monoamine oxidase inhibitors such as phenelzine (Nardil), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), and rasagiline (Azilect)
• medications that block the enzyme CYP2D6 such as paroxetine (Paxil), quinidine, and fluoxetine (Sarafem, Prozac)
• digoxin (Lanoxin)
• clonidine (Catapres)
• calcium channel blockers such as nifedipine (Adalat, Nifedical, Procardia), amlodipine (Norvasc), verapamil (Calan, Isoptin, Covera, Verelan), and diltiazem (Cardizem)

This is not a complete list of Lopressor drug interactions. Ask your doctor or pharmacist for more information.

• Store Lopressor at room temperature between 15 and 30°C (59- 86°F).
• Protect from moisture and heat.
• Keep it in the original container.
• Keep this and all medications out of the reach of children.

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and to check for unwanted effects.

Metoprolol may worsen the symptoms of heart failure in some patients. Check with your doctor right away if you are having chest pain or discomfort, dilated neck veins, extreme fatigue, irregular breathing, an irregular heartbeat, shortness of breath, swelling of the face, fingers, feet, or lower legs, weight gain, or wheezing.

Do not suddenly stop taking this medicine without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely. Some conditions may become worse when the medicine is stopped suddenly, which can be dangerous.

This medicine may cause changes in blood sugar levels. Also, this medicine may cover up the symptoms of low blood sugar, such as a rapid pulse rate. Check with your doctor if you notice a change in your normal symptoms or a change in the results of your blood or urine sugar tests.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery.

This medicine may cause some people to become less alert than they are normally. If this side effect occurs, do not drive, use machines, or do anything else that could be dangerous if you are not alert.

Dizziness, lightheadedness, or even fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem. Also, lying down for a while may relieve the dizziness or lightheadedness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, since they may increase your blood pressure.

Mechanism of Action:

Lopressor is a beta1-selective (cardioselective) adrenergic receptor blocker. This preferential effect is not absolute, however, and at higher plasma concentrations, Lopressor also inhibits beta2-adrenoreceptors, chiefly located in the bronchial and vascular musculature.

Clinical pharmacology studies have demonstrated the beta-blocking activity of metoprolol, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia.

Hypertension

The mechanism of the antihypertensive effects of beta-blocking agents has not been fully elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity.

Angina Pectoris

By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, Lopressor reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris.

Myocardial Infarction

The precise mechanism of action of Lopressor in patients with suspected or definite myocardial infarction is not known.

Pharmacodynamics

Relative beta1 selectivity is demonstrated by the following: (1) In healthy subjects, Lopressor is unable to reverse the beta2-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective (beta1 plus beta2) beta blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, Lopressor reduces FEV1 and FVC significantly less than a nonselective beta blocker, propranolol, at equivalent beta1-receptor blocking doses.

Lopressor has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at doses much greater than required for beta blockade. Animal and human experiments indicate that Lopressor slows the sinus rate and decreases AV nodal conduction.

Significant beta-blocking effect (as measured by reduction of exercise heart rate) occurs within 1 hour after oral administration, and its duration is dose-related. For example, a 50% reduction of the maximum effect after single oral doses of 20, 50, and 100 mg occurred at 3.3, 5.0, and 6.4 hours, respectively, in normal subjects. After repeated oral dosages of 100 mg twice daily, a significant reduction in exercise systolic blood pressure was evident at 12 hours. When the drug was infused over a 10-minute period, in normal volunteers, maximum beta blockade was achieved at approximately 20 minutes. Equivalent maximal beta-blocking effect is achieved with oral and intravenous doses in the ratio of approximately 2.5:1.

There is a linear relationship between the log of plasma levels and reduction of exercise heart rate. However, antihypertensive activity does not appear to be related to plasma levels. Because of variable plasma levels attained with a given dose and lack of a consistent relationship of antihypertensive activity to dose, selection of proper dosage requires individual titration.

In several studies of patients with acute myocardial infarction, intravenous followed by oral administration of Lopressor caused a reduction in heart rate, systolic blood pressure and cardiac output. Stroke volume, diastolic blood pressure and pulmonary artery end diastolic pressure remained unchanged.

In patients with angina pectoris, plasma concentration measured at 1 hour is linearly related to the oral dose within the range of 50-400 mg. Exercise heart rate and systolic blood pressure are reduced in relation to the logarithm of the oral dose of metoprolol. The increase in exercise capacity and the reduction in left ventricular ischemia are also significantly related to the logarithm of the oral dose.

Pharmacokinetics

Absorption: The estimated oral bioavailability of immediate release metoprolol is about 50% because of pre-systemic metabolism which is saturable leading to non-proportionate increase in the exposure with increased dose.

Distribution: Metoprolol is extensively distributed with a reported volume of distribution of 3.2 to 5.6 L/kg. About 10% of metoprolol in plasma is bound to serum albumin. Metoprolol is known to cross the placenta and is found in breast milk. Metoprolol is also known to cross the blood brain barrier following oral administration and CSF concentrations close to that observed in plasma have been reported. Metoprolol is not a significant P-glycoprotein substrate

Metabolism: Lopressor is primarily metabolized by CYP2D6. Metoprolol is a racemic mixture of R- and S- enantiomers, and when administered orally, it exhibits stereoselective metabolism that is dependent on oxidation phenotype. CYP2D6 is absent (poor metabolizers) in about 8% of Caucasians and about 2% of most other populations. Poor CYP2D6 metabolizers exhibit several-fold higher plasma concentrations of Lopressor than extensive metabolizers with normal CYP2D6 activity thereby decreasing Lopressor’s cardioselectivity.

Elimination: Elimination of Lopressor is mainly by biotransformation in the liver. The mean elimination half-life of metoprolol is 3 to 4 hours; in poor CYP2D6 metabolizers the half-life may be 7 to 9 hours. Approximately 95% of the dose can be recovered in urine. In most subjects (extensive metabolizers), less than 5% of an oral dose and less than 10% of an intravenous dose are excreted as unchanged drug in the urine. In poor metabolizers, up to 30% or 40% of oral or intravenous doses, respectively, may be excreted unchanged; the rest is excreted by the kidneys as metabolites that appear to have no beta blocking activity. The renal clearance of the stereo-isomers does not exhibit stereo-selectivity in renal excretion.

Special populations

Geriatric patients: The geriatric population may show slightly higher plasma concentrations of metoprolol as a combined result of a decreased metabolism of the drug in elderly population and a decreased hepatic blood flow. However, this increase is not clinically significant or therapeutically relevant.

Renal impairment: The systemic availability and half-life of Lopressor in patients with renal failure do not differ to a clinically significant degree from those in normal subjects.

Hepatic Impairment: Since the drug is primarily eliminated by hepatic metabolism, hepatic impairment may impact the pharmacokinetics of metoprolol. The elimination half-life of metoprolol is considerably prolonged, depending on severity (up to 7.2 h).

Clinical Studies:

Hypertension

In controlled clinical studies, Lopressor has been shown to be an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics, at dosages of 100-450 mg daily. In controlled, comparative, clinical studies, Lopressor has been shown to be as effective an antihypertensive agent as propranolol, methyldopa, and thiazide-type diuretics, to be equally effective in supine and standing positions.

Angina Pectoris

In controlled clinical trials, Lopressor, administered two or four times daily, has been shown to be an effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance. The dosage used in these studies ranged from 100-400 mg daily. A controlled, comparative, clinical trial showed that Lopressor was indistinguishable from propranolol in the treatment of angina pectoris.

Myocardial Infarction

In a large (1,395 patients randomized), double-blind, placebo-controlled clinical study, Lopressor was shown to reduce 3-month mortality by 36% in patients with suspected or definite myocardial infarction.

Patients were randomized and treated as soon as possible after their arrival in the hospital, once their clinical condition had stabilized and their hemodynamic status had been carefully evaluated. Subjects were ineligible if they had hypotension, bradycardia, peripheral signs of shock, and/or more than minimal basal rales as signs of congestive heart failure. Initial treatment consisted of intravenous followed by oral administration of Lopressor or placebo, given in a coronary care or comparable unit. Oral maintenance therapy with Lopressor or placebo was then continued for 3 months. After this double-blind period, all patients were given Lopressor and followed up to 1 year.

The median delay from the onset of symptoms to the initiation of therapy was 8 hours in both the Lopressor- and placebo-treatment groups. Among patients treated with Lopressor, there were comparable reductions in 3-month mortality for those treated early (≤8 hours) and those in whom treatment was started later. Significant reductions in the incidence of ventricular fibrillation and in chest pain following initial intravenous therapy were also observed with Lopressor and were independent of the interval between onset of symptoms and initiation of therapy.

In this study, patients treated with metoprolol received the drug both very early (intra-venously) and during a subsequent 3-month period, while placebo patients received no beta-blocker treatment for this period. The study thus was able to show a benefit from the overall metoprolol regimen but cannot separate the benefit of very early intravenous treatment from the benefit of later beta-blocker therapy. Nonetheless, because the overall regimen showed a clear beneficial effect on survival without evidence of an early adverse effect on survival, one acceptable dosage regimen is the precise regimen used in the trial. Because the specific benefit of very early treatment remains to be defined however, it is also reasonable to administer the drug orally to patients at a later time as is recommended for certain other beta blockers.

Hypertension

Individualize the dosage of Lopressor tablets. Lopressor tablets should be taken with or immediately following meals.

The usual initial dosage of Lopressor tablets is 100 mg daily in single or divided doses, whether used alone or added to a diuretic. Increase the dosage at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. The effective dosage range of Lopressor tablets is 100-450 mg per day. Dosages above 450 mg per day have not been studied. While once-daily dosing is effective and can maintain a reduction in blood pressure throughout the day, lower doses (especially 100 mg) may not maintain a full effect at the end of the 24-hour period, and larger or more frequent daily doses may be required. This can be evaluated by measuring blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. Beta1 selectivity diminishes as the dose of Lopressor is increased.

Angina Pectoris

The dosage of Lopressor tablets should be individualized. Lopressor tablets should be taken with or immediately following meals.

The usual initial dosage of Lopressor tablets is 100 mg daily, given in two divided doses. gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is pronounced slowing of the heart rate. The effective dosage range of Lopressor tablets is 100-400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, gradually decrease the dosage over a period of 1-2 weeks (see WARNINGS).

Myocardial Infarction

Early Treatment: During the early phase of definite or suspected acute myocardial infarction, initiate treatment with Lopressor as soon as possible after the patient’s arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized.

Begin treatment in this early phase with the intravenous administration of three bolus injections of 5 mg of Lopressor each; give the injections at approximately 2-minute intervals. During the intravenous administration of Lopressor, monitor blood pressure, heart rate, and electrocardiogram.

In patients who tolerate the full intravenous dose (15 mg), initiate Lopressor tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose and continue for 48 hours. Thereafter, the maintenance dosage is 100 mg twice daily (see Late Treatment below).

Start patients who appear not to tolerate the full intravenous dose on Lopressor tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows. In patients with severe intolerance, discontinue Lopressor (see WARNINGS).

Late Treatment:

Start patients with contraindications to treatment during the early phase of suspected or definite myocardial infarction, patients who appear not to tolerate the full early treatment, and patients in whom the physician wishes to delay therapy for any other reason on Lopressor tablets, 100 mg twice daily, as soon as their clinical condition allows. Continue therapy for at least 3 months. Although the efficacy of Lopressor beyond 3 months has not been conclusively established, data from studies with other beta blockers suggest that treatment should be continued for 1-3 years.

Special populations

Pediatric patients: No pediatric studies have been performed. The safety and efficacy of Lopressor in pediatric patients have not been established.

Renal impairment: No dose adjustment of Lopressor is required in patients with renal impairment.

Hepatic impairment: Lopressor blood levels are likely to increase substantially in patients with hepatic impairment. Therefore, Lopressor should be initiated at low doses with cautious gradual dose titration according to clinical response.

Geriatric patients (>65 years): 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.

Method of administration:

For oral treatment, the tablets should be swallowed un-chewed with a glass of water. Lopressor should always be taken in standardized relation with meals. If the physician asks the patient to take Lopressor either before breakfast or with breakfast, then the patient should continue taking Lopressor with the same schedule during the course of therapy.

An infant consuming 1 L of breast milk a day would receive a dose of less than 1 mg of drug.

AU and UK: Use is not recommended unless benefit outweighs risk. US: This drug has been used without apparent harmful effects; caution is recommended. Excreted into human milk: Yes (in small amounts) Comments: This drug has been used without apparent harmful effects in the nursing infant.

Summary of Use during Lactation

Because of the low levels of metoprolol in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. Studies on the use of metoprolol during breastfeeding have found no adverse reactions in breastfed infants. No special precautions are required.

Drug Levels

The excretion of beta-adrenergic blocking drugs into breastmilk is largely determined by their protein binding. Those with low binding are more extensively excreted into breastmilk.[1] Accumulation of the drugs in the infant is related to the fraction excreted in urine. With 10% protein binding, 40% renal excretion and a moderate half-life, metoprolol presents moderately low risk for accumulation in infants.

Maternal Levels. With metoprolol doses of 50 mg orally twice daily, milk levels are usually less than 420 mcg/L.[2][3][4] Five women taking oral metoprolol 100 to 200 mg daily had average milk metoprolol levels of 316 mcg/L.[5] It is estimated that a breastfed infant would receive a dose of about 0.07 mg/kg daily in breastmilk with a maternal dose of 200 mg daily.[4]

Peak milk levels of 106 to 689 mcg/L have been reported following doses of 100 mg orally twice daily.[4][6] Peak milk levels occurred about 30 minutes after peak serum levels, at 1.5 hours after the dose in two patients, and 6 hours after the dose in a third.[6]

Two women who were taking metoprolol (dosage not specified). Milk samples were obtained over one dosage interval. The dosage of metoprolol and alpha-hydroxymetoprolol in breastmilk was less than 2% of the mother's weight-adjusted dose.[7]

Three mothers who took metoprolol in unspecified dosages during breastfeeding had breastmilk samples collected every 2 to 3 hours over one dosage interval. The average amount of metoprolol excreted in breast milk was 71.5 mcg/day (range 17.0 to 158.7). The average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. Renal clearance of metoprolol was increased during lactation at 3 to 4 months postpartum, possibly related to increased maternal prolactin.[8]

Infant Levels. Metoprolol was undetectable (<2.7 mcg/L) in the plasma of 3 infants aged 4, 10 and 60 days after maternal oral doses of 100 mg daily.[2]

Metoprolol serum levels in 3- to 5-day-old breastfed infants ranged from 0.5 to 2.9 mcg/L after maternal doses of 50 or 100 mg twice daily.[3][9]

A woman was taking metoprolol 100 mg daily for hypertension during pregnancy and postpartum. Her breastfed infant's serum concentrations of metoprolol and its active metabolite, alpha-hydroxymetoprolol, were undetectable on days 4 and 182 postpartum.[10]

Effects in Breastfed Infants

A study of mothers taking beta-blockers during nursing found a numerically, but not statistically significant increased number of adverse reactions in those taking any beta-blocker. Although the ages of infants were matched to control infants, the ages of the affected infants were not stated. Of 6 mothers taking metoprolol, none reported adverse effects in her breastfed infant.[11][12]

Effects on Lactation and Breastmilk

Relevant published information on the effects of beta-blockade or metoprolol during normal lactation was not found as of the revision date. A study in 6 patients with hyperprolactinemia and galactorrhea found no changes in serum prolactin levels following beta-adrenergic blockade with propranolol.[13]

Alternate Drugs to Consider

Propranolol, Labetalol

References

1. Riant P, Urien S, Albengres E et al. High plasma protein binding as a parameter in the selection of betablockers for lactating women. Biochem Pharmacol. 1986;35:4579-81. PMID: 2878668

2. Kulas J, Lunell NO, Rosing U et al. Atenolol and metoprolol. A comparison of their excretion into human breast milk. Acta Obstet Gynecol Scand Suppl. 1984;Suppl 118:65-9. PMID: 4043203

3. Lindeberg S, Sandstrom B, Lundborg P et al. Disposition of the adrenergic blocker metoprolol in the late-pregnant woman, the amniotic fluid, the cord blood and the neonate. Acta Obstet Gynecol Scand Suppl. 1984;Suppl 118:61-4. PMID: 6587729

4. Sandstrom B, Regardh CG. Metoprolol excretion into breast milk. Br J Clin Pharmacol. 1980;9:518-9. PMID: 7397065

5. Sandstrom B. Antihypertensive treatment with the adrenergic beta-receptor blocker metoprolol during pregnancy. Gynecol Invest. 1978;9:195-204. PMID: 750326

6. Liedholm H, Melander A, Bitzen PO et al. Accumulation of atenolol and metoprolol in human breast milk. Eur J Clin Pharmacol. 1981;20:229-31. PMID: 7286041

7. Yep T, Eyal S, Easterling TR et al. The pharmacokinetics of metoprolol during pregnancy. Pharmacotherapy. 2011;31:439e. Abstract. DOI: doi:10.1592/phco.31.10.311e

8. Ryu RJ, Eyal S, Easterling TR et al. Pharmacokinetics of metoprolol during pregnancy and lactation. J Clin Pharmacol. 2016;56:581-9. PMID: 26461463

9. Sandstrom B, Lindeberg S, Lundborg P et al. Disposition of the adrenergic blocker metoprolol in the late pregnant woman, the amniotic fluid, the cord blood and the neonate. Clin Exp Hypertens B. 1983;2:75-82. PMID: 6135523

10. Grundmann M, Kacirova I, Duricova J, Perinova I. Metoprolol and alfa-hydroxymetoprolol concentrations during lactation - a case report. Ther Drug Monit. 2011;33:504. Abstract. DOI: doi:10.1097/01.ftd.0000400651.94145.ba

11. Ho TK, Moretti ME, Schaeffer JK et al. Maternal beta-blocker usage and breast feeding in the neonate. Pediatr Res. 1999;45:67A. Abstract 385.

12. Schimmel MS, Eidelman AI, Wilschanski MA et al. Toxic effects of atenolol consumed during breast feeding. J Pediatr. 1989;114:476-8. PMID: 2921694

13. Board JA, Fierro RJ, Wasserman AJ et al. Effects of alpha- and beta-adrenergic blocking agents on serum prolactin levels in women with hyperprolactinemia and galactorrhea. Am J Obstet Gynecol. 1977;127:285-7. PMID: 556882

LactMed Record Number

296

Last Revision Date

20170411

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.