Metoprolol (Lopressor) is a cardioselective Beta-1 adrenergic blocker that is used in the treatment of patients with hypertension, stable (symptomatic with NYHA 1, II) heart failure and cardiac arrhythmias.

Metoprolol (Lopressor) Uses:

• Angina:

  • It is indicated for the long-term treatment of angina pectoris.

• Heart failure with reduced ejection fraction (HFrEF) (ER oral formulation):

  • It is indicated for the treatment of stable, symptomatic (NYHA class II or III) heart failure of hypertensive, ischemic, or cardiomyopathic origin to reduce the rate of mortality plus hospitalization in patients already receiving ACE inhibitors, diuretics, and/or digoxin.

• Hypertension:

  • To manage Hypertensive patient

Note: As first-line therapy Beta blockers are not supported.

• Myocardial infarction:

  • It is indicated fr the treatment of hemodynamically stable acute myocardial infarction (MI) to reduce cardiovascular mortality (injection to be used in combination with metoprolol oral maintenance therapy).

• Off Label Use of Metoprolol in Adults:

  • Atrial fibrillation and atrial flutter
  • To prevent Atrial fibrillation in post cardiac surgery patients.
  • Hypertrophic cardiomyopathy
  • Marfan syndrome with aortic aneurysm
  • Prophylactic treatment of migraine
  • Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, focal atrial tachycardia)
  • Thyrotoxicosis
  • Ventricular arrhythmias

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Metoprolol Dose in Adults:

Metoprolol (Lopressor) Dose in the treatment of Angina:

Note:

• For vasospastic angina, beta-blockers are not recommended; Preferably use calcium channel blockers and nitrates.
• For non-vasospastic angina, guidelines recommend beta-blockers titrating the dose to a resting heart rate of 55 to 60 bpm, while other experts recommend a target of 60 to 70 bpm.

• Immediate release (metoprolol tartrate):

  • Oral:
    • Initial: 50 mg two times per day;
    • The dose may be increased at weekly intervals to the desired effect;
    • The usual dosage range is 50 to 200 mg two times per day;
    • The maximum dose is 400 mg per day

• Extended-release (metoprolol succinate):

  • Oral:
    • Initial: 100 mg once a day;
    • The dose may be increased at weekly intervals to the desired effect;
    • The maximum dose is 400 mg/day

Note:

• For microvascular angina, some experts start with 50 mg/day (divided twice daily for the immediate-release formulation or once daily for the extended-release formulation) and increase to 100 to 200 mg/day as needed to control symptoms.

Metoprolol (Lopressor) Dose in the treatment of Atrial fibrillation and flutter (off-label):

• Acute ventricular rate control:

  • IV: 2.5 to 5 mg over two minutes;
  • The dose may be repeated every five minutes as needed to the maximum total dose of 15 mg.
  • Note:
    • Initiate cautiously in patients with concomitant heart failure.
    • Avoid in patients with decompensated heart failure;
    • electrical cardioversion preferred.

• Maintenance of ventricular rate control:

  • Immediate release (metoprolol tartrate):
    • Oral: 25 to 100 mg two times a day.
    • Note: More frequent dosing is appropriate in the acute setting while titrating to a maintenance dose.
  • Extended-release (metoprolol succinate):
    • 50 to 400 mg once a day oral intake

Metoprolol (Lopressor) Dose in the treatment of Atrial fibrillation prevention after cardiac surgery:

Note:

• Initiate prior to surgery (preferentially at least 48 hours before) or postoperatively when hemodynamically stable.
• Continue therapy at least until the first postoperative visit in patients with no other indication for beta-blocker therapy.

• Immediate release (metoprolol tartrate) :

  • Oral:
    • Initial: 25 to 50 mg two times a day;
    • Titrate the dose based on daily evaluation of hemodynamic response to the maximally tolerated dose;
    • The maximum dose is 200 mg/day.

• Extended-release (metoprolol succinate):

  • Oral:
    • Initial: 50 mg once a day;
    • titrate based on daily evaluation of hemodynamic response to the maximally tolerated dose;
    • The maximum dose is 200 mg/day.

Metoprolol (Lopressor) Dose in the treatment of Heart failure with reduced ejection fraction (HFrEF):

Note:

• Initiate treatment only in stable patients.
• In hospitalized patients, volume status should be optimized and intravenous diuretics, vasodilators, and inotropic agents successfully discontinued.
• Use caution when initiating in patients with NYHA class IV symptoms or recent HF exacerbation (particularly in those who required inotropes during their hospital course).

• Extended-release (metoprolol succinate):

  • Oral:
    • Initial: 12.5 to 25 mg once a day;
    • up-titrate gradually (eg, doubling the dose every 2 or more weeks) to the maximum tolerated dose while monitoring for signs and symptoms of heart failure;
    • The maximum dose is 200 mg/day.

Metoprolol (Lopressor) Dose as an alternative agent in the treatment of Hypertension:

Note: Not recommended in the absence of specific comorbidities such as ischemic heart disease, HFrEF, and arrhythmia.

• Immediate-release (metoprolol tartrate):

  • Oral:
    • Initial: 50 mg two times a day;
    • Titrate the dose at weekly (or longer) intervals as needed based on patient response to the maximum dose of 400 mg/day;
    • The usual dosage range is 100 to 200 mg/day in 2 divided doses.

• Extended-release (metoprolol succinate):

  • Oral:
    • Initial: 25 to 100 mg once a day;
    • Titrate at weekly (or longer) intervals as needed based on patient response to the maximum daily dose of 400 mg.
    • The usual dosage range is 50 to 200 mg once a day.

Metoprolol (Lopressor) Dose in the treatment of Migraine prophylaxis (off-label):

• Immediate release (metoprolol tartrate):

  • Oral:
    • Initial: 25 mg two times a day;
    • Titrate the dose slowly (eg, every 1 to 2 weeks) based on the patient's response and tolerability up to 200 mg/day in divided doses;
    • Maintain for at least 3 months before considering treatment failure.

Metoprolol (Lopressor) Dose in the treatment of Myocardial infarction, early treatment, and secondary prevention:

Note:

• An oral beta-blocker is recommended within the first 24 hours if there are no contraindications.
• Do not initiate treatment in patients with signs of heart failure, a low output state, increased risk of cardiogenic shock, or other contraindications for beta-blockade such as a second or third-degree heart block.
• Patients who did not receive a beta-blocker within the last 24 hours of myocardial infarction because of early contraindications should be subsequently reevaluated for secondary prevention.
• The optimal duration of therapy is no known;
• Some experts treat for a minimum of three years and use a longer duration for patients with high-risk features such as those with cardiogenic shock, heart failure, and chronic kidney disease at initial presentation.
• IV:
• Note: Small doses of intravenous metoprolol at the time of presentation may be considered for ST-elevation myocardial infarction (STEMI) patients with hypertension or ongoing ischemia if no contraindications exist.
  • Initial: 5 mg;
  • Repeat the dose every 5 minutes for up to 3 doses as needed based on heart rate and blood pressure;
  • The maximum total dose is 15 mg;
  • Begin oral therapy 15 to 30 minutes after the last IV dose.
• Oral:
  • Immediate release (metoprolol tartrate):
    • Initial: 25 to 50 mg every 6 to 12 hours in the acute setting;
    • Some experts suggest a lower starting dose of 12.5 mg every 6 to 12 hours when concern for side effects remain;
    • for outpatients, a transition to twice-daily dosing of metoprolol tartrate (immediate-release) or to daily metoprolol succinate (extended-release);
    • titrate dose based on heart rate and blood pressure as tolerated up to a maximum dose of 200 mg/day.
  • Extended-release (metoprolol succinate):
    • Initial: 25 to 50 mg once a day is also recommended by some experts;
    • Titrate the dose based on heart rate and blood pressure as tolerated up to 200 mg once daily.

Metoprolol (Lopressor) Dose in the treatment of Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, and focal atrial tachycardia) (off-label):

• Acute treatment:

  • IV: 2.5 to 5 mg over two minutes;
  • Repeat the dose every five minutes as needed to a maximum total dose of 15 mg.
  • Note:
    • Initiate cautiously in patients with concomitant heart failure.
    • Avoid in patients with decompensated heart failure; electrical cardioversion preferred.

• Maintenance therapy:

  • Immediate release (metoprolol tartrate):
    • Oral: Initial: 25 mg two times a day;
    • A maximum dose of 400 mg/day.
  • Extended-release (metoprolol succinate):
    • Oral: Initial: 50 mg once a day;
    • A maximum dose of 400 mg/day.

Metoprolol (Lopressor) Dose in the treatment of Thyrotoxicosis (off-label):

• Immediate release (metoprolol tartrate):

  • Oral: 25 to 50 mg every 8 to 12 hours;
  • may also consider administering an equivalent dose of the once-daily extended-release formulation (metoprolol succinate).

Metoprolol (Lopressor) Dose in the treatment of Ventricular arrhythmias (off-label):

• Sustained ventricular tachycardia (VT), incessant VT, or electric storm (hemodynamically stable):

Note:

• Beta-blockers are generally administered in addition to an antiarrhythmic drug (eg, amiodarone) for these indications.
• A beta-blocker is also used to reduce shocks in patients who receive an implantable cardioverter-defibrillator for these indications.
• Propranolol may be the preferred beta-blocker in these situations.
  • Acute ventricular tachycardia (eg, sustained VT):
    • IV: 5 mg every 5 minutes up to 3 doses.

Metoprolol (Lopressor) Dose in the Prevention of ventricular arrhythmias :

• Immediate release (metoprolol tartrate):

  • Oral:
    • Initial: 12.5 to 25 mg two times a day;
    • Increase the dose as needed based on patient response;
    • The maximum dose is 200 mg/day in 2 or 3 divided doses.

• Extended-release (metoprolol succinate):

  • Oral: 25 to 100 mg 1 to 2 times daily.

Metoprolol (Lopressor) Dose in the treatment of Non-sustained VT or symptomatic ventricular premature beats:

Note: Unless there are other indications for a beta-blocker (eg, prior MI or heart failure), use the lowest dose that alleviates symptoms.

• Immediate release (metoprolol tartrate):

  • Oral: 50 to 200 mg/day in 2 or 3 divided doses.

• Extended-release (metoprolol succinate):

  • Oral: 25 to 100 mg 1 to 2 times a day.

Switching dosage forms:

• Switching from immediate-release (metoprolol tartrate) to extended-release (metoprolol succinate):

  • The same total daily dose of metoprolol should be used.
  • Metoprolol tartrate is typically administered in 2 to 3 divided daily doses and metoprolol succinate is administered once a day.

• Switching between oral and intravenous dosage forms:

  • In most cases, an equivalent beta-blocking effect is achieved when a 2.5:1 (Oral: IV) ratio is used.
  • Patient variability may exist and a specific ratio may not apply to all patients, especially if comorbid conditions are present.
  • The estimated equivalent IV total daily dose should be divided into 4 equal doses.
  • For example, if a patient is receiving a chronic oral dose of metoprolol tartrate 25 mg two times a day (total daily dose of 50 mg), this could translate to a range of 2.5 mg intravenously every 6 hours (based on a 5:1 ratio) to 5 mg intravenous every 6 hours (based on a 2.5:1 ratio).
  • Recognizing that patients receiving larger chronic oral doses should not automatically be converted to a large intravenous dose, consideration should be given to further reducing the initial IV dose and basing subsequent doses on the clinical response.

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Metoprolol Dose in Childrens:

Metoprolol (Lopressor) Dose in the treatment of Heart failure (dilated cardiomyopathy): Limited data available:

• Children and Adolescents:

  • Oral: Immediate release (metoprolol tartrate):
    • Initial: 0.1 to 0.2 mg/kg/dose two times a day,
    • The dose may be increased slowly (usually every 2 weeks) as needed up to 1 mg/kg/day;
    • The maximum daily dose is 2 mg/kg/day or 200 mg/day, whichever is less.

Metoprolol (Lopressor) Dose in the treatment of Hypertension:

Note:

• Guidelines do not recommend beta-blockers as initial therapy in pediatric patients;
• Beta-blockers should be reserved for use in patients who have contraindications to preferred agents or after 2 or more preferred agents have failed in patients with hypertension and chronic kidney disease, proteinuria, or diabetes mellitus.

• Immediate-release tablets (metoprolol tartrate):

  • Children and Adolescents ≤17 years:
    • Oral: Initial: 0.5 to 1 mg/kg/dose (maximum initial dose: 25 mg/dose) two times a day.
    • Adjust the dose based on patient response to the maximum daily dose of 6 mg/kg/day or 200 mg/day, whichever is less.

• Extended-release sprinkle capsules or tablets (metoprolol succinate):

  • Children ≥6 years and Adolescents:
    • Oral: Initial: 1 mg/kg/dose once a day (maximum initial dose: 50 mg/dose);
    • Adjust the dose based on the patient's response to the maximum daily dose: 2 mg/kg/day or 200 mg/day, whichever is less;
    • Higher doses have not been studied.

Metoprolol (Lopressor) dose in the treatment of Vagal Syncope: 

• Children ≥7 years and Adolescents:

  • Tilt-table test:
    • IV: 0.1 to 0.2 mg/kg;
    • maximum dose: 10 mg/dose.

Metoprolol (Lopressor) dose as a chronic treatment: Oral:

• Immediate release (metoprolol tartrate):

  • 5 to 1 mg/kg/dose two times a day;
  • The maximum daily dose: 6 mg/kg/day.

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Metoprolol Pregnancy Risk Category: C

• The drug and its metabolites alpha-hydroxy-metoprolol can cross the placental barrier.
• Beta-blockers may be used during pregnancy to increase the chance of adverse events in the neonate.
• If beta-blocker use is necessary, it is important to monitor fetal growth during pregnancy.
• Also, newborns should be checked for hypoglycemia, respiratory depression, bradycardia and respiratory depression for 48 hours following delivery.
• Chronic maternal hypertension can also be associated with poor maternal and fetal outcomes.
• Chronic maternal hypertension can increase the likelihood of stillbirths, birth defects, low birth weight, premature births, and even neonatal deaths.
• The severity and duration of maternal hypertension may have an impact on the actual fetal and neonatal risk.
• Chronic hypertension left untreated can also increase the risk of adverse maternal outcomes such as strokes, gestational diabetes, preeclampsia, MI and delivery complications.
• Pregnancy can alter the pharmacokinetic properties of metoprolol; the extent of these changes will depend on maternal CYP2D6 genotype.
• Beta-blockers can be used to treat hypertension during pregnancy. Although specific recommendations may vary according to guideline, metoprolol might be considered.
• Pre-existing hypertension in women may be continued during pregnancy, unless contraindications are present.
• Metoprolol can be used to treat maternal ventricular arrhythmias and supraventricular tachycardia. Refer to current guidelines for more information.
• If migraine prophylaxis is required in a pregnant lady, metoprolol might be an option.

Use during breastfeeding:

• Breast milk contains metoprolol.
• Manufacturers recommend monitoring breastfed babies for signs of neonatal distress, such as bradycardia and constipation.
• A lactating woman may prefer to use a beta-blocker that is not metoprolol.

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Dose in Kidney Disease:

No dosage adjustment is necessary.

Metoprolol Dose in Liver disease:

There are no specific dosage adjustments provided in the manufacturer's labeling. Consider initiating with reduced doses and gradual dosage titration due to the extensive metabolism of the drug in liver.

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Side effects of Metoprolol (Lopressor).

• Cardiovascular:

  • Hypotension
  • Bradycardia
  • First Degree Atrioventricular Block
  • Arterial Insufficiency
  • Cardiac Failure
  • Cerebrovascular Accident
  • Cold Extremities
  • Palpitations
  • Peripheral Edema
  • Claudication

• Central Nervous System:

  • Dizziness
  • Fatigue
  • Depression
  • Vertigo
  • Confusion
  • Disturbed Sleep
  • Hallucination
  • Headache
  • Insomnia
  • Nightmares
  • Temporary Amnesia

• Dermatology:

  • Pruritus
  • Skin Rash
  • Exacerbation Of Psoriasis
  • Skin Photosensitivity

• Endocrine & Metabolic:

  • Decreased Libido
  • Unstable Diabetes

• Gastrointestinal:

  • Diarrhea
  • Constipation
  • Flatulence
  • Heartburn
  • Stomach Pain
  • Xerostomia
  • Nausea
  • Vomiting

• Neuromuscular & Skeletal:

  • Musculoskeletal Pain

• Ophthalmic:

  • Blurred Vision
  • Visual Disturbance

• Otic:

  • Tinnitus

• Respiratory:

  • Dyspnea
  • Bronchospasm
  • Wheezing
  • Rhinitis

• Miscellaneous:

  • Accidental Injury

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Contraindications to Metoprolol (Lopressor):

• Allergies to the drug or any component of it, as well as other beta-blockers.
• Second-degree or third-degree heart blocks

Notice:Additional contraindications can be formulation- and/or indication-specific.

Injectable/immediate-release tablets:

• Hypertension and angina (oral only).
  • Sinus bradycardia
  • Cardiogenic shock
  • overt heart failure;
  • sick sinus syndrome;
  • Grave peripheral arterial circulation disorders

Myocardial Infarction (oral or injection):

• Sinus bradycardia severe (heart rate 45 beats/minute);
• Significant first-degree blockage of the heart (P-R interval >=0.24 second);
• Systolic blood pressure of 100 mm Hg
• Moderate to severe heart failure

Extended-release formulation

• Bradycardia severe
• Cardiogenic shock
• Decompensated Heart Failure
• Sick sinus syndrome (except for patients with an artificial pacemaker in use)

Canadian labeling: Additional contraindications not in US labeling

• Cor pulmonale
• Untreated pheochromocytoma
• Injection only for asthma and other obstructive breathing diseases
• Use of anesthesia drugs that cause myocardial depressibility in combination

Warnings and precautions

• Anaphylactic reactions

  • Be cautious if you have a history of severe allergic reactions to allergens.
  • Beta-blockers can make patients more sensitive to repeated allergen challenges.
  • Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

• Block of the Atrioventricular (AV),

  • Metoprolol users are at high risk for mild first-degree heartblock.
  • It can also cause severe heart block (first-, second-, or third degree).
  • Acute myocardial Infarction patients (especially those with right ventricular myocardial injury) are at high risk for developing heart block.
  • Metoprolol should not be used if severe heart block is present. Instead, you should consider taking measures to increase your heart rate.

• Bradycardia

  • Bradycardia can occur, which may include sinus pause, heart block and cardiac arrest.
  • Patients with conduction disorders, first-degree AV blocking, or sinus node dysfunction may be more at risk for beta-blocking.
  • Monitoring heart beat and rhythm is important. If severe bradycardia develops, decrease the dosage or discontinue therapy.

• CNS depression:

  • Beta-blockers can cause depression in the Central Nervous system that can lead to mental or physical impairments.
  • Before performing any task that requires mental awareness, patients must be alert

• Hypotension

  • Hypotension may be caused by beta-blockers

• Bronchospastic disease

  • Patients with bronchospastic diseases should not be given beta-blockers.
  • However, metoprolol with B-1 selectivity has been administered cautiously at lower doses under close supervision.

• Conductive abnormality

  • Pre-existing conditions like sick sinus syndrome should be considered before initiating beta blocker therapy.

• Diabetes:

  • Beta-blockers should be used with caution by diabetics as they can cause hypoglycemia and mask symptoms.

• Heart failure:

  • Patients with compensated cardiac failure should use it with caution.
  • Patients should be closely monitored for signs of heart disease. Only the ER formulation is recommended for patients with heart failure.
  • Until the patient is stable, it may be necessary to increase the dose of diuretics.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious when using beta-blockers.

• Myasthenia gravis:

  • Patients with myasthenia gravis should be careful when taking beta-blockers.

• Raynaud and peripheral vascular disease (PVD).

  • It can cause or exacerbate arterial insufficiency symptoms in patients with Raynaud and PVD.
  • Be cautious and watch for arterial obstruction.

• Untreated Pheochromocytoma

  • Patients with untreated pheochromocytoma must have adequate alpha-blockade before any beta-blocker can be used.

• Angina Prinzmetal version:

  • Patients with Prinzmetal angina should avoid beta-blockers that do not block alpha-1-adrenergic activity.
  • This is because unopposed alpha1 receptors mediate the coronary vasoconstriction and can make the angina worse.

• Psoriasis:

  • Beta-blocker use has been linked to psoriasis exacerbation or induction, although cause and effect are not clear.

• Supraventricular tachycardia (SVT):

  • Avoid AV node-specific blockers such as adenosine and digoxin if you suspect antidromic atrioventricular reentrant tachycardia or pre-excited arrhythmia.
  • These types of supraventricular Tachycardia may be caused by enhanced antegrade conduction between the atria and ventricles.
  • If the atrioventricular Node is blocked, this accessory pathway can lead to ventricular arrhythmias.
  • Because orthodromic AVRT is safe, you can use AV-specific blocking drugs to protect the AV node.
  • Antegrade conduction happens through the AV Node. Retrograde conduction from ventricles into atria only occurs through the accessory pathway.

• Thyroid disease:

  • Beta-blockers can mask signs of hyperthyroidism like tachycardia.
  • Hyperthyroid patients should be monitored closely as sudden withdrawals can worsen hyperthyroidism symptoms or cause a thyroid storm.
  • Test results for thyroid function may reveal changes.

Metoprolol: Drug Interaction

Risk Factor C (Monitor therapy)
Acetylcholinesterase Inhibitors	May enhance the bradycardic effect of Beta-Blockers.
Ajmaline	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Alfuzosin	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Alpha1-Blockers	Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1Blockers. The risk associated with ophthalmic products is probably less than systemic products.
Aminoquinolines (Antimalarial)	May decrease the metabolism of Beta-Blockers.
Amiodarone	May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers.
Amphetamines	May diminish the antihypertensive effect of Antihypertensive Agents.
Antipsychotic Agents (Phenothiazines)	May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers.
Antipsychotic Agents (Second Generation [Atypical])	Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
Barbiturates	May decrease the serum concentration of Beta-Blockers.
Barbiturates	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Benperidol	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Beta2-Agonists	Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers.
Bradycardia-Causing Agents	May enhance the bradycardic effect of other Bradycardia-Causing Agents.
Brigatinib	May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents.
Brimonidine (Topical)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Bupivacaine	Beta-Blockers may increase the serum concentration of Bupivacaine.
Calcium Channel Blockers (Nondihydropyridine)	May enhance the hypotensive effect of BetaBlockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil.
Cardiac Glycosides	Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides.
Cholinergic Agonists	Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction.
CloBAZam	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Cobicistat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
CYP2D6 Inhibitors (Moderate)	May increase the serum concentration of Metoprolol.
CYP2D6 Inhibitors (Strong)	May increase the serum concentration of Metoprolol.
Darunavir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Dexmethylphenidate	May diminish the therapeutic effect of Antihypertensive Agents.
Diazoxide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Dipyridamole	May enhance the bradycardic effect of Beta-Blockers.
Disopyramide	May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide.
DULoxetine	Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine.
EPINEPHrine (Nasal)	Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Nasal).
EPINEPHrine (Oral Inhalation)	Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Oral Inhalation).
Epinephrine (Racemic)	Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of Epinephrine (Racemic).
EPINEPHrine (Systemic)	Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Systemic).
Herbs (Hypertensive Properties)	May diminish the antihypertensive effect of Antihypertensive Agents.
Herbs (Hypotensive Properties)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Imatinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Insulins	Beta-Blockers may enhance the hypoglycemic effect of Insulins.
Ivabradine	Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine.
Lacosamide	Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.
Lercanidipine	May enhance the hypotensive effect of Metoprolol. Metoprolol may decrease the serum concentration of Lercanidipine.
Levodopa-Containing Products	Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.
Lidocaine (Systemic)	Beta-Blockers may increase the serum concentration of Lidocaine (Systemic).
Lidocaine (Topical)	Beta-Blockers may increase the serum concentration of Lidocaine (Topical).
Lormetazepam	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Lumefantrine	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Mepivacaine	Beta-Blockers may increase the serum concentration of Mepivacaine.
Methacholine	Beta-Blockers may enhance the adverse/toxic effect of Methacholine.
Methoxyflurane	May enhance the hypotensive effect of Beta-Blockers.
Methylphenidate	May diminish the antihypertensive effect of Antihypertensive Agents.
Midodrine	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Mirabegron	May diminish the antihypertensive effect of Metoprolol. Mirabegron may increase the serum concentration of Metoprolol.
Molsidomine	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Naftopidil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicergoline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicorandil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
NIFEdipine	May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers.
Nitroprusside	Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.
Nonsteroidal Anti-Inflammatory Agents	May diminish the antihypertensive effect of BetaBlockers.
Opioids (Anilidopiperidine)	May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers.
Panobinostat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Peginterferon Alfa-2b	May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Pentoxifylline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Perhexiline	CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Pholcodine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.
Phosphodiesterase 5 Inhibitors	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Propafenone	May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity.
Prostacyclin Analogues	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Quinagolide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
QuiNINE	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Regorafenib	May enhance the bradycardic effect of Beta-Blockers.
Reserpine	May enhance the hypotensive effect of Beta-Blockers.
Rifamycin Derivatives	May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin.
Ruxolitinib	May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible.
Selective Serotonin Reuptake Inhibitors	May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE.
Sulfonylureas	Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents.
Terlipressin	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Theophylline Derivatives	Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Theophylline Derivatives. Management: Monitor for reduced theophylline efficacy during concomitant use with any beta-blocker. Beta-1 selective agents are less likely to antagonize theophylline than nonselective agents, but selectivity may be lost at higher doses.
Tofacitinib	May enhance the bradycardic effect of Bradycardia-Causing Agents.
Yohimbine	May diminish the antihypertensive effect of Antihypertensive Agents.
Risk Factor D (Consider therapy modification)
Abiraterone Acetate	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.
Alpha2-Agonists	May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Apraclonidine.
Amifostine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.
Asunaprevir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Ceritinib	Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs.
Dacomitinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index.
Dronedarone	May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in betablocker dose.
Ergot Derivatives	Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline.
Fingolimod	Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia.
Grass Pollen Allergen Extract (5 Grass Extract)	Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers.
Obinutuzumab	May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion.
Siponimod	Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia.
Risk Factor X (Avoid combination)
Bromperidol	Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents.
Fexinidazole [INT]	Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT].
Floctafenine	May enhance the adverse/toxic effect of Beta-Blockers.
Rivastigmine	May enhance the bradycardic effect of Beta-Blockers.

 

Monitoring parameters:

Acute cardiac treatment:

• Monitor ECG, heart rate, and blood pressure with intravenous administration;
• heart rate, rhythm, and blood pressure with oral administration.

IV use in a nonemergency situation:

• Necessary monitoring for surgical patients who are unable to take oral beta-blockers (because of prolonged ileus) has not been defined.
• Some institutions require monitoring of baseline and post-infusion heart rate and blood pressure when a patient's response to beta-blockade has not been characterized (ie, the patient's initial dose or following a change in dose).

Hypertension:

The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults:

• Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%:
  • Target blood pressure <130/80 mm Hg is recommended.
• Confirmed hypertension without markers of increased ASCVD risk:
  • Target blood pressure <130/80 mm Hg may be reasonable.

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How to administer Metoprolol (Lopressor)?

Oral:

• Immediate release (metoprolol tartrate):
  • Administer with or immediately following meals.
• Extended-release (metoprolol succinate):
  • According to the manufacturer, it is preferable to administer with or immediately following meals; however, may also administer without regard to meals.
  • May divide tablets in half. Avoid crushing or chewing the tablets.
• Sprinkle capsule:
  • The capsule may be swallowed whole or it may be opened and contents sprinkled on a small amount (1 teaspoonful) of soft food (eg, applesauce, pudding, or yogurt) to be used within 60 minutes (do not store for future use).
• Nasogastric tube administration:
  • Open the capsule and add contents to an all-plastic oral tip syringe;
  • add 15 mL of water.
  • Gently shake the syringe for about 10 seconds.
  • Immediately deliver the mixture through a ≥12 French nasogastric tube.
  • No granules should remain in the syringe; rinse the syringe with additional water if necessary.

IV:

• The drug may be administered undiluted by rapid infusion (IV push) over one minute for acute treatment.
• It may also be administered by slow infusion i.e. 5 to 10 mg of metoprolol in 50 mL of fluid over ~30 to 60 minutes during less urgent situations (eg, substitution for oral metoprolol).

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Mechanism of action of Metoprolol (Lopressor):

It acts as a selective antagonist of beta-1-adrenergic and other receptors. It blocks beta-1 receptors competitively at doses less than 100 mg, but has little to no effect on beta-2 receptors. It has no membrane-stabilizing or intrinsic sympathomimetic effects

Notice:

• The pharmacokinetics and pharmacokinetics for metoprolol succinate extended release capsule or tablet in hypertensive adolescents aged 6-17 years were similar to those of adults.

The onset of action:

• Oral: Immediate-release tablets: Within 1 hour;
• Peak effect: Oral: 1 to 2 hours;
• IV: 20 minutes (when infused over 10 minutes)

Duration:

• Oral: Immediate release:
  • Variable (dose-related; 50% reduction in maximum heart rate after single doses of 20, 50, and 100 mg occurred at 3.3, 5, and 6.4 hours, respectively);
• Extended-release:
  • ~24 hours

Absorption:

• Rapid and complete absorption

Distribution:

• It crosses the blood-brain barrier;
• CSF concentrations are 78% of plasma concentrations

Protein binding:

• ~10% to 12% to albumin

Metabolism:

• Extensively hepatic via CYP2D6;
• significant first-pass effect (~50%)

Bioavailability: Oral:

• Immediate release: ~40% to 50%;
• Extended-release: 77% relative to immediate release

Half-life elimination:

• Neonates: 5 to 10 hours
• Adults: 3 to 4 hours (7 to 9 hours in poor CYP2D6 metabolizers or hepatic impairment)

Excretion:

• Urine (95%, <5% to 10% as unchanged drug; increased to 30% to 40% in poor CYP2D6 metabolizers)

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International Brand Names of Metoprolol:

• First - Metoprolol
• Kapspargo Sprinkle
• Lopressor
• Toprol XL
• AG-Metoprolol-L
• APO-Metoprolol
• APO-Metoprolol SR
• APO-Metoprolol-Type L
• Betaloc
• DOM-Metoprolol
• DOM-Metoprolol-L
• JAMP-Metoprolol-L
• Lopresor
• Lopresor SR
• Metoprolol-100
• Metoprolol-25
• Metoprolol-50
• Metoprolol-L
• MYLAN-Metoprolol
• PMS-Metoprolol-B
• PMSMetoprolol-L
• RIVA-Metoprolol-L
• SANDOZ Metoprolol
• Sandoz Metoprolol SR
• TEVAMetoprolol
• Angilat
• Angimet
• Beloc
• Beloc Duriles
• Beloc Zok
• Beloken
• Beloken Retard
• Belozok
• Betacard
• Betaloc
• Betaloc CR
• Betaloc Zoc
• Betaloc ZOK
• Betaloc Zok
• Betaloc Zox
• Betaloc-ZOK
• Betalok
• Betawin
• Betazok
• Bloxan
• Bloxazoc
• Cardeloc
• Cardiosel
• Cardiosel-OD
• Cardiostat
• Cardiotab
• Cardoxone
• Corvital
• Corvitol
• Denex
• Egilok
• Egilok Succ
• Emzok
• Fapresor
• Huma-Metoprol
• Hypetor
• Jutabloc
• Lenopres
• Lofarbil
• Lopresor
• Lopresor Divitab
• Lopresor OROS
• Lopresor Retard
• Lopressor
• Low Press
• Metazero
• Meto-Hennig
• Metocell
• Metocor
• Metohexal
• MetoHEXAL
• Metohexal Retard
• Metolol-CP
• Metoprim
• Metoprogamma
• Metoprolol Stada
• Metoprolol-B
• Metoprolol-rpm
• Metostad
• Metracin
• Metrol
• Mezelol
• Minax
• Minax XL
• Myloc CR
• Neobloc
• Neox
• Nipresol
• Prolol
• Prolomet XL
• Promiced
• Prontol
• Revelol XL
• Revelol-XL-50
• Ritmetol
• Sefloc
• Selo-zok
• Selokeen ZOC
• Seloken
• Seloken Retard
• Seloken Zoc
• Seloken Zok
• Seloken-Zok
• Selopral
• Selozok
• Selozok LP
• Slow-Lopresor
• Succiprol
• Topress
• Toprol XL
• Vasocardin
• Voxuten

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Metoprolol Brand Names in Pakistan:

Metoprolol Tartrate Injection 1 mg/ml in Pakistan
Lopresor	Novartis Pharma (Pak) Ltd
Mepresor	Novartis Pharma (Pak) Ltd

 

Metoprolol Tartrate Tablets 25 Mg in Pakistan
Carsel	Unimark Pharmaceuticals
Merol	Atco Laboratories Limited

 

Metoprolol Tartrate Tablets 50 mg in Pakistan
Carsel	Unimark Pharmaceuticals
Carsel Plus	Unimark Pharmaceuticals
Merol	Atco Laboratories Limited

 

Metoprolol Tartrate Tablets 95 mg in Pakistan
Merol-Xl	Atco Laboratories Limited

 

Metoprolol Tartrate Tablets 100 mg in Pakistan
Aksopressor	Akson Pharmaceuticals (Pvt) Ltd.
Betaloc-Zok	Barrett Hodgson Pakistan (Pvt) Ltd.
Carsel	Unimark Pharmaceuticals
Carsel Plus	Unimark Pharmaceuticals
Fynkard	Fynk Pharmaceuticals
Megatop	Mega Pharmaceuticals (Pvt) Ltd
Mepresor	Novartis Pharma (Pak) Ltd
Meprol	Obsons Pharmaceuticals
Merol	Atco Laboratories Limited
Metapressor	Hygeia Pharmaceuticals
Metcard	Batala Pharmaceuticals.
Metocard	Consolidated Chemical Laboratories (Pvt) Ltd.
Metolol	Multinational Buisness Link
Metoscot	Scotmann Pharmaceuticals
Metsu Xl	Genix Pharma (Pvt) Ltd
Refit	Mass Pharma (Private) Limited
Toprol	Raazee Theraputics (Pvt) Ltd.

 

Metoprolol Tartrate Tablets 200 mg in Pakistan
Carsel	Unimark Pharmaceuticals
Merol-Xl	Atco Laboratories Limited

 

Metoprolol Tartrate Tablets SR 200 mg in Pakistan
Mepresor	Novartis Pharma (Pak) Ltd