metoprolol (Rx)

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

Hallucinations

Paresthesia

Hepatitis

Vomiting

Arthralgia

Male impotence

Reversible alopecia

Agranulocytosis

Dry eyes

Worsening of psoriasis

Pyronie’s disease

Sweating

Photosensitivity

Taste disturbance

Contraindications

Hypersensitivity

Lopressor

• Hypertension and angina: Sinus bradycardia, 2°/3° heart block, cardiogenic shock, sick sinus syndrome (unless permanent pacemaker in place), severe peripheral vascular disease, pheochromocytoma
• Myocardial infarction: Severe sinus bradycardia, heart rate <45 beats/min, systolic BP <100 mmHg, significant first-degree heart block ((PR interval at least 0.24 seconds), 2°/3° heart block, moderate-to-severe cardiac failure

Toprol XL

• Second- and third-degree heart block, deompensated heart failure, sick sinus syndrome (except in patients with functioning artificial pacemaker), severe bradycardia, cardiogenic shock

Kapspargo Sprinkle

• Severe bradycardia, second or third degree heart block, cardiogenic shock, decompensated heart failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product

Cautions

Use with caution in cerebrovascular insufficiency, CHF, cardiomegaly, myasthenia gravis, hyperthyroidism or thyrotoxicosis (may mask signs or symptoms), liver disease, renal impairment, peripheral vascular disease, psoriasis (may cause exacerbation of psoriasis)

May exacerbate bronchospastic disease; monitor closely

Beta blockers can cause myocardial depression and may precipitate heart failure and cardiogenic shock

Sudden discontinuance can exacerbate angina and lead to MI and ventricular arrhythmias in patients with CAD

Worsening cardiac failure may occur during up-titration of metoprolol succinate; if such symptoms occur, increase diuretics and restore clinical stability before advancing the dose of metoprolol succinate; it may be necessary to lower the dose of metoprolol succinate or temporarily discontinue it

Bradycardia, including sinus pause, heart block, and cardiac arrest, has been reported; patients with 1° atrioventricular block, sinus node dysfunction, or conduction disorders may be at increased risk

Increased risk of stroke after surgery

May potentiate hypoglycemia in patients with diabetes mellitus and may mask signs and symptoms

Avoid starting high-dose regimen of extended-release metoprolol in patients undergoing noncardiac surgery; use in patients with cardiovascular risk factors is associated with bradycardia, hypotension, stroke, and death

Long-term beta blockers should not be routinely withdrawn before major surgery; however, impaired ability of the heart to respond to reflex adrenergic stimuli may augment risks of general anesthesia and surgical procedures

Metoprolol loses beta-receptor selectivity at high doses and in poor metabolizers

If drug is administered for tachycardia secondary to pheochromocytoma, it should be given in combination with an alpha blocker (which should be started before metoprolol is started)

While taking beta blockers, patients with history of severe anaphylactic reaction to variety of allergens may be more reactive to repeated challenge

Extended release tablet should not be withdrawn routinely prior to major surgery

Hydrochlorothiazide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma, which can lead to permanent vision loss if not treated; discontinue hydrochlorothiazide as rapidly as possible if symptoms occur; prompt medical or surgical treatments may need to be considered if intraocular pressure remains uncontrolled; risk factors for developing acute angle-closure glaucoma may include history of sulfonamide or penicillin allergy

Caution in patients with history of psychiatric illness; may cause or exacerbate CNS depression

Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease

Drug interactions overview

• Catecholamine depleting drugs (eg, reserpine, monoamine oxidase (MAO) inhibitors) may have an additive effect when given with beta-blocking agents; monitor when coadministration with catecholamine depleting drugs for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension
• While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine used to treat an allergic reaction
• Drugs that are strong inhibitors of CYP2D6, such as quinidine, fluoxetine, paroxetine, and propafenone, were shown to double metoprolol concentrations; no information about moderate or weak inhibitors, but are likely to increase metoprolol concentration; closely monitor patients when the combination cannot be avoided
• Digitalis glycosides, clonidine, diltiazem and verapamil slow atrioventricular conduction and decrease heart rate
• Concomitant administration of hydralazine may inhibit presystemic metabolism of metoprolol leading to increased concentrations of metoprolol
• Concomitant use with beta blockers can increase the risk of bradycardia; if clonidine and a beta blocker, such as metoprolol are coadministered, withdraw the beta-blocker several days before the gradual withdrawal of clonidine because beta-blockers may exacerbate the rebound hypertension that can follow the withdrawal of clonidine
• If replacing clonidine by beta-blocker therapy, delay introduction of beta-blockers for several days after clonidine administration has stopped
• Metoprolol succinate is released faster from Kapspargo Sprinkle in the presence of alcohol; may increase the risk for adverse events associated with Kapspargo Sprinkle
• Avoid alcohol consumption

Pregnancy

There are no adequate and well-controlled studies in pregnant women

Limited data on the use of metoprolol in pregnant women

Risk to fetus/mother is unknown; because animal reproduction studies are not always predictive of human response, use if clearly needed

Animal data

• Lopressor has been shown to increase postimplantation loss and decrease neonatal survival in rats at doses up to 11 times the maximum daily human dose of 450 mg, when based on surface area
• Distribution studies in mice confirm exposure of the fetus when Lopressor is administered to the pregnant animal
• These limited animal studies do not indicate direct or indirect harmful effects with respect to teratogenicity

Fertility

• Drug effects on the fertility of human have not been studied
• Lopressor showed effects on spermatogenesis in male rats at a therapeutic dose level, but had no effect on rates of conception at higher doses in animal fertility studies

Lactation

Lopressor is excreted in breast milk in a very small quantity

An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Blocks response to beta-adrenergic stimulation; cardioselective for beta1 receptors at low doses, with little or no effect on beta2 receptors

Absorption

Bioavailability: 40-50% (immediate-release) ; 65-77% (extended-release) relative to immediate release

Onset: 20 min (IV), when infused over 10 min; onset may be immediate, depending on clinical setting; 1-2 hr (PO)

Duration: 3-6 hr (PO); duration is dose-related; 24 hr (ER); 5-8 hr (IV)

Peak plasma time: 1.5-2 hr (immediate-release); 3.3 hr (extended-release)

Therapeutic range: 35-212 ng/mL

Distribution

Protein bound: 10%

Vd: 3.2-5.6 L/kg

Metabolism

Metabolized in liver by CYP2D6

Metabolites: Inactive

Elimination

Half-life: 3-4 hr (average); 7.5 hr (poor metabolizers); 2.8 hr (extensive metabolizers)

Excretion: Urine (95%)

IV Compatibilities

Solution: D5W, NS

Y-site: Abciximab, alteplase, argatroban, meperidine, morphine sulfate

IV Incompatibilities

Y-site: Amphotericin B cholesteryl sulfate

IV Administration

Give undiluted by direct injection

Oral Administration

Metoprolol tartrate: Take with or immediately after meals

Metoprolol succinate: Tablet should not be chewed or crushed

Kapspargo Sprinkle

• Swallow whole
• For patients unable to swallow an intact capsule, alternative administration options are available

• Directions for use with soft food (applesauce, pudding, or yogurt)

  • Open capsule and sprinkle contents soft food
  • Contents of the capsules should be swallowed along with a small amount (teaspoonful) of soft food (such as applesauce, pudding, or yogurt)
  • Drug/food mixture should be swallowed within 60 minutes and not stored for future use

Nasogastric tube administration

Kapspargo Sprinkle

• Open and add contents of capsule to an all plastic oral tip syringe and add 15 mL of water
• Gently shake the syringe for ~10 seconds
• Promptly deliver through a 12 French or larger nasogastric tube
• Ensure no granules are left in the syringe
• Rinse with additional water if needed

Storage

Do not freeze

Lopressor

• Tablets: Store at room temperature
• Unused vials: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F); protect from light and heat

Kapspargo Sprinkle

• Store at 20- 25°C (68-77°F)