metoprolol

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Genetic Implications:

Pronunciation:
me-toe-proe-lole

Trade Name(s)

• Kapspargo Sprinkle
• Lopresor SR 
• Lopressor
• Toprol XL

Ther. Class.
antianginals
antihypertensives

Pharm. Class.
beta blockers

Indications

• Hypertension.
• Angina pectoris.
• Prevention of MI and decreased mortality in patients with recent MI.
• Management of stable, symptomatic (class II or III) heart failure due to ischemic, hypertensive or cardiomyopathic origin (may be used with ACE inhibitors, diuretics and/or digoxin; Toprol XL only).

Unlabeled Use(s):

• Ventricular arrhythmias/tachycardia.
• Migraine prophylaxis.
• Tremors.
• Aggressive behavior.
• Drug-induced akathisia.
• Anxiety.

Action

Blocks stimulation of beta₁ (myocardial)-adrenergic receptors. Does not usually affect beta₂ (pulmonary, vascular, uterine)-adrenergic receptor sites.

Therapeutic Effect(s):

• Decreased BP and heart rate.
• Decreased frequency of attacks of angina pectoris.
• Decreased rate of cardiovascular mortality and hospitalization in patients with heart failure.

Pharmacokinetics

Absorption: Well absorbed after oral administration.

Distribution: Crosses the blood-brain barrier, crosses the placenta; small amounts enter breast milk.

Metabolism and Excretion: Mostly metabolized by the liver (primarily by CYP2D6; the CYP2D6 enzyme system exhibits genetic polymorphism);  ~7% of population may be poor metabolizers and may have significantly ↑ metoprolol concentrations and an ↑ risk of adverse effects.

Half-life: 3–7 hr.

TIME/ACTION PROFILE (cardiovascular effects)

Contraindication/Precautions

Contraindicated in:

• Uncompensated HF;
• Pulmonary edema;
• Cardiogenic shock;
• Bradycardia, heart block, or sick sinus syndrome (in absence of a pacemaker).

Use Cautiously in:

• Renal impairment;
• Hepatic impairment;
• Pulmonary disease (including asthma; beta₁  selectivity may be lost at higher doses);
• Diabetes mellitus (may mask signs of hypoglycemia);
• Thyrotoxicosis (may mask symptoms);
• Patients with a history of severe allergic reactions (intensity of reactions may be ↑);
• Untreated pheochromocytoma (initiate only after alpha blocker therapy started);
• OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk; crosses the placenta and may cause fetal/neonatal bradycardia, hypotension, hypoglycemia, or respiratory depression
• Lactation:  Use while breastfeeding only if potential maternal benefit justifies potential risk to infant; may result in bradycardia, constipation, diarrhea, and dry mouth/skin/eyes in infant, especially in mothers who are CYP2D6 poor metabolizers.
• Pedi:  Safety and effectiveness not established in children <18 yr (tablets, extended-release tablets, and injection) or <6 yr (extended-release capsules);
• Geri:  Older adults may have ↑ sensitivity to beta blockers; initial dose ↓ recommended.

Adverse Reactions/Side Effects

CV: BRADYCARDIA, HF, PULMONARY EDEMA, hypotension, peripheral vasoconstriction

Derm: rash

EENT: blurred vision, stuffy nose

Endo: hyperglycemia, hypoglycemia

GI: constipation, diarrhea, drug-induced hepatitis, dry mouth, flatulence, gastric pain, heartburn, ↑ liver enzymes, nausea, vomiting

GU: erectile dysfunction, ↓ libido, urinary frequency

MS: arthralgia, back pain, joint pain

Neuro: fatigue, weakness, anxiety, depression, dizziness, drowsiness, insomnia, memory loss, mental status changes, nervousness, nightmares

Resp: bronchospasm, wheezing

Misc: drug-induced lupus syndrome

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  General anesthesia,  IV   phenytoin, and  verapamil  may cause ↑ myocardial depression.
• ↑ risk of bradycardia when used with  digoxin,  verapamil,  diltiazem, or  clonidine.
• ↑ hypotension may occur with other  antihypertensives, acute ingestion of  alcohol, or  nitrates.
• Concurrent use with  amphetamines,  cocaine,  ephedrine,  epinephrine,  norepinephrine,  phenylephrine, or  pseudoephedrine  may result in unopposed alpha-adrenergic stimulation (excessive hypertension, bradycardia).
• Concurrent administration of  thyroid  administration may ↓ effectiveness.
• May alter the effectiveness of  insulins  or  oral hypoglycemic agents  (dose adjustments may be necessary).
• May ↓ the effectiveness of  theophylline.
• May ↓ the beneficial beta₁ -cardiovascular effects of  dopamine  or  dobutamine.
• Use cautiously within 14 days of  MAO inhibitor  therapy (may result in hypertension).

Route/Dosage

When switching from immediate-release to extended-release product, the same total daily dose can be used

PO (Adults): Hypertension/angina– 25–100 mg/day as a single dose initially or 2 divided doses; may be ↑ every 7 days as needed up to 450 mg/day (immediate-release) or 400 mg/day (extended-release) (for angina, give in divided doses). Extended-release products are given once daily.  MI– 25–50 mg (starting 15 min after last IV dose) every 6 hr for 48 hr, then 100 mg twice daily.  Heart failure– 12.5–25 mg once daily (of extended-release), can be doubled every 2 wk up to 200 mg/day.  Migraine prevention– 50–100 mg 2–4 times daily (unlabeled).

IV (Adults): MI– 5 mg every 2 min for 3 doses, followed by oral dosing.

PO (Children ≥6 yr): Hypertension– 1 mg/kg once daily (extended-release capsules); may be titrated, as needed (not to exceed 50 mg/day).

Availability (generic available)

Tablets (tartrate): 25 mg, 37.5 mg, 50 mg, 75 mg, 100 mg

Cost:

Generic: All strengths $7.18/100

Extended-release capsules (succinate; Kapspargo Sprinkle): 25 mg, 50 mg, 100 mg, 200 mg

Extended-release tablets (succinate; Toprol XL): 25 mg, 50 mg, 100 mg, 200 mg

Cost:

Generic: 25 mg $35.68/100, 50 mg $41.93/100, 100 mg $53.95/100, 200 mg $84.54/100

Solution for injection: 1 mg/mL

In Combination with: hydrochlorothiazide (Dutoprol, Lopressor HCT). See combination drugs.

Assessment

• Monitor BP, ECG, and pulse frequently during dose adjustment and periodically during therapy.
• Monitor frequency of prescription refills to determine compliance.
• Monitor vital signs and ECG every 5–15 min during and for several hrs after parenteral administration. If heart rate <40 bpm, especially if cardiac output is also decreased, administer atropine 0.25–0.5 mg IV.
• Monitor intake and output ratios and daily weights. Assess routinely for signs and symptoms of HF (dyspnea, rales/crackles, weight gain, peripheral edema, jugular venous distention).
• Angina: Assess frequency and characteristics of anginal attacks periodically during therapy.

Lab Test Considerations:

May cause ↑ BUN, serum lipoprotein, potassium, triglyceride, and uric acid levels.

• May cause ↑ ANA titers.
• May cause ↑ in blood glucose levels.
• May cause ↑ serum alkaline phosphatase, LDH, AST, and ALT levels.

Implementation

• High Alert: IV vasoactive medications are inherently dangerous. Before administering intravenously, have second practitioner independently check original order and dose calculations.
• High Alert: Do not confuse Toprol-XL (metoprolol succinate) with Topamax (topiramate). Do not confuse Lopressor (metoprolol tartrate) with Lyrica (pregabalin). Do not confuse metoprolol tartrate with metoprolol succinate.
• PO 

  Take apical pulse before administering. If <50 bpm or if arrhythmia occurs, withhold medication and notify health care professional.

  • Administer metoprolol with meals or directly after eating.
  •  DNC: Extended-release tablets may be broken in half; do not crush or chew.
  • Swallow  Kapspargo Sprinkle  whole. If unable to swallow a capsule, may be opened and contents sprinkled over soft food (applesauce, pudding, yogurt). Swallow contents of capsule along with a small amount (tsp) of soft food. Swallow drug/food mixture within 60 min; do not store for future use. May also be administered via NG tube by opening and adding capsule contents to an all plastic oral tip syringe and adding 15 mL of water. Gently shake syringe for about 10 sec. Promptly administer through a 12 French or larger NG tube. Rinse with additional water to ensure no granules are left in syringe.

Patient/Family Teaching

• Instruct patient to take medication as directed, at the same time each day, even if feeling well; do not skip or double up on missed doses. Take missed doses as soon as possible up to 8 hr before next dose. Abrupt withdrawal may precipitate life-threatening arrhythmias, hypertension, or myocardial ischemia.
• Teach patient and family how to check pulse daily and BP biweekly and to report significant changes to health care professional.
• May cause drowsiness. Caution patient to avoid driving or other activities that require alertness until response to the drug is known.
• Advise patient to change positions slowly to minimize orthostatic hypotension.
• Caution patient that this medication may increase sensitivity to cold.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any Rx, OTC, or herbal products, especially cold preparations, concurrently with this medication. Patients on antihypertensive therapy should also avoid excessive amounts of coffee, tea, and cola.
• Diabetics should closely monitor blood glucose, especially if weakness, malaise, irritability, or fatigue occurs. Medication does not block sweating as a sign of hypoglycemia.
• Advise patient to notify health care professional if slow pulse, difficulty breathing, wheezing, cold hands and feet, dizziness, light-headedness, confusion, depression, rash, fever, sore throat, unusual bleeding, or bruising occurs.
• Instruct patient to inform health care professional of medication regimen before treatment or surgery.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breast feeding. Monitor neonates of women taking metoprolol for symptoms of hypotension, bradycardia, hypoglycemia, and respiratory depression and manage accordingly. Monitor breast-fed infants for bradycardia, dry mouth, skin or eyes, and diarrhea or constipation.
• Advise patient to carry identification describing disease process and medication regimen at all times.
• Hypertension: Reinforce the need to continue additional therapies for hypertension (weight loss, sodium restriction, stress reduction, regular exercise, moderation of alcohol consumption, and smoking cessation). Medication controls but does not cure hypertension.

Evaluation/Desired Outcomes

• Decrease in BP.

• Reduction in frequency of anginal attacks.

  • Increase in activity tolerance.
• Prevention of MI.