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Pronunciation
(la BET a lole)
Generic Available (U.S.)
Yes
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of mild-to-severe hypertension; I.V. for severe hypertension (eg, hypertensive emergencies)
Use: Unlabeled/Investigational
Pediatric hypertension; management of pre-eclampsia; severe hypertension in pregnancy; hypertension during acute ischemic stroke
Pregnancy Risk Factor
C
Pregnancy Considerations
Because adverse events were observed in some animal reproduction studies, labetalol is classified as pregnancy category C. Labetalol crosses the placenta and can be detected in cord blood and infant serum after delivery. It has been shown to decrease maternal blood pressure without significantly effecting placental blood flow. In a cohort study, an increased risk of cardiovascular defects was observed following maternal use of beta-blockers during pregnancy. Intrauterine growth restriction (IUGR), small placentas, as well as fetal/neonatal bradycardia, hypoglycemia, and/or respiratory depression have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth should be available. Untreated chronic maternal hypertension and pre-eclampsia are also associated with adverse events in the fetus, infant, and mother. The pharmacokinetics of labetalol are not significantly changed during the third trimester of pregnancy. Labetalol is considered an appropriate agent for the treatment of hypertension in pregnancy; intravenous labetalol is also used for the management of pre-eclampsia.
Lactation
Enters breast milk/use caution (AAP rates "compatible"; AAP 2001 update pending)
Breast-Feeding Considerations
Low amounts of labetalol are found in breast milk and can be detected in the serum of nursing infants. The manufacturer recommends that caution be exercised when administering labetalol to nursing women.
Contraindications
Hypersensitivity to labetalol or any component of the formulation; severe bradycardia; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; bronchial asthma; uncompensated cardiac failure; conditions associated with severe and prolonged hypotension
Warnings/Precautions
Concerns related to adverse effects:
• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Hepatic injury: Severe hepatic injury including some fatalities have also been rarely reported with use; periodically monitor LFTs with prolonged use.
• Hypotension/syncope: Symptomatic hypotension with or without syncope may occur with labetalol; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Initiation with a low dose and gradual up-titration may help to decrease the occurrence of hypotension or syncope. Patients should be advised to avoid driving or other hazardous tasks during initiation of therapy due to the risk of syncope. Orthostatic hypotension may occur with I.V. administration; patient should remain supine during and for up to 3 hours after I.V. administration
Disease-related concerns:
• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms. May also reduce release of insulin in response to hyperglycemia; dosage of antidiabetic agents may need to be adjusted.
• Heart failure (HF): Use with extreme caution in patients with compensated heart failure and monitor for a worsening of the condition.
• Hepatic impairment: Use with caution in patients with hepatic impairment; bioavailability is increased due to decreased first-pass metabolism.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Peripheral vascular disease (PVD): May precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease; use with caution and monitor for progression of arterial obstruction.
• Pheochromocytoma (untreated): If possible, obtain diagnostic tests for pheochromocytoma prior to use. Labetalol has been shown to be effective in lowering blood pressure and relieving symptoms in patients with pheochromocytoma. However, some patients have experienced paradoxical hypertensive responses; use with caution in patients with pheochromocytoma. Additional alpha-blockade may be required during use of labetalol.
• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.
• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
Concurrent drug therapy issues:
• Anesthetic agents: Use with caution in patients receiving anesthetic agents which decrease myocardial function.
• Calcium channel blockers: Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur. Avoid concurrent I.V. use of both agents.
Special populations:
• Elderly: Elimination of labetalol is reduced in elderly patients; lower maintenance doses may be required.
Other warnings/precautions:
• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia.
Adverse Reactions
>10%:
Cardiovascular: Postural hypotension (I.V. use; ≤58%)
Central nervous system: Dizziness (1% to 20%), fatigue (1% to 11%)
Gastrointestinal: Nausea (≤19%)
1% to 10%:
Cardiovascular: Hypotension (1% to 5%), edema (≤2%), flushing (1%), ventricular arrhythmia (I.V. use; 1%)
Central nervous system: Somnolence (3%), headache (2%), vertigo (1% to 2%)
Dermatologic: Scalp tingling (≤7%), pruritus (1%), rash (1%)
Gastrointestinal: Dyspepsia (≤4%), vomiting (≤3%), taste disturbance (1%)
Genitourinary: Ejaculatory failure (≤5%), impotence (1% to 4%)
Hepatic: Transaminases increased (4%)
Neuromuscular & skeletal: Paresthesia (≤5%), weakness (1%)
Ocular: Vision abnormal (1%)
Renal: BUN increased (≤8%)
Respiratory: Nasal congestion (1% to 6%), dyspnea (2%)
Miscellaneous: Diaphoresis (≤4%)
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Alopecia (reversible), anaphylactoid reaction, ANA positive, angioedema, bradycardia, bronchospasm, cholestatic jaundice, CHF, diabetes insipidus, heart block, hepatic necrosis, hepatitis, hypersensitivity, Peyronie's disease, psoriaform rash, Raynaud's syndrome, syncope, systemic lupus erythematosus, toxic myopathy, urinary retention, urticaria
Other adverse reactions noted with beta-adrenergic blocking agents include mental depression, catatonia, disorientation, short-term memory loss, emotional lability, clouded sensorium, intensification of pre-existing AV block, laryngospasm, respiratory distress, agranulocytosis, thrombocytopenic purpura, nonthrombocytopenic purpura, mesenteric artery thrombosis, and ischemic colitis.
Drug Interactions
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Risk D: Consider therapy modification
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk D: Consider therapy modification
Alpha2-Agonists: Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk D: Consider therapy modification
Beta2-Agonists: Alpha-/Beta-Blockers may diminish the therapeutic effect of Beta2-Agonists. Risk D: Consider therapy modification
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy
Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
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 beta-blocker dose. Risk D: Consider therapy modification
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Lidocaine: Beta-Blockers may increase the serum concentration of Lidocaine. Risk C: Monitor therapy
Lidocaine (Systemic): Beta-Blockers may decrease the metabolism of Lidocaine (Systemic). Risk C: Monitor therapy
Lidocaine (Topical): Beta-Blockers may decrease the metabolism of Lidocaine (Topical). Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk X: Avoid combination
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy
Propoxyphene: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Alpha-/Beta-Blockers. Exceptions: FluvoxaMINE. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Labetalol serum concentrations may be increased if taken with food.
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid natural licorice (causes sodium and water retention and increases potassium loss). Avoid garlic (may have increased antihypertensive effect).
Storage
Tablets: Store tablets at 2°C to 30°C (36°F to 86°F). Protect from light and excessive moisture.
Vials: Store unopened injectable vials at 20°C to 25°C (68°F to 77°F); do not freeze. Protect from light. The solution is clear to slightly yellow.
Parenteral admixture: Stability of parenteral admixture at room temperature (25°C) and refrigeration temperature (4°C): 3 days.
Reconstitution
Standard concentration: 500 mg/250 mL D5W.
Minimum volume: 250 mL D5W.
Compatibility
Stable in D5LR, D2.51/2NS, D51/4NS, D51/3NS, D5NS, D5W, LR, NS, Ringer's; most stable at pH of 2-4. Incompatible with sodium bicarbonate 5% and alkaline solutions.
Y-site administration: Compatible: Amikacin, aminophylline, amiodarone, ampicillin, butorphanol, calcium gluconate, cefazolin, ceftazidime, ceftizoxime, chloramphenicol, cimetidine, clindamycin, diltiazem, dobutamine, dopamine, enalaprilat, epinephrine, erythromycin lactobionate, esmolol, famotidine, fentanyl, gatifloxacin, gentamicin, hydromorphone, lidocaine, linezolid, lorazepam, magnesium sulfate, meperidine, metronidazole, midazolam, milrinone, morphine, nicardipine, nitroglycerin, norepinephrine, oxacillin, penicillin G potassium, piperacillin, potassium chloride, potassium phosphates, propofol, ranitidine, sodium acetate, sodium nitroprusside, tobramycin, trimethoprim/sulfamethoxazole, vancomycin, vecuronium. Incompatible: Amphotericin B cholesteryl sulfate complex, cefoperazone, ceftriaxone, nafcillin, thiopental, warfarin. Variable (consult detailed reference): Furosemide, heparin, insulin (regular).
Compatibility when admixed: Incompatible: Sodium bicarbonate.
Mechanism of Action
Blocks alpha-, beta1-, and beta2-adrenergic receptor sites; elevated renins are reduced. The ratios of alpha- to beta-blockade differ depending on the route of administration: 1:3 (oral) and 1:7 (I.V.).
Pharmacodynamics/Kinetics
Onset of action: Oral: 20 minutes to 2 hours; I.V.: 2-5 minutes
Peak effect: Oral: 1-4 hours; I.V.: 5-15 minutes
Duration: Blood pressure response:
Oral: 8-12 hours (dose dependent)
I.V.: 2-18 hours (dose dependent; based on single and multiple sequential doses of 0.25-0.5 mg/kg with cumulative dosing up to 3.25 mg/kg)
Absorption: Complete
Distribution: Vd: Adults: 3-16 L/kg; mean: <9.4 L/kg; moderately lipid soluble, therefore, can enter CNS
Protein binding: 50%
Metabolism: Hepatic, primarily via glucuronide conjugation; extensive first-pass effect
Bioavailability: Oral: 25%; increased with liver disease, elderly, and concurrent cimetidine
Half-life elimination: Oral: 6-8 hours; I.V.: ~5.5 hours
Time to peak, plasma: Oral: 1-2 hours
Excretion: Urine (55% to 60% as glucuronide conjugates, <5% as unchanged drug)
Clearance: Possibly decreased in neonates/infants
Dosage
Children: Due to limited documentation of its use, labetalol should be initiated cautiously in pediatric patients with careful dosage adjustment and blood pressure monitoring.
Oral: Hypertension (unlabeled use): Initial: 1-3 mg/kg/day, in 2 divided doses; maximum: 10-12 mg/kg/day, up to 1200 mg/day
I.V., intermittent bolus doses of 0.3-1 mg/kg/dose have been reported.
For treatment of pediatric hypertensive emergencies, initial continuous infusions of 0.4-1 mg/kg/hour with a maximum of 3 mg/kg/hour have been used. Administration requires the use of an infusion pump.
Adults:
Hypertension: Oral: Initial: 100 mg twice daily, may increase as needed every 2-3 days by 100 mg twice daily (titration increments not to exceed 200 mg twice daily) until desired response is obtained; usual dose: 200-400 mg twice daily; may require up to 2.4 g/day.
Usual dose range (JNC 7): 200-800 mg/day in 2 divided doses
Acute hypertension (hypertensive emergency/urgency):
I.V. bolus: Per the manufacturer: Initial: 20 mg I.V. push over 2 minutes; may administer 40-80 mg at 10-minute intervals, up to 300 mg total cumulative dose; as appropriate, follow with oral antihypertensive regimen
I.V. infusion (acute loading): Per the manufacturer: Initial: 2 mg/minute; titrate to response up to 300 mg total cumulative dose (eg, discontinue after 2.5 hours of 2 mg/minute); as appropriate, follow with oral antihypertensive regimen
Note: Although loading infusions are well described in the product labeling, the labeling is silent in specific clinical situations, such as in the patient who has an initial response to labetalol infusions but cannot be converted to an oral route for subsequent dosing. There is limited documentation of prolonged continuous infusions (ie, >300 mg/day). In rare clinical situations, higher continuous infusion doses up to 6 mg/minute have been used in the critical care setting (eg, aortic dissection) and up to 8 mg/minute (eg, hypertension with ongoing acute ischemic stroke). At these doses, it may be best to consider an alternative agent if the labetalol infusion is not meeting the goals of therapy. At the other extreme, continuous infusions at relatively low doses (0.03-0.1 mg/minute) have been used in some settings (following loading infusion in patients who are unable to be converted to oral regimens or in some cases as a continuation of outpatient oral regimens). These prolonged infusions should not be confused with loading infusions. Because of wide variation in the use of infusions, an awareness of institutional policies and practices is extremely important. Careful clarification of orders and specific infusion rates/units is required to avoid confusion. Due to the prolonged duration of action, careful monitoring should be extended for the duration of the infusion and for several hours after the infusion. Excessive administration may result in prolonged hypotension and/or bradycardia.
Arterial hypertension in acute ischemic stroke (unlabeled use [Adams, 2007; Jauch, 2010]): I.V.:
Patient otherwise eligible for reperfusion treatment (eg, alteplase): Blood pressure (BP): Systolic >185 mm Hg or diastolic >110 mm Hg: 10-20 mg over 1-2 minutes; may repeat once. If BP does not decline and remains >185/110 mm Hg, alteplase should not be administered.
Management of BP during and after reperfusion treatment (eg, alteplase): BP: Systolic ≥180 mm Hg or diastolic ≥105 mm Hg: 10 mg over 1-2 minutes; may repeat every 10-20 minutes (maximum dose: 300 mg) or 10 mg followed by an infusion of 2-8 mg/minute. If hypertension is refractory, consider other I.V. antihypertensives (eg, nitroprusside)
Elderly: Hypertension: Oral:
Manufacturer's recommendations: Initial: 100 mg twice daily; may titrate in increments of 100 mg twice daily; usual maintenance: 100-200 mg twice daily
ACCF/AHA Expert Consensus recommendations: Consider lower initial doses and titrating to response (Aronow, 2011)
Dosage adjustment in renal impairment: Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
Dosage adjustment in hepatic impairment: Dosage reduction may be necessary.
Administration: I.V.
Bolus dose may be administered I.V. push at a rate of 10 mg/minute; may follow with continuous I.V. infusion
Administration: I.V. Detail
pH: 3-4
Monitoring Parameters
Blood pressure, standing and sitting/supine, pulse, cardiac monitor and blood pressure monitor required for I.V. administration
Test Interactions
False-positive urine catecholamines, vanillylmandelic acid (VMA) if measured by fluorometric or photometric methods; use HPLC or specific catecholamine radioenzymatic technique; false-positive amphetamine if measured by thin-layer chromatography or radioenzymatic assay (gas chromatographic-mass spectrometer technique should be used)
Patient Education
Take with meals. This medication does not replace other antihypertensive interventions; follow prescriber's instructions for diet and lifestyle changes. If you have diabetes, monitor serum glucose closely and notify prescriber of changes (this medication can alter glycemic response). You may experience drowsiness, dizziness, postural hypotension, or dry mouth. Report altered CNS status (eg, fatigue, depression, numbness or tingling of fingers, toes, or skin), palpitations or slowed heartbeat, respiratory difficulty, edema, or cold extremities.
Geriatric Considerations
Due to alterations in the beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response than seen in younger adults. Studies indicate that despite decreased sensitivity to the chronotropic effects of beta-blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress (ie, exercise). Controlled trials have shown the overall response rate for propranolol to be only 20% to 50% in elderly populations. Therefore, all beta-adrenergic blocking drugs may result in a decreased response as compared to younger adults.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Due to alterations in the beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response in the elderly than seen in younger adults. Despite decreased sensitivity to the chronotropic effects of beta-blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress (eg, exercise).
Evidence-Based Information:
Blood Pressure Management of Intracerebral Hemorrhage (ICH): In addition to standard management of ICH, blood pressure (BP) management in patients who are hypertensive is also of paramount importance when treating ICH. The primary rationale for lowering BP is to prevent further progression of the bleed. This can be accomplished using a number of different pharmacologic treatments (eg, nicardipine, labetalol, nitroprusside). Nitroprusside may increase ICP due to the pronounced vasodilatory actions and as a result may be less preferable. Specific BP targets are not supported by available evidence. The 2007 AHA/ASA Guidelines recommend initiating antihypertensive therapy if the SBP >180 mm Hg or if MAP >130 mm Hg (Broderick, 2007).
Surgery: The ACCF/AHA 2009 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery recommend beta-blockers be continued in patients undergoing surgery who are receiving beta-blockers to treat ACCF/AHA Class I guideline indications such as angina, symptomatic arrhythmias, or hypertension (Class I recommendation).
The majority of published trials suggest a benefit of perioperative beta-blocker use during noncardiac surgery especially in high-risk patients; however, more recent clinical trials have not shown a benefit to perioperative beta-blockade for noncardiac surgery especially when higher fixed-dose regimens are employed (Juul, 2006; POISE study group, 2008; Yang, 2006). Therefore, the guidelines suggest that perioperative beta-blocker therapy titrated to goal heart rate and blood pressure may be beneficial to patients undergoing intermediate risk (eg, carotid endarterectomy, prostate surgery) or vascular surgeries who have coronary artery disease identified or are at high cardiac risk (Class IIa recommendation). High cardiac risk is defined as having >1 of the following clinical risk factors: History of ischemic heart disease, compensated or prior heart failure, cerebrovascular disease, diabetes mellitus, or renal insufficiency (serum creatinine: >2 mg/dL). The use of beta-blockers is uncertain in patients undergoing intermediate risk or vascular surgery with ≤1 clinical risk factor (Class IIb recommendation). Based on available evidence, beta-blockers should be started days to weeks before elective surgery in selected patients when possible and titrated to adequate heart rate control (eg, between 60-80 beats per minute) while avoiding clinically significant bradycardia and hypotension. Routine administration of high fixed-dose beta blockade without dose titration is not useful and may be harmful to beta-blocker naïve patients undergoing noncardiac surgery.
Cardiovascular Considerations
Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. According to the 2003 JNC-VII guidelines for the treatment of hypertension, most patients with hypertension will require treatment with at least 2 antihypertensives. First-line therapy for hypertension is a diuretic (eg, hydrochlorothiazide or chlorthalidone). When a diuretic cannot be used or when a compelling indication exists for another drug, other types of antihypertensives may be used (eg, ACEIs, ARBs, beta-blockers, CCBs). Beta-blockers are among the multiple choices of agents that have shown benefit in a number of different patient subtypes. Compelling indications for a beta-blocker include patients with heart failure, postmyocardial infarction, high coronary disease risk, or diabetes. In type 2 diabetic patients, a UK Prospective Diabetes Study Group (UKPDS) trial showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.
Treatment should be targeted to a goal blood pressure of <140/90 mm Hg. If diabetes or renal disease coexists, the blood pressure goal should be <130/80 mm Hg.
Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Taste disorder.
Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Use with caution; epinephrine has interacted with nonselective beta-blockers to result in initial hypertensive episode followed by bradycardia
Mental Health: Effects on Mental Status
Dizziness is common; may cause sedation
Mental Health: Effects on Psychiatric Treatment
Barbiturates may decrease effects of beta-blockers; low potency antipsychotic and TCAs may potentiate the hypotensive effects of beta-blockers
Nursing: Physical Assessment/Monitoring
Blood pressure and heart rate should be assessed prior to and following first dose and any change in dosage. Caution patients with diabetes to monitor glucose levels closely; beta-blockers may alter glucose tolerance. Monitor for CHF.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as hydrochloride: 5 mg/mL (4 mL, 20 mL, 40 mL)
Trandate®: 5 mg/mL (20 mL, 40 mL) [contains edetate disodium]
Tablet, oral, as hydrochloride: 100 mg, 200 mg, 300 mg
Trandate®: 100 mg [scored]
Trandate®: 200 mg [scored; contains sodium benzoate]
Trandate®: 300 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Labetalol HCl)
100 mg (60): $26.99
200 mg (60): $28.99
300 mg (60): $38.99
Tablets (Trandate)
200 mg (60): $66.99
Extemporaneously Prepared
A 40 mg/mL labetalol hydrochloride oral suspension may be made with tablets and one of three different vehicles (cherry syrup, a 1:1 mixture of Ora-Sweet® and Ora-Plus®, or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®). Crush sixteen 300 mg tablets in a mortar and reduce to a fine powder. Add 20 mL of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "protect from light". Stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated (Allen, 1996).
Extemporaneously prepared solutions of labetalol hydrochloride (approximate concentrations 7-10 mg/mL) prepared in distilled water, simple syrup, apple juice, grape juice, and orange juice were stable for 4 weeks when stored in amber glass or plastic prescription bottles at room temperature or refrigerated (Nahata, 1991).
Allen LV Jr and Erickson MA 3rd, "Stability of Labetalol Hydrochloride, Metoprolol Tartrate, Verapamil Hydrochloride, and Spironolactone with Hydrochlorothiazide in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1996, 53(19):2304-9.
Nahata MC, "Stability of Labetalol Hydrochloride in Distilled Water, Simple Syrup, and Three Fruit Juices," DICP, 1991, 25(5):465-9.
References
“ACOG Practice Bulletin. Chronic Hypertension in Pregnancy. ACOG Committee on Practice Bulletins,” Obstet Gynecol, 2001, 98(Suppl 1):177-85.
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Last full review/revision June 2011
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