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Labetalol Hydrochloride

Pronunciation

Class: beta-Adrenergic Blocking Agents
VA Class: CV100
Chemical Name: 2-Hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]benzamide monohydrochloride
Molecular Formula: C19H24N2O3•HCl
CAS Number: 32780-64-6
Brands: Normodyne, Trandate

Introduction

Selective α- and nonselective β-adrenergic blocking agent.1 2 3 4 5 6 7 8 9 19 21 22 23 32 336

Uses for Labetalol Hydrochloride

Hypertension

Management of hypertension, alone or in combination with other classes of antihypertensive agents.2 4 13 253 293

One of several preferred initial therapies in hypertensive patients with heart failure, post-MI, high coronary disease risk, or diabetes mellitus.326

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.326

Effective in controlling BP in pregnant women with moderate to severe hypertension,64 68 185 285 297 severe pregnancy-induced hypertension,64 68 95 185 244 285 297 298 or hypertension with superimposed pregnancy-induced hypertension.64 68 185 285 Has reduced proteinuria and prevented eclampsia in hypertensive pregnant women with proteinuria.64 65 68 185

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Severe Hypertension and Hypertensive Crisis

Used parenterally for immediate BP reduction in severe hypertension or in hypertensive crises when considered an emergency;1 3 7 8 13 14 15 16 51 52 53 73 79 93 94 152 197 198 209 210 235 236 240 293 331 336 generally suitable for most hypertensive emergencies except when acute cardiac failure is present.239 331

Has been used for rapid reduction of BP in pediatric patients 1–17 years of age with hypertensive urgencies or emergencies.333

Pheochromocytoma

Has been used alone in patients with pheochromocytoma to control hypertension and symptoms resulting from excessive β-receptor stimulation.51 85 181 182 183 184 However, some clinicians caution against use unless pretreatment with α-adrenergic blocking agents (e.g., IV phentolamine) has occurred.7 May be more effective when tumors predominantly secrete epinephrine rather than norepinephrine, and with sustained rather than paroxysmal hypertension.85 (See Pheochromocytoma under Cautions.)

Preeclampsia

As an alternative to IV hydralazine, administered IV for controlling BP in pregnant women with preeclampsia when delivery is imminent.331

Controlled Hypotension during Anesthesia

Treatment to produce controlled hypotension during anesthesia to reduce bleeding resulting from surgical procedures.7 183 190 191 192 193 194 195

Angina

Management of chronic stable angina pectoris.7 17 18 127

Tetanus

Management of sympathetic overactivity syndrome associated with severe tetanus.196 200 201 202

Labetalol Hydrochloride Dosage and Administration

General

Hypertension

  • Monitor BP during initial titration or subsequent upward dosage adjustment; large or abrupt reductions in BP generally should be avoided. With continued oral dosing, BP can be measured approximately 12 hours after a dose to determine if further dosage titration is necessary.2 4 (See Absorption under Pharmacokinetics.)

  • Adjust oral dosage according to standing BP.2 4 293 Adjust gradually (e.g., every 2–4 weeks)203 over a period of 4–12 weeks9 75 76 203 to minimize or avoid adverse effects (e.g., nausea, dizziness) and improve patient tolerance.203

  • If long-term therapy is discontinued, gradually reduce dosage over a period of 1–2 weeks.2 4 293 (See Abrupt Withdrawal of Therapy under Cautions.)

  • When transferring from other hypotensive agents, start with usual initial labetalol dosage, and gradually decrease dosage of the existing regimen.2 4

Severe Hypertension and Hypertensive Crisis

  • Adjust dosage according to the severity of hypertension and the patient’s supine BP response and tolerance.1 3 293

  • Initial goal of IV therapy is to reduce mean arterial BP by no more than 25% within minutes to 1 hour, followed by further reduction if stable toward 160/100 to 110 mm Hg within the next 2–6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary insufficiency.293 If this BP is well tolerated and the patient is clinically stable, further gradual reductions toward normal can be implemented in the next 24–48 hours.331

  • Patients with aortic dissection should have systolic pressure reduced to <100 mm Hg if tolerated.331

Preeclampsia

  • Administer antihypertensives before labor induction for persistent DBPs ≥105–110 mm Hg, aiming for levels of 95–105 mm Hg.331

  • Monitor BP closely.331

Administration

Administer orally,2 4 7 8 19 23 47 49 by direct IV injection, or by continuous IV infusion.1 3 7 19 23 51 52 53 73 79 93 94 210

Oral Administration

Usually administered in 2 divided doses daily.2 4 If adverse effects (e.g., nausea, dizziness) occur and are intolerable (particularly with dosages ≥1.2 g daily), administration in 3 divided doses daily may improve patient tolerance and/or facilitate dosage titration.2 4

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow, direct IV injection or by slow, continuous IV infusion.1 3 7 19 23 51 52 53 73 79 93 94 210

Labetalol injection is intended for use in hospitalized patients.1

Patients must be kept in a supine position during and for 3 hours after IV administration since symptomatic orthostatic hypotension is likely to occur if patients are tilted upward or allowed to assume an upright position.1 3 (See Hypotension under Cautions.)

Dilution

For IV infusion, dilute labetalol injection to an appropriate concentration in a compatible IV infusion solution (e.g., add 200 mg of the drug to 160 mL of 5% dextrose injection to provide a solution containing 1 mg/mL).1 3

Rate of Administration

Administer repeat doses by slow, direct IV injection over a 2-minute period at intervals of 10 minutes.1 3 53 73 79 94 277 293 297 298

Administer diluted solutions by slow, continuous IV infusion1 3 51 73 210 277 293 297 with a controlled-infusion device to facilitate a desired rate of infusion.1 3

Dosage

Available as labetalol hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Hypertension
Oral

Initially, 1–3 mg/kg daily given in 2 divided doses.333 Increase dosage as necessary up to a maximum of 10–12 mg/kg or 1.2 g daily given in 2 divided doses.333

Severe Hypertension and Hypertensive Crisis
IV Injection

Children 1–17 years of age: 0.2–1 mg/kg up to maximum of 40 mg per dose by direct IV injection.333

IV Infusion

Alternatively, 0.25–3 mg/kg per hour by continuous IV infusion.333

Adults

Hypertension
Monotherapy
Oral

Initially, 100 mg twice daily.2 4 277 293

Adjust dosage in increments of 100 mg twice daily every 2 or 3 days until optimum BP response is achieved.2 4

For maintenance, manufacturer recommends a usual dosage of 200–400 mg twice daily.2 4 277 293 326 331 Manufacturer states that some adults with severe hypertension may require up to 1.2 g–2.4 g administered in 2 or 3 divided doses daily.2 4 a

JNC 7 recommends a usual range of 100–400 mg twice daily.326 JNC recommends adding another drug, if needed, rather than continuing to increase dosage.326

Combination Therapy
Oral

Initially, 100 mg twice daily, in combination with a diuretic.2 4 277 293

Adjustment of labetalol dosage may be necessary when diuretic is initiated in a patient already receiving labetalol; optimum maintenance dosage is usually lower.2 4

Severe Hypertension and Hypertensive Crisis
IV Injection

Initially, 20–80 mg by slow, direct IV injection.1 3 7 19 53 79 94 274 277 293 336

Higher initial doses (e.g., 1–2 mg/kg) have been administered,51 55 235 but the 20-mg dose is recommended to minimize adverse effects and the risks associated with too rapid reduction in BP.23 53 79

May give additional doses, usually 40–80 mg1 3 7 53 79 94 (range: 20–80 mg),19 73 79 274 277 293 336 at 10-minute intervals until the desired supine BP is achieved or up to a total cumulative dose of 300 mg.1 3 7 19 53 73 79 94 274 297 298 336

IV Infusion

Alternatively, initial rate of 0.5–2 mg/minute by continuous IV infusion; adjust rate according to the BP response.1 3 7 19 52 73 210 274 277 293 297

The usual effective, cumulative dose is 50–200 mg; up to 300 mg may be required.1 3

Progressive, incremental IV infusion regimen (i.e., infusing 20, 40, 80, and 160 mg/hour for 1 hour at each dose level, or until the desired BP is achieved) has been used, and may result in more gradual BP reduction, minimizing adverse effects compared with repeated IV injections of the drug.21 51 197 Controlled comparisons of various IV administration methods are not available.

Oral (following IV dosage)

Discontinue IV therapy and initiate oral labetalol therapy when the DBP begins to increase.1 3

Initially 200 mg, followed in 6–12 hours by an additional dose of 200 or 400 mg, depending on the BP response.1 3

If necessary, oral dosage may be increased in usual increments at 1-day intervals while the patient is hospitalized.1 3

Follow the usual oral dosage recommendations for subsequent outpatient dosage titration or maintenance dosing.1 3

Preeclampsia
IV

Initially, 20 mg by slow, direct IV injection, followed by 40 mg IV 10 minutes later and then 80-mg doses at 10-minute intervals for 2 additional doses.331

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Maximum 10–12 mg/kg or 1.2 g daily.333

Severe Hypertension and Hypertensive Crisis
IV Injection

Children 1–17 years of age: Maximum 40 mg per dose.333

Adults

Hypertension
Oral

Maximum titration increment of 200 mg twice daily.a

Severe Hypertension and Hypertensive Crisis
IV

Maximum cumulative dose of 300 mg.1 3 7 19 53 73 79 94 274 297 298

Preeclampsia
IV

Maximum cumulative dose of 220 mg.331

Special Populations

Hepatic Impairment

Dosage reduction may be necessary, but specific data are currently not available.7 39

Renal Impairment

No dosage adjustment required in patients with mild to moderate renal impairment.60 146 147 239 In patients with severe renal impairment (i.e., Clcr <10 mL/minute) undergoing dialysis, once-daily dosing may be adequate.241

Geriatric Patients

Oral

Adjustment in initial dosage not required.a Maintenance dosage requirements are lower in most geriatric patients; 100–200 mg twice daily usually required.4 a 4

Cautions for Labetalol Hydrochloride

Contraindications

  • Obstructive airway disease (e.g., bronchial asthma).1 2 3 4 311

  • Overt cardiac failure.1 2 3 4 311

  • Heart block greater than first degree.1 2 3 4 311

  • Cardiogenic shock.1 2 3 4 311

  • Severe bradycardia.1 2 3 4 311

  • Other conditions associated with severe and prolonged hypotension.1 3 4 247

  • Known hypersensitivity to labetalol or any ingredient in the formulation.1 3 4 247

Warnings/Precautions

Warnings

Hepatic Effects

Rarely, jaundice, hepatitis, severe hepatocellular injury, and elevated liver function test results have occurred; usually reversible following discontinuance,1 2 3 4 247 248 however, hepatic necrosis and death have been reported.1 2 3 4 247 248 254 255 275 276

Discontinue immediately if jaundice or laboratory evidence of hepatic injury occurs.1 2 3 4 247 248

Perform liver function tests at the first signs or symptoms of liver dysfunction (e.g., pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness, flu-like syndrome).1 2 3 4 247 248

Cardiac Failure

Possible precipitation of CHF.1 2 3 4 7 Use contraindicated in patients with overt CHF;1 2 3 4 may use cautiously in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).1 2 3 4 Use with caution in patients with inadequate cardiac function.1 2 3 4 7

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs and symptoms of impending cardiac failure occur; if cardiac failure continues, discontinue therapy, gradually if possible.1 2 3 4

Abrupt Withdrawal of Therapy

Abrupt withdrawal may exacerbate angina symptoms or precipitate MI in patients with CAD.1 2 3 4 Avoid abrupt discontinuance.2 4 Gradually decrease dosage over a period of 1–2 weeks, particularly in patients with ischemic heart disease and monitor patients carefully.1 2 3 4 If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly, at least temporarily, and initiate appropriate measures for the management of unstable angina pectoris.1 2 3 4

Labetalol may be less likely than pure β-adrenergic blocking agents to produce adverse cardiovascular withdrawal reactions (e.g., angina, rebound hypertension) following abrupt withdrawal;9 74 75 76 77 78 164 angina pectoris has not been reported to date following discontinuance of labetalol.1 2 3 4

Bronchospastic Disease

Possible inhibition of bronchodilation produced by endogenous catecholamines; use generally not recommended in patients with bronchospastic disease.2 4

May use oral labetalol with caution in patients with nonallergic bronchospasm (e.g., chronic bronchitis, emphysema) who do not respond to or cannot tolerate other hypotensive agents;2 4 use smallest effective dose to minimize inhibition of endogenous or exogenous β-adrenergic agonist activity.2 4

Do not use IV labetalol in patients with nonallergic bronchospasm at the usual therapeutic doses; has not been studied adequately.1 3

Pheochromocytoma

Use with caution in patients with pheochromocytoma;1 2 3 4 186 187 oral labetalol may induce paradoxical hypertensive crisis.7 186 187 203 Use not recommended unless pretreatment with α-adrenergic blocking agents (e.g., IV phentolamine) has occurred.7

Employ appropriate methods for determining urinary catecholamines if used in known or suspected pheochromocytoma.1 2 3 4 (See Specific Drugs and Laboratory Tests under Interactions.)

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, BP changes),1 2 3 4 impaired glucose tolerance, delayed rate of recovery of blood glucose concentration following drug-induced hypoglycemia, altered hemodynamic response to hypoglycemia (possibly resulting in exaggerated hypertensive response), and impaired peripheral circulation.211 212

Use with caution in patients with diabetes mellitus;1 2 3 4 dosage adjustment of the hypoglycemic agent may be necessary.1 2 3 4

Major Surgery

Severe, protracted hypotension and difficulty in restarting or maintaining a heart beat have occurred during surgery in some patients receiving β-adrenergic blocking agents;1 2 3 4 however, withdrawal of β-adrenergic blocking agent prior to major surgery is controversial.1 2 3 4

Effect of labetalol’s α-adrenergic activity in patients undergoing major surgery has not been evaluated,1 2 3 4 but several deaths have been reported with the use of the injection during surgery, including when used to control bleeding.1 3

Synergistic hypotensive response occurs with concomitant use of IV labetalol and halothane anesthesia.1 2 3 4 183 190 191 192 193 194 195 (See Specific Drugs and Laboratory Tests under Interactions.)

Severely Elevated BP

Use caution when reducing severely elevated BP.1 3

Use IV labetalol in hospitalized patients,1 3 and achieve the desired reduction over longest period of time compatible with the patient’s clinical status.1 3

Avoid rapid or excessive reductions in SBP or DBP.1 3

Serious adverse effects (e.g., cerebral infarction, optic nerve infarction, angina, and ischemic changes in the ECG)51 79 197 have been reported when severely elevated BP was reduced over several hours to up to 1 or 2 days with other hypotensive agents.311

General Precautions

Hypotension

Orthostatic hypotension associated with loss of consciousness reported occasionally following IV administration51 54 55 132 and rarely following oral administration.2 4 Symptomatic orthostatic hypotension is likely to occur if supine patients are tilted upward or allowed to assume the upright position within 3 hours following IV administration.1 3

If hypotension occurs, place the patient in Trendelenburg’s position, administer IV fluids, and/or temporarily discontinue administration of the drug.51 79 94 197

Patients should remain supine during and for up to 3 hours after IV administration.1 3 Establish patient’s ability to tolerate an upright position before any ambulation (e.g., use of toilet facilities) is permitted; advise patient on how to proceed gradually to become ambulatory and observe at the time of initial ambulation.1 3

Laboratory Tests

Monitor laboratory parameters at regular intervals in patients receiving long-term oral therapy.2 4

Routine laboratory tests are usually not required before or after IV administration.1 3

In patients with concomitant illnesses (e.g., impaired renal function), perform appropriate tests to monitor these conditions.1 2 3 4

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling of labetalol hydrochloride and Lamictal (lamotrigine, an anticonvulsant agent) has resulted in dispensing errors.319 320 Errors may be associated with serious adverse events (e.g., status epilepticus, serious lamotrigine rash) in patients receiving the wrong drug.319 320

History of Anaphylactic Reactions

Possible increased reactivity to a variety of allergens;1 patients may be less responsive to usual doses of epinephrine used to treat anaphylactic reactions.1 3 4

Other Precautions

Shares the toxic potentials of β-adrenergic and postsynaptic α1-adrenergic blocking agents;1 2 3 4 7 8 9 observe the usual precautions of these agents.1 2 3 4 7

Specific Populations

Pregnancy

Category C.1 2 3 4 247 248 a (See Hypertension and also see Preeclampsia under Uses.)

Lactation

Distributed into milk.1 2 3 4 6 7 64 68 69 Caution if used in nursing women.1 2 3 4

Pediatric Use

Safety and efficacy not fully established;1 2 3 4 247 248 however, some experts have recommended dosages for hypertension based on current limited clinical experience.333

Geriatric Use

Orthostatic symptoms (e.g., orthostatic hypotension, dizziness, lightheadedness) are more likely in geriatric individuals than in younger adults; caution geriatric patients about the possibility of such symptoms.4

A lower maintenance dosage may be required because of reduced elimination in geriatric patients.4 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution; metabolism of the drug may be decreased.1 2 3 4 7 39 247 248 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Elimination half-life may be increased in patients with severe renal impairment undergoing dialysis; once-daily dosing may be possible in these patients.241 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Symptomatic orthostatic hypotension,1 2 3 4 7 8 9 19 23 46 51 54 55 79 81 83 88 91 94 96 100 108 122 129 132 158 159 247 248 dizziness1 2 3 4 8 23 74 75 76 79 80 81 82 88 90 158 159 or lightheadedness,23 51 53 85 fatigue,1 2 3 4 23 75 76 78 87 159 nausea,1 2 3 4 7 8 19 23 51 53 74 75 76 78 79 80 81 82 83 87 90 93 94 158 159 247 248 dyspepsia.1 2 3 4 7 8 23 74 75 76 79 82 83 93 94 158 159 247 248

Interactions for Labetalol Hydrochloride

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

β-adrenergic agonists

Labetalol may antagonize bronchodilating effects1 2 3 4

Greater than usual dosages of β-adrenergic agonist bronchodilators may be required1 2 3 4

Calcium-channel blocking agents (e.g., verapamil, diltiazem)

Possible additive therapeutic256 257 258 259 260 261 262 263 264 265 267 268 269 270 271 272 273 and adverse effects257 261 264 266 267 268 271 272 273

Use concomitantly with caution1 3 4 247 258 259 260 261 264 266 268 271 272 273 290 291

Cimetidine

Absolute bioavailability of oral labetalol substantially increased, possibly via enhanced absorption or decreased first-pass hepatic metabolism 1 2 3 4 180 229

Carefully adjust labetalol dosage for optimal BP control with concomitant use1 2 3 4 229

Diuretics

Increased hypotensive effect 2 4 7 8 9 13 15 19 72 76 77 78 80 81 82 83 85 87 90 91 96 97 99 231 234

Usually used to therapeutic advantage; careful dosage adjustments recommended2 4 7 8 9 13 15 19 72 76 77 78 80 81 82 83 85 87 90 91 96 97 99 231 234

Glutethimide

Absolute bioavailability of oral labetalol decreased, possibly by increasing first-pass hepatic metabolism 229

Carefully adjust labetalol dosage for optimal BP control with concomitant use229

Halothane

Synergistic hypotensive effect; 183 190 191 192 193 194 195 may result in large reduction in cardiac output and increase in central venous pressure1 2 3 4 183 190 191 192 193 194 195

Adjust halothane concentration to control the degree and duration of hypotension;183 190 191 192 193 194 195 to minimize the risk of excessive hypotension, inspired halothane concentrations of ≥3% should not be used1 2 3 4

Inform anesthesiologist if labetalol therapy is continued in a patient undergoing major surgery1 2 3 4

Mibefradil (no longer commercially available in the US)

Slowing or complete suppression of SA node activity, with slow ventricular rates290 291

Nitroglycerin

Possible additive hypotensive effects1 2 3 4 and antagonism of the reflex tachycardia produced by nitroglycerin1 2 3 4

Tricyclic antidepressants

Possible increased incidence of tremor 1 2 3 4

Tests for urinary catecholamines

Labetalol metabolites in urine may result in false-positive elevations of urinary free216 and total217 catecholamines, metanephrine, normetanephrine, and 3-methoxy-4-hydroxymandelic acid (vanillylmandelic acid, VMA) measured by fluorometric or photometric methods1 2 3 4 216 217 218 248

When screening labetalol-treated patients suspected of having pheochromocytoma or when evaluating labetalol-treated patients with the tumor, use specific assay methods such as high-performance liquid chromatography (HPLC) with solid phase extraction1 2 3 4 218 248 252 to determine concentrations of catecholamines or their metabolites1 2 3 4 216 217 218 248

Labetalol Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed (i.e., 90–100%) from the GI tract following oral administration.2 4 5 6 7 8 10 34 58 59

Undergoes extensive first-pass metabolism in the liver and/or GI mucosa.2 4 5 6 7 8 10 23 33 34 35 37 41 58 Absolute bioavailability is about 25%.2 4 5 6 7 34 37

Onset

Following oral administration, hypotensive effect is generally apparent within 20 minutes to 2 hours,6 10 34 43 48 56 57 and maximal within 1–4 hours.2 4 5 6 7 34 43 48 56

Maximum, steady-state BP response with twice-daily dosing occurs within 1–3 days.2 4

Following slow, direct IV injection, hypotensive effect is apparent within 2–5 minutes,5 6 7 33 47 51 52 53 54 55 240 and usually maximal within 5–15 minutes.1 3 53 54 55 240

Duration

Dose dependent; about 8–12 or 12–24 hours after a single 200- or 300-mg dose, respectively.2 4 5 6 43 57

Following slow, direct IV injection, the hypotensive effect generally persists for about 2–4 hours,6 53 55 although a longer duration of effect (i.e., up to 24 hours) has been reported in some patients.6 33 53 55 240

Food

Delays absorption,36 but increases absolute bioavailability.2 4 5 7 10 36 37

Special Populations

Relative bioavailability is increased in hepatic impairment.a 1 2 3 4 5 10 39

First-pass metabolism may be reduced and bioavailability substantially increased in geriatric patients.7 10 38

Distribution

Extent

Following IV administration, rapidly and widely distributed into the extravascular space.5 7 10 33 34 35

In animals, highest concentrations in the lungs, liver, and kidneys;5 7 10 58 only minimal amounts cross the blood-brain barrier.1 2 3 4 5 7 10 58

Crosses the placenta;1 2 3 4 5 6 58 64 65 66 67 70 distributed into milk,1 2 3 4 5 6 7 64 68 69 principally as unbound labetalol.5

Plasma Protein Binding

Approximately 50%.1 2 3 4 5 7 10 58

Special Populations

In patients with impaired hepatic function, the apparent volume of distribution is decreased.39

Elimination

Metabolism

Following oral administration, extensively metabolized in the liver and possibly in the GI mucosa principally by conjugation with glucuronic acid,1 2 3 4 5 7 10 58 principally to O-alkylglucuronide5 and smaller amounts of O-phenylglucuronide and N-glucuronide.5 10 58

Undergoes extensive first-pass metabolism in the liver and/or GI mucosa.2 4 5 6 7 8 10 23 33 34 35 37 41 58

Elimination Route

Excreted in feces via biliary elimination (30% within 4 days) and in urine (55–60% within 24 hours), mainly as glucuronide conjugates.1 2 3 4 5 7 10 58 1 2 3 4 5 7 10 58

Less than 5% of a dose is excreted unchanged in urine.7 10 58

Half-life

Biphasic5 7 10 33 35 43 58 59 or possibly triphasic;10 33 241 terminal half-life averages 2.5–8 hours.1 2 3 4 5 7 10 33 35 37 38 39 41 43 58 60 63 Manufacturers specify half-life of 5.5 or 6–8 hours following IV or oral administration, respectively.1 2 3 4

Special Populations

Elimination may be reduced and half-life may be slightly increased in geriatric individuals.4 7 10 38

Half-life apparently unchanged in individuals with renal1 2 3 4 5 10 60 71 239 or hepatic impairment,1 2 3 4 39 but may be increased in patients with severe renal impairment (i.e., Clcr <10 mL/minute) undergoing dialysis.241

Not appreciably removed (<1% of a dose) by hemodialysis203 204 241 242 or peritoneal dialysis.203 223 241 242

Stability

Storage

Oral

Tablets

Well-closed containers20 at 2–30°C.2 4 5 6

Protect tablets in unit-dose packages from excessive moisture.2 4 5 6

Parenteral

Injection

2–30°C; protect from light and freezing.1 3 5 6

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in Ringer’s injection

Dextrose 5% in Ringer’s injection, lactated

Dextrose 2.5% in sodium chloride 0.45%

Dextrose 5% in sodium chloride 0.2, 0.33, or 0.9%

Dextrose 5% in water

Polysal in dextrose 5%

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.9%

Incompatible

Sodium bicarbonate 5%

Drug Compatibility
Y-Site CompatibilityHID

Compatible

Amikacin sulfate

Aminophylline

Amiodarone HCl

Ampicillin sodium

Bivalirudin

Butorphanol tartrate

Calcium gluconate

Cefazolin sodium

Ceftazidime

Chloramphenicol sodium succinate

Clindamycin phosphate

Clonidine HCl

Co-trimoxazole

Dexmedetomidine HCl

Diltiazem HCl

Dobutamine HCl

Dopamine HCl

Doripenem

Enalaprilat

Epinephrine HCl

Erythromycin lactobionate

Esmolol HCl

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Gentamicin sulfate

Hetastarch in lactated electrolyte injection (Hextend)

Hydromorphone HCl

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Lidocaine HCl

Linezolid

Lorazepam

Magnesium sulfate

Meperidine HCl

Metronidazole

Micafungin sodium

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nicardipine HCl

Nitroglycerin

Norepinephrine bitartrate

Oxacillin sodium

Penicillin G potassium

Potassium chloride

Potassium phosphates

Propofol

Ranitidine HCl

Sodium acetate

Sodium nitroprusside

Telavancin HCl

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Incompatible

Amphotericin B cholesteryl sulfate complex

Ceftaroline fosamil

Ceftriaxone sodium

Furosemide

Nafcillin sodium

Warfarin sodium

Variable

Heparin sodium

Actions

  • Competitively blocks adrenergic stimulation of β-receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors) and α1-receptors within vascular smooth muscle.1 2 3 4 7 8 9 21 22 23 24 28 29 30 32 44

  • Has some intrinsic β2-agonist activity in animals,1 2 3 4 7 30 62 221 222 but exerts little, if any, intrinsic β1-agonist activity;1 2 3 4 7 8 9 30 62 107 does not exhibit intrinsic α-adrenergic agonist activity.7 28 30

  • Unlike pure β-adrenergic blocking agents, produces a dose-dependent (at usual doses) decrease in systemic arterial BP and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently because of its combined α- and β-adrenergic blocking activity.1 2 3 4 7 112 113 114

  • Effectively reduces BP in the standing or supine position, but because of the drug’s α1-adrenergic blocking activity, the effect on BP is position dependent; labetalol-induced decreases in BP are greater in the standing than in the supine position, and orthostatic hypotension can occur.1 2 3 4 7 8 9 112 113 114 115 116 117 118 119 120 121 122 123 124

  • Electrophysiologic effects of labetalol are variable and appear to be mediated via the drug’s myocardial β1-adrenergic blocking activity.1 2 3 4 7 111 219 220

  • May decrease conduction velocity through the AV node and increase the atrial effective refractory period (ERP), but the drug appears to have inconsistent effects on SA conduction time and the AV nodal refractory period;1 2 3 4 7 111 the decrease in AV nodal conduction velocity produced by labetalol is less than that produced by pure β-adrenergic blocking agents.7

  • Generally has little effect on sinus rate, intraventricular conduction, the His-Purkinje system, or duration of the QRS complex.1 2 3 4 7 111

Advice to Patients

  • Importance of taking medication exactly as prescribed.a

  • Importance of not interrupting or discontinuing therapy without consulting clinician; patients should temporarily limit their physical activity when discontinuing therapy.1 2 3 4

  • Importance of patients informing anesthesiologist or dentist about labetalol therapy before undergoing major surgery.1 2 3 4

  • Importance of immediately informing clinician at the first sign or symptom of impending cardiac failure or if any difficulty in breathing occurs.1 2 3 4

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 2 3 4

  • Advise patients that transient scalp tingling may occur, usually during initiation of labetalol therapy.1 2 3 4

  • Caution geriatric patients about the possibility of orthostatic symptoms (orthostatic hypotension, dizziness, lightheadedness).4

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 3 4 247 248

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Labetalol Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

100 mg*

Labetalol Hydrochloride Tablets

Trandate (scored)

Prometheus

200 mg*

Labetalol Hydrochloride Tablets

Trandate (scored)

Prometheus

300 mg*

Labetalol Hydrochloride Tablets

Trandate (scored)

Prometheus

Parenteral

Injection, for IV use

5 mg/mL*

Labetalol Hydrochloride Injection

Trandate

Prometheus

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Labetalol HCl 100MG Tablets (IVAX PHARMACEUTICALS): 60/$26.99 or 180/$60.97

Labetalol HCl 200MG Tablets (SANDOZ): 30/$17.99 or 60/$26.97

Labetalol HCl 300MG Tablets (WATSON LABS): 60/$38.99 or 180/$99.95

Trandate 200MG Tablets (PROMETHEUS): 60/$66.99 or 180/$195.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 10, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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