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
Selective α1- and nonselective β-adrenergic blocking agent.1 2 3 4 5 6 7 8 9 19 21 22 23 32
Uses for Labetalol Hydrochloride
Management of hypertension, alone or in combination with other classes of antihypertensive agents.2 4 253 500
β-Blockers generally not preferred for initial management of hypertension, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).337 501 502 503 504 515 523 524 527 700
Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers.327 334 335 500 501 504 However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.500
Recommended by ACOG and other experts as an appropriate drug of choice in pregnant women who require antihypertensive therapy.298 502 540
Severe Hypertension and Hypertensive Crisis
Used parenterally for immediate BP reduction in severe hypertension or hypertensive emergency;1 3 7 8 14 15 16 51 52 53 73 79 93 94 152 197 198 209 210 235 236 240 500 502 542 generally suitable for most hypertensive emergencies except when acute cardiac failure is present.239 500
One of several recommended parenteral agents for use in the hospital setting to urgently lower BP in severely hypertensive pregnant women, including those with preeclampsia†.298 338 500 540
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.)
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
Chronic Stable Angina
Management of chronic stable angina pectoris†.7 17 18 127
β-Blockers are recommended as first-line anti-ischemic drugs in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this use.1101
Management of sympathetic overactivity syndrome associated with severe tetanus†.196 200 201 202
Labetalol Hydrochloride Dosage and Administration
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.)
BP Monitoring and Treatment Goals
Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501 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
When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501
Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501
Severe Hypertension and Hypertensive Crisis
Adjust dosage according to the severity of hypertension and the patient’s supine BP response and tolerance.1 3 500
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.500 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.500
Patients with aortic dissection should have systolic pressure reduced to <100 mm Hg if tolerated.500
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
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
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.)
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 94 298 500
Administer diluted solutions by slow, continuous IV infusion1 3 51 73 210 with a controlled-infusion device to facilitate a desired rate of infusion.1 3
Available as labetalol hydrochloride; dosage expressed in terms of the salt.
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
Rapid Reduction of BP†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.333IV Infusion
Alternatively, 0.25–3 mg/kg per hour by continuous IV infusion.333
Initially, 100 mg twice daily, either alone or in combination with a diuretic.2 4 293
Adjust dosage in increments of 100 mg twice daily every 2 or 3 days until optimum BP response is achieved.2 4
For maintenance, manufacturers recommend a usual dosage of 200–400 mg twice daily.2 4 Manufacturers state that some adults with severe hypertension may require up to 1.2–2.4 g daily in 2 or 3 divided doses.2 4 a
Some experts recommend a usual range of 100–400 mg twice daily.500 Rationale for lower dosage range is that it may be preferable to add another drug rather than continue to increase dosage.332
If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501
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
When transferring from other antihypertensive agents, start with usual initial labetalol dosage and gradually decrease dosage of the existing regimen.2 4
Severe Hypertension and Hypertensive Crisis
Initially, 20–80 mg by slow, direct IV injection.1 3 7 19 53 79 94 274 500
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 79 274 500 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 94 274 298
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 73 210 274 500
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
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.500
Maximum 10–12 mg/kg or 1.2 g daily.333
Children 1–17 years of age: Maximum 40 mg per dose.333
Maximum titration increment of 200 mg twice daily.a
Severe Hypertension and Hypertensive Crisis
Maximum cumulative dose of 300 mg.1 3 7 19 53 73 79 94 274 298
Maximum cumulative dose of 220 mg.500
Dosage reduction may be necessary, but specific data are currently not available.7 39
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
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
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
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
Possible precipitation of heart failure.1 2 3 4 7 Use contraindicated in patients with overt heart failure;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
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
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
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
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
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
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
Category C.1 2 3 4 247 248 a
Distributed into milk.1 2 3 4 6 7 64 68 69 Caution if used in nursing women.1 2 3 4
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
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.)
Use with caution; metabolism of the drug may be decreased.1 2 3 4 7 39 247 248 (See Special Populations under Pharmacokinetics.)
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
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
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
Increased hypotensive effect 2 4 7 8 9 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 15 19 72 76 77 78 80 81 82 83 85 87 90 91 96 97 99 231 234
Glutethimide (no longer commercially available in the US)
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
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
Possible additive hypotensive effects1 2 3 4 and antagonism of the reflex tachycardia produced by nitroglycerin1 2 3 4
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
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
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
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
Delays absorption,36 but increases absolute bioavailability.2 4 5 7 10 36 37
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
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
In patients with impaired hepatic function, the apparent volume of distribution is decreased.39
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
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
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
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
Well-closed containers20 at 2–30°C.2 4 5 6
Protect tablets in unit-dose packages from excessive moisture.2 4 5 6
2–30°C; protect from light and freezing.1 3 5 6
For information on systemic interactions resulting from concomitant use, see Interactions.
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, lactated
Sodium chloride 0.9%
Sodium bicarbonate 5%
Chloramphenicol sodium succinate
Hetastarch in lactated electrolyte injection (Hextend)
Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%
Penicillin G potassium
Amphotericin B cholesteryl sulfate complex
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.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Labetalol Hydrochloride Tablets
Labetalol Hydrochloride Tablets
Labetalol Hydrochloride Tablets
Injection, for IV use
Labetalol Hydrochloride Injection
AHFS DI Essentials. © Copyright 2017, Selected Revisions October 30, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. Schering Corporation. Normodyne (labetalol hydrochloride) injection prescribing information (dated 1997 Feb). In: Physicians’ desk reference. 52nd ed. Montvale, NJ: Medical Economical Company Inc; 1998(Suppl A):A280-2.
2. Schering Corporation. Normodyne tablets prescribing information. Kenilworth, NJ; 1990 Apr.
3. Glaxo Wellcome. Hanburys. Trandate (labetalol hydrochloride) injection prescribing information. Research Triangle Park, NC; 1998 Apr.
4. Glaxo Wellcome. Trandate (labetalol hydrochloride) tablets prescribing information. Research Triangle Park, NC; 1998 Jun.
5. Schering Corporation. Normodyne (labetalol HCl) product monograph. Kenilworth, NJ; 1984.
6. Glaxo Inc. Product information form for American Hospital Formulary Service on Trandate. Research Triangle Park, NC; 1984 Aug 24.
7. MacCarthy EP, Bloomfield SS. Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. Pharmacotherapy. 1983; 3:193-219. [PubMed 6310529]
8. Wallin JD, O’Neill WM. Labetalol: current research and therapeutic status. Arch Intern Med. 1983; 143:485-90. [PubMed 6338850]
9. Michelson EL, Frishman WH. Labetalol: an alpha- and beta-adrenoceptor blocking drug. Ann Intern Med. 1983; 99:553-5. [PubMed 6137987]
10. McNeil JJ, Louis WJ. Clinical pharmacokinetics of labetalol. Clin Pharmacokinet. 1984; 9:157-67. [PubMed 6370541]
11. Weber MA. Beta blockers in the initial therapy of hypertension. Drug Ther. 1980; 10(11):77-80.
12. Anon. Beta-blocker poisoning. Lancet. 1980; 1:803-4.
14. Pearson RM, Griffith DNW, Woollard M et al. Comparison of effects on cerebral blood flow of rapid reduction in systemic arterial pressure by diazoxide and labetalol in hypertensive patients: preliminary findings. Br J Clin Pharmacol. 1979; 8(Suppl 2):195-8S.
15. MacCarthy EP, Frost GW, Stokes GS. Labetalol in hypertensive emergencies. Med J Aust. 1978; 1:399-400. [PubMed 672732]
16. Yeung CK, Thomas GW, Whitworth JA et al. Comparison of labetalol, clonidine and diazoxide intravenously administered in severe hypertension. Med J Aust. 1979; 2:499-500. [PubMed 522807]
17. Quyyumi AA, Wright C, Mockus L et al. Effects of combined alpha and beta adrenoceptor blockade in patients with angina pectoris. A double blind study comparing labetalol with placebo. Br Heart J. 1985; 53:47-52. [PubMed 3881105]
18. Upward JW, Akhras F, Jackson G. Oral labetalol in the management of stable angina pectoris in normotensive patients. Br Heart J. 1985; 53:53-7. [PubMed 3917674]
19. Anon. Labetalol for hypertension. Med Lett Drugs Ther. 1984; 26:83-5. [PubMed 6147747]
20. USP DI Update. No. 1. Labetalol. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1985:5-8.
21. Robertson JIS. Labetalol: the nineteen-eighties. Br J Clin Pharmacol. 1982; 13(Suppl 1):137-41S.
22. Conner CS. Labetalol: an alpha- and beta-blocker. Drug Intell Clin Pharm. 1983; 17:543-4. [PubMed 6135593]
23. Carter BL. Labetalol (Trandate, Glaxo Inc.; Normodyne, Schering Corp.). Drug Intell Clin Pharm. 1983; 17:704-12. [PubMed 6354658]
24. Gross F. The place of α-adrenoceptor and β-adrenoceptor blockade in the treatment of hypertension. Br J Clin Pharmacol. 1982; 13(Suppl 1):5-11S. [PubMed 7039647]
25. Semplicini A, Pessina AC, Rossi GP et al. Alpha-adrenoceptor blockade by labetalol during long-term dosing. Clin Pharmacol Ther. 1983; 33:279-82.
26. Brittain RT, Drew GM, Levy GP. The α- and β-adrenoceptor potencies of labetalol and its individual stereoisomers. Br J Pharmacol. 1981; 73:282-3P.
27. Bellamy GR, Hunyor SN, Roffe D et al. Magnitude and mechanisms of the antihypertensive action of labetalol, including ambulatory assessment. Br J Clin Pharmacol. 1983; 16:9-16. [PubMed 6882628]
28. Farmer JB, Kennedy I, Levy GB et al. Pharmacology of AH 5158; a drug which blocks both α- and β-adrenoceptors. Br J Pharmacol. 1972; 45:660-75. [PubMed 4404413]
29. Weber MA, Drayer JIM. Central and peripheral blockade of the sympathetic nervous system. Am J Med. 1984; 77(Suppl 4A):110-8. [PubMed 6148889]
30. Baum T, Sybertz EJ. Pharmacology of labetalol in experimental animals. Am J Med. 1983; 75(Suppl 4A):15-23. [PubMed 6314811]
31. Yuen PC, Taddei CR, Wyka BE et al. Compatibility and stability of labetalol hydrochloride in commonly used intravenous solutions. Am J Hosp Pharm. 1983; 40:1007-9. [PubMed 6869384]
32. Richards DA, Prichard BNC. Clinical pharmacology of labetalol. Br J Clin Pharmacol. 1979; 8(Suppl 2):89-93S. [PubMed 552303]
33. McNeil JJ, Anderson AE, Louis WJ. Pharmacokinetics and pharmacodynamic studies of labetalol in hypertensive subjects. Br J Clin Pharmacol. 1979; 8(Suppl 2):157-61S.
34. Leitz F, Bariletto S, Chung M et al. Bioavailability/pharmacokinetics of labetalol in normotensive male volunteers. Fed Proc. 1982; 41:1557.
35. Kanto J, Allonen H, Kleimola T et al. Pharmacokinetics of labetalol in healthy volunteers. Int J Clin Pharmacol Ther Toxicol. 1981; 19:41-4. [PubMed 7203731]
36. Mantyla R, Allonen H, Kanto J et al. Effect of food on the bioavailability of labetalol. Br J Clin Pharmacol. 1980; 9:435-7. [PubMed 7378263]
37. Daneshmend TK, Roberts CJC. The influence of food on the oral and intravenous pharmacokinetics of a high clearance drug: a study with labetalol. Br J Clin Pharmacol. 1982; 14:73-8. [PubMed 7104169]
38. Kelly JG, McGarry K, O’Malley K et al. Bioavailability of labetalol increases with age. Br J Clin Pharmacol. 1982; 14:304-5. [PubMed 7104187]
39. Homeida M, Jackson L, Roberts CJC. Decreased first-pass metabolism of labetalol in chronic liver disease. Br Med J. 1978; 2:1048-50. [PubMed 709214]
40. Daneshmend TK, Homeida M, Roberts CJC. The effect of hepatosplenic schistosomiasis on the pharmacokinetics of metronidazole and labetalol. Br J Clin Pharmacol. 1982; 14:152-3P.
41. McNeil JJ, Anderson AE, Louis WJ et al. Labetalol steady-state pharmacokinetics in hypertensive patients. Br J Clin Pharmacol. 1982; 13(Suppl 1):75-80S.
42. Sanders GL, Routledge PA, Ward A et al. Mean steady-state plasma concentrations of labetalol in patients undergoing antihypertensive therapy. Br J Clin Pharmacol. 1979; 8(Suppl 2):153-5S.
43. Maronde RF, Robinson D, Vlachakis ND et al. Study of single and multiple dose pharmacokinetic/pharmacodynamic modeling of antihypertensive effects of labetalol. Am J Med. 1983; 75(Suppl 4A):40-6. [PubMed 6356898]
44. Brittain RT, Drew GM, Levy GP. The α- and β-adrenoceptor blocking potencies of labetalol and its individual stereoisomers in anaesthetized dogs and in isolated tissues. Br J Pharmacol. 1982; 77:105-14. [PubMed 6127131]
45. Alam AS. Identification of labetalol precipitate. Am J Hosp Pharm. 1984; 41:74. [PubMed 6695936]
46. McNeil JJ, Anderson AE, Louis WJ. An analysis of the blood pressure response to labetalol in hypertensive patients. Clin Sci. 1981; 61(Suppl):449-52S.
47. Lund-Johansen P. Short- and long-term (six-year) hemodynamic effects of labetalol in essential hypertension. Am J Med. 1983; 75(Suppl 4A):24-31. [PubMed 6638038]
48. Serlin MJ, Orme MC, Maciver M et al. Rate of onset of hypotensive effect of oral labetalol. Br J Clin Pharmacol. 1979; 7:165-8. [PubMed 760748]
49. Lund-Johansen P, Bakke OM. Haemodynamic effects and plasma concentrations of labetalol during long-term treatment of essential hypertension. Br J Clin Pharmacol. 1979; 7:169-74. [PubMed 760749]
50. Richards DA, Maconochie JG, Bland RE et al. Relationship between plasma concentrations and pharmacological effects of labetalol. Eur J Clin Pharmacol. 1977; 11:85-90. [PubMed 14010]
51. Cumming AMM, Brown JJ, Lever AF et al. Intravenous labetalol in the treatment of severe hypertension. Br J Clin Pharmacol. 1982; 13(Suppl 1):93-6S.
52. Dal Palu C, Pessina AC, Semplicini A et al. Intravenous labetalol in severe hypertension. Br J Clin Pharmacol. 1982; 13(Suppl 1):97-9S.
53. Cressman MD, Vidt DG, Gifford RW et al. Intravenous labetalol in the management of severe hypertension and hypertensive emergencies. Am Heart J. 1984; 107(5 Part 1):980-5. [PubMed 6720529]
54. Trust PM, Rosei EA, Brown JJ et al. Effect of blood pressure, angiotensin II and aldosterone concentrations during treatment of severe hypertension with intravenous labetalol: comparison with propranolol. Br J Clin Pharmacol. 1976; 3(Suppl 3):799-803. [PubMed 791333]
55. Rosei EA, Trust PM, Brown JJ et al. Effects of intravenous labetalol on blood pressure, angiotensin II and aldosterone in hypertension: comparison with propranolol. Clin Sci Mol Med. 1976; 51(Suppl 3):497-9S.
56. Davies AB, Bala Subramanian V, Gould B et al. Rapid reduction of blood pressure with acute oral labetalol. Br J Clin Pharmacol. 1982; 13:705-10. [PubMed 7082539]
57. Rossi A, Ziacchi V, Lomanto B. The hypotensive effect of a single daily dose of labetalol: a preliminary study. Int J Clin Pharmacol Ther Toxicol. 1982; 20:438-45. [PubMed 6754634]
58. Martin LE, Hopkins R, Bland R. Metabolism of labetalol by animals and man. Br J Clin Pharmacol. 1976; 3(Suppl 3):695-710. [PubMed 990152]
59. Chung M, Ning J, Radwanski E et al. Multiple-dose pharmacokinetics of labetalol in hypertensive patients. In: Abstracts of papers presented before the APhA Academy of Pharmaceutical Sciences. Washington, DC: American Pharmaceutical Association; 1982; 12(1):49. Abstract.
60. Wood AJ, Ferry DG, Bailey RR. Elimination kinetics of labetalol in severe renal failure. Br J Clin Pharmacol. 1982; 13(Suppl 1):81-6S. [PubMed 7066158]
61. Baum T, Watkins RW, Sybertz EJ et al. Antihypertensive and hemodynamic actions of SCH 19927, the R, R-isomer and labetalol. J Pharmacol Exp Ther. 1981; 218:444-52. [PubMed 7252843]
62. Sybertz EJ, Sabin CS, Pula KK et al. Alpha and beta adrenoceptor blocking properties of labetalol and its R, R-isomer, SCH 19927. J Pharmacol Exp Ther. 1981; 218:435-43. [PubMed 6114171]
63. Rubin PC, Butters L, Kelman AW et al. Labetalol disposition and concentration-effect relationships during pregnancy. Br J Clin Pharmacol. 1983; 15:465-70. [PubMed 6849783]
64. Michael CA. Use of labetalol in the treatment of severe hypertension during pregnancy. Br J Clin Pharmacol. 1979; 8(Suppl 2):211-5S.
65. Riley AJ. Clinical pharmacology of labetalol in pregnancy. J Cardiovasc Pharmacol. 1982; 3(Suppl 1):S53-9.
66. Nylund L, Lunell NO, Lewander R et al. Labetalol for the treatment of hypertension in pregnancy: pharmacokinetics and effects on the uteroplacental blood flow. Acta Obstet Gynecol Scand. 1984; 118(Suppl):71-3.
67. Poynter D, Martin LE, Harrison C et al. Affinity of labetalol for ocular melanin. Br J Clin Pharmacol. 1976; 3(Suppl 3):711-20. [PubMed 990153]
68. Michael CA. The evaluation of labetalol in the treatment of hypertension complicating pregnancy. Br J Clin Pharmacol. 1982; 13(Suppl 1):127-31S. [PubMed 7066151]
69. Leitz F, Bariletto S, Gural R et al. Secretion of labetalol in breast milk in lactating women. Fed Proc. 1983; 42:378.
70. Lardoux H, Gerard J, Blazquez G et al. Which beta-blocker in pregnancy-induced hypertension? Lancet. 1983; 2:1194. Letter. (IDIS 178452)
71. Walstad AA, Berg KJ, Wessel-Aas T et al. Labetalol in the treatment of hypertension in patients with normal and impaired renal function. Acta Med Scand. 1982; 212(Suppl):135-41.
72. Anon. Drugs for hypertension. Med Lett Drugs Ther. 1984; 26:107-12. [PubMed 6150424]
73. Anon. Drugs for hypertensive emergencies. Med Lett Drugs Ther. 1985; 27:22-4. [PubMed 3883117]
74. Davidov ME, Moir GD, Poland MP et al. Monotherapy in the treatment of mild hypertension: a double-blind study. Am J Med. 1983; 75(Suppl 4A): 47-53.
75. Frishman WH, Michelson EL, Johnson BF et al. Multiclinic comparison of labetalol and metoprolol in treatment of mild to moderate systemic hypertension. Am J Med. 1983; 75(Suppl 4A):54-67. [PubMed 6356900]
76. Michelson EL, Frishman WH, Lewis JE et al. Multicenter clinical evaluation of long-term efficacy and safety of labetalol in treatment of hypertension. Am J Med. 1983; 75(Suppl 4A):68-80. [PubMed 6356901]
77. Bloomfield SS, Lucas CP, Gantt CL et al. Step II treatment with labetalol for essential hypertension. Am J Med. 1983; 75(Suppl 4A):81-6. [PubMed 6356902]
78. Wallin JD, Wilson D, Winer N et al. Treatment of severe hypertension with labetalol compared with methyldopa and furosemide. Am J Med. 1983; 75(Suppl 4A):87-94. [PubMed 6356903]
79. Wilson DJ, Wallin JD, Vlachakis ND et al. Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies. Am J Med. 1983; 75(Suppl 4A):95-102. [PubMed 6139020]
80. McAreavey D, Ramsey LE, Latham L et al. “Third drug” trial: comparative study of antihypertensive agents added to treatment when blood pressure remains uncontrolled by a beta blocker plus thiazide diuretic. BMJ. 1984; 288:106-11. [PubMed 6419809]
81. Waal-Manning HJ, Simpson FO. Review of long-term treatment with labetalol. Br J Clin Pharmacol. 1982; 13(Suppl 1):66-73S.
82. Kane JA. Labetalol in general practice: a review. Br J Clin Pharmacol. 1982; 13(Suppl 1):59-63S.
83. Breckenridge A, Orme M, Serlin MJ et al. Labetalol in essential hypertension. Br J Clin Pharmacol. 1982; 13(Suppl 1):37-39S.
84. Mancia G, Pomidossi G, Parati G et al. Blood pressure response to labetalol in twice and three times daily administration during a 24-hour period. Br J Clin Pharmacol. 1982; 13(Suppl 1):27-35S.
85. Takeda T, Kaneko Y, Omae T et al. The use of labetalol in Japan: results of multicentre clinical trials. Br J Clin Pharmacol. 1982; 13(Suppl 1):49-57S.
86. Sanders GL, Davies DM, Gales GM et al. A comparative study of methyldopa and labetalol in the treatment of hypertension. Br J Clin Pharmacol. 1979; 8(Suppl 2):149-51S. [PubMed 385023]
87. NcNeil JJ, Louis WJ. A double-blind crossover comparison of pindolol, metoprolol, atenolol and labetalol in mild to moderate hypertension. Br J Clin Pharmacol. 1979; 8(Suppl 2):163-6S. [PubMed 486291]
88. Kane J, Gregg I. A long-term study of labetalol in general practice. Br J Clin Pharmacol. 1979; 8(Suppl 2):167-70S.
89. Prichard BNC, Boakes HJ, Hernandez R. Long-term treatment of hypertension with labetalol. Br J Clin Pharmacol. 1979; 8(Suppl 2):171-7S.
90. New Zealand Hypertension Study Group. A multicentre open trial of labetalol in New Zealand. Br J Clin Pharmacol. 1979; 8(Suppl 2):179-82S. [PubMed 486293]
91. Williams LC, Murphy MJ, Parsons V. Labetalol in severe and resistant hypertension. Br J Clin Pharmacol. 1979; 8(Suppl 2):143-7S. [PubMed 39585]
92. Ghose RR. Acute management of severe hypertension with oral labetalol. Br J Clin Pharmacol. 1979; 8(Suppl 2):189-93S. [PubMed 385027]
93. Cumming AMM, Brown JJ, Lever AF et al. Treatment of severe hypertension by repeated bolus injections of labetalol. Br J Clin Pharmacol. 1979; 8(Suppl 2):199-204S.
94. Smith WB, Clifton GG, O’Neill WM et al. Antihypertensive effectiveness of intravenous labetalol in accelerated hypertension. Hypertension. 1983; 5:579-83. [PubMed 6862581]
95. Lamming GD, Symonds EM. Use of labetalol and methyldopa in pregnancy-induced hypertension. Br J Clin Pharmacol. 1979; 8(Suppl 2):217-22S.
96. Prichard BNC, Richards DA. Comparison of labetalol with other anti-hypertensive drugs. Br J Clin Pharmacol. 1982; 13(Suppl 1):41-7S.
97. Seedat YK. The stepped-care approach to the treatment of hypertension in black patients. S Afr Med J. 1982; 62:1033-5. [PubMed 6817425]
98. Thompson FD, Joekes AM, Hussein MM. Monotherapy with labetalol for hypertensive patients with normal and impaired renal function. Br J Clin Pharmacol. 1979; 8(Suppl 2):129-33S.
99. van der Veur E, ten Berge BS, Donker AJ et al. Comparison of labetalol, propranolol and hydralazine in hypertensive out-patients. Eur J Clin Pharmacol. 1982; 21:457-60. [PubMed 7042373]
100. Weber MA, Drayer JIM, Kaufman CA. The combined alpha- and beta-adrenergic blocker labetalol and propranolol in the treatment of high blood pressure: similarities and differences. J Clin Pharmacol. 1984; 24:103-2. [PubMed 6143765]
101. Cubeddu LX, Carr ME, Fuenmayor NJ. Beta blockade by oral propranolol and labetalol. Clin Pharmacol Ther. 1985; 37:277-83. [PubMed 2857602]
102. Koch G. Combined α- and β-adrenoceptor blockade with oral labetalol in hypertensive patients with reference to haemodynamic effects at rest and during exercise. Br J Clin Pharmacol. 1976; 3(Suppl 3):729-32. [PubMed 10951]
103. Lijnen PJ, Amery AK, Fagard RH et al. Effects of labetalol on plasma renin, aldosterone, and catecholamines in hypertensive patients. J Cardiovasc Pharmacol. 1979; 1:625-32. [PubMed 94628]
104. Weidmann P, de Chatel R, Zeigler WH et al. Alpha and beta adrenergic blockade with orally administered labetalol in hypertension. Am J Cardiol. 1978; 41:570-6. [PubMed 343564]
105. Salvetti A, Pedrinelli R, Sassano P et al. Effect of increasing doses of labetalol on blood pressure, plasma renin activity and aldosterone in hypertensive patients. Clin Sci. 1979; 57:401-4S. [PubMed 519947]
106. Dawson A, Johnson BF, Smith IK. Comparison of the effects of labetalol, bendrofluazide and their combination in hypertension. Br J Clin Pharmacol. 1979; 8:149-54. [PubMed 385023]
107. Frishman W, Halprin S. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 7. New horizons in beta-adrenoceptor blockade therapy: labetalol. Am Heart J. 1979; 98:660-5. [PubMed 386753]
108. Brogden RN, Heel RC, Speight TM et al. Labetalol: a review of its pharmacology and therapeutic uses in hypertension. Drugs. 1978; 15:251-70. [PubMed 25757]
109. Tcherdakoff P. Side effects with long term labetalol: open study of 251 patients in a single center. Pharmatherapeutica. 1983; 3:342-8. [PubMed 6844370]
110. Michelson EL, Frishman WH, Sawin HS et al. Long-term efficacy and safety of labetalol in the treatment of hypertension. J Am Coll Cardiol. 1983; 1:611.
111. Harley A, Coverdale HA. The electrophysiological effects of intravenous labetalol in man. Eur J Clin Pharmacol. 1981; 20:241-4. [PubMed 7308279]
112. Mehta J, Cohn JN. Hemodynamic effects of labetalol, an alpha and beta adrenergic blocking agent, in hypertensive subjects. Circulation. 1977; 55:370-5. [PubMed 12880]
113. Koch G. Cardiovascular dynamics after acute and long-term α- and β-adrenoceptor blockade at rest, supine and standing, and during exercise. Br J Clin Pharmacol. 1979; 8(Suppl 2):101-5S.
114. Svendsen TL, Rasmussen S, Hartling OJ. Sequential haemodynamic effects of labetalol at rest and during exercise in essential hypertension. Postgrad Med J. 1980; 56(Suppl 2):21-6. [PubMed 7433338]
115. Joekes AM, Thompson FD. Acute hemodynamic effects of labetalol and its subsequent use as an oral hypotensive agent. Br J Clin Pharmacol. 1976; 3(Suppl 3):789-93. [PubMed 990156]
116. Prichard BNC, Thompson FO, Boakes AJ et al. Some haemodynamic effects of compound AH 5158 compared with propranolol, propranolol plus hydralazine, and diazoxide: the use of AH 5158 in the treatment of hypertension. Clin Sci Mol Med. 1975; 48:97-100S. [PubMed 1167821]
117. Bahlmann J, Brod J, Hubrich W et al. Effect of and α-and β-adrenoceptor-blocking agent (labetalol) on haemodynamics in hypertension. Br J Clin Pharmacol. 1979; 8(Suppl 2):113-7S.
118. Trap-Jensen J, Clausen JP, Hartling OJ et al. Immediate effects of labetalol on central, splanchnic-hepatic, and forearm haemodynamics during pleasant emotional stress in hypertensive patients. Postgrad Med J. 1980; 56(Suppl 2):37-42. [PubMed 7433341]
119. Agabiti-Rosei E, Alicandri CL, Beschi M et al. The acute and chronic hypotensive effect of labetalol and the relationship with pretreatment plasma noradrenaline levels. Br J Clin Pharmacol. 1982; 13(Suppl 1):87-92S. [PubMed 7039649]
120. Dunn FG, Oigman W, Messerli FH et al. Hemodynamic effects of intravenous labetalol in essential hypertension. Clin Pharmacol Ther. 1983; 33:139-43. [PubMed 6822026]
121. Edwards RC, Raftery EB. Haemodynamic effects of long-term oral labetalol. Br J Clin Pharmacol. 1976; 3(Suppl 3):733-6. [PubMed 791328]
122. Fagard R, Amery A, Reybrouck T et al. Response of the systemic and pulmonary circulation to alpha- and beta-receptor blockade (labetalol) at rest and during exercise in hypertensive patients. Circulation. 1979; 69:1214-9.
123. Lund-Johansen P. Comparative haemodynamic effects of labetalol, timolol, prazosin and the combination of tolamolol and prazosin. Br J Clin Pharmacol. 1979; 8(Suppl 2):107-11S.
124. Griffith DNW, James IM, Newbury PA et al. The effect of β-adrenergic receptor blocking drugs on cerebral blood flow. Br J Clin Pharmacol. 1979; 7:491-4. [PubMed 38822]
125. Taylor SH, Silke B, Nelson GIC et al. Haemodynamic advantages of combined alpha-blockade and beta-blockade over beta-blockade alone in patients with coronary heart disease. BMJ. 1982; 285:325-7. [PubMed 6807469]
126. Gagnon RM, Morissette M, Presant S et al. Hemodynamic and coronary effects of intravenous labetalol in coronary artery disease. Am J Cardiol. 1982; 49:1267-9. [PubMed 7064851]
127. Condorelli M, Brevetti G, Chiarello M et al. Effects of combined α- and β-blockade by labetalol in patients with coronary artery disease. Br J Clin Pharmacol. 1982; 13(Suppl 1):101-10S.
128. Richards DA. Pharmacological effects of labetalol in man. Br J Clin Pharmacol. 1976; 3(Suppl 3):721-3. [PubMed 10949]
129. Louis WJ, Christophidis N, Brignell M et al. Labetalol: bioavailability, drug plasma levels, plasma renin and catecholamines in acute and chronic treatment of resistant hypertension. Aust N Z J Med. 1978; 8:602-9. [PubMed 285681]
130. Larochelle P, Hamet P, Hoffman B et al. Labetalol in essential hypertension. J Cardiovasc Pharmacol. 1980; 2:751-9. [PubMed 6160325]
131. Kornerup HJ, Pedersen EB, Christensen NJ et al. Effect of oral labetalol on plasma catecholamines, renin and aldosterone in patients with severe arterial hypertension. Eur J Clin Pharmacol. 1979; 16:305-10. [PubMed 520398]
132. Cumming AMM, Brown JJ, Fraser R et al. Blood pressure reduction by incremental infusion of labetalol in patients with severe hypertension. Br J Clin Pharmacol. 1979; 8:359-64. [PubMed 508511]
133. Barbieri C, Ferrari C, Caldara R et al. Endocrine and metabolic effects of labetalol in man. J Cardiovasc Pharmacol. 1981; 3:986-91. [PubMed 6168866]
134. Riley AJ. Some further evidence for partial agonist activity of labetalol. Br J Clin Pharmacol. 1980; 9:517-8. [PubMed 6104978]
135. Andersson O, Berglund G, Hansson L. Antihypertensive action, time of onset and effects on carbohydrate metabolism of labetalol. Br J Clin Pharmacol. 1976; 3(Suppl 3):757-61. [PubMed 1032990]
136. Sommers DEK, DeVilliers LS, Van Wyk M et al. The effects of labetalol and oxprenolol on blood lipids. S Afr Med J. 1981; 60:379-80. [PubMed 7025257]
137. Pagnan A, Pessina AC, Zanetti G et al. Effects of labetalol on lipid and carbohydrate metabolism. Pharmacol Res Commun. 1979; 11:227-36. [PubMed 223175]
138. McGonigle RJS, Williams L, Murphy MJ. Labetalol and lipids. Lancet. 1981; 1:163. [PubMed 6109848]
139. Frishman W, Michelson E, Johnson B et al. Effects of beta-adrenergic blockade on plasma lipids: a double-blind randomized placebo-controlled multi-center comparison of labetalol and metoprolol in patients with hypertension. Am J Cardiol. 1982; 49:284.
140. Barbieri C, Larovere MT, Mariotti G et al. Prolactin stimulation by intravenous labetalol is mediated inside the central nervous system. Clin Endocrinol. 1982; 16:615-9.
141. Rasmussen S, Nielsen PE. Blood pressure, body fluid volumes and glomerular filtration rate during treatment with labetalol in essential hypertension. Br J Clin Pharmacol. 1981; 12:349-53. [PubMed 7295465]
142. Pedersen EB, Larsen JS. Effect of propranolol and labetalol on renal haemodynamics at rest and during exercise in essential hypertension. Postgrad Med J. 1980; 56(Suppl 2):27-32. [PubMed 7433339]
143. Cruz F, O’Neill WM, Clifton G et al. Effects of labetalol and methyldopa on renal function. Clin Pharmacol Ther. 1981; 30:57-63. [PubMed 7237899]
144. Valvo E, Previato G, Tessitore N et al. Effects of the long-term administration of labetalol on blood pressure, hemodynamics and renal function in essential and renal hypertension. Curr Ther Res. 1981; 29:634-43.
145. Malini PL, Strocchi E, Negroni S et al. Renal haemodynamics after chronic treatment with labetalol and propranolol. Br J Clin Pharmacol. 1982; 13(Suppl 1):123-6S.
146. Bailey RR. Labetalol in the treatment of patients with hypertension and renal function impairment. Br J Clin Pharmacol. 1979; 8(Suppl 2):134-40S.
147. Williams JG, DeVoss K, Croswell PW. Labetalol in the treatment of hypertensive renal patients. Med J Aust. 1978; 1:225-8. [PubMed 26015]
148. Hunyor SN, Bauer GE, Ross M et al. Labetalol and propranolol in mild hypertensives: comparison of blood pressure and plasma volume effects. Aust N Z J Med. 1980; 10:162-6. [PubMed 6930206]
149. Adam WR, Meagher EJ, Barter CE. Labetalol, beta-blockers and acute deterioration of chronic airway obstruction. Clin Exp Hypertens. 1982; 4:1419-28.
150. Richards DA, Woodings EP, Maconochie JG. Comparison of the effects of labetalol and propranolol in healthy men at rest and during exercise. Br J Clin Pharmacol. 1977; 4:15-21. [PubMed 843418]
151. Maconochie JG, Woodings EP, Richards DA. Effects of labetalol and propranolol on histamine-induced bronchoconstriction in normal subjects. Br J Clin Pharmacol. 1977; 4:157-62. [PubMed 861131]
152. Pearson RM, Havard CWH. Intravenous labetalol in hypertensive patients treated with β-adrenoceptor blocking drugs. Br J Clin Pharmacol. 1976; 3(Suppl 3):795-8. [PubMed 10953]
153. Breckenridge AM, Macnee CM, Orme ML et al. Rate of onset of hypotensive response with oral labetalol. Br J Clin Pharmacol. 1977; 4:388P. [PubMed 901712]
154. Skinner C, Gaddie J, Palmer KNV. Comparison of intravenous AH 5158 (ibidomide) and propranolol in asthma. Br Med J. 1975; 2:59-61. [PubMed 236806]
155. Mazzola C, Guffanti E, Vacarella A et al. Respiratory effects of labetalol in anginous or hypertensive patients. Curr Ther Res. 1982; 31:219-31.
156. George RB, Manocha K, Burford JG et al. Effects of labetalol in hypertensive patients with chronic obstructive pulmonary disease. Chest. 1983; 83:457-60. [PubMed 6337786]
157. Anavekar SN, Barter C, Adam WR et al. A double-blind comparison of verapamil and labetalol in hypertensive patients with coexisting chronic obstructive airways disease. J Cardiovasc Pharmacol. 1982; 4:374-7.
158. Nicholls DP, Husaini MH, Bulpitt CJ et al. Comparison of labetalol and propranolol in hypertension. Br J Clin Pharmacol. 1980; 9:233-7. [PubMed 6988003]
159. Gomez G, Phillips LA. Labetalol (″Trandate’) in hypertension: a multicentre study in general practice. Curr Med Res Opin. 1980; 6:677-84. [PubMed 7428406]
160. Lubbe WF, White DA. Labetalol in hypertensive patients with angina pectoris: beneficial effect of combined α- and β-blockade. Clin Sci Mol Med. 1978; 55:283-6S.
161. Besterman EMM, Spencer M. Open evaluation of labetalol in the treatment of angina pectoris occurring in hypertensive patients. Br J Clin Pharmacol. 1979; 8(Suppl 2):205-9S. [PubMed 497086]
162. Halprin S, Frishman W, Kirschner M et al. Clinical pharmacology of the new β-adrenergic blocking drugs. Part II. Effects of oral labetalol in patients with both angina pectoris and hypertension: a preliminary experience. Am Heart J. 1980; 99:388-96. [PubMed 7355700]
163. Opie LH, White D, Lee J. Alternatives to β-blockade in therapy of hypertension with angina pectoris: role of nifedipine or of labetalol. Br J Clin Pharmacol. 1982; 13(Suppl 1):115-22S.
164. Frishman WH, Strom JA, Kirschner M et al. Labetalol therapy in patients with systemic hypertension and angina pectoris: effects of combined alpha and beta adrenoceptor blockade. Am J Cardiol. 1981; 48:917-28. [PubMed 6118060]
165. Marx PG, Reid DS. Labetalol infusion in acute myocardial infarction with systemic hypertension. Br J Clin Pharmacol. 1979; 8(Suppl 2):233-8S. [PubMed 497089]
166. Timmis AD, Fowler MB, Jaggarao NSV et al. Role of labetalol in acute myocardial infarction. Br J Clin Pharmacol. 1982; 13(Suppl 1):111-4S.
167. Timmis AD, Fowler MB, Jaggarao NSV et al. Labetalol infusion for the treatment of hypertension in acute myocardial infarction. Eur Heart J. 1980; 1:413-6. [PubMed 7274255]
168. Hua ASP, Thomas GW, Kincaid-Smith P. Scalp tingling in patients on labetalol. Lancet. 1977; 2:295. [PubMed 69898]
169. Bailey RR. Scalp tingling and difficulty in micturition in patients on labetalol. Lancet. 1977; 2:720. [PubMed 71532]
170. Gabriel R. Circumoral paraesthesiae and labetalol. Br Med J. 1978; 1:580. [PubMed 630239]
171. Kristensen BO. Labetalol-induced Peyronie’s disease. A case report. Acta Med Scand. 1979; 206:511-2. [PubMed 231377]
172. Law MR, Copland RFP, Armistead JG et al. Labetalol and priapism. Br Med J. 1980; 1:115.
173. Teicher A, Rosenthal T, Kissin E et al. Labetalol-induced toxic myopathy. BMJ. 1981; 282:1824-5. [PubMed 6786636]
174. Frais MA, Bayley TJ. Left ventricular failure with labetalol. Postgrad Med J. 1979; 55:567-8. [PubMed 514938]
175. Griffiths ID, Richardson J. Lupus-type illness associated with labetalol. Br Med J. 1979; 2:496-7. [PubMed 314829]
176. Booth RJ, Wilson JD, Bullock JY. β-Adrenergic-receptor blockers and antinuclear antibodies in hypertension. Clin Pharmacol Ther. 1982; 31:555-63. [PubMed 6122525]
177. Wilson JD, Booth RJ, Bullock JY et al. Anti-mitochondrial antibodies associated with labetalol. Lancet. 1980; 2:312-3. [PubMed 6105456]
178. Richards DA, Prichard BNC, Boakes AJ et al. Pharmacological basis for antihypertensive effects of intravenous labetalol. Br Heart J. 1977; 39:99-106. [PubMed 12778]
179. Gosselin RE, Smith RP, Hodge HC. Clinical toxicology of commercial products. 5th ed. Baltimore: The Williams & Wilkins Co; 1984:I-10.
180. Daneshmend TK, Roberts CJC. Cimetidine and bioavailability of labetalol. Lancet. 1981; 1:565. [PubMed 6111669]
181. Agabiti-Rosei E, Brown JJ, Lever AF et al. Treatment of phaeochromocytoma and of clonidine withdrawal hypertension with labetalol. Br J Clin Pharmacol. 1976; 3(Suppl 3):809-15. [PubMed 990158]
182. Bailey RR. Labetalol in the treatment of a patient with phaeochromocytoma: a case report. Br J Clin Pharmacol. 1979; 8(Suppl 2):141-2S.
183. Kaufman L. Use of labetalol during hypotensive anaesthesia and in the management of phaeochromocytoma. Br J Clin Pharmacol. 1979; 8(Suppl 2):229-32S. [PubMed 497088]
184. Reach G, Thibonnier M, Chevillard C et al. Effect of labetalol on blood pressure and plasma catecholamine concentrations in patients with phaeochromocytoma. Br Med J. 1980; 1:1300-1.
185. Lubbe WF. Hypertension in pregnancy: pathophysiology and management. Drugs. 1984; 28:170-88. [PubMed 6147240]
186. Briggs RSJ, Birtwell AJ, Pohl JEF. Hypertensive response to labetalol in phaeochromocytoma. Lancet. 1978; 1:1045-6.
187. Feek CM, Earnshaw PM. Hypertensive response to labetalol in phaeochromocytoma. Br Med J. 1980; 2:387.
188. Rosenthal T, Rabinowitz B, Boichis H et al. Use of labetalol in hypertensive patients during discontinuation of clonidine therapy. Eur J Clin Pharmacol. 1981; 20:237-40. [PubMed 6273179]
189. Hurley DM, Vandogen R, Beilin LJ. Failure of labetalol to prevent hypertension due to clonidine withdrawal. Br Med J. 1979; 1:1122-3. [PubMed 444961]
190. Scott DB, Buckley FP, Drummond GB et al. Cardiovascular effects of labetalol during halothane anaesthesia. Br J Clin Pharmacol. 1976; 3(Suppl 3):817-21. [PubMed 990159]
191. Scott DB. The use of labetalol in anaesthesia. Br J Clin Pharmacol. 1982; 13(Suppl 1):133-5S. [PubMed 6121571]
192. Cope DHP. Use of labetalol during halothane anaesthesia. Br J Clin Pharmacol. 1979; 8(Suppl 2):223-7S.
193. Cope DHP, Crawford MC. Labetalol in controlled hypotension. Administration of labetalol when adequate hypotension is difficult to achieve. Br J Anaesth. 1979; 51:359-65. [PubMed 465259]
194. Jones SEF. Coarctation in children. Controlled hypotension using labetalol and halothane. Anaesthesia. 1979; 34:1052-5. [PubMed 539643]
195. Kanto J, Pakkanen A, Allonen H et al. The use of labetalol as a moderate hypotensive agent in otological operations—plasma concentrations after intravenous administration. Int J Clin Pharmacol Ther Toxicol. 1980; 18:191-4. [PubMed 7390669]
196. Domenighetti GM, Savary G, Stricker H. Hyperadrenergic syndrome in severe tetanus: extreme rise in catecholamines responsive to labetalol. BMJ. 1984; 288:1483-4. [PubMed 6426611]
197. Cumming AMM, Brown JJ, Fraser R et al. Blood pressure reduction by incremental infusion of labetalol in patients with severe hypertension. Br J Clin Pharmacol. 1979; 8:359-64. [PubMed 508511]
198. Pearson RM, Havard CWH. Intravenous labetalol in hypertensive patients given by fast and slow injection. Br J Clin Pharmacol. 1978; 5:401-5. [PubMed 350248]
199. Rumboldt Z, Bagatin J, Vidovic A. Diazoxide vs labetalol: a crossover comparison of short-term effects in hypertension. Int J Clin Pharm Res. 1983; 3:47-54.
200. Dundee JW, Morrow WFK. Labetalol in severe tetanus. Br Med J. 1979; 1:1121-2. [PubMed 444960]
201. Hanna W, Grell GAC. Oral labetalol in the management of the sympathetic overactivity of severe tetanus. South Med J. 1980; 73:653-4. [PubMed 6103586]
202. Wesley AG, Hariparasad D, Pataher M et al. Labetalol in tetanus: the treatment of sympathetic nervous system overactivity. Anaesthesia. 1983; 38:243-9. [PubMed 6837902]
203. Reviewers’ comments (personal observations); 1985 Jul.
204. Modrak JB (Glaxo Inc, Research Triangle Park, NC): Personal communication; 1985 Jul.
205. Jennings K, Parsons V. A study of labetalol in patients of European, West Indian and West African origin. Br J Clin Pharmacol. 1976; 3(Suppl 3):773-5. [PubMed 990155]
206. Seedat YK. Labetalol hydrochloride in the treatment of black and Indian hypertensive patients. Med Proc. 1979; 25:53-7.
207. Olivier LR, Retief JH, Buchel EH et al. Evaluation of labetalol hydrochloride in hospital outpatients. Clin Trials J. 1980; 17:75-80.
208. Flamenbaum W, Weber MA, McMahon FG et al. Monotherapy with labetalol compared with propranolol: differential effects by race. J Clin Hypertens. 1985; 1:56-69. [PubMed 3915317]
209. Jackson SHD, Beevers DG, Owen L et al. Labetalol: a comparison of intravenous infusions and injections. J Pharmacother. 1980; 3:131-3.
210. Lebel M, Langlois S, Belleau LJ et al. Labetalol infusion in hypertensive emergencies. Clin Pharmacol Ther. 1985; 37:615-8. [PubMed 3891186]
211. Koda-Kimble MA, Rotblatt MD. Diabetes mellitus. In: Katcher BS, Young LY, Koda-Kimble MA, eds. Applied therapeutics: the clinical use of drugs. 3rd ed. San Francisco: Applied Therapeutics, Inc; 1983:1335-414.
212. Hansten PD. Drug interactions. 4th ed. Philadelphia: Lea & Febiger; 1979:14,93-109.
213. Meretoja OA, Allonen H, Arola M et al. Combined alpha- and beta-blockade with labetalol in post-open heart surgery hypertension: reversal of hemodynamic deterioration with glucagon. Chest. 1980; 78:810-5. [PubMed 7004797]
214. Anon. Beta-blocker poisoning. Lancet. 1980; 1:803-4.
215. Weinstein RS. Recognition and management of poisoning with beta-adrenergic blocking agents. Ann Emerg Med. 1984; 13:1123-31. [PubMed 6150667]
216. Hamilton CA, Jones DH, Dargie HJ et al. Does labetalol increase excretion of urinary catecholamines? Br Med J. 1978; 277:800. (IDIS 87272)
217. Miano L, Kolloch R, de Quattro V. Increased catecholamine excretion after labetalol therapy: a spurious effect of drug metabolites. Clin Chim Acta. 1979; 95:211-7. [PubMed 527220]
218. Richards DA, Harris DM, Martin LE. Labetalol and urinary catecholamines. Br Med J. 1979; 278:685.
219. Romano S, Orfei S, Pozzoni L et al. Preliminary clinical trial on hypotensive and antiarrhythmic effect of labetalol. Drugs Exp Clin Res. 1981; 7:65-8.
220. Mazzola C, Ferrario N, Calzavara MP et al. Acute antihypertensive and antiarrhythmic effects of labetalol. Curr Ther Res. 1981; 29:613-33.
221. Carey B, Whalley ET. Labetalol possesses β-adrenoceptor agonist action on the rat isolated uterus. J Pharm Pharmacol. 1979; 31:791-2. [PubMed 41918]
222. Carey B, Whalley ET. β-Adrenoceptor agonist activity of labetalol on the isolated rat uterus. Br J Pharmacol. 1979; 67:13-5. [PubMed 40642]
223. Iezzoni DG (Schering Corporation, Kenilworth, NJ): Personal communication; 1985 Jul.
224. Woods PB, Robinson ML. An investigation of the comparative liposolubilities of β-adrenoceptor blocking agents. J Pharm Pharmacol. 1981; 33:172-3. [PubMed 6116760]
225. Dage RC, Hsieh CP. Direct vasodilatation by labetalol in anaesthetized dogs. Br J Pharmacol. 1980; 70:287-93. [PubMed 7426837]
226. Silke B, Nelson GIC, Ahuja RC et al. Comparison of haemodynamic dose-response effects of beta- and alpha-blockade in acute myocardial infarction. Int J Cardiol. 1984; 5:317-25. [PubMed 6706437]
227. George RB, Light RW, Hudson L et al. The use of labetalol for the treatment of hypertension in patients with reversible airway obstruction. J Clin Hypertens. 1985; 1:80-3. [PubMed 3836298]
228. Gribbin HR, Mackay AD, Baldwin CJ et al. Bronchial and cardiac β-adrenoceptor blockade: a comparison of atenolol, acebutolol and labetalol. Br J Clin Pharmacol. 1981; 12:61-5. [PubMed 6264936]
229. Daneshmend TK, Roberts CJC. The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics. Br J Clin Pharmacol. 1984; 18:393-400. [PubMed 6487478]
230. Horvath JS, Caterson RJ, Collett P et al. Labetalol and bendrofluazide: comparison of their antihypertensive effects. Med J Aust. 1979; 1:626-8. [PubMed 386062]
231. Labetalol/Hydrochlorothiazide Multicenter Study Group. Labetalol and hydrochlorothiazide in hypertension. Clin Pharmacol Ther. 1985; 38:24-7. [PubMed 2860990]
232. Dargie HJ, Dollery CT, Daniel J. Labetalol in resistant hypertension. Br J Clin Pharmacol. 1976; 3(Suppl 3):751-5. [PubMed 990154]
233. Lilja M, Jounela AJ, Karppanen H. Comparison of labetalol and clonidine in hypertension. Eur J Clin Pharmacol. 1982; 21:363-7. [PubMed 7075640]
234. Whiting G, Craswell P, Boyles P et al. Minoxidil and labetalol: very effective antihypertensive combination. Med J Aust. 1980; 1:225-6. [PubMed 7374568]
235. McGrath BP, Matthews PG, Walter NM et al. Emergency treatment of severe hypertension with intravenous labetalol. Med J Aust. 1978; 2:410-1. [PubMed 732728]
236. Papademetriou V, Notargiacomo AV, Khatri IM et al. Treatment of severe hypertension with intravenous labetalol. Clin Pharmacol Ther. 1982; 32:431-5. [PubMed 7116758]
237. Lewis M, Kallenbach J, Germond C et al. Survival following massive overdose of adrenergic blocking agents (acebutolol and labetalol). Eur Heart J. 1983; 4:328-32. [PubMed 6617679]
238. Frishman W, Jacob H, Eisenberg E et al. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 8. Self-poisoning with beta-adrenoceptor blocking agents: recognition and management. Am Heart J. 1979; 98:798-811. [PubMed 40429]
239. Walstad RA, Berg KJ, Wessel-Aas T et al. Labetalol in the treatment of hypertension in patients with normal and impaired renal function. Acta Med Scand Suppl. 1982; 665:135-41. [PubMed 6961760]
240. Vlachakis ND, Maronde RF, Maloy JW et al. Pharmacodynamics of intravenous labetalol and follow-up therapy with oral labetalol. Clin Pharmacol Ther. 1985; 38:503-8. [PubMed 4053487]
241. Halstenson CE, Opsahl JA, Pence TV et al. The disposition and dynamics of labetalol in patients on dialysis. Clin Pharmacol Ther. 1986; 40:462-8. [PubMed 3757409]
242. Schering Corporation. Normodyne injection prescribing information. Kenilworth, NJ; 1986 Aug.
243. Stricker BHC, Heijermans HSF, Braat H et al. Fever induced by labetalol. JAMA. 1986; 256:619-20. [PubMed 3723760]
244. Jouppila P, Kirkinen P, Koivula A et al. Labetalol does not alter the placental and fetal blood flow or maternal prostanoids in pre-eclampsia. Br J Obstet Gynaecol. 1986; 93:543-7. [PubMed 3524664]
245. Macpherson M, Pipkin FB, Rutter N. The effect of maternal labetalol on the newborn infant. Br J Obstet Gynaecol. 1986; 93:539-42. [PubMed 3730323]
246. Mehta JL, Lopez LM. Rebound hypertension following abrupt cessation of clonidine and metoprolol: treatment with labetalol. Arch Intern Med. 1987; 147:389-90. [PubMed 3813760]
247. Allen & Hanburys. Trandate HCT tablets prescribing information. Research Triangle Park, NC; 1991 Apr.
248. Schering Corporation. Normozide tablets prescribing information. Kenilworth, NJ; 1989 Apr.
249. Grubb BP, Sirio C, Zelis R. Intravenous labetalol in acute aortic dissection. JAMA. 1987; 258:78-9. [PubMed 3586295]
250. Cumming AMM, Davies DL. Intravenous labetalol in hypertensive emergency. Lancet. 1979; 1:929-30. [PubMed 86702]
251. Grubb BP, Zelis R. Intravenous labetalol in acute aortic dissection. JAMA. 1987; 258:1732-3.
252. Binder SR, Biaggi ME. Analysis of urinary catecholamines by high-performance liquid chromatography in the presence of labetalol metabolites. J Chromatogr. 1987; 385:241-7. [PubMed 3558579]
253. 1988 Joint National Committee. The 1988 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1988; 148:1023-38. [PubMed 3365073]
254. Douglas DD, Yang RD, Jansen P et al. Fatal labetalol-induced hepatic injury. Am J Med. 1989; 87:235-6. [PubMed 2757062]
255. Clark JA, Zimmerman HJ, Tanner LA. Labetalol hepatotoxicity. Ann Intern Med. 1990; 113:485.
256. Hansten PD. Drug Interactions. 6th ed. Philadelphia: Lea & Febiger, 1989:35-6.
257. Keech AC, Harper RW, Harrison PM et al. Pharmacokinetic interaction between oral metoprolol and verapamil for angina pectoris. Am J Cardiol. 1986; 58:551-2. [PubMed 3529913]
258. Murad F. Drugs used for the treatment of angina: organic nitrates, calcium-channel blockers, and β-adrenergic antagonists. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Macmillan Publishing Company; 1990:764-813.
259. Gerber JG, Nies AS. Antihypertensive agents and the drug therapy of hypertension. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Macmillan Publishing Company; 1990; 784-813.
260. Zipes DP. Management of cardiac arrhythmias: pharmacological, electrical, and surgical techniques. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 3rd ed. Philadelphia: WB Saunders Company; 1988:621-57.
261. Rutherford JD, Braunwald E, Cohn P. Chronic ischemic heart disease. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 3rd ed. Philadelphia: WB Saunders Company; 1988:1314-78.
262. Dahlöf B, Eggerstsen R, Hansson L. Calcium antagonists combined with beta-blockers or ACE inhibitors in the treatment of hypertension. J Cardiovasc Pharmacol. 1988; 12(Suppl 6):S104-8.
263. Mac Carthy EP. Combination therapy of hypertension with beta-adrenoreceptor blockers and the calcium channel antagonist nitrendipine. J Cardiovasc Pharmacol. 1988; 12(Suppl 4):S76-9. [PubMed 2468880]
264. Dargie HJ. Beta-blockers and calcium antagonists in angina pectoris: the potential role of combination therapy. Drugs. 1988; 35(Suppl 4):44-50. [PubMed 2897903]
265. Müller FB, Bolli P, Linder L et al. Calcium antagonists and the second drug for hypertensive therapy. Am J Med. 1986; 81:25-9. [PubMed 2879444]
266. Brouwer RM, Follath F, Bühler FR. Review of the cardiovascular adversity of the calcium antagonist beta-blocker combination: implications for antihypertensive therapy. J Cardiovasc Pharmacol. 1985; 7(Suppl 4):S38-44.
267. Vanhaleweyk GL, Serruys PW, Hugenholtz PG. Anti-anginal, electrophysiologic and hemodynamic effects of combined beta-blocker/calcium antagonist therapy. Eur Heart J. 1983; 4(Suppl D):117-28. [PubMed 6137370]
268. O’Hara MJ, Khurmi NS, Bowles MJ et al. Diltiazem and propranolol combination for the treatment of chronic stable angina pectoris. Clin Cardiol. 1987; 10:115-23. [PubMed 3545577]
269. Dargie HJ, Lynch PG, Krikler DM et al. Nifedipine and propranolol: a beneficial drug interaction. Am J Med. 1981; 71:676-82. [PubMed 7025625]
270. Pfisterer M, Müller-Brand J, Burkart F. Combined acebutolol/nifedipine therapy in patients with chronic coronary artery disease: additional improvement of ischemia-induced left ventricular dysfunction. Am J Cardiol. 1982; 49:1259-66. [PubMed 7064850]
271. Kieval J, Kirsten EB, Kessler KM et al. The effects of intravenous verapamil on hemodynamic status of patients with coronary artery disease receiving propranolol. Circulation. 1982; 65:653-9. [PubMed 7060243]
272. Packer M, Meller J, Medina N et al. Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man. Circulation. 1982; 65:660-8. [PubMed 7060244]
273. Packer M, Leon MB, Bonow RO et al. Hemodynamic and clinical effects of combined verapamil and propranolol therapy in angina pectoris. Am J Cardiol. 1982; 50:903-12. [PubMed 6751066]
274. Gifford RW Jr. Management of hypertensive crises. JAMA. 1991; 266:829-35. [PubMed 1865522]
275. Michelson EL. Labetalol hepatotoxicity. Ann Intern Med. 1991; 114:341. [PubMed 2018583]
276. Harvengt C. Labetalol hepatotoxicity. Ann Intern Med. 1991; 114:341. [PubMed 2018583]
278. Weber MA, Laragh JH. Hypertension: steps forward and steps backward: the Joint National Committee fifth report. Arch Intern Med. 1993; 153:149-52. [PubMed 8422205]
279. Collins R, Peto R, MacMahon S et al. Blood pressure, stroke, and coronary heart disease. Part 2, short-term reductions in blood pressure: an overview of randomized drug trials in their epidemiological context. Lancet. 1990; 335:827-38. [PubMed 1969567]
280. Alderman MH. Which antihypertensive drugs first—and why! JAMA. 1992; 267:2786-7. Editorial.
281. MacMahon S, Peto R, Cutler J et al. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990; 335:765-74. [PubMed 1969518]
282. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991; 265:3255-64. [PubMed 2046107]
283. Dahlof B, Lindholm LH, Hansson L et al. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-hypertension). Lancet. 1991; 338:1281-5. [PubMed 1682683]
284. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992; 304:405-12. [PubMed 1445513]
285. National High Blood Pressure Education Program Working Group. National High Blood Pressure Education Program Working Group report on high blood pressure in pregnancy. Am J Obstet Gynecol. 1990; 163:1689-1712.
286. National Heart, Lung, and Blood Institute. NHLBI panel reviews safety of calcium channel blockers. Rockville, MD; 1995 Aug 31. Press release.
287. National Heart, Lung, and Blood Institute. New analysis regarding the safety of calcium-channel blockers: a statement for health professionals from the National Heart, Lung, and Blood Institute. Rockville, MD; 1995 Sep 1.
288. Psaty BM, Heckbert SR, Koepsell TD et al. The risk of myocardial infarction associated with antihypertensive drug therapies. JAMA. 1995; 274:620-5. [PubMed 7637142]
289. Yusuf S. Calcium antagonists in coronary artery disease and hypertension: time for reevaluation? Circulation. 1995; 92:1079-82. Editorial.
290. Roche. Posicor (mibefradil hydrochloride) tablets prescribing information. Nutley, NJ; 1997 Dec.
291. Ellison RH. Dear doctor letter regarding appropriate use of Posicor. Nutley, NJ: Roche Laboratories; 1997 Dec.
292. Sidmark Laboratories. Verapamil hydrochloride tablets prescribing information. East Hanover, NJ; 1996 Apr.
293. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)
294. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [PubMed 8622249]
295. Psaty BM, Smith NL, Siscovich DS et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and meta-analysis. JAMA. 1997; 277:739-45. [PubMed 9042847]
298. ACOG task force on hypertension in pregnancy: hypertension in pregnancy. Washington, DC: American College of Obstetricians and Gynecologists; 2013.
299. Whelton PK, Appel LJ, Espeland MA et al. for the TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998; 279:839-46. [PubMed 9515998]
301. Genuth P. United Kingdom prospective diabetes study results are in. J Fam Pract. 1998; 47:(Suppl 5):S27.
303. Watkins PJ. UKPDS: a message of hope and a need for change. Diabet Med. 1998; 15:895-6. [PubMed 9827842]
304. Bretzel RG, Voit K, Schatz H et al. The United Kingdom Prospective Diabetes Study (UKPDS): implications for the pharmacotherapy of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1998; 106:369-72. [PubMed 9831300]
305. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317:703-13. [PubMed 9732337]
306. American Diabetes Association. The United Kingdom Prospective Diabetes Study (UKPDS) for type 2 diabetes: what you need to know about the results of a long-term study. Washington, DC; 1998 Sep 15 from American Diabetes Association web site.
307. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317:713-20. [PubMed 9732338]
308. Davis TME. United Kingdom Prospective Diabetes Study: the end of the beginning? Med J Aust. 1998; 169:511-2.
310. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: apporaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9A-38A.
311. Glaxo Wellcome. Trandate (labetalol hydrochloride) injection prescribing information. In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999 (Suppl A):A166.
312. Lim PO, MacDonald TM. Antianginal and β-adrenergic blocking drugs. In: Dukes MNG, ed. Meyler’s side effects of drugs. 13th ed. New York: Elsevier/North Holland Inc; 1996:488-535.
313. Gress TW, Nieto FJ, Shahar E et al. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. N Engl J Med. 2000; 342:905-12. [PubMed 10738048]
314. Sowers JR, Bakris GL. Antihypertensive therapy and the risk of type 2 diabetes mellitus. N Engl J Med. 2000; 342:969-70. [PubMed 10738057]
315. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]
316. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]
317. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [PubMed 10977801]
318. Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998; 351:1755-62. [PubMed 9635947]
319. Pattishall EN. Dear healthcare provider letter regarding dispensing errors involving Lamictal (lamotrigine). Research Triangle Park, NC: GlaxoSmithKline; undated.
320. Pattishall EN. Dear healthcare provider letter regarding dispensing errors involving Lamictal (lamotrigine). Research Triangle Park, NC: GlaxoSmithKline; 2001 Aug.
322. Williams CL, Hayman LL, Daniels SR et al. Cardiovascular health in childhood: a statement for health professional from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation. 2002; 106:143-60. [PubMed 12093785]
324. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. [PubMed 12479770]
325. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [PubMed 12479763]
327. Douglas JG, Bakris GL, Epstein M et al. Management of high blood pressure in African Americans: Consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003; 163:525-41.
329. The Guidelines Subcommitee of the WHO/ISH Mild Hypertension Liaison Committee. 1999 guidelines for the management of hypertension. J Hypertension. 1999; 17:392-403.
332. Carter B for the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Personal communication.
333. National high blood pressure education program working group on hypertension control in children and adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114(Suppl 2):555-76. [PubMed 15286277]
334. Wright JT, Dunn JK, Cutler JA et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. JAMA. 2005; 293:1595-607. [PubMed 15811979]
335. Neaton JD, Kuller LH. Diuretics are color blind. JAMA. 2005; 293:1663-6. [PubMed 15811986]
337. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE). Lancet. 2002;359:995-1003. [PubMed 11937178]
338. Duley L, Meher S, Jones L. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2013; 7:CD001449. [PubMed 23900968]
500. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: National Institutes of Health; 2004 Aug. (NIH publication No. 04-5230.)
501. James PA, Oparil S, Carter BL et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311:507-20. [PubMed 24352797]
502. Mancia G, Fagard R, Narkiewicz K et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281-357. [PubMed 23817082]
503. Go AS, Bauman MA, Coleman King SM et al. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014; 63:878-85. [PubMed 24243703]
504. Weber MA, Schiffrin EL, White WB et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014; 16:14-26. [PubMed 24341872]
515. Thomas G, Shishehbor M, Brill D et al. New hypertension guidelines: one size fits most?. Cleve Clin J Med. 2014; 81:178-88. [PubMed 24591473]
523. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471. [PubMed 23166211]
524. WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128:e240-327. [PubMed 23741058]
527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425. [PubMed 23247304]
540. Magee LA, Pels A, Helewa M et al., for the Canadian Hypertensive Disorders of Pregnancy (HDP) Working Group. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. Pregnancy Hypertens. 2014; 4:105-45.
542. Marik PE, Varon J. Hypertensive crises: challenges and management. Chest. 2007; 131:1949-62. [PubMed 17565029]
700. Yancy CW, Jessup M, Bozkurt B et al. 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016; :. [PubMed 27208050]
1101. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012; 126:e354-471. [PubMed 23166211]
HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:687-91.
a. Prometheus Laboratories. Trandate tablets prescribing information. San Diego, CA; 2002 Dec.
b. Prometheus Laboratories. Trandate injection prescribing information. San Diego, CA; 2003 Jan.
More about labetalol
- Side Effects
- During Pregnancy or Breastfeeding
- Dosage Information
- Drug Images
- Drug Interactions
- Compare Alternatives
- Support Group
- Pricing & Coupons
- En Español
- 2 Reviews – Add your own review/rating
- Drug class: non-cardioselective beta blockers
Other brands: Trandate