Labetalol Hydrochloride

Selective α1- and nonselective β-adrenergic blocking agent.1 2 3 4 5 6 7 8 9 19 21 22 23 32

Hypertension

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 for rapid reduction of BP in pediatric patients 1–17 years of age† with severe hypertension†.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.)

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

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

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 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.)

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.)

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

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

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

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

Specific Populations

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

Specific Drugs and Laboratory Tests

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