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Labetalol: Drug information

Labetalol: Drug information
(For additional information see "Labetalol: Patient drug information" and see "Labetalol: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: Canada
  • APO-Labetalol;
  • RIVA-Labetalol;
  • Trandate
Pharmacologic Category
  • Antihypertensive;
  • Beta-Blocker With Alpha-Blocking Activity
Dosing: Adult

Dosage guidance:

Safety: Accumulation can occur with high-dose continuous infusions and may result in severe hypotension and bradycardia (Ref). There is limited documentation of prolonged continuous infusions (Ref).

Acute aortic syndromes/acute aortic dissection

Acute aortic syndromes/acute aortic dissection (alternative agent) (off-label use):

Note: Manage patients on an emergency basis (including operative assessment) by first controlling pain with IV opioids and heart rate (target 60 to 80 beats per minute) with a parenteral beta blocker (eg, labetalol) while targeting systolic BP of ≤120 mm Hg (or lowest tolerated pressure without compromising perfusion). If systolic BP remains elevated after heart rate is controlled at 60 to 80 beats per minute with beta-blockade, may consider adding an additional parenteral vasodilator (ie, nitroprusside or nicardipine). Invasive BP monitoring, preferably via arterial line, in a critical care unit is recommended for appropriate dose titration (Ref). Although manufacturer's labeling recommends against exceeding a cumulative IV dose of 300 mg, it may be reasonable to exceed this dose in select patients, while monitoring for accumulation (Ref).

Intermittent IV: Initial: 20 mg over 2 minutes followed by 20 to 80 mg every 10 minutes until target heart rate and BP are reached; may transition to continuous infusion if unable to obtain target goals (Ref).

Continuous IV infusion: Initial loading dose: 20 mg over 2 minutes (optional if intermittent dosing is used), followed by 0.5 to 2 mg/minute; some patients may require titration up to 10 mg/minute for optimal response (Ref).

Acute ischemic stroke, BP management with reperfusion therapy

Acute ischemic stroke, BP management with reperfusion therapy (off-label use):

Note: Prior to reperfusion therapy (thrombolytic and/or mechanical thrombectomy), maintain a target BP of ≤185/110 mm Hg. If BP remains >185/110 mm Hg, do not administer thrombolytic. During and 24 hours after start of thrombolytic therapy, maintain a target BP of ≤180/105 mm Hg; if hypertension is refractory or diastolic BP >140 mm Hg, consider alternative therapy (Ref).

Prior to reperfusion therapy:

IV: 10 to 20 mg over 1 to 2 minutes; may repeat once (Ref).

During and after reperfusion therapy:

IV: 10 mg over 1 to 2 minutes, followed by 2 to 8 mg/minute continuous infusion (Ref). Although manufacturer's labeling recommends against exceeding a cumulative IV dose of 300 mg, it may be reasonable to exceed this dose in select patients, while monitoring for accumulation (Ref).

Hypertension, acute/severe inpatient

Hypertension, acute/severe inpatient (including perioperative hypertension):

Note: The benefit of using IV antihypertensive agents to treat acute severe asymptomatic hypertension is not well established; in general, address underlying causes (eg, pain, agitation, withdrawal, hypervolemia) prior to initiating antihypertensive therapy. Rapid or excessive blood pressure reduction may be associated with severe adverse effects (eg, cerebral or myocardial ischemia) (Ref). For patients with chronic hypertension prior to surgery, restart oral therapies as soon as appropriate once hemodynamically stable (Ref).

Intermittent IV: Initial: 5 to 20 mg over 2 minutes; repeat dose every 10 minutes until target blood pressure is reached (Ref). Although manufacturer's labeling recommends against exceeding a cumulative IV dose of 300 mg, it may be reasonable to exceed this dose in selected patients, while monitoring for accumulation (Ref).

Hypertension, chronic/resistant

Hypertension, chronic/resistant:

Note: Not recommended for initial management of hypertension, but may be considered as additional therapy in patients who do not respond adequately to combination therapy with preferred agents (Ref).

Oral: Initial: 100 mg twice daily; may increase as needed every 2 to 3 days by 100 mg twice daily (titration increments not to exceed 200 mg twice daily) until desired response is obtained; usual dosage range: 200 to 800 mg/day in 2 divided doses (Ref). In patients with resistant hypertension, doses up to 1.2 to 2.4 g/day in 2 or 3 divided doses may be required; however, combination therapy is preferred over dose escalation beyond the usual dosage range (Ref).

Hypertensive emergency

Hypertensive emergency:

Note: In general, reduce mean arterial blood pressure gradually by ~10% to 20% over the first hour, then by an additional 5% to 15% over the next 23 hours, unless there is a compelling indication (eg, acute aortic dissection, severe preeclampsia, eclampsia) for more rapid blood pressure and heart rate control (Ref). Although manufacturer's labeling recommends against exceeding a cumulative IV dose of 300 mg, it may be reasonable to exceed this dose in select patients, while monitoring for accumulation (Ref).

Intermittent IV: Initial: 10 to 20 mg over 1 to 2 minutes followed by 20 to 80 mg every 10 minutes until target blood pressure is reached; consider a continuous infusion if unable to obtain target blood pressure (Ref).

Continuous IV infusion: Initial loading dose: 10 to 20 mg over 2 minutes (optional if intermittent dosing is used), followed by 0.5 to 2 mg/minute; some patients may require titration up to 10 mg/minute (Ref).

Hypertensive emergency in pregnancy or postpartum

Hypertensive emergency in pregnancy or postpartum (including acute-onset severe hypertension in preeclampsia/eclampsia) (off-label use):

Note: For acute-onset, severe, persistent hypertension (eg, systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) (Ref). Although manufacturer's labeling recommends against exceeding a cumulative IV dose of 300 mg, it may be reasonable to exceed this dose in selected patients, while monitoring for accumulation (Ref).

Intermittent IV: Initial: 20 mg over 2 minutes; if blood pressure exceeds thresholds after 10 to 30 minutes, increase dose in increments of 20 to 40 mg every 10 to 30 minutes; maximum single dose: 80 mg. Note: If blood pressures remain above threshold after several intermittent doses, another agent should be used (Ref).

Continuous IV infusion: Initial loading dose: 20 mg over 2 minutes (optional if intermittent dosing is used), followed by 0.5 to 2 mg/minute titrated to response (Ref).

Oral (alternative route): Initial: 200 mg every 60 minutes for up to 3 doses. Note: May use as alternative route to other ineffective oral therapy; IV therapy (intermittent or continuous infusion) may be needed for more acute treatment (Ref).

Intracerebral hemorrhage, acute, blood pressure management

Intracerebral hemorrhage, acute, blood pressure management (off-label use):

Note: For use in patients with mild to moderate intracerebral hemorrhage with a presenting systolic BP ≥150 mm Hg; acute lowering to <130 mm Hg is potentially harmful (Ref). Although manufacturer's labeling recommends against exceeding a cumulative IV dose of 300 mg, it may be reasonable to exceed this dose in select patients, while monitoring for accumulation (Ref).

Patients who present with systolic BP 150 to 220 mm Hg:

Intermittent IV: Initial: 5 to 20 mg IV push over 2 minutes. May repeat every 10 to 15 minutes; repeat doses may be increased incrementally up to 80 mg as needed based on response and tolerability until target systolic BP is reached; may consider a continuous infusion if unable to obtain target goals (Ref).

Patients who present with systolic BP >220 mm Hg (alternative agent):

Continuous IV infusion: Initial loading dose: 20 mg over 2 minutes, followed by 0.5 to 2 mg/minute; titrate to target systolic BP (Ref).

Subarachnoid hemorrhage, blood pressure management

Subarachnoid hemorrhage, blood pressure management (off-label use):

Note: Optimal therapy is not well established. Cautious use of antihypertensive therapy to decrease the risk of rebleeding may be appropriate in some patients with systolic BP >160 mm Hg or mean arterial pressure >110 mm Hg with adequate cerebral perfusion pressures (Ref). Although manufacturer's labeling recommends against exceeding a cumulative IV dose of 300 mg, it may be reasonable to exceed this dose in selected patients, while monitoring for accumulation (Ref).

Intermittent IV: Initial: 10 to 20 mg over 2 minutes; followed by 20 to 80 mg every 10 to 15 minutes until systolic BP <160 mm Hg or mean arterial pressure <100 mm Hg (Ref).

Continuous IV infusion: 0.5 to 2 mg/minute titrated to response; based on very limited data (Ref).

IV to oral conversion:

Upon discontinuation of continuous IV infusion, may initiate oral dose of 200 mg followed in 6 to 12 hours with an additional dose of 200 to 400 mg; adjust dose based on response at ≥1-day intervals to a range of 400 mg/day to 2.4 g/day in 2 to 3 divided doses. Note: For hypertension, the usual dosage range is 200 to 800 mg/day in 2 divided doses (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

IV, Oral:

Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).

Hemodialysis, intermittent (thrice weekly): Poorly dialyzed (manufacturer’s labeling); no supplemental dose or dosage adjustment necessary (expert opinion).

Peritoneal dialysis: Poorly dialyzed (manufacturer’s labeling); no dosage adjustment necessary (expert opinion).

CRRT: No dosage adjustment necessary (expert opinion).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling. However, dosage reduction may be necessary in hepatic impairment due to decreased metabolism and increased oral bioavailability, use with caution.

Dosing: Older Adult

Refer to adult dosing.

Hypertension: Oral:

Manufacturer's labeling: Initial: 100 mg twice daily; may titrate in increments of 100 mg twice daily; usual maintenance: 100 to 200 mg twice daily

ACCF/AHA Expert Consensus recommendations: Consider lower initial doses and titrating to response (Ref)

Dosing: Pediatric

(For additional information see "Labetalol: Pediatric drug information")

Dosage guidance:

Dosing: Use care with labetalol continuous IV infusions; the rate of administration is different for pediatric patients (mg/kg/hour) versus adult patients (mg/minute).

Hypertension

Hypertension:

Acute severe hypertension with life-threatening symptoms: Limited data available:

IV (intermittent bolus): Children and Adolescents: 0.2 to 1 mg/kg/dose; maximum dose: 40 mg/dose (Ref).

Continuous IV infusion: Infants, Children, and Adolescents: 0.25 to 3 mg/kg/hour; initiate at lower end of range and titrate up slowly to effect (Ref). In one retrospective study in infants and children ≤24 months of age, reductions in blood pressure were observed at doses up to 0.59 mg/kg/hour, with little additional benefit at higher doses (Ref).

Chronic hypertension: Limited data available: Children and Adolescents: Oral: Initial: 1 to 3 mg/kg/day in 2 divided doses; maximum daily dose: 10 to 12 mg/kg/day, up to 1,200 mg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. <1% removed by hemo- or peritoneal dialysis.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; however, dosage reduction may be necessary in hepatic impairment due to decreased metabolism and increased oral bioavailability; use with caution.

Adverse Reactions (Significant): Considerations
Bradyarrhythmias

Beta-blockers may cause bradycardia and heart block, including first-degree atrioventricular (AV) block, second-degree AV block, or complete AV block (Ref). At maintenance dosing, second- or third-degree AV block are less likely (Ref). Beta-blocking agents with intrinsic sympathomimetic activity (ISA) (eg, pindolol) may cause fewer AV conduction abnormalities than those without intrinsic sympathomimetic activity (eg, carvedilol) due to their partial agonist effects (Ref); labetalol possesses a very small degree of ISA and exhibits a slight, but irregular effect on AV conduction (Ref). In most cases (up to 72%), AV block associated with a beta-blocker will resolve upon discontinuation; however, there are reported cases of recurrent AV block and nearly 50% of patients with more severe AV block may require a permanent pacemaker (Ref).

Mechanism: Dose-related; related to the pharmacologic action. Blockade of cardiac beta-1 adrenergic receptors results in slowed conduction and prolongation of the refractory period of the AV node. Slowing of AV conduction can lead to AV block (Ref).

Onset: Varied; one study included patients who were on a beta-blocker for more than 1 month (Ref); however, other studies noted prolongation AV nodal refractory period occurring anywhere from 1 dose to several days following treatment initiation (Ref).

Risk factors:

• Impaired AV node conduction or sinus node function (Ref)

• Concurrent use of other agents that impair AV nodal conduction (eg, nondihydropyridine calcium channel blockers, digoxin, ivabradine, select antiarrhythmic agents) (Ref)

• Older patients (Ref)

Bronchospasm

Nonselective beta-blockers (eg, labetalol) have a higher risk of bronchospasm compared to cardioselective beta-blockers and may lead to drug discontinuation in patients with chronic obstructive pulmonary diseases (COPD) or asthma (Ref). Use of labetalol in patients with hypertension and COPD or asthma has been associated with varying degrees of impact on FEV1, forced expiratory flow, and/or forced vital capacity (Ref). Based on the use of other beta-blockers in this setting, concurrent use of inhaled bronchodilators and/or corticosteroids are protective against beta-blocker-induced bronchospasm in patients with COPD or asthma (Ref). Bronchospasm is reversible upon discontinuation (Ref).

Mechanism: Dose-related; related to pharmacologic action. Beta-blocking agents can lead to airway smooth muscle constriction by antagonism of beta-2 receptors (Ref).

Onset: Varied; changes in pulmonary function tests have occurred after 1 dose (Ref).

Risk factors:

• Reactive airway disease (asthma) (Ref)

CNS effects

Beta-blockers may cause CNS effects such as fatigue, sleep disorder, insomnia, and vivid dreams (Ref). Lipophilic beta-blockers (including labetalol) penetrate the blood-brain barrier to a greater extent than hydrophilic beta-blockers, possibly leading to a greater incidence of CNS effects; however, other studies have refuted this theory (Ref). Sexual disorders may occur; however, patients who require beta-blocker therapy have risk factors for erectile dysfunction (eg, coronary artery disease, heart failure) (Ref). Memory impairment has been reported with the use of other lipophilic beta-blockers (eg, carvedilol); however newer data suggests carvedilol may be helpful for patients with Alzheimer disease (Ref). CNS effects generally resolve with dose reduction or discontinuation (Ref).

Mechanism: Dose-related; exact mechanism is not fully understood. Proposed mechanisms include presence of beta receptors in the brain, affinity and in some instances, inhibition of beta-blocking agents towards serotonin (5-HT) receptors in the brain (affecting mood and sleep), and beta-blocker-induced decreases in central sympathetic output (Ref). Beta-1 blockade may also impact sleep by blocking sympathetic signaling to the pineal gland, resulting in suppression of nighttime levels of melatonin (Ref). Beta-blockers may cause erectile dysfunction through decreased sympathetic nervous system output and subsequent decreases in luteinizing hormone secretion and testosterone stimulation (Ref).

Onset: Intermediate; CNS effects often occur within the first few weeks of treatment (Ref).

Risk factors:

• Higher starting doses (Ref)

• Older patients (Ref)

Potentiation/masking of hypoglycemia

Beta-blockers may worsen, prolong, or cause hypoglycemia (Ref). Additionally, beta-blockers may mask symptoms of hypoglycemia (tremor, irritability, palpitations), making diaphoresis the only symptom unaffected by beta-blockers (Ref). It is unclear if nonselective or selective beta-blockers are more likely to cause hypoglycemia; as data are conflicting (Ref).

Mechanism: Dose-related; related to the pharmacologic action. Beta-blockers inhibit hepatic gluconeogenesis and glycogenolysis (Ref). Beta-blockers also reduce activation of the sympathetic nervous system, therefore masking hypoglycemic symptoms that are catecholamine-mediated (Ref).

Onset: Varied; hypoglycemia (<70 mg/dL) was reported significantly more after 24 hours of nonselective beta-blocker (ie, carvedilol) use compared to patients not on beta-blockers (Ref). In another study, episodes of severe hypoglycemia (<50 mg/dL) were reported over the course of 4 years (Ref).

Risk factors:

• Insulin-dependent diabetes (Ref)

• Type 2 diabetes mellitus (Ref)

• Patients who are hospitalized and not requiring basal insulin (Ref)

Withdrawal

Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia in patients with underlying cardiovascular disease (Ref). Some studies have found an increase in propensity-adjusted mortality and cardiovascular events; however, one study did not find changes in infarct size and left ventricular function when beta-blocker was abruptly withdrawn in patients with myocardial infarction (Ref).

Mechanism: Dose-dependent; related to the pharmacologic action. Beta blockade causes upregulation of beta-receptors, enhanced receptor sensitivity, and decreased sympathetic nervous system response. Abrupt withdrawal leads to a transient sympathetic hyper-response (Ref). Another proposed mechanism involves increased platelet aggregability to epinephrine and thrombin (Ref).

Onset: Rapid/varied and transient; increases in heart rate and blood pressure appear 24 hours after abrupt withdrawal, peak after 48 hours, and subside after 7 days (Ref). In other nonselective beta-blockers (propranolol), anginal symptoms reported to begin 12 to 24 hours after discontinuation. Development of adverse reactions also reported to occur 1 to 21 days after withdrawal (Ref).

Risk factors:

• Abrupt withdrawal in chronic users (Ref)

• Past medical history of coronary artery disease (including chronic stable angina) (Ref)

• Past medical history of hypertension (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Orthostatic hypotension (IV: 58%; oral: 1%)

Gastrointestinal: Nausea (≤19%)

Nervous system: Dizziness (1% to 16%)

1% to 10%:

Cardiovascular: Edema (oral: 1% to 2%), flushing (IV: 1%), hypotension (IV: 1%), ventricular arrhythmia (IV: 1%)

Dermatologic: Diaphoresis (IV: 4%; oral: <1%), pruritus (IV: 1%), skin rash (oral: 1%)

Gastrointestinal: Dysgeusia (1%), dyspepsia (IV: 1%; oral: 1% to 4%), vomiting (oral: ≤4%)

Genitourinary: Ejaculatory failure (oral: 1% to 5%), impotence (oral: 1% to 4%)

Hepatic: Increased serum transaminases (oral: 4%)

Nervous system: Drowsiness (IV: ≤3%), fatigue (oral: 1% to 10%) (table 1), headache (oral: 2%), hypoesthesia (IV: 1%), paresthesia (≤7%), vertigo (1% to 2%), yawning (IV: ≤3%)

Labetalol: Adverse Reaction: Fatigue

Drug (Labetalol)

Comparator (Propranolol)

Comparator (Metoprolol)

Placebo

Dose

Number of Patients (Labetalol)

Number of Patients (Propranolol)

Number of Patients (Metoprolol)

Number of Patients (Placebo)

10%

N/A

N/A

N/A

2,400 mg/day

175

N/A

N/A

N/A

7%

N/A

N/A

N/A

1,200 mg/day

411

N/A

N/A

N/A

6%

N/A

N/A

N/A

1,600 mg/day

242

N/A

N/A

N/A

5%

12%

12%

0%

N/A

227

84

49

98

5%

N/A

N/A

N/A

800 mg/day

503

N/A

N/A

N/A

4%

N/A

N/A

N/A

400 mg/day

606

N/A

N/A

N/A

4%

N/A

N/A

N/A

600 mg/day

608

N/A

N/A

N/A

3%

N/A

N/A

N/A

900 mg/day

117

N/A

N/A

N/A

2%

N/A

N/A

N/A

200 mg/day

522

N/A

N/A

N/A

1%

N/A

N/A

N/A

300 mg/day

181

N/A

N/A

N/A

Ophthalmic: Visual disturbance (oral: 1%)

Renal: Increased blood urea nitrogen (≤8%), increased serum creatinine (IV: 8%)

Respiratory: Dyspnea (oral: 2%), nasal congestion (oral: 1% to 6%), wheezing (IV: 1%)

<1%: Gastrointestinal: Diarrhea

Postmarketing:

Cardiovascular: Bradycardia, heart block, heart failure, syncope

Dermatologic: Facial erythema, lichen planus (bullous), lichenoid eruption, maculopapular rash, psoriasiform eruption, transient alopecia, urticaria

Genitourinary: Acute urinary retention, difficulty in micturition, Peyronie disease

Hematologic & oncologic: Positive ANA titer

Hepatic: Cholestatic jaundice, hepatic injury, hepatic necrosis, hepatitis

Hypersensitivity: Angioedema, hypersensitivity reaction, nonimmune anaphylaxis

Immunologic: Antibody development (antimitochondrial)

Neuromuscular & skeletal: Muscle cramps, myopathy (Willis 1990), systemic lupus erythematosus

Ophthalmic: Dry eye syndrome

Respiratory: Bronchospasm

Miscellaneous: Fever

Contraindications

Hypersensitivity to labetalol or any component of the formulation; severe bradycardia; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; bronchial asthma or a history of obstructive airway disease; uncompensated cardiac failure; conditions associated with severe and prolonged hypotension

Canadian labeling: Additional contraindications (not in the US labeling): Sick sinus syndrome (except in patients with a functioning artificial pacemaker); state of hypoperfusion; severe peripheral arterial circulatory disorders.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.

• Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were treated with alpha1-blockers. There appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery.

• Hepatic injury: Severe hepatocellular injury has been reported (rare). The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. Injury has occurred after both short- and long-term treatment and may be slowly progressive despite minimal symptomatology.

Disease-related concerns:

• Heart failure (HF): Use with extreme caution in patients with compensated heart failure and monitor for a worsening of the condition.

• Hepatic impairment: Use with caution in patients with hepatic impairment; bioavailability is increased due to decreased first-pass metabolism.

• Myasthenia gravis: Use beta blockers with caution in patients with myasthenia gravis.

• Peripheral vascular disease (PVD) and Raynaud disease: Beta blockers may precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud disease; use with caution and monitor for progression of arterial obstruction.

• Pheochromocytoma: Labetalol may be effective in lowering blood pressure and relieving symptoms in patients with pheochromocytoma; however, patients may experience paradoxical hypertensive responses due to inadequate alpha-1 blockade (Manger 2002; Mazza 2014). Adequate alpha-1 blockade should be initiated prior to use of any beta-blocker in this setting; use with caution in patients with pheochromocytoma or consider alternative therapy. If possible, obtain diagnostic tests for pheochromocytoma prior to use since labetalol may spuriously cause falsely elevated levels of plasma catecholamine and urinary metanephrine (Bravo 2002; MacCarthy 1983).

• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.

• Thyroid disease: Beta blockers may mask signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.

Special populations:

• Older adult: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Other warnings/precautions:

• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as hydrochloride:

Generic: 5 mg/mL (4 mL, 20 mL, 40 mL); 100 mg/100 mL (1 mg/mL) with NaCl 0.72% (100 mL); 200 mg/200 mL (1 mg/mL) with NaCl 0.72% (200 mL); 200 mg/200 mL (1 mg/mL) with dextrose 5% (200 mL); 300 mg/300 mL (1 mg/mL) in NaCl 0.72% (300 mL)

Solution Prefilled Syringe, Intravenous [preservative free]:

Generic: 10 mg/2 mL (2 mL)

Tablet, Oral, as hydrochloride:

Generic: 100 mg, 200 mg, 300 mg

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Labetalol HCl Intravenous)

5 mg/mL (per mL): $0.13 - $0.69

Solution (Labetalol HCl-Dextrose Intravenous)

200 mg/200 mL 5% (per mL): $0.17

Solution (Labetalol HCl-Sodium Chloride Intravenous)

100MG/100ML 0.72% (per mL): $0.17

200MG/200ML 0.72% (per mL): $0.17

300MG/300ML 0.72% (per mL): $0.17

Solution Prefilled Syringe (Labetalol HCl Intravenous)

10 mg/2 mL (per mL): $3.60

Tablets (Labetalol HCl Oral)

100 mg (per each): $0.17 - $0.67

200 mg (per each): $0.26 - $1.14

300 mg (per each): $0.35 - $1.15

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as hydrochloride:

Generic: 5 mg/mL (20 mL, 40 mL)

Tablet, Oral, as hydrochloride:

Trandate: 100 mg [contains sodium benzoate]

Trandate: 200 mg [contains fd&c yellow #6 (sunset yellow), sodium benzoate]

Generic: 100 mg, 200 mg

Administration: Adult

Oral: Administer without regard to food; however, the absolute bioavailability of labetalol is increased when administered with food. Administer in a consistent manner with regards to meals.

Parenteral: Bolus dose of 10 mg may be administered IV push at a rate of 10 mg/minute; bolus doses of ≥20 mg may be administered IV push over 2 minutes; may follow with continuous IV infusion if clinically indicated (Ref). Orthostatic hypotension may occur with IV administration; patient should remain supine during and for up to 3 hours after IV administration; patient’s ability to tolerate an upright position should be established before permitting ambulation or assuming an upright position.

Administration: Pediatric

Oral: Administer without regard to food; however, the absolute bioavailability of labetalol is increased when administered with food. Administer in a consistent manner with regards to meals.

Parenteral:

IV bolus: Based on adult information, may administer undiluted over 2 minutes; maximum: 10 mg/minute.

Continuous IV infusion: Administer as a continuous IV infusion with the use of an infusion pump.

Usual Infusion Concentrations: Adult

Note: Premixed solutions are available.

IV infusion: 200 mg in 200 mL (concentration: 1 mg/mL) or 400 mg in 200 mL (concentration: 2 mg/mL) or 500 mg in 250 mL (concentration: 2 mg/mL) of D5W.

Usual Infusion Concentrations: Pediatric

IV infusion: 1 mg/mL, 5 mg/mL.

Use: Labeled Indications

Hypertension: Management of hypertension (IV indicated for severe hypertension only [eg, hypertensive emergencies]). Note: Beta-blockers are not recommended as first-line therapy (ACC/AHA [Whelton 2018]).

Use: Off-Label: Adult

Acute aortic syndromes/Acute aortic dissection; Acute ischemic stroke, BP management with reperfusion therapy; Hypertensive emergency in pregnancy or postpartum (including acute-onset severe hypertension in preeclampsia/eclampsia); Intracerebral hemorrhage, acute, blood pressure management; Subarachnoid hemorrhage, blood pressure management

Medication Safety Issues
Sound-alike/look-alike issues:

Labetalol may be confused with betaxolol, LaMICtal, lamoTRIgine, Lipitor

Normodyne may be confused with Norpramin

Trandate may be confused with traMADol, Trental

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication (IV formulation) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Administration issues:

Significant differences exist between oral and IV dosing. Use caution when converting from one route of administration to another.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Risk D: Consider therapy modification

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Antidiabetic Agents: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Cannabis: Beta-Blockers may enhance the adverse/toxic effect of Cannabis. Specifically, the risk of hypoglycemia may be increased. Risk C: Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification

Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Risk C: Monitor therapy

DOBUTamine: Beta-Blockers may diminish the therapeutic effect of DOBUTamine. Risk C: Monitor therapy

Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Increase monitoring for clinical response and adverse effects. Risk D: Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

EPHEDrine (Systemic): Beta-Blockers may diminish the therapeutic effect of EPHEDrine (Systemic). Risk C: Monitor therapy

EPINEPHrine (Nasal): Beta-Blockers (with Alpha-Blocking Properties) may diminish the therapeutic effect of EPINEPHrine (Nasal). Risk C: Monitor therapy

EPINEPHrine (Oral Inhalation): Beta-Blockers (with Alpha-Blocking Properties) may diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy

Epinephrine (Racemic): Beta-Blockers (with Alpha-Blocking Properties) may diminish the therapeutic effect of Epinephrine (Racemic). Risk C: Monitor therapy

EPINEPHrine (Systemic): Beta-Blockers (with Alpha-Blocking Properties) may diminish the therapeutic effect of EPINEPHrine (Systemic). Risk C: Monitor therapy

Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy

Etilefrine: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may diminish the therapeutic effect of Etilefrine. Risk C: Monitor therapy

Etofylline: Beta-Blockers may diminish the therapeutic effect of Etofylline. Risk X: Avoid combination

Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination

Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification

Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Management: Consider alternatives to either grass pollen allergen extract (5 grass extract) or beta-blockers in patients with indications for both agents. Canadian product labeling specifically lists this combination as contraindicated. Risk D: Consider therapy modification

Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Insulins: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapy

Iobenguane Radiopharmaceutical Products: Labetalol may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer labetalol until at least 7 days after each iobenguane dose. Risk X: Avoid combination

Isoproterenol: Beta-Blockers may diminish the therapeutic effect of Isoproterenol. Risk C: Monitor therapy

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Mavacamten: Beta-Blockers may enhance the adverse/toxic effect of Mavacamten. Specifically, negative inotropic effects may be increased. Risk C: Monitor therapy

Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk C: Monitor therapy

Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Mivacurium: Beta-Blockers may enhance the therapeutic effect of Mivacurium. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Risk C: Monitor therapy

Nitrendipine: May enhance the therapeutic effect of Beta-Blockers. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Beta-Blockers. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Reserpine: May enhance the bradycardic effect of Beta-Blockers. Reserpine may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification

Succinylcholine: Beta-Blockers may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy

Sulfonylureas: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Sulfonylureas. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Sulfonylureas. Risk C: Monitor therapy

Tasimelteon: Beta-Blockers may diminish the therapeutic effect of Tasimelteon. Management: Consider avoiding nighttime administration of beta-blockers during tasimelteon therapy due to the potential for reduced tasimelteon efficacy. Risk D: Consider therapy modification

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy

Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk C: Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy

White Birch Allergen Extract: Beta-Blockers may enhance the adverse/toxic effect of White Birch Allergen Extract. Specifically, beta-blockers may reduce the effectiveness of beta-agonists that may be required to treat systemic reactions to white birch allergen extract. Risk X: Avoid combination

Food Interactions

Labetalol serum concentrations may be increased if taken with food. Management: Administer with food.

Reproductive Considerations

Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be continued in patients trying to conceive. Labetalol is one of the medications patients can transition to if currently taking an agent that is ineffective or should be avoided during pregnancy (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).

Erectile dysfunction and inhibition of sperm motility are noted in product labeling following use of beta-blockers, including labetalol. As a class, outcomes from available studies evaluating beta-blockers and sexual dysfunction are inconsistent, and the negative effects on erectile function are considered controversial. A clear relationship between use of beta-blockers and erectile dysfunction has not been established. Hypertension itself is associated with erectile dysfunction. Patients on a beta-blocker presenting with sexual dysfunction should be evaluated for underlying disease (Farmakis 2021; Levine 2012; Semet 2017; Terentes-Printzios 2022; Viigimaa 2020).

Pregnancy Considerations

Labetalol crosses the placenta.

Exposure to beta-blockers during pregnancy may increase the risk for adverse events in the neonate. If maternal use of a beta-blocker is needed, monitor fetal growth during pregnancy; monitor the newborn for 48 hours after delivery for bradycardia, hypoglycemia, and respiratory depression (ESC [Regitz-Zagrosek 2018]).

Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of labetalol may be altered (Mulrenin 2021; van de Vusse 2022). Dose adjustments may be required; close monitoring is recommended (Mulrenin 2021; SOGC [Magee 2022]).

Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). When treatment for hypertension is initiated during pregnancy, oral labetalol is one of the preferred agents (ACOG 2019; ESC [Cífková 2020]; ESC [Regitz-Zagrosek 2018]; SOGC [Magee 2022]). IV labetalol is recommended for use in the management of hypertensive emergencies in pregnant or postpartum patients (including acute-onset severe hypertension in preeclampsia/eclampsia) (ACOG 2020a; SOGC [Magee 2022]).

Breastfeeding Considerations

Labetalol is present in breast milk.

Data related to the presence of labetalol in breast milk are available following maternal administration of oral labetalol 300 mg twice daily to a woman for preeclampsia. Delivery was at 26 weeks' gestation; breast milk concentrations ~8 days postpartum were 0.71 mcg/mL (Mirpuri 2008). Using a milk concentration of 0.71 mcg/mL, the estimated daily infant dose via breast milk is 0.1065 mg/kg/day providing a relative infant dose (RID) of 3.6% compared to an infant therapeutic dose of 3 mg/kg/day. In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).

Breast milk concentrations have not been found to correspond to maternal serum concentrations (Lunell 1985; Michael 1979). Peak breast milk concentrations are noted to occur 1 to 3 hours after the maternal dose (Lunell 1985).

Asymptomatic bradycardia was observed in a preterm infant exclusively breastfed following maternal use of labetalol (Mirpuri 2008). Nipple pain and Raynaud phenomenon of the nipple has been associated with labetalol in case reports (Rolfes 2014).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Labetalol is considered compatible for use in patients who are breastfeeding (ACOG 2019; ESC [Cífková 2020]; SOGC [Magee 2022]).

Monitoring Parameters

BP (especially with initial dosing and dosing increases), heart rate, continuous cardiac monitoring recommended for IV administration (consult individual institutional policies and procedures); periodic LFTs if clinically indicated; mental alertness; signs and symptoms of bronchospasm in patients with existing bronchospastic disease; serum glucose (in patients with diabetes).

Hypertension, acute in pregnancy (hypertensive emergency/urgency): Once target BP is achieved, monitor every 10 minutes for the first hour, then every 15 minutes for 1 hour, then every 30 minutes for 1 hour, then every hour for 4 hours (ACOG 2020b).

Reference Range

BP goal: May vary depending on clinical conditions, different clinical practice guidelines, and expert opinion. Refer to "Clinical Practice Guidelines" for specific treatment goals.

Mechanism of Action

Blocks alpha1-, beta1-, and beta2-adrenergic receptor sites; elevated renins are reduced. The ratios of alpha- to beta-blockade differ depending on the route of administration estimated to be 1:3 (oral) and 1:7 (IV) (Goa 1989).

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Oral: 20 minutes to 2 hours (McNeil 1984); IV: Within 5 minutes (Goa 1989)

Peak effect: Oral: 2 to 4 hours; IV: 5 to 15 minutes (Goa 1989)

Duration: Blood pressure response:

Oral: 8 to 12 hours (dose dependent)

IV: Average: 16 to 18 hours (dose dependent)

Absorption: Complete

Distribution: Apparent Vd: Adults: 2.5 to 15.7 L/kg (Goa 1989)

Protein binding: ~50%

Metabolism: Hepatic, primarily via glucuronide conjugation; extensive first-pass effect

Bioavailability: Oral: 25%; increased with liver disease, elderly, and concurrent cimetidine

Half-life elimination: Oral: 6 to 8 hours; IV: ~5.5 hours

Time to peak, plasma: Oral: 1 to 2 hours

Excretion: Urine (55% to 60% as glucuronide conjugates, <5% as unchanged drug [Goa 1989]); feces (12% to 27% as metabolites) (Goa 1989)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Older adult: Elimination is reduced in elderly patients.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Biascor | Blocamine | Labetalol | Labetalol richet;
  • (AT) Austria: Trandate;
  • (AU) Australia: Labetalol sxp | Presolol | Trandate;
  • (BD) Bangladesh: Labecard | Labegest | Labeta;
  • (BE) Belgium: Trandate;
  • (CH) Switzerland: Trandate;
  • (CL) Chile: Trandate;
  • (CN) China: Labetalol;
  • (CO) Colombia: Diblorec | Labetalol | Labetalol clorhidrato | Labetalol HCL | Presequil | Telabelol | Trandate;
  • (CZ) Czech Republic: Labetalol | Trandate;
  • (EC) Ecuador: Biascor | Diblorec;
  • (EE) Estonia: Labetalolo s.a.l.f. | Trandate;
  • (EG) Egypt: Labipress;
  • (ES) Spain: Trandate;
  • (FI) Finland: Albetol | Labetalol s.a.l.f | Trandate;
  • (FR) France: Labetalol Dci | Trandate;
  • (GB) United Kingdom: Labetalol | Labetalol astec | Labetalol cox | Labetalol dc | Labetalol kent | Labetalol sandoz | Labrocol | Trandate;
  • (GR) Greece: Trandate;
  • (HK) Hong Kong: Labetalol HCL | Trandate;
  • (HU) Hungary: Trandate;
  • (ID) Indonesia: Trandate;
  • (IE) Ireland: Trandate;
  • (IL) Israel: Trandate;
  • (IN) India: Alphadopa l | Culol | Eubet | Evabet | Gravidol | Gynapres L | Labebet | Labepure | Labetamac | Labetol | Labil | Lablol | Lebatens | Lexol | Lobet | Lopih | Pregnasafe | Tiplab;
  • (IT) Italy: Amipress | Ipolab | Labetalolo s.a.l.f. | Trandate;
  • (JP) Japan: Amitalol | Ascool | Labestonin | Resporito | Trandate | Trandate glaxosmithkline | Trandate takeda;
  • (KR) Korea, Republic of: Betasin | Labesin | Trandate;
  • (KW) Kuwait: Labetalol | Labetalol HCL | Trandate;
  • (LT) Lithuania: Coreton | Labetalol | Norbetol | Trandate | Trandate aspen;
  • (LU) Luxembourg: Trandate;
  • (LV) Latvia: Coreton | Trandate;
  • (MY) Malaysia: Labetalol | Labetalol pharmaniaga | Pharmaniaga labetalol hydrochloride | Tolbetol | Trandate | Trantalol;
  • (NG) Nigeria: Labetalol HCL;
  • (NL) Netherlands: Labetalol | Labetalol B-Medical | Labetalol HCL | Labetalol hcl Alpharma | Labetalol Hcl CF | Labetalol Hcl Katwijk | Labetalol Hcl Merck | Labetalol hcl PCH | Labetalol Hcl Sandoz | Trandate;
  • (NO) Norway: Labetalol bedford | Labetalol s.a.l.f | Trandate;
  • (NZ) New Zealand: Hybloc | Labetalol | Presolol | Trandate;
  • (PH) Philippines: Abetol;
  • (PK) Pakistan: Labetalol | Labetol | Letol;
  • (PL) Poland: Coreton | Labetalol HCL | Pressocard | Trandate;
  • (PR) Puerto Rico: Labetalol | Labetalol HCL | Normodyne | Trandate;
  • (PT) Portugal: Labetalol pharmakern | Trandate;
  • (PY) Paraguay: Biascor;
  • (QA) Qatar: Labever | Trandate;
  • (SA) Saudi Arabia: Trandate;
  • (SE) Sweden: Labetalol s.a.l.f | Trandate;
  • (SG) Singapore: Trandate | Trantalol;
  • (SI) Slovenia: Trandate;
  • (SK) Slovakia: Trandate;
  • (TH) Thailand: Avexa | Labesin;
  • (TN) Tunisia: Trandate;
  • (TR) Turkey: Trandate;
  • (TW) Taiwan: Abetol | Chenday | Labedin | Labenon | Labtal | Latol | Lavocohere | Presolol | Trandate | Tranmin;
  • (UY) Uruguay: Labetalol;
  • (VE) Venezuela, Bolivarian Republic of: Trandate;
  • (ZA) South Africa: Trandate
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