Note: IV administration: There is limited documentation of prolonged continuous infusions; most patients respond to initial IV bolus dosing and are then transitioned to an oral antihypertensive (Huey 1988; Papademetriou 1982; Wright 1986). Accumulation can occur with high-dose continuous infusions and may result in severe hypotension and bradycardia (Fahed 2008).
Acute aortic syndromes/Acute aortic dissection (alternative agent) (off-label use):
Note: Manage patients immediately (including operative assessment) by controlling heart rate (target <60 bpm), pain with IV opioids, and systolic BP (target 100 to 120 mm Hg or lowest tolerated pressure) (ACCF/AHA [Hiratzka 2010]; Black 2019). 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 (Goldsmith 1990).
Intermittent IV: Initial: 20 mg over 2 minutes; followed by 20 to 80 mg every 10 minutes until target heart rate and blood pressure is reached; may transition to continuous infusion if unable to obtain target goals (ACC/AHA [Whelton 2018]; Black 2019; MacCarthy 1983; Marik 2011; Peacock 2012; Sarafidis 2012).
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 (ACC/AHA [Whelton 2018]; Black 2019; Marik 2007; Marik 2011; Peixoto 2019; Sarafidis 2012).
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 (AHA/ASA [Powers 2019]).
Prior to reperfusion therapy:
IV: 10 to 20 mg over 1 to 2 minutes; may repeat once (AHA/ASA [Powers 2019]).
During and after reperfusion therapy:
IV: 10 mg over 1 to 2 minutes, followed by 2 to 8 mg/minute continuous infusion (AHA/ASA [Powers 2019]). 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 (Goldsmith 1990).
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) (Axon 2015; Stanistreet 2020; Varon 2019). For patients with chronic hypertension prior to surgery, restart oral therapies as soon as appropriate once hemodynamically stable (Bisognano 2019; Lien 2012).
Intermittent IV: Initial: 5 to 20 mg over 2 minutes; repeat dose every 10 minutes until target blood pressure is reached (Bisognano 2019; London 2019; MacCarthy 1983; Mann 2020; manufacturer's labeling). 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 (Goldsmith 1990).
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 (ACC/AHA [Whelton 2018]).
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 (ACC/AHA [Whelton 2018]). In patients with severe or resistant hypertension, doses up to 1.2 to 2.4 g/day in 2 or 3 divided doses may be required according to the manufacturer's labeling; however, some experts prefer combinations of agents dosed within usual range rather than further dose escalation (ACC/AHA [Whelton 2018]; Brook 2020; MacCarthy 1983).
Hypertensive emergency:
Note: In general, reduce mean arterial BP ~10% to 20% over the first hour, then 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 (ACC/AHA [Whelton 2018]; Elliott 2021b). 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 (Goldsmith 1990).
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 (ACC/AHA [Whelton 2018]; Cannon 2013; Elliott 2022a; MacCarthy 1983; Marik 2011; Peacock 2012; Sarafidis 2012).
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 (ACC/AHA [Whelton 2018]; Marik 2007; Marik 2011; Peixoto 2019; Sarafidis 2012).
Hypertensive emergency in pregnancy or postpartum (including acute-onset hypertension in preeclampsia/eclampsia) (off-label use):
Note: For acute-onset, severe, persistent (eg, ≥15 minutes) hypertension (ACOG 2019b). 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 (Goldsmith 1990).
Intermittent IV: Initial: 20 mg over 2 minutes; if blood pressure exceeds thresholds after 10 minutes, increase dose in increments of 20 to 40 mg every 10 minutes; maximum single dose: 80 mg. Note: If blood pressures remain above threshold after several intermittent doses, another agent should be used (ACOG 2019b; ACOG 2020; Magee 2014).
Continuous IV infusion: Initial loading dose: 20 mg over 2 minutes (optional if intermittent dosing is used), followed by 1 to 2 mg/minute titrated to response (ACOG 2020; Magee 2014).
Oral (alternative route): Initial: 200 mg every 12 hours. Dose may be increased up to 800 mg every 8 to 12 hours as needed based on response and tolerability. Maximum: 2.4 g/day. IV therapy may be needed for acute treatment; combination therapy with another agent may be needed if maximum dose is ineffective or must be limited due to adverse effects (ACOG 2020).
Intracerebral hemorrhage, blood pressure management (off-label use):
Note: In patients who present within 6 hours of acute intracranial hemorrhage and have systolic BP between 150 and 220 mm Hg, decreasing systolic BP to <140 mm Hg is not beneficial and can be harmful (ACC/AHA [Whelton 2018]). 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 (Goldsmith 1990).
Patients who present with systolic BP >150 mm Hg:
Intermittent IV: Initial: 5 to 20 mg IV push over 2 minutes, followed by 20 to 80 mg every 10 to 15 minutes until recommended target systolic BP is reached; may consider a continuous infusion if unable to obtain target goals (AHA/ASA [Broderick 2007]; AHA/ASA [Hemphill 2015]; Rordorf 2022; Rose 2004).
Patients who present with systolic BP >220 mm Hg:
Continuous IV infusion: Initial loading dose: 20 mg over 2 minutes, followed by 0.5 to 2 mg/minute, titrate to recommended target systolic BP (AHA/ASA [Broderick 2007]; Mocco 2006; Ortega-Gutierrez 2013; Rordorf 2022; Rose 2004).
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 (AHA/ASA [Connolly 2012]; Singer 2020). 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 (Goldsmith 1990).
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 (Liu-DeRyke 2013; Mocco 2006; Patel 1993; Woloszyn 2012).
Continuous IV infusion: 0.5 to 2 mg/minute titrated to response; based on very limited data (Mocco 2006).
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 (ACC/AHA [Whelton 2018]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 (Walstad 1982; Wood 1982).
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).
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.
(For additional information see "Labetalol: Pediatric drug information")
Note: 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: Children and Adolescents: Limited data available:
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 (NHLBI 2011)
IV (intermittent bolus): 0.2 to 1 mg/kg/dose; maximum dose: 40 mg/dose; use should be reserved for severe hypertension (NHBPEP 2004)
Hypertensive emergency/urgency: Limited data available: Infants, Children, and Adolescents:
IV (intermittent bolus): 0.2 to 1 mg/kg/dose; maximum dose: 40 mg/dose (Flynn 2009)
Continuous IV infusion: 0.25 to 3 mg/kg/hour; initiate at lower end of range, and titrate up slowly (Flynn 2009; NHBPEP 2004). One retrospective study in infants and children ≤24 months of age observed reductions in blood pressure at doses up to 0.59 mg/kg/hour with little additional benefit at higher doses (Thomas 2011).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
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.
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 (Aronow 2011)
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)
Solution Prefilled Syringe, Intravenous, as hydrochloride:
Generic: 20 mg/4 mL (4 mL)
Tablet, Oral, as hydrochloride:
Generic: 100 mg, 200 mg, 300 mg
Yes
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
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 may be administered IV push at a rate of 10 mg/minute; may follow with continuous IV infusion
Oral: May administer with food but should be administered in a consistent manner with regards to meals
Parenteral:
IV bolus: 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; adjust infusion rate to effect.
IV infusion: 200 mg in 200 mL (concentration: 1 mg/mL) or 500 mg in 250 mL (concentration: 2 mg/mL) of D5W
IV infusion: 1 mg/mL
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]).
Acute aortic syndromes/Acute aortic dissection; Acute ischemic stroke, BP management with reperfusion therapy; Hypertensive emergency in pregnancy or postpartum (including acute-onset hypertension in preeclampsia/eclampsia); Intracerebral hemorrhage, blood pressure management; Subarachnoid hemorrhage, blood pressure management
Labetalol may be confused with betaxolol, LaMICtal, lamoTRIgine, Lipitor
Normodyne may be confused with Norpramin
Trandate may be confused with traMADol, TRENtal
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.
Significant differences exist between oral and IV dosing. Use caution when converting from one route of administration to another.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Orthostatic hypotension (intravenous: 58%; tablet: 1%)
Central nervous system: Dizziness (1% to 20%), fatigue (1% to 11%)
Gastrointestinal: Nausea (≤19%)
1% to 10%:
Cardiovascular: Edema (1% to 2%), flushing (1%), hypotension (1%), ventricular arrhythmia (intravenous: 1%)
Central nervous system: Paresthesia (≤7%), drowsiness (≤3%), yawning (≤3%), headache (2%), vertigo (1% to 2%), hypoesthesia (1%)
Dermatologic: Diaphoresis (≤4%), pruritus (1%), skin rash (1%)
Gastrointestinal: Dyspepsia (≤4%), vomiting (≤4%), dysgeusia (1%)
Genitourinary: Ejaculatory failure (1% to 5%), impotence (1% to 4%)
Hepatic: Increased serum transaminases (4%)
Neuromuscular & skeletal: Asthenia (1%)
Ophthalmic: Visual disturbance (1%)
Renal: Increased blood urea nitrogen (≤8%), increased serum creatinine (≤8%)
Respiratory: Nasal congestion (1% to 6%), dyspnea (2%), wheezing (1%)
<1%, postmarketing, and/or case reports: Anaphylactoid reaction, angioedema, antibody development (antimitochondrial), bradycardia, bronchospasm, cardiac failure, cholestatic jaundice, diabetes mellitus, diarrhea, difficulty in micturition, facial erythema, fever, heart block, hepatic injury, hepatic necrosis, hepatitis, hypersensitivity reaction, increased liver enzymes, jaundice, lichenoid eruption, lichen planus, maculopapular rash, muscle cramps, myopathy, Peyronie disease, positive ANA titer, psoriasiform eruption, syncope, systemic lupus erythematosus, transient alopecia, urinary retention, urticaria, xerophthalmia
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; state of hypoperfusion; severe peripheral arterial circulatory disorders.
Documentation of allergenic cross-reactivity for alpha/beta adrenergic blocking agents is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
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. Periodically monitor LFTs. If liver injury or jaundice occurs, discontinue labetalol and do not restart.
• Hypotension/syncope: Symptomatic hypotension with or without syncope may occur with labetalol; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Initiation with a low dose and gradual up-titration may help to decrease the occurrence of hypotension or syncope. Advise patients to avoid driving or other hazardous tasks during initiation of therapy due to the risk of syncope. Orthostatic hypotension may occur with IV administration; patient should remain supine during and for up to 3 hours after IV administration
Disease-related concerns:
• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms. May also reduce release of insulin in response to hyperglycemia; dosage of antidiabetic agents may need to be adjusted.
• Heart failure (HF): Use with extreme caution in patients with compensated heart failure and monitor for a worsening of the condition.
• Hepatic impairment: Use with caution in patients with hepatic impairment; bioavailability is increased due to decreased first-pass metabolism.
• Myasthenia gravis: Use 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:
• Elderly: 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:
• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.
• Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.
In children, two cases of reversible myopathy have been reported (Willis 1990).
None known.
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
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk 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
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
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
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. 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
Etofylline: Beta-Blockers may diminish the therapeutic effect of Etofylline. Risk X: Avoid combination
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
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
Insulins: Beta-Blockers may enhance the hypoglycemic 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
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-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk 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
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
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
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. 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 hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination
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 may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy
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
Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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
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
Labetalol serum concentrations may be increased if taken with food. Management: Administer with food.
Labetalol crosses the placenta.
Exposure to labetalol during pregnancy may increase the risk for adverse events in the neonate. If maternal use of a beta-blocker is needed, fetal growth should be monitored during pregnancy and the newborn should be monitored 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 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 2019a).
Most pharmacokinetic properties of labetalol are not significantly changed by pregnancy (Fischer 2014; Rogers 1990; Rubin 1983; Saotome 1993).
Oral labetalol is considered appropriate for the treatment of chronic hypertension in pregnancy (ACOG 2019a; Magee 2014). Intravenous labetalol is recommended for use in the management of acute onset, severe hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) in pregnant and postpartum women. In general, avoid use of labetalol in women with asthma or heart failure (ACOG 2019b; ACOG 2020; Magee 2014).
Labetalol is present in breast milk.
The relative infant dose (RID) of labetalol is 3.6% when calculated using the highest breast milk concentration located and 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).
Using the highest milk concentration (0.71 mcg/mL), the estimated daily infant dose via breast milk is 0.1065 mg/kg/day. This milk concentration was obtained following maternal administration of oral labetalol 300 mg twice daily (Mirpuri 2008). Milk concentrations have not been found to correspond to maternal serum concentrations (Lunell 1985; Michael 1979). Peak 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). The manufacturer recommends that caution be exercised when administering labetalol to breastfeeding women. However, labetalol may be one of the preferred beta-blockers in breastfeeding females (Anderson 2017; Ito 2000; Magee 2014).
BP, standing and sitting/supine, pulse, cardiac monitor and BP monitor recommended for IV administration; consult individual institutional policies and procedures.
Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2018]):
Confirmed hypertension and known cardiovascular disease or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%: Target BP <130/80 mm Hg is recommended.
Confirmed hypertension without markers of increased ASCVD risk: Target BP <130/80 mm Hg may be reasonable.
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 2019b).
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).
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)
Geriatric: Elimination is reduced in elderly patients.
Solution (Labetalol HCl Intravenous)
5 mg/mL (per mL): $0.13 - $1.56
Tablets (Labetalol HCl Oral)
100 mg (per each): $0.23 - $0.67
200 mg (per each): $0.39 - $1.14
300 mg (per each): $0.65 - $1.15
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