(la BET a lole)
- Ibidomide Hydrochloride
- Labetalol HCl
- Labetalol Hydrochloride
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as hydrochloride:
Generic: 5 mg/mL (4 mL, 20 mL, 40 mL)
Solution Prefilled Syringe, Intravenous, as hydrochloride:
Generic: 25 mg/5 mL (5 mL); 50 mg/10 mL (10 mL)
Tablet, Oral, as hydrochloride:
Trandate: 100 mg [DSC], 200 mg [DSC], 300 mg [DSC]
Generic: 100 mg, 200 mg, 300 mg
Brand Names: U.S.
- Trandate [DSC]
- Beta-Blocker With Alpha-Blocking Activity
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).
Apparent Vd: Adults: 2.5 to 15.7 L/kg (Goa 1989)
Hepatic, primarily via glucuronide conjugation; extensive first-pass effect
Urine (55% to 60% as glucuronide conjugates, <5% as unchanged drug [Goa 1989]); feces (12% to 27% as metabolites) (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)
Time to Peak
Plasma: Oral: 1 to 2 hours
Duration of Action
Blood pressure response:
Oral: 8 to 12 hours (dose dependent)
IV: Average: 16 to 18 hours (dose dependent)
Oral: 6 to 8 hours; IV: ~5.5 hours
Special Populations: Elderly
Elimination is reduced in elderly patients.
Use: Labeled Indications
Hypertension: Management of hypertension (IV indicated for severe hypertension only [eg, hypertensive emergencies])
The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients (JNC8 [James, 2013]):
• Patients ≥60 years of age, with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.
• Patients <60 years of age, with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
• Patients ≥18 years of age with diabetes, with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
• Patients ≥18 years of age with chronic kidney disease (CKD), with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
In patients with CKD, regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.
Off Label Uses
Hypertensive emergency in pregnancy
Based on the American College of Obstetricians and Gynecologists (ACOG) guidelines on the management of hypertension in pregnancy, the use of labetalol is effective and recommended as a treatment option in pregnant and postpartum patients who are experiencing acute onset, severe hypertension with preeclampsia or eclampsia [ACOG 2015].
Clinical guidelines recommend use of antihypertensives during the period between onset of SAH and surgical obliteration. Clinical study results and institutional experience are generally supportive of labetalol use in SAH. Nicardipine appears to have more beneficial outcomes than sodium nitroprusside and labetalol; however, only a small number of studies have compared the agents directly. Additional large-scale, multicenter, randomized controlled studies with more standardized interventions are needed to assess efficacy and safety of labetalol for SAH antihypertensive therapy.
Additional Off-Label Uses
Hypertension during acute ischemic stroke; Pediatric hypertension; Chronic hypertension in pregnancy
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
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.
Hypertension: 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 (ASH/ISH [Weber 2014]): 100 to 300 mg twice daily; may require up to 2,400 mg daily.
Acute hypertension (hypertensive emergency/urgency):
IV: Initial: 10 to 20 mg IV push over 2 minutes; may administer additional injections using double the dose (maximum dose: 80 mg/dose) at 10-minute intervals until target SBP is reached; total maximum dose: 300 mg. May consider a continuous infusion (MacCarthy 1983; Marik 2011; Sarafidis 2012).
Continuous IV infusion: Initial: 0.5 to 2 mg/minute (Sarafidis 2012; Marik 2007). Some patients may require doses within the range of 2 to 10 mg/minute (Marik 2011).
Note: Although loading infusions are well described in the product labeling, the labeling is silent in specific clinical situations, such as in the patient who has an initial response to labetalol infusions but cannot be converted to an oral route for subsequent dosing. There is limited documentation of prolonged continuous infusions (ie, >300 mg/day). In rare clinical situations, higher continuous infusion doses up to 6 mg/minute have been used in the critical care setting (eg, aortic dissection) and up to 8 mg/minute (eg, hypertension with ongoing acute ischemic stroke). At these doses, it may be best to consider an alternative agent if the labetalol infusion is not meeting the goals of therapy. At the other extreme, continuous infusions at relatively low doses (0.03 to 0.1 mg/minute) have been used in some settings (following loading infusion in patients who are unable to be converted to oral regimens or in some cases as a continuation of outpatient oral regimens). These prolonged infusions should not be confused with loading infusions. Because of wide variation in the use of infusions, an awareness of institutional policies and practices is extremely important. Careful clarification of orders and specific infusion rates/units is required to avoid confusion. Due to the prolonged duration of action, careful monitoring should be extended for the duration of the infusion and for several hours after the infusion. Excessive administration may result in prolonged hypotension and/or bradycardia.
Arterial hypertension in acute ischemic stroke (off-label use): IV:
Patient otherwise eligible for reperfusion treatment (eg, alteplase) except blood pressure (BP) >185/110 mm Hg: 10 to 20 mg over 1 to 2 minutes; may repeat once. If BP does not decline and remains >185/110 mm Hg, alteplase should not be administered (AHA/ASA [Jauch 2013]).
Management of BP during and after reperfusion treatment (eg, alteplase) to maintain BP ≤180/105 mm Hg: If systolic BP >180 to 230 mm Hg or diastolic >105 to 120 mm Hg, then administer 10 mg over 1 to 2 minutes followed by an infusion of 2 to 8 mg/minute. If hypertension is refractory or diastolic BP >140 mm Hg, consider other IV antihypertensives (eg, nitroprusside) (AHA/ASA [Jauch 2013]).
Arterial hypertension in intracranial hemorrhage (off-label use):
IV: Initial: 5 to 20 mg IV push over 2 minutes; may administer additional doses every 15 minutes until target SBP is reached; total maximum dose: 300 mg (AHA/ASA [Broderick 2007]). Some have suggested initial doses in the range of 20 to 80 mg administered every 10 minutes (Rose 2004).
Continuous IV infusion: Initial: 0.5 to 2 mg/minute (AHA/ASA [Broderick 2007]; Mocco 2006; Ortega-Gutierrez 2013; Rose 2004).
Hypertensive emergency in pregnancy (systolic BP ≥160 mm Hg or diastolic BP ≥110 mm Hg) (off-label dose): IV: Initial: 20 mg; if blood pressure still exceeds thresholds, may increase dose every 10 minutes in increments of 20 to 40 mg to a maximum single dose of 80 mg (Refer to administration protocols developed by the American College of Obstetricians and Gynecologists; ACOG 2015). A maximum total cumulative dose of 300 mg is recommended (Magee 2014). Note: After the initial dose, may initiate a continuous infusion of 1 to 2 mg/minute instead of intermittent dosing (Magee 2014).
Subarachnoid hemorrhage (off-label use):
IV bolus: Initial: 5 to 40 mg (Liu-DeRyke 2008; Patel 1993; Woloszyn 2012). Some have recommended 20 to 80 mg every 10 minutes up to a maximum of 300 mg followed by a continuous IV infusion (Mocco 2006).
IV infusion: 0.5 to 2 mg/minute; based on very limited information (Mocco 2006)
IV to oral conversion: Upon discontinuation of IV infusion, may initiate oral dose of 200 mg followed in 6 to 12 hours with an additional dose of 200 to 400 mg. Thereafter, dose patients with 400 to 2,400 mg/day in divided doses depending on blood pressure response.
Refer to adult dosing.
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)
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 (off-label): 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; use should be reserved for severe hypertension (NHBPEP 2004).
Hypertensive emergency: Infants, Children, and Adolescents: Continuous IV infusion: 0.25 to 3 mg/kg/hour; initiate at lower end of range and titrate up slowly (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).
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling. Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
Dosing: Hepatic Impairment
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.
Parenteral: Continuous IV infusion: Further dilute in a compatible solution (eg, D5W, NS) to a concentration of 1 mg/mL; higher concentrations up to 3.75 mg/mL have been shown to be stable (Yuen 1983).
40 mg/mL Oral Suspension (ASHP Oral Suspension) (ASHP 2017)
A 40 mg/mL labetalol hydrochloride oral suspension may be made with tablets and one of three different vehicles (cherry syrup, a 1:1 mixture of Ora-Sweet and Ora-Plus, or a 1:1 mixture of Ora-Sweet SF and Ora-Plus). Crush sixteen 300 mg tablets in a mortar and reduce to a fine powder. Add 20 mL of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "protect from light." Stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated (Allen 1996).Allen LV Jr and Erickson MA 3rd. Stability of Labetalol Hydrochloride, Metoprolol Tartrate, Verapamil Hydrochloride, and Spironolactone with Hydrochlorothiazide in Extemporaneously Compounded Oral Liquids. Am J Health Syst Pharm. 1996;53(19):2304-2309.8893069
10 mg/mL Oral Suspension
A 10 mg/mL labetalol hydrochloride oral suspension may be made with tablets and simple syrup. Crush twelve 100 mg tablets in a mortar and reduce to a fine powder. Add a small quantity of simple syrup and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with simple syrup, and add sufficient quantity to make 120 mL. Label "shake well" and "refrigerate." Stable for 4 weeks when stored under refrigeration (preferred) or at room temperature (Nahata 1991; Nahata 2014).Nahata MC. Stability of Labetalol Hydrochloride in Distilled Water, Simple Syrup, and Three Fruit Juices. DICP. 1991;25(5):465-469.Nahata MC, Pai VB. Pediatric Drug Formulations. 6th ed, Cincinnati, OH: Harvey Whitney Books Co, 2014.
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
Tablets: Store between 2°C and 30°C (36°F and 86°F). Protect from light and excessive moisture.
Injectable: Store between 20°C and 25°C (68°F and 77°F); do not freeze. Protect from light.
Parenteral admixture: Stability of parenteral admixture at room temperature (25°C [77°F]) and refrigeration temperature (4°C [39°F]): 3 days (Yuen 1983).
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Consider therapy modification
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. 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. Exceptions: Apraclonidine. Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Monitor therapy
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. Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. 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. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Barbiturates: May decrease the serum concentration of Beta-Blockers. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy
Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. 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. Avoid combination
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. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. 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. Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Consider therapy modification
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Avoid combination
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. Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Insulins: Beta-Blockers may enhance the hypoglycemic effect of Insulins. Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Monitor therapy
Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Avoid combination
Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. 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. Consider therapy modification
Opioids (Anilidopiperidine): May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Avoid combination
Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. 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. Monitor therapy
Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Consider therapy modification
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
False-positive urine catecholamines, metanephrine, normetanephrine, and vanillylmandelic acid (VMA) if measured by fluorometric or photometric methods (high performance liquid chromatographic [HPLC] assay with solid phase extraction should be used to determine levels of catecholamines); false-positive urine amphetamine if measured by thin-layer chromatography or radioenzymatic assay (gas chromatographic-mass spectrometer technique should be used); may lead to false-positive aldosterone/renin ratio (ARR) (Funder 2016)
Cardiovascular: Orthostatic hypotension (intravenous: ≤58%)
Central nervous system: Dizziness (1% to 20%), fatigue (1% to 11%)
Gastrointestinal: Nausea (≤19%)
1% to 10%:
Cardiovascular: Hypotension (1% to 5%), edema (≤2%), flushing (1%), ventricular arrhythmia (intravenous: 1%)
Central nervous system: Paresthesia (≤7%; includes tingling of the scalp), drowsiness (3%), headache (2%), vertigo (1% to 2%)
Dermatologic: Diaphoresis (≤4%), pruritus (1%), skin rash (1%)
Gastrointestinal: Dyspepsia (≤4%), vomiting (≤3%), dysgeusia (1%)
Genitourinary: Ejaculatory failure (≤5%), impotence (1% to 4%)
Hepatic: Increased serum transaminases (4%)
Neuromuscular & skeletal: Weakness (1%)
Ophthalmic: Visual disturbance (1%)
Renal: Increased blood urea nitrogen (≤8%)
Respiratory: Nasal congestion (1% to 6%), dyspnea (2%)
<1%, postmarketing, and/or case reports: Anaphylactoid reaction, angioedema, bradycardia, bronchospasm, cardiac failure, cholestatic jaundice, diabetes insipidus, heart block, hepatic necrosis, hepatitis, hypersensitivity reaction, myopathy, Peyronie's disease, positive ANA titer, psoriasiform eruption, Raynaud's phenomenon, syncope, systemic lupus erythematosus, transient alopecia, urinary retention, urticaria
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
• 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.
• Psychiatric disease: Use with caution in patients with a history of psychiatric illness. Although the risk is small, labetalol may cause or exacerbate CNS depression; however, the use of beta-blockers should not be withheld if benefit exceeds this risk (Verbeek 2011).
• 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.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• 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.
• 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.
Blood pressure, standing and sitting/supine, pulse, cardiac monitor and blood pressure monitor recommended for IV administration; consult individual institutional policies and procedures
Pregnancy Risk Factor
Adverse events have been observed in some animal reproduction studies. Labetalol crosses the placenta and can be detected in cord blood and infant serum after delivery (Haraldsson 1989; Rogers 1990). Fetal/neonatal bradycardia, hypoglycemia, hypotension, and/or respiratory depression have been observed following in utero exposure to labetalol. Reduced birth weight has also been observed following in utero exposure to beta-blockers as a class; adequate facilities for monitoring infants at birth is generally recommended.
Untreated chronic maternal hypertension and preeclampsia are also associated with adverse events in the fetus, infant, and mother. Oral labetalol is considered an appropriate agent for the treatment of chronic hypertension in pregnancy (ACOG 2013; 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) with preeclampsia or eclampsia in pregnant and postpartum women. In general, avoid use of labetalol in women with asthma or heart failure (ACOG 2015; Magee 2014).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience loss of strength and energy, nausea, rhinorrhea, or scalp tingling. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of heart problems (cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out), severe dizziness, burning or numbness feeling, passing out, angina, or bradycardia (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: non-cardioselective beta blockers
Other brands: Trandate