Labetalol HCl Injection is indicated in severe hypertension, to lower blood pressure.

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Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit.

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are ready-to-use solutions and do not require further dilution. Check for leaks by squeezing the bag firmly. If leaks are found, discard solution, as sterility may be impaired.  Do not add any additional medications to the bag.

Once infusion has started, discard any remaining at 24 hours.

Labetalol HCl Injection, USP, in a prefilled syringe is a ready-to-use solution that does not require further dilution.  The prefilled syringe is intended for single dose. Discard any unused portion.

Choose intravenous administration by slow continuous infusion or repeated injection. The usual intravenous dose is in the range of 50 to 200 mg, but the safety of doses above 300 mg has not been established. Once supine diastolic blood pressure has begun to rise, transition to oral labetalol HCl.

Slow Continuous Infusion:Initiate at 2 mg/minute. Monitor blood pressure and adjust the dosage and duration of infusion accordingly.

Repeated Intravenous Injection:Administer 0.25 mg/kg up to 20 mg over 2 minutes. Administer 20 to 80 mg over 2 minutes at 10-minute intervals until a desired supine blood pressure is achieved. The maximum effect usually occurs within 5 minutes of each injection.

CAUTION: Glass syringes may malfunction, break or clog when connected to some Needleless Luer Access Devices (NLADs) and needles. The external collar must remain attached to the syringe (See Figure 1). Spontaneous disconnection of this glass syringe from needles and NLADs with leakage of drug product may occur. Assure that the needle or NLAD is securely attached before beginning the injection. Inspect the glass syringe-needle or glass syringe –NLAD connection before and during drug administration.

Figure 1

Figure 1

1. Push plunger rod slightly to break the stopper loose while tip cap is still on.

2. Remove tip cap by twisting it off. (See Figure 2)

Figure 2

Figure 2

3. Connect the syringe to an appropriate injection connection.

4. Depress plunger rod to deliver the required dose.

Labetalol HCl in Sodium Chloride Injection is available as 1 mg/mL in 100-, 200-, or 300-mL bags.

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Labetalol HCl in Dextrose Injection is available as 1 mg/mL in 200-mL bags.

{ "type": "p", "children": [], "text": "Labetalol HCl in Dextrose Injection is available as 1 mg/mL in 200-mL bags." }

Labetalol HCl Injection, USP, in a prefilled syringe is available as 10 mg in 2 mL

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Labetalol Hydrochloride Injection iscontraindicated in patients with:

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{ "type": "ul", "children": [ "Bronchial asthma or obstructive airway disease.", "Severe sinus bradycardia: ", "Heart block greater than first degree. ", "Cardiogenic shock. ", "IV administration of non-dihydropyridine calcium-channel antagonists (e.g., verapamil) ", "Hypersensitivity reactions, including anaphylaxis, to labetalol " ], "text": "" }

Symptomatic postural hypotension (incidence, 58%) is likely to occur if patients are tilted or allowed to assume the upright position within 3 hours of receiving labetalol HCl injection. Before permitting any ambulation, establish patient’s ability to tolerate an upright position and observe the patient at the time of first ambulation.

Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of beta blockers. Monitor heart rate and rhythm in patients receiving labetalol hydrochloride injection.

Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure. Beta-blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure. Avoid labetalol HCl injection in patients with overt congestive heart failure. If patients develop signs or symptoms of heart failure during administration, discontinue labetalol and treat appropriately.

Abrupt cessation of therapy with beta blocking agents in patients with coronary artery disease, can cause exacerbations of angina pectoris and, in some cases, myocardial infarction has been reported. Therefore, even in the absence of overt angina pectoris, after the discontinuation of labetalol HCl injection observe patients for development or worsening of angina. If patient experiences angina or angina markedly worsens or if acute coronary insufficiency develops, promptly reinstitute labetalol HCl injection and manage as unstable angina.

Patients with reactive airways disease should, in general, not receive beta blockers. Labetalol HCl at the usual intravenous therapeutic doses has not been studied in patients with nonallergic bronchospastic disease. In the event of bronchospasm, stop the infusion immediately, and treat as appropriate.

Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed to see medical treatment.

Intravenous labetalol has been shown to lower blood pressure and relieve symptoms in patients with pheochromocytoma; higher than usual doses may be required. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, monitor blood pressure when administering intravenous labetalol HCl to patients with pheochromocytoma.

Severe hepatocellular injury occurs rarely with labetalol therapy. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. If the patient develops signs or symptoms of liver injury, institute appropriate treatment and investigate the probable cause. Do not restart labetalol in patients without another explanation for the observed liver injury.

Patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic). Patients using beta-blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions. Avoid labetalol HCl injection in patients at high risk of anaphylactic reactions.

IFIS has been observed during cataract surgery in some patients treated with alpha-1 blockers (labetalol is an alpha/beta blocker). This variant of small pupil syndrome is characterized by the combination of flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. Inform the patient’s ophthalmologist to be prepared for possible modifications to the surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Most adverse effects have been mild and transient and, in controlled trials involving 92 patients, did not require labetalol withdrawal. Symptomatic postural hypotension (incidence, 58%) is likely to occur if patients are tilted or allowed to assume the upright position within 3 hours of receiving labetalol HCl. Moderate hypotension occurred in 1 of 100 patients while supine. Increased sweating was noted in 4 of 100 patients, and flushing occurred in 1 of 100 patients.

The following also were reported with labetalol HCl with the incidence as noted:

Central and Peripheral Nervous Systems

Dizziness in 9%

Paresthesia, most frequently described as tingling of the scalp/skin in 7%

Gastrointestinal System

Nausea in 13%

Vomiting in 4%

Metabolic Disorders

Transient increases in blood urea nitrogen and serum creatinine levels occurred in 8%; these were associated with drops in blood pressure, generally in patients with prior renal insufficiency.

Respiratory System

Bronchospasm

In addition, a number of other less common adverse events have been reported:

Cardiovascular:

Hypotension, and rarely, syncope, bradycardia, heart block.

Liver and Biliary System

Hepatic necrosis, hepatitis, cholestatic jaundice, elevated liver function tests.

Hypersensitivity

Rare reports of hypersensitivity (e.g., rash, urticaria, pruritus, angioedema, dyspnea) and anaphylactoid reactions.

The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with labetalol HCl during investigational use and extensive foreign marketing experience.

Clinical Laboratory Tests

Among patients dosed with labetalol tablets, there have been reversible increases of serum transaminases in 4% of patients tested and, more rarely, reversible increases in blood urea.

Labetalol HCl antagonizes the bronchodilatory effect of beta-receptor agonist drugs; therefore, labetalol HCl is contraindicated in patients with bronchial asthma [see Contraindications (4)].

Synergism has been shown between halothane anesthesia and intravenously administered labetalol. During controlled hypotensive anesthesia using labetalol in association with halothane, high concentrations (3% or above) of halothane should not be used because the degree of hypotension will be increased and because of the possibility of a large reduction in cardiac output and an increase in central venous pressure.

Coadministration of labetalol HCl and nitroglycerin will have an additive effect in lowering blood pressure. Additionally, labetalol HCl blunts the reflex tachycardia produced by nitroglycerin. If labetalol is used in patients with angina pectoris on nitroglycerin, monitor patients’ blood pressure and adjust labetalol HCl injection dose as needed. In these patients, avoid initiating labetalol HCl tablets.

Coadministration of labetalol HCl with non-dihydropyrindine calcium-channel antagonists (e.g., verapamil) is contraindicated [see Contraindications (4)]. Avoid the use of labetalol in patients receiving calcium-channel antagonists.

The presence of labetalol metabolites in the urine may result in falsely elevated levels of urinary catecholamines, metanephrine, normetanephrine, and vanillylmandelic acid (VMA) when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with labetalol, a specific method, such as a high-performance liquid chromatographic assay with solid phase extraction should be employed in determining levels of catecholamines.

Labetalol has also been reported to produce a false-positive test for amphetamine when screening urine for the presence of drugs using the commercially available assay methods. When patients being treated with labetalol have a positive urine test for amphetamine using these techniques, confirm using more specific methods, such as a gas chromatographic-mass spectrometer technique.

Risk Summary

The extensive experience with use of labetalol in pregnant women, based on published interventional and observational studies, has not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Untreated hypertension during pregnancy can lead to serious adverse outcomes for the mother and the fetus (see Clinical Considerations). In animal reproduction studies, oral administration of labetalol to pregnant rats and rabbits during organogenesis at doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively, resulted in no fetal malformations; however, increased fetal resorptions were seen in both species at doses approximating the MRHD (see Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.  Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal Adverse Reactions

Labetalol crosses the placenta. Neonates born to mothers who are receiving labetalol during pregnancy, may be at risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Neonates should be monitored for symptoms of hypotension, bradycardia, hypoglycemia and respiratory depression and manage accordingly.

Data

Human Data

Data from published interventional and observational studies did not demonstrate an association between major congenital malformations and the use of labetalol in pregnancy, however, most studies reported the maternal use of intravenous labetalol occurring after 20 weeks gestation.The published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of labetalol during pregnancy; however, these studies have methodological limitations hindering interpretation. These studies cannot definitively establish the absence of risk during pregnancy.

Animal Data

Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD.

A teratology study performed with labetalol in rabbits at intravenous doses up to 1.7 times the MRHD revealed no evidence of drug-related harm to the fetus.

Oral administration of labetalol to rats during late gestation through weaning at doses of two to four times the MRHD caused a decrease in neonatal survival.

Risk Summary

Available published data report the presence oflabetalol in human milk at low levels. There are no data on the effects on the breastfed infant and on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for labetalol and any potential adverse effects on the breastfed infant from labetalol or from the underlying maternal condition.

Infertility

Based on the published literature, beta blockers, including labetalol, may cause erectile dysfunction and inhibit sperm motility.

Safety and effectiveness in pediatric patients have not been established.

Some pharmacokinetic studies indicate that the elimination of labetalol is reduced in elderly patients [see Clinical Pharmacology (12.3)]. Geriatric patients treated with labetalol could initiate therapy at the currently recommended dose of 2 mg/minute by continuous intravenous infusion; however, lower maintenance dosages are generally required for elderly patients than nonelderly patients. Monitor blood pressure and adjust the dosage and duration of infusion accordingly until the desired response is obtained [see Dosage and Administration (2)].

Overdosage with labetalol HCl causes excessive hypotension that is posture sensitive and, sometimes, excessive bradycardia. Patients should be placed supine and their legs raised if necessary, to improve the blood supply to the brain. Treat symptoms of overdose with standard supportive care.  If overdosage with labetalol HCl follows oral ingestion, gastric lavage or pharmacologically induced emesis (using syrup of ipecac) may be useful for removal of the drug shortly after ingestion.

Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol from the general circulation (<1%).

The oral LD50 value of labetalol HCl in the mouse is approximately 600 mg/kg and in the rat is greater than 2 g/kg. The intravenous LD50 in these species is 50 to 60 mg/kg.

Labetalol HCl in Sodium Chloride Injection, Labetalol HCl in Dextrose Injection and Labetalol Hydrochloride Injection, USP contain labetalol HCl an adrenergic receptor blocking agent that has both selective alpha1-adrenergic and nonselective beta-adrenergic receptor blocking actions in a single substance. Labetalol hydrochloride (HCl) is a racemate chemically designated as 5-[1-Hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]-salicylamide monohydrochloride and it has the following structural formula:

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Labetalol HCl is a white or off-white crystalline powder, soluble in water. Labetalol HCl has the molecular formula C19H24N2O3•HCl and a molecular weight of 364.87. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs.

{ "type": "p", "children": [], "text": "Labetalol HCl is a white or off-white crystalline powder, soluble in water. Labetalol HCl has the molecular formula C19H24N2O3•HCl and a molecular weight of 364.87. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs. " }

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are two preservative-free, ready-to use formulations of labetalol.Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are clear, colorless to light yellow, aqueous, sterile, isotonic solution for intravenous injection.

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Each milliliter of Labetalol HCl in Sodium Chloride Injection contains 1 mg of labetalol HCl, 7.2 mg sodium chloride, 9 mg of anhydrous dextrose, 0.02 mg of edetate disodium; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.5 to 4.5.

{ "type": "p", "children": [], "text": "Each milliliter of Labetalol HCl in Sodium Chloride Injection contains 1 mg of labetalol HCl, 7.2 mg sodium chloride, 9 mg of anhydrous dextrose, 0.02 mg of edetate disodium; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.5 to 4.5. " }

Each milliliter of Labetalol HCl in Dextrose Injection contains 1 mg of labetalol HCl, 45 mg of anhydrous dextrose, 0.02 mg of edetate disodium; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.5 to 4.5.

{ "type": "p", "children": [], "text": "Each milliliter of Labetalol HCl in Dextrose Injection contains 1 mg of labetalol HCl, 45 mg of anhydrous dextrose, 0.02 mg of edetate disodium; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.5 to 4.5." }

Labetalol Hydrochloride Injection in a prefilled syringe is a preservative-free, ready-to use formulation of labetalol.Labetalol Hydrochloride Injection is a clear, colorless to light yellow, aqueous, sterile, isotonic solution for intravenous injection.

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Injection in a prefilled syringe is a preservative-free, ready-to use formulation of labetalol.Labetalol Hydrochloride Injection is a clear, colorless to light yellow, aqueous, sterile, isotonic solution for intravenous injection. " }

Each milliliter of the Labetalol Hydrochloride Injection, USP 2 mL prefilled syringe contains labetalol hydrochloride 5 mg; anhydrous dextrose 45 mg; edetate disodium 0.1 mg; citric acid monohydrate and sodium hydroxide as necessary to bring the pH into a range of 3.0 to 4.5.

{ "type": "p", "children": [], "text": "Each milliliter of the Labetalol Hydrochloride Injection, USP 2 mL prefilled syringe contains labetalol hydrochloride 5 mg; anhydrous dextrose 45 mg; edetate disodium 0.1 mg; citric acid monohydrate and sodium hydroxide as necessary to bring the pH into a range of 3.0 to 4.5." }

Labetalol has both competitive alpha1-adrenergic blocking and competitive beta-adrenergic blocking activity. In man, the ratio of alpha- to beta-blockade has been estimated to be approximately 1:7 following intravenous administration. Beta2-agonist activity has been demonstrated in animals with minimal beta1-agonist activity detected.

In a clinical pharmacologic study in severe hypertensives, an initial 0.25 mg/kg injection of labetalol HCl administered to patients in the supine position decreased blood pressure by an average of 11/7 mmHg. Additional injections of 0.5 mg/kg at 15-minute intervals up to a total cumulative dose of 1.75 mg/kg of labetalol HCl caused further dose-related decreases in blood pressure. Some patients required cumulative doses of up to 3.25 mg/kg. The maximal effect of each dose level occurred within 5 minutes. Following discontinuation of intravenous treatment with labetalol HCl, the blood pressure rose gradually and progressively, approaching pretreatment baseline values within an average of 16 to 18 hours in the majority of patients.

Similar results were obtained in the treatment of patients with severe hypertension who required urgent blood pressure reduction with an initial dose of 20 mg (which corresponds to 0.25 mg/kg for an 80 kg patient) followed by additional doses of either 40 or 80 mg at 10 minute intervals to achieve the desired effect, or up to a cumulative dose of 300 mg.

Labetalol HCl administered as a continuous intravenous infusion, with a mean dose of 136 mg (27 to 300 mg) over a period of 2 to 3 hours (mean of 2 hours and 39 minutes), lowered the blood pressure by an average of 60/35 mmHg.

Distribution

Labetalol has been shown to cross the placental barrier in humans. Only negligible amounts of the drug crossed the blood-brain barrier in animal studies. Labetalol is approximately 50% protein bound. Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol from the systemic circulation (<1%).

Elimination

Following intravenous infusion of labetalol, the elimination half-life is about 5.5 hours and the total body clearance is approximately 33 mL/min/kg. Steady-state plasma levels of labetalol during repetitive dosing are reached following 22 to 28 hours of continuous infusion.

Metabolism

The metabolism of labetalol is mainly through conjugation to glucuronide metabolites.

Excretion

Approximately 55% to 60% of a dose appears in the urine as conjugates or unchanged labetalol within the first 24 hours of dosing. The metabolites are present in plasma and are excreted in the urine and, via the bile, into the feces.

Specific Populations

Patients with Renal or Hepatic Impairment

In patients with decreased hepatic or renal function, the elimination half-life of labetalol is not altered.

Geriatric Patients

Some pharmacokinetic studies indicate that the elimination of labetalol is reduced in elderly patients.

Long-term oral dosing studies with labetalol for 18 months in mice and for 2 years in rats showed no evidence of carcinogenesis. Studies with labetalol using dominant lethal assays in rats and mice and exposing microorganisms according to modified Ames tests showed no evidence of mutagenesis.

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are preservative-free, clear, colorless to light yellow sterile solutions that are available in a single-dose single-port bag with an aluminum overwrap.  The container closure is not made with natural rubber latex. It is available in the following presentations:

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="25.22%"/> <col width="25.22%"/> <col width="23.96%"/> <col width="25.6%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Product</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Strength</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Package</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">NDC Number</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol HCl in Sodium Chloride Injection</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">100 mg/100 mL (1 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose bag</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9363-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Box of 10 bags</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9363-10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol HCl in Sodium Chloride Injection</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">200 mg/200 mL (1 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose bag</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9364-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Box of 10 bags</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9364-10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol HCl in Sodium Chloride Injection</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">300 mg/300 mL (1 mg/mL) preservative-free<br/> <br/> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose bag</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9365-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Box of 10 bags</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9365-10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol HCl in Dextrose Injection</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">200 mg/200 mL (1 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose bag</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9366-01</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Box of 10 bags</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9366-10</p> </td> </tr> </tbody> </table></div>

Labetalol Hydrochloride Injection, USP is a preservative-free, clear, colorless to light yellow sterile solution that is available in a single-dose prefilled syringe. It is available in the following presentations: 

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="23.54%"/> <col width="23.54%"/> <col width="32.56%"/> <col width="20.34%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Product</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Strength</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Package</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">NDC Number</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol Hydrochloride Injection, USP</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">10 mg/2 mL (5 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose prefilled syringe</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0641-6252-01</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Carton of 10 prefilled syringes</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0641-6252-10</p> </td> </tr> </tbody> </table></div>

Store at 20° to 25°C (68° to 77°F) with excursions permitted between 15° to 30° C (59° to 86° F) [see USP Controlled Room Temperature]. Do not freeze. Protect from light.

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection: Do not remove from overwrap until ready to use.

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Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

Distributed by

{ "type": "p", "children": [], "text": "Distributed by" }

Hikma Pharmaceuticals USA Inc.

{ "type": "p", "children": [], "text": "Hikma Pharmaceuticals USA Inc. " }

Berkeley Heights, NJ 07922

{ "type": "p", "children": [], "text": "Berkeley Heights, NJ 07922 " }

Revised: April 2023

{ "type": "p", "children": [], "text": "Revised: April 2023" }

PIN539-WES/4

{ "type": "p", "children": [], "text": "PIN539-WES/4" }

NDC 0641-6252-01 Rx only

{ "type": "p", "children": [], "text": "NDC 0641-6252-01 Rx only" }

2 mL Single-Dose Prefilled Syringe

{ "type": "p", "children": [], "text": "\n2 mL Single-Dose Prefilled Syringe" }

Labetalol HCl Injection, USP

{ "type": "p", "children": [], "text": "Labetalol HCl Injection, USP" }

10 mg per 2 mL (5 mg/mL)

{ "type": "p", "children": [], "text": "10 mg per 2 mL (5 mg/mL)" }

For Intravenous Use ONLY. Protect from freezing and light.

{ "type": "p", "children": [], "text": "For Intravenous Use ONLY. Protect from freezing and light." }

NDC 0641-6252-10 Rx only

{ "type": "p", "children": [], "text": "NDC 0641-6252-10 Rx only" }

Labetalol HCl Injection, USP

{ "type": "p", "children": [], "text": "Labetalol HCl Injection, USP" }

10 mg per 2 mL (5 mg/mL)

{ "type": "p", "children": [], "text": "10 mg per 2 mL (5 mg/mL)" }

For Intravenous Use ONLY.

{ "type": "p", "children": [], "text": "\nFor Intravenous Use ONLY.\n" }

Preservative Free

{ "type": "p", "children": [], "text": "\nPreservative Free\n" }

10 x 2 mL Single-Dose Prefilled Syringes

{ "type": "p", "children": [], "text": "\n10 x 2 mL Single-Dose Prefilled Syringes\n" }

Discard unused portion

{ "type": "p", "children": [], "text": "\nDiscard unused portion\n" }

Labetalol HCl Injection is indicated in severe hypertension, to lower blood pressure.

{ "type": "p", "children": [], "text": "Labetalol HCl Injection is indicated in severe hypertension, to lower blood pressure." }

Inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit.

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection:

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are ready-to-use solutions and do not require further dilution. Check for leaks by squeezing the bag firmly. If leaks are found, discard solution, as sterility may be impaired. Do not add any additional medications to the bag.

Once infusion has started, discard any remaining at 24 hours.

Labetalol HCl Injection in a prefilled syringe or vial:

Labetalol HCl Injection, USP, in a prefilled syringe or vial are ready-to-use solutions that do not require further dilution. The prefilled syringe and vial are intended for single dose. Discard any unused portion.

Labetalol HCI can be administered by slow continuous intravenous infusion or repeated intravenous injection. Once supine diastolic blood pressure has begun to rise, transition to oral labetalol HCl.

Slow Continuous Intravenous Infusion: Initiate at 2 mg/minute. Monitor blood pressure and adjust the dosage and duration of infusion accordingly.

Repeated Intravenous Injection: Administer 0.25 mg/kg up to 20 mg over 2 minutes. Administer 20 mg to 80 mg over 2 minutes at 10-minute intervals until a desired supine blood pressure is achieved. The maximum effect usually occurs within 5 minutes of each injection.

The safety of doses above 300 mg has not been established.

CAUTION: Glass syringes may malfunction, break or clog when connected to some Needleless Luer Access Devices (NLADs) and needles. The external collar must remain attached to the syringe (See Figure 1). Spontaneous disconnection of this glass syringe from needles and NLADs with leakage of drug product may occur. Assure that the needle or NLAD is securely attached before beginning the injection. Inspect the glass syringe-needle or glass syringe –NLAD connection before and during drug administration.

Figure 1

1. Push plunger rod slightly to break the stopper loose while tip cap is still on.

2. Remove tip cap by twisting it off. (See Figure 2)

Figure 2

3. Connect the syringe to an appropriate injection connection.

4. Depress plunger rod to deliver the required dose.

Labetalol HCl in Sodium Chloride Injection is a clear, colorless to pale yellow solution available as:

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{ "type": "ul", "children": [ "100 mg/100 mL (1 mg/mL) in a single-dose bag", "200 mg/200 mL (1 mg/mL) in a single-dose bag", "300 mg/300 mL (1 mg/mL) in a single-dose bag" ], "text": "" }

Labetalol HCl in Dextrose Injection is a clear, colorless to pale yellow solution available as:

{ "type": "p", "children": [], "text": "Labetalol HCl in Dextrose Injection is a clear, colorless to pale yellow solution available as:" }

{ "type": "ul", "children": [ "200 mg/200 mL (1 mg/mL) in a single-dose bag" ], "text": "" }

Labetalol HCl Injection is a clear, colorless to pale yellow solution available as:

{ "type": "p", "children": [], "text": "Labetalol HCl Injection is a clear, colorless to pale yellow solution available as:" }

{ "type": "ul", "children": [ "10 mg/2 mL (5 mg/mL) in a single-dose prefilled syringe", "20 mg/4 mL (5 mg/mL) in a single-dose vial" ], "text": "" }

Labetalol Hydrochloride Injection is contraindicated in patients with:

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{ "type": "ul", "children": [ "Bronchial asthma or obstructive airway disease.", "Severe sinus bradycardia: ", "Heart block greater than first degree. ", "Cardiogenic shock. ", "IV administration of non-dihydropyridine calcium-channel antagonists (e.g., verapamil) ", "Hypersensitivity reactions, including anaphylaxis, to labetalol " ], "text": "" }

Symptomatic postural hypotension (incidence, 58%) is likely to occur if patients are tilted or allowed to assume the upright position within 3 hours of receiving labetalol HCl injection. Before permitting any ambulation, establish patient’s ability to tolerate an upright position and observe the patient at the time of first ambulation.

Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of beta blockers. Monitor heart rate and rhythm in patients receiving labetalol hydrochloride injection.

Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure. Beta-blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure. Avoid labetalol HCl injection in patients with overt congestive heart failure. If patients develop signs or symptoms of heart failure during administration, discontinue labetalol and treat appropriately.

Abrupt cessation of therapy with beta blocking agents in patients with coronary artery disease, can cause exacerbations of angina pectoris and, in some cases, myocardial infarction has been reported. Therefore, even in the absence of overt angina pectoris, after the discontinuation of labetalol HCl injection observe patients for development or worsening of angina. If patient experiences angina or angina markedly worsens or if acute coronary insufficiency develops, promptly reinstitute labetalol HCl injection and manage as unstable angina.

Patients with reactive airways disease should, in general, not receive beta blockers. Labetalol HCl at the usual intravenous therapeutic doses has not been studied in patients with nonallergic bronchospastic disease. In the event of bronchospasm, stop the infusion immediately, and treat as appropriate.

Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed to see medical treatment.

Intravenous labetalol has been shown to lower blood pressure and relieve symptoms in patients with pheochromocytoma; higher than usual doses may be required. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, monitor blood pressure when administering intravenous labetalol HCl to patients with pheochromocytoma.

Severe hepatocellular injury occurs rarely with labetalol therapy. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. If the patient develops signs or symptoms of liver injury, institute appropriate treatment and investigate the probable cause. Do not restart labetalol in patients without another explanation for the observed liver injury.

Patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic). Patients using beta-blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions. Avoid labetalol HCl injection in patients at high risk of anaphylactic reactions.

IFIS has been observed during cataract surgery in some patients treated with alpha-1 blockers (labetalol is an alpha/beta blocker). This variant of small pupil syndrome is characterized by the combination of flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. Inform the patient’s ophthalmologist to be prepared for possible modifications to the surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Most adverse effects have been mild and transient and, in controlled trials involving 92 patients, did not require labetalol withdrawal. Symptomatic postural hypotension (incidence, 58%) is likely to occur if patients are tilted or allowed to assume the upright position within 3 hours of receiving labetalol HCl. Moderate hypotension occurred in 1 of 100 patients while supine. Increased sweating was noted in 4 of 100 patients, and flushing occurred in 1 of 100 patients.

The following also were reported with labetalol HCl with the incidence as noted:

Central and Peripheral Nervous Systems

Dizziness in 9%

Paresthesia, most frequently described as tingling of the scalp/skin in 7%

Gastrointestinal System

Nausea in 13%

Vomiting in 4%

Metabolic Disorders

Transient increases in blood urea nitrogen and serum creatinine levels occurred in 8%; these were associated with drops in blood pressure, generally in patients with prior renal insufficiency.

Respiratory System

Bronchospasm

In addition, a number of other less common adverse events have been reported:

Cardiovascular:

Hypotension, and rarely, syncope, bradycardia, heart block.

Liver and Biliary System

Hepatic necrosis, hepatitis, cholestatic jaundice, elevated liver function tests.

Hypersensitivity

Rare reports of hypersensitivity (e.g., rash, urticaria, pruritus, angioedema, dyspnea) and anaphylactoid reactions.

The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with labetalol HCl during investigational use and extensive foreign marketing experience.

Clinical Laboratory Tests

Among patients dosed with labetalol tablets, there have been reversible increases of serum transaminases in 4% of patients tested and, more rarely, reversible increases in blood urea.

Labetalol HCl antagonizes the bronchodilatory effect of beta-receptor agonist drugs; therefore, labetalol HCl is contraindicated in patients with bronchial asthma [see Contraindications (4)].

Synergism has been shown between halothane anesthesia and intravenously administered labetalol. During controlled hypotensive anesthesia using labetalol in association with halothane, high concentrations (3% or above) of halothane should not be used because the degree of hypotension will be increased and because of the possibility of a large reduction in cardiac output and an increase in central venous pressure.

Coadministration of labetalol HCl and nitroglycerin will have an additive effect in lowering blood pressure. Additionally, labetalol HCl blunts the reflex tachycardia produced by nitroglycerin. If labetalol is used in patients with angina pectoris on nitroglycerin, monitor patients’ blood pressure and adjust labetalol HCl injection dose as needed. In these patients, avoid initiating labetalol HCl tablets.

Coadministration of labetalol HCl with non-dihydropyrindine calcium-channel antagonists (e.g., verapamil) is contraindicated [see Contraindications (4)]. Avoid the use of labetalol in patients receiving calcium-channel antagonists.

The presence of labetalol metabolites in the urine may result in falsely elevated levels of urinary catecholamines, metanephrine, normetanephrine, and vanillylmandelic acid (VMA) when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with labetalol, a specific method, such as a high-performance liquid chromatographic assay with solid phase extraction should be employed in determining levels of catecholamines.

Labetalol has also been reported to produce a false-positive test for amphetamine when screening urine for the presence of drugs using the commercially available assay methods. When patients being treated with labetalol have a positive urine test for amphetamine using these techniques, confirm using more specific methods, such as a gas chromatographic-mass spectrometer technique.

Risk Summary

The extensive experience with use of labetalol in pregnant women, based on published interventional and observational studies, has not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Untreated hypertension during pregnancy can lead to serious adverse outcomes for the mother and the fetus (see Clinical Considerations). In animal reproduction studies, oral administration of labetalol to pregnant rats and rabbits during organogenesis at doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively, resulted in no fetal malformations; however, increased fetal resorptions were seen in both species at doses approximating the MRHD (see Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.  Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal Adverse Reactions

Labetalol crosses the placenta. Neonates born to mothers who are receiving labetalol during pregnancy, may be at risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Neonates should be monitored for symptoms of hypotension, bradycardia, hypoglycemia and respiratory depression and manage accordingly.

Data

Human Data

Data from published interventional and observational studies did not demonstrate an association between major congenital malformations and the use of labetalol in pregnancy, however, most studies reported the maternal use of intravenous labetalol occurring after 20 weeks gestation. The published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of labetalol during pregnancy; however, these studies have methodological limitations hindering interpretation. These studies cannot definitively establish the absence of risk during pregnancy.

Animal Data

Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD.

A teratology study performed with labetalol in rabbits at intravenous doses up to 1.7 times the MRHD revealed no evidence of drug-related harm to the fetus.

Oral administration of labetalol to rats during late gestation through weaning at doses of two to four times the MRHD caused a decrease in neonatal survival.

Risk Summary

Available published data report the presence of labetalol in human milk at low levels. There are no data on the effects on the breastfed infant and on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for labetalol and any potential adverse effects on the breastfed infant from labetalol or from the underlying maternal condition.

Infertility

Based on the published literature, beta blockers, including labetalol, may cause erectile dysfunction and inhibit sperm motility.

Safety and effectiveness in pediatric patients have not been established.

Some pharmacokinetic studies indicate that the elimination of labetalol is reduced in elderly patients [see Clinical Pharmacology (12.3)]. Geriatric patients treated with labetalol could initiate therapy at the currently recommended dose of 2 mg/minute by continuous intravenous infusion; however, lower maintenance dosages are generally required for elderly patients than nonelderly patients. Monitor blood pressure and adjust the dosage and duration of infusion accordingly until the desired response is obtained [see Dosage and Administration (2)].

Overdosage with labetalol HCl causes excessive hypotension that is posture sensitive and, sometimes, excessive bradycardia. Patients should be placed supine and their legs raised if necessary, to improve the blood supply to the brain. Treat symptoms of overdose with standard supportive care.  If overdosage with labetalol HCl follows oral ingestion, gastric lavage or pharmacologically induced emesis (using syrup of ipecac) may be useful for removal of the drug shortly after ingestion.

Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol from the general circulation (<1%).

The oral LD50 value of labetalol HCl in the mouse is approximately 600 mg/kg and in the rat is greater than 2 g/kg. The intravenous LD50 in these species is 50 to 60 mg/kg.

Labetalol HCl in Sodium Chloride Injection, Labetalol HCl in Dextrose Injection and Labetalol Hydrochloride Injection, USP contain labetalol HCl an adrenergic receptor blocking agent that has both selective alpha1-adrenergic and nonselective beta-adrenergic receptor blocking actions. Labetalol hydrochloride (HCl) is a racemate chemically designated as 5-[1-Hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]-salicylamide monohydrochloride and it has the following structural formula:

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Labetalol HCl is a white or off-white crystalline powder, soluble in water. Labetalol HCl has the molecular formula C19H24N2O3•HCl and a molecular weight of 364.87. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs.

{ "type": "p", "children": [], "text": "Labetalol HCl is a white or off-white crystalline powder, soluble in water. Labetalol HCl has the molecular formula C19H24N2O3•HCl and a molecular weight of 364.87. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs." }

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are two preservative-free, ready- to use formulations of labetalol. Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are clear, colorless to pale yellow, aqueous, sterile, isotonic solution for intravenous injection.

{ "type": "p", "children": [], "text": "Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are two preservative-free, ready- to use formulations of labetalol. Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are clear, colorless to pale yellow, aqueous, sterile, isotonic solution for intravenous injection." }

Each milliliter of Labetalol HCl in Sodium Chloride Injection contains 1 mg of labetalol HCl, 7.2 mg sodium chloride, 9 mg of anhydrous dextrose, 0.02 mg of edetate disodium; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.5 to 4.5.

{ "type": "p", "children": [], "text": "Each milliliter of Labetalol HCl in Sodium Chloride Injection contains 1 mg of labetalol HCl, 7.2 mg sodium chloride, 9 mg of anhydrous dextrose, 0.02 mg of edetate disodium; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.5 to 4.5." }

Each milliliter of Labetalol HCl in Dextrose Injection contains 1 mg of labetalol HCl, 45 mg of anhydrous dextrose, 0.02 mg of edetate disodium; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.5 to 4.5.

{ "type": "p", "children": [], "text": "Each milliliter of Labetalol HCl in Dextrose Injection contains 1 mg of labetalol HCl, 45 mg of anhydrous dextrose, 0.02 mg of edetate disodium; and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.5 to 4.5." }

Labetalol Hydrochloride Injection prefilled syringe and vial are two preservative-free, ready-to use formulations of labetalol. Labetalol Hydrochloride Injection is a clear, colorless to pale yellow, aqueous, sterile, isotonic solution for intravenous injection.

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Injection prefilled syringe and vial are two preservative-free, ready-to use formulations of labetalol. Labetalol Hydrochloride Injection is a clear, colorless to pale yellow, aqueous, sterile, isotonic solution for intravenous injection." }

Each milliliter of Labetalol Hydrochloride Injection, USP, contains 5 mg of labetalol HCI, 45 mg of anhydrous dextrose, 0.1 mg of edetate disodium, and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.0 to 4.5.

{ "type": "p", "children": [], "text": "Each milliliter of Labetalol Hydrochloride Injection, USP, contains 5 mg of labetalol HCI, 45 mg of anhydrous dextrose, 0.1 mg of edetate disodium, and citric acid monohydrate and sodium hydroxide, as necessary, to bring the solution into the pH range of 3.0 to 4.5." }

Labetalol has both competitive alpha1-adrenergic blocking and competitive beta-adrenergic blocking activity. In man, the ratio of alpha- to beta-blockade has been estimated to be approximately 1:7 following intravenous administration. Beta2-agonist activity has been demonstrated in animals with minimal beta1-agonist activity detected.

In a clinical pharmacologic study in severe hypertensives, an initial 0.25 mg/kg injection of labetalol HCl administered to patients in the supine position decreased blood pressure by an average of 11/7 mmHg. Additional injections of 0.5 mg/kg at 15-minute intervals up to a total cumulative dose of 1.75 mg/kg of labetalol HCl caused further dose-related decreases in blood pressure. Some patients required cumulative doses of up to 3.25 mg/kg. The maximal effect of each dose level occurred within 5 minutes. Following discontinuation of intravenous treatment with labetalol HCl, the blood pressure rose gradually and progressively, approaching pretreatment baseline values within an average of 16 to 18 hours in the majority of patients.

Similar results were obtained in the treatment of patients with severe hypertension who required urgent blood pressure reduction with an initial dose of 20 mg (which corresponds to 0.25 mg/kg for an 80 kg patient) followed by additional doses of either 40 mg or 80 mg at 10 minute intervals to achieve the desired effect, or up to a cumulative dose of 300 mg.

Labetalol HCl administered as a continuous intravenous infusion, with a mean dose of 136 mg (27 mg to 300 mg) over a period of 2 to 3 hours (mean of 2 hours and 39 minutes), lowered the blood pressure by an average of 60/35 mmHg.

Distribution

Labetalol has been shown to cross the placental barrier in humans. Only negligible amounts of the drug crossed the blood-brain barrier in animal studies. Labetalol is approximately 50% protein bound. Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol from the systemic circulation (<1%).

Elimination

Following intravenous infusion of labetalol, the elimination half-life is about 5.5 hours and the total body clearance is approximately 33 mL/min/kg. Steady-state plasma levels of labetalol during repetitive dosing are reached following 22 to 28 hours of continuous infusion.

Metabolism

The metabolism of labetalol is mainly through conjugation to glucuronide metabolites.

Excretion

Approximately 55% to 60% of a dose appears in the urine as conjugates or unchanged labetalol within the first 24 hours of dosing. The metabolites are present in plasma and are excreted in the urine and, via the bile, into the feces.

Specific Populations

Patients with Renal or Hepatic Impairment

In patients with decreased hepatic or renal function, the elimination half-life of labetalol is not altered.

Geriatric Patients

Some pharmacokinetic studies indicate that the elimination of labetalol is reduced in elderly patients.

Long-term oral dosing studies with labetalol for 18 months in mice and for 2 years in rats showed no evidence of carcinogenesis. Studies with labetalol using dominant lethal assays in rats and mice and exposing microorganisms according to modified Ames tests showed no evidence of mutagenesis.

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are preservative-free, clear, colorless to pale yellow sterile solutions that are available in a single-dose single-port bag with an aluminum overwrap. The container closure is not made with natural rubber latex. It is available in the following presentations:

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col width="108.3pt"/> <col width="108.3pt"/> <col width="95.1pt"/> <col width="95.1pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Product</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Strength</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Package</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">NDC Number</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol HCl in Sodium Chloride Injection</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">100 mg/100 mL (1 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose bag</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9363-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Box of 10 bags</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9363-10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol HCl in Sodium Chloride Injection</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">200 mg/200 mL (1 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose bag</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9364-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Box of 10 bags</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9364-10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol HCl in Sodium Chloride Injection</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">300 mg/300 mL (1 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose bag</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9365-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Box of 10 bags</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9365-10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol HCl in Dextrose Injection</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">200 mg/200 mL (1 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose bag</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9366-01</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Box of 10 bags</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0143-9366-10</p> </td> </tr> </tbody> </table></div>

Labetalol Hydrochloride Injection, USP is a preservative-free, clear, colorless to pale yellow sterile solution that is available in a single-dose prefilled syringe or vial. It is available in the following presentations:

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col width="132.2pt"/> <col width="93.75pt"/> <col width="115.1pt"/> <col width="59.25pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Product</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Strength</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Package</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">NDC Number</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">Labetalol Hydrochloride Injection, USP</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">10 mg/2 mL (5 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">1 single-dose prefilled syringe</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0641-6252-01</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Carton of 10 prefilled syringes</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">0641-6252-10</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2">Labetalol Hydrochloride Injection, USP </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">20 mg/4 mL (5 mg/mL) preservative-free</p> </td><td class="Botrule Lrule Rrule Toprule">1 single-dose vial</td><td class="Botrule Lrule Rrule Toprule">0143-9183-01</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Carton of 10 vials</td><td class="Botrule Lrule Rrule Toprule">0143-9183-10</td> </tr> </tbody> </table></div>

Store at 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C to 30° C (59°F to 86° F) [see USP Controlled Room Temperature]. DO NOT FREEZE. PROTECT FROM LIGHT.

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection: Do not remove from overwrap until ready to use.

Labetalol Hydrochloride Injection, USP, prefilled syringe and vial: Retain in carton until time of use.

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Distributed by

{ "type": "p", "children": [], "text": "\nDistributed by\n" }

Hikma Pharmaceuticals USA Inc.

{ "type": "p", "children": [], "text": "Hikma Pharmaceuticals USA Inc. " }

Berkeley Heights, NJ 07922

{ "type": "p", "children": [], "text": "Berkeley Heights, NJ 07922" }

PIN539-WES/6

{ "type": "p", "children": [], "text": "PIN539-WES/6" }

Revised: August 2024

{ "type": "p", "children": [], "text": "Revised: August 2024" }

NDC 0143-9363-01      Rx only    100 mLLabetalol Hydrochloridein 0.72% Sodium Chloride Injection100 mg per 100 mL (1 mg/mL)For Intravenous Infusion     Ready to Use Sterile, nonpyrogenic     Single-Dose Flexible Container

{ "type": "p", "children": [], "text": "NDC 0143-9363-01      Rx only    100 mLLabetalol Hydrochloridein 0.72% Sodium Chloride Injection100 mg per 100 mL (1 mg/mL)For Intravenous Infusion     Ready to Use\nSterile, nonpyrogenic     Single-Dose Flexible Container" }

NDC 0143-9363-01      Rx only    100 mLLabetalol Hydrochloridein 0.72% Sodium Chloride Injection100 mg per 100 mL (1 mg/mL)For Intravenous Infusion     Ready to Use Sterile, nonpyrogenic     Single-Dose Flexible Container

{ "type": "p", "children": [], "text": "NDC 0143-9363-01      Rx only    100 mLLabetalol Hydrochloridein 0.72% Sodium Chloride Injection100 mg per 100 mL (1 mg/mL)For Intravenous Infusion     Ready to Use\nSterile, nonpyrogenic     Single-Dose Flexible Container" }

NDC 0143-9364-01      Rx only      200 mL Labetalol Hydrochloridein 0.72% Sodium Chloride Injection200 mg per 200 mL(1 mg/mL)For Intravenous Infusion     Ready to Use Sterile, nonpyrogenic     Single-Dose Flexible Container

{ "type": "p", "children": [], "text": "NDC 0143-9364-01      Rx only      200 mL\n\nLabetalol Hydrochloridein 0.72% Sodium Chloride Injection200 mg per 200 mL(1 mg/mL)For Intravenous Infusion     Ready to Use\nSterile, nonpyrogenic     Single-Dose Flexible Container" }

NDC 0143-9364-01      Rx only      200 mL Labetalol Hydrochloridein 0.72% Sodium Chloride Injection200 mg per 200 mL (1 mg/mL)For Intravenous Infusion     Ready to Use Sterile, nonpyrogenic     Single-Dose Flexible Container

{ "type": "p", "children": [], "text": "NDC 0143-9364-01      Rx only      200 mL\n\nLabetalol Hydrochloridein 0.72% Sodium Chloride Injection200 mg per 200 mL (1 mg/mL)For Intravenous Infusion     Ready to Use\nSterile, nonpyrogenic     Single-Dose Flexible Container" }

NDC 0143-9365-01      Rx only     300 mL Labetalol Hydrochloridein 0.72% Sodium Chloride Injection300 mg per 300 mL (1 mg/mL) For Intravenous Infusion     Ready to Use Sterile, nonpyrogenic     Single-Dose Flexible Container

{ "type": "p", "children": [], "text": "NDC 0143-9365-01      Rx only     300 mL\n\nLabetalol Hydrochloridein 0.72% Sodium Chloride Injection300 mg per 300 mL\n(1 mg/mL)\nFor Intravenous Infusion     Ready to Use\nSterile, nonpyrogenic     Single-Dose Flexible Container" }

NDC 0143-9365-01      Rx only     300 mL Labetalol Hydrochloridein 0.72% Sodium Chloride Injection300 mg per 300 mL (1 mg/mL) For Intravenous Infusion     Ready to Use Sterile, nonpyrogenic     Single-Dose Flexible Container

{ "type": "p", "children": [], "text": "\nNDC 0143-9365-01      Rx only     300 mL\n\nLabetalol Hydrochloridein 0.72% Sodium Chloride Injection300 mg per 300 mL (1 mg/mL)\nFor Intravenous Infusion     Ready to Use\nSterile, nonpyrogenic     Single-Dose Flexible Container\n" }

NDC 0143-9366-01     Rx only    200 mL Labetalol Hydrochloridein 5% Dextrose Injection200 mg per 200 mL(1 mg/mL)For Intravenous Infusion     Ready to Use Sterile, nonpyrogenic     Single-Dose Flexible Container

{ "type": "p", "children": [], "text": "NDC 0143-9366-01     Rx only    200 mL\n\nLabetalol Hydrochloridein 5% Dextrose Injection200 mg per 200 mL(1 mg/mL)For Intravenous Infusion     Ready to Use\nSterile, nonpyrogenic     Single-Dose Flexible Container" }

NDC 0143-9366-01     Rx only    200 mL Labetalol Hydrochloridein 5% Dextrose Injection200 mg per 200 mL (1 mg/mL)For Intravenous Infusion     Ready to Use Sterile, nonpyrogenic     Single-Dose Flexible Container

{ "type": "p", "children": [], "text": "NDC 0143-9366-01     Rx only    200 mL\n\nLabetalol Hydrochloridein 5% Dextrose Injection200 mg per 200 mL (1 mg/mL)For Intravenous Infusion     Ready to Use\nSterile, nonpyrogenic     Single-Dose Flexible Container" }

NDC 0143-9183-01Rx only

{ "type": "p", "children": [], "text": "NDC 0143-9183-01Rx only" }

Labetalol HCI Injection, USP

{ "type": "p", "children": [], "text": "\nLabetalol HCI Injection, USP\n" }

20 mg per 4 mL

{ "type": "p", "children": [], "text": "\n20 mg per 4 mL\n" }

(5 mg/mL)

{ "type": "p", "children": [], "text": "\n(5 mg/mL)\n" }

For Intravenous Use ONLY

{ "type": "p", "children": [], "text": "\nFor Intravenous Use ONLY\n" }

Preservative-Free

{ "type": "p", "children": [], "text": "Preservative-Free" }

4 mL Single-Dose Vial

{ "type": "p", "children": [], "text": "4 mL Single-Dose Vial" }

Discard unused portion

{ "type": "p", "children": [], "text": "Discard unused portion" }

NDC 0143-9183-10 Rx only

{ "type": "p", "children": [], "text": "NDC 0143-9183-10 Rx only" }

Labetalol HCI Injection, USP

{ "type": "p", "children": [], "text": "\nLabetalol HCI Injection, USP\n" }

20 mg per 4 mL

{ "type": "p", "children": [], "text": "\n20 mg per 4 mL\n" }

(5 mg/mL)

{ "type": "p", "children": [], "text": "\n(5 mg/mL)\n" }

For Intravenous Use ONLY

{ "type": "p", "children": [], "text": "\nFor Intravenous Use ONLY\n" }

Preservative-Free

{ "type": "p", "children": [], "text": "Preservative-Free" }

10 X 4 mL Single-Dose Vials

{ "type": "p", "children": [], "text": "10 X 4 mL Single-Dose Vials" }

Discard unused portion

{ "type": "p", "children": [], "text": "Discard unused portion" }

Labetalol Hydrochloride is indicated in the management of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including beta adrenergic blockers.

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride is indicated in the management of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including beta adrenergic blockers." }

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

{ "type": "p", "children": [], "text": "Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC)." }

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

{ "type": "p", "children": [], "text": "Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly." }

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

{ "type": "p", "children": [], "text": "Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal." }

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

{ "type": "p", "children": [], "text": "Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy." }

Labetalol Hydrochloride Tablets, USP may be used alone or in combination with other antihypertensive agents, especially thiazide and loop diuretics.

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Tablets, USP may be used alone or in combination with other antihypertensive agents, especially thiazide and loop diuretics." }

Labetalol Hydrochloride dosage must be individualized.

The recommended initial dosage of labetalol hydrochloride is 100 mg twice daily. Adjust dosage in increments of 100 mg twice daily at 2-to 3-day intervals based on response. The recommended maintenance dosage of labetalol hydrochloride is between 200 and 400 mg twice daily.

Labetalol Hydrochloride Tablets, USP are available in the following strengths:

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Tablets, USP are available in the following strengths:" }

• 100 mg - White to off-white, biconvex, film coated tablets with “ET20” debossed on one side and non-functional scoring on the other side

{ "type": "p", "children": [], "text": " •\t100 mg - White to off-white, biconvex, film coated tablets with “ET20” debossed on one side and non-functional scoring on the other side" }

• 200 mg - White to off-white, biconvex, film coated tablets with “ET21” debossed on one side and non-functional scoring on the other side

{ "type": "p", "children": [], "text": " •\t200 mg - White to off-white, biconvex, film coated tablets with “ET21” debossed on one side and non-functional scoring on the other side" }

• 300 mg - White to off-white, biconvex, film coated tablets with “ET22” debossed on one side and non-functional scoring on the other side

{ "type": "p", "children": [], "text": " •\t300 mg - White to off-white, biconvex, film coated tablets with “ET22” debossed on one side and non-functional scoring on the other side" }

Labetalol Hydrochloride Tablets are contraindicated in patients with:

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Tablets are contraindicated in patients with:" }

{ "type": "ul", "children": [ "bronchial asthma or obstructive airway disease", "decompensated heart failure", "greater than first degree heart block", "cardiogenic shock", "severe bradycardia", "Hypersensitivity reactions, including anaphylaxis, to labetalol", "non-dihydropyridine calcium-channel antagonists " ], "text": "" }

Monitor patients for symptomatic postural hypotension and syncope after initial dosing or dose increments with Labetalol Hydrochloride Tablets. Elderly patients are generally more likely than younger patients to experience orthostatic symptoms [see Dosage and Administration (2.1), Use in Specific Populations (8.5), Clinical Pharmacology (12.2)].

Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of beta blockers. Monitor heart rate and rhythm in patients receiving Labetalol Hydrochloride Tablets.

Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure. Beta blockade carries a potential hazard of further depressing myocardial contractility and precipitating more severe failure. Avoid Labetalol Hydrochloride Tablets in patients with overt congestive heart failure. If patients develop signs or symptoms of heart failure during administration, discontinue Labetalol Hydrochloride Tablets and treat appropriately.

Abrupt cessation of therapy with beta blocking agents in patients with coronary artery disease can cause exacerbations of angina pectoris and, in some cases, myocardial infarction has been reported. Therefore, even in the absence of overt angina pectoris, after the discontinuation of Labetalol Hydrochloride Tablets observe patients for development or worsening of angina. If patient experiences angina or angina markedly worsens or if acute coronary insufficiency develops, promptly reinstitute Labetalol Hydrochloride Tablets and manage as unstable angina.

Avoid use in patients with reactive airways disease. If Labetalol Hydrochloride Tablets are used, use the smallest effective dose, to minimize inhibition of endogenous or exogenous beta agonists.

Beta-blockers may prevent early warning signs of hypoglycemia, such as tachycardia, and increase the risk for severe or prolonged hypoglycemia at any time during treatment, especially in patients with diabetes mellitus or children and patients who are fasting (i.e., surgery, not eating regularly, or are vomiting). If severe hypoglycemia occurs, patients should be instructed to seek emergency treatment.

Labetalol hydrochloride has been shown to be effective in lowering blood pressure and relieving symptoms in patients with pheochromocytoma; higher than usual doses may be required. However, paradoxical hypertensive responses have been reported in a few patients with this tumor; therefore, blood pressure when administering labetalol hydrochloride to patients with pheochromocytoma.

Severe hepatocellular injury occurs rarely with labetalol therapy. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. If the patient develops signs or symptoms of liver injury, institute appropriate treatment and investigate the probable cause. Do not restart labetalol in patients without another explanation for the observed liver injury.

Patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic). Patients using beta-blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions. Avoid Labetalol Hydrochloride Tablets in patients at high risk of anaphylactic reactions.

Do not routinely withdraw chronic beta blocker therapy prior to surgery. The effect of labetalol’s alpha adrenergic activity has not been evaluated in this setting. A synergism between labetalol hydrochloride and halothane anesthesia has been shown [see Drug Interactions (7.3)].

IFIS has been observed during cataract surgery in some patients treated with alpha-1 blockers (labetalol is an alpha/beta blocker). This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. Inform the patient’s ophthalmologist to be prepared for possible modifications to the surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In controlled clinical trials of 3 to 4 months' duration, discontinuation of Labetalol Hydrochloride Tablets due to one or more adverse effects was required in 7% of all patients.

The incidence rates of adverse reactions listed in Table 1 were derived from multicenter, controlled clinical trials comparing labetalol hydrochloride and placebo over treatment periods of 3 and 4 months.

Table 1: Adverse Reactions Occurring in at Least 2% of Patients and More Frequent on Labetalol

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="middle"> </td><td class="Rrule" valign="middle"><span class="Bold">Labetalol HCl </span> <br/> <span class="Bold">(n=227)</span> <br/> </td><td class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(n=98)</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"><span class="Bold"> Body as a whole </span>             </td><td class="Rrule" colspan="2" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"> Fatigue</td><td class="Rrule" valign="middle"> 5%</td><td class="Rrule" valign="middle"> 0%</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"> Headache</td><td class="Rrule" valign="middle"> 2%</td><td class="Rrule" valign="middle"> 1%</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"><span class="Bold"> Gastrointestinal</span></td><td class="Rrule" colspan="2" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"> Nausea</td><td class="Rrule" valign="middle"> 6%</td><td class="Rrule" valign="middle"> 1%</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"> Dyspepsia</td><td class="Rrule" valign="middle"> 3%</td><td class="Rrule" valign="middle"> 1%</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"><span class="Bold"> Central and peripheral nervous system</span></td><td class="Rrule" colspan="2" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"> Dizziness</td><td class="Rrule" valign="middle"> 11%</td><td class="Rrule" valign="middle"> 3%</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"> <span class="Bold">Autonomic nervous system</span></td><td class="Rrule" colspan="2" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Nasal stuffiness</td><td class="Rrule" valign="middle"> 3%</td><td class="Rrule" valign="middle"> 0%</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"><span class="Bold">Respiratory</span></td><td class="Rrule" colspan="2" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"> Dyspnea</td><td class="Rrule" valign="middle"> 2%</td><td class="Rrule" valign="middle"> 0%</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"><span class="Bold"> Special senses</span></td><td class="Rrule" colspan="2" valign="middle"> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle"> Vertigo</td><td class="Rrule" valign="middle"> 2%</td><td class="Rrule" valign="middle"> 1%</td> </tr> </tbody> </table></div>

The adverse effects were reported spontaneously and are representative of the incidence of adverse effects that may be observed in a properly selected hypertensive patient population, i.e., a group excluding patients with bronchospastic disease, overt congestive heart failure, or other contraindications to beta-blocker therapy.

Clinical trials also included studies utilizing daily doses up to 2,400 mg in more severely hypertensive patients. Certain of the side effects increased with increasing dose, as shown in Table 2 that depicts the entire US therapeutic trials data base for adverse reactions that are clearly or possibly dose related.

Digitalis glycosides, diltiazem, verapamil, and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use with negative chronotropes can increase the risk of bradycardia or hypotension[see Warnings and Precautions (5.2)]. Coadministration of labetalol HCl with non-dihydropyridine calcium-channel antagonists (e.g., verapamil) is contraindicated [see Contraindications (4)].

Labetalol HCl antagonizes the bronchodilatory effect of beta-receptor agonist drugs; therefore, labetalol HCl is contraindicated in patients with bronchial asthma [see Contraindications (4)].

Synergism has been shown between halothane anesthesia and intravenously administered labetalol. During controlled hypotensive anesthesia using labetalol in association with halothane, high concentrations (3% or above) of halothane should not be used because the degree of hypotension will be increased and because of the possibility of a large reduction in cardiac output and an increase in central venous pressure.

Coadministration of labetalol HCl and nitroglycerine will have an additive effect in lowering blood pressure. Additionally, labetalol HCl blunts the reflex tachycardia produced by nitroglycerin. If labetalol HCl is used in patients with angina pectoris on nitroglycerin, monitor patients’ blood pressure and adjust labetalol dose as needed. In these patients, avoid initiating Labetalol Hydrochloride Tablets.

The presence of labetalol metabolites in the urine may result in falsely elevated levels of urinary catecholamines, metanephrine, normetanephrine, and vanillylmandelic acid (VMA) when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with labetalol, a specific method, such as a high-performance liquid chromatographic assay with solid phase extraction should be employed in determining levels of catecholamines. Labetalol has also been reported to produce a false positive test for amphetamine when screening urine for the presence of drugs using the commercially available assay methods. When patients being treated with labetalol have a positive urine test for amphetamine using these techniques, confirm using more specific methods, such as a gas chromatographic mass spectrometer technique.

Risk Summary 

The extensive experience with use of labetalol in pregnant women, based on published interventional and observational studies, has not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). Untreated hypertension during pregnancy can lead to serious adverse outcomes for the mother and the fetus (see Clinical Considerations). In animal reproductive studies, oral administration of labetalol to pregnant rats and rabbits during organogenesis at doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively, resulted in no fetal malformations; however, increased fetal resorptions were seen in both species at doses approximating the MRHD (see Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Consideration

Disease-Associated Materanl and/or Embryo/Fetal Risk 

Hypertension in pregnancy increase the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal Adverse Reactions 

Labetalol crosses the placenta. Newonates born to mothers who are receiving labetalol during pregnancy, may be at risk for hypotension, bradycardia, hypoglycemia, and respiratory depression. Neonates should be monitored for symptoms of hypotension, bradycardia, hypoglycemia and respiratly depression and mange accordingly.

Data

Human Data

Data from published interventional and observational studies did not demonstrate an association between major congenital malformations and the use of labetalol in pregnancy, however, most studies reported the maternal use of intravenous labetalol occurring after 20 weeks gestation. The published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of labetalol during pregnancy; however, these studies have methodological limitations hindering interpretation. These studies cannot definitively establish the absence of risk during pregnancy.

Animal Data 

Teratogenic studies were performed with labetalol in rats and rabbits at oral doses up to approximately six and four times the maximum recommended human dose (MRHD), respectively. No reproducible evidence of fetal malformations was observed. Increased fetal resorptions were seen in both species at doses approximating the MRHD. A teratology study performed with labetalol in rabbits at intravenous doses up to 1.7 times the MRHD revealed no evidence of drug-related harm to the fetus. Oral administration of labetalol to rats during late gestation through weaning at doses of two to four times the MRHD caused a decrease in neonatal survival.

Risk Summary

Available published data report the presence of labetalol in human milk at low levels. There are no data on the effects on the breastfed infant and on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for labetalol and any potential adverse effects on the breastfed infant from labetalol or from the underlying maternal condition.

Safety and effectiveness in pediatric patients have not been established.

Pharmacokinetic studies indicate that the elimination of labetalol is reduced in elderly patients. Although elderly patients may initiate therapy at the currently recommended dosage of 100 mg twice daily, elderly patients will generally require lower maintenance dosages than nonelderly patients.

Overdosage with labetalol hydrochloride causes excessive hypotension that is posture sensitive and, sometimes, excessive bradycardia. Patients should be placed supine and their legs raised if necessary to improve the blood supply to the brain. Treat symptoms of overdose with standard supportive care. If overdosage with labetalol hydrochloride follows oral ingestion, gastric lavage or pharmacologically induced emesis (using syrup of ipecac) may be useful for removal of the drug shortly after ingestion. Treat symptoms of overdose with standard supportive care.

{ "type": "p", "children": [], "text": "Overdosage with labetalol hydrochloride causes excessive hypotension that is posture sensitive and, sometimes, excessive bradycardia. Patients should be placed supine and their legs raised if necessary to improve the blood supply to the brain. Treat symptoms of overdose with standard supportive care. If overdosage with labetalol hydrochloride follows oral ingestion, gastric lavage or pharmacologically induced emesis (using syrup of ipecac) may be useful for removal of the drug shortly after ingestion. Treat symptoms of overdose with standard supportive care." }

Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol hydrochloride from the general circulation (<1%).

{ "type": "p", "children": [], "text": "Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol hydrochloride from the general circulation (<1%)." }

The oral LD50 value of labetalol hydrochloride in the mouse is approximately 600 mg/kg and in the rat is >2 g/kg. The IV LD50in these species is 50 mg/kg to 60 mg/kg.

{ "type": "p", "children": [], "text": "The oral LD50 value of labetalol hydrochloride in the mouse is approximately 600 mg/kg and in the rat is >2 g/kg. The IV LD50in these species is 50 mg/kg to 60 mg/kg." }

Labetalol Hydrochloride Tablets, USP contain labetalol hydrochloride, an adrenergic receptor blocking agent that has both selective alpha1 adrenergic and nonselective beta-adrenergic receptor blocking actions in a single substance.  

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Tablets, USP contain labetalol hydrochloride, an adrenergic receptor blocking agent that has both selective alpha1 adrenergic and nonselective beta-adrenergic receptor blocking actions in a single substance.   " }

Labetalol hydrochloride is a racemate chemically designated as 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl) amino] ethyl] benzamide monohydrochloride, and it has the following structural formula:

{ "type": "p", "children": [], "text": "Labetalol hydrochloride is a racemate chemically designated as 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl) amino] ethyl] benzamide monohydrochloride, and it has the following structural formula:" }

Labetalol hydrochloride has the empirical formula C19H24N2O3•HCl and a molecular weight of 364.9. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs. Dilevalol, the R,R' stereoisomer, makes up 25% of racemic labetalol.

{ "type": "p", "children": [], "text": "\n Labetalol hydrochloride has the empirical formula C19H24N2O3•HCl and a molecular weight of 364.9. It has two asymmetric centers and therefore exists as a molecular complex of two diastereoisomeric pairs. Dilevalol, the R,R' stereoisomer, makes up 25% of racemic labetalol." }

Labetalol hydrochloride is a white or off-white crystalline powder, soluble in water.

{ "type": "p", "children": [], "text": "\n Labetalol hydrochloride is a white or off-white crystalline powder, soluble in water." }

Labetalol Hydrochloride Tablets, USP contain 100 mg, 200 mg, or 300 mg of labetalol hydrochloride and are for oral administration. The tablets also contain the inactive ingredients lactose monohydrate, magnesium stearate, pregelatinized corn starch, sodium starch glycolate.

{ "type": "p", "children": [], "text": "\n Labetalol Hydrochloride Tablets, USP contain 100 mg, 200 mg, or 300 mg of labetalol hydrochloride and are for oral administration. The tablets also contain the inactive ingredients lactose monohydrate, magnesium stearate, pregelatinized corn starch, sodium starch glycolate." }

FDA approved dissolution test specifications differ from USP.

{ "type": "p", "children": [], "text": "FDA approved dissolution test specifications differ from USP." }

Labetalol hydrochloride combines both selective, competitive, alpha1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity. The ratios of alpha- to beta-blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively.

The capacity of labetalol hydrochloride to block alpha receptors in man has been demonstrated by attenuation of the pressor effect of phenylephrine and by a significant reduction of the pressor response caused by immersing the hand in ice cold water ("cold pressor test"). Labetalol hydrochloride's beta1 receptor blockade in man was demonstrated by a small decrease in the resting heart rate, attenuation of tachycardia produced by isoproterenol or exercise, and by attenuation of the reflex tachycardia to the hypotension produced by amyl nitrite. Beta2 receptor blockade was demonstrated by inhibition of the isoproterenol induced fall in diastolic blood pressure. Both the alpha- and beta blocking actions of orally administered labetalol hydrochloride contribute to a decrease in blood pressure in hypertensive patients. Labetalol hydrochloride consistently, in dose related fashion, blunted increases in exercise induced blood pressure and heart rate, and in their double product. The pulmonary circulation during exercise was not affected by labetalol hydrochloride dosing.

The effects on A-V nodal refractoriness were inconsistent. Single oral doses of labetalol hydrochloride administered to patients with coronary artery disease had no significant effect on sinus rate, intraventricular conduction, or QRS duration. The atrioventricular (A-V) conduction time was modestly prolonged in two of seven patients. In another study, IV labetalol hydrochloride slightly prolonged A V nodal conduction time and atrial effective refractory period with only small changes in heart rate.

Labetalol hydrochloride produces dose-related falls in blood pressure without reflex tachycardia and without significant reduction in heart rate, presumably through a mixture of its alpha- and beta-blocking effects. Hemodynamic effects are variable, with small, nonsignificant changes in cardiac output seen in some studies but not others, and small decreases in total peripheral resistance. Elevated plasma renins are reduced.

Due to the alpha1- receptor blocking activity of labetalol hydrochloride, blood pressure is lowered more in the standing than in the supine position, and symptoms of postural hypotension (2%), including rare instances of syncope, can occur. Following oral administration, when postural hypotension has occurred, it has been transient and is uncommon when the recommended starting dose and titration increments are closely followed [see Dosage and Administration (2.1)]. Symptomatic postural hypotension is most likely to occur 2 to 4 hours after a dose, especially following the use of large initial doses or upon large changes in dose.

The peak effects of single oral doses of labetalol hydrochloride occur within 2 to 4 hours. The duration of effect depends upon dose, lasting at least 8 hours following single oral doses of 100 mg and more than 12 hours following single oral doses of 300 mg. The maximum, steady state blood pressure response upon oral, twice-a-day dosing occurs within 24 to 72 hours.

The antihypertensive effect of labetalol has a linear correlation with the logarithm of labetalol plasma concentration, and there is also a linear correlation between the reduction in exercise induced tachycardia occurring at 2 hours after oral administration of labetalol hydrochloride and the logarithm of the plasma concentration.

About 70% of the maximum beta-blocking effect is present for 5 hours after the administration of a single oral dose of 400 mg with suggestion that about 40% remains at 8 hours.

Absorption 

Labetalol hydrochloride is absorbed with peak plasma levels occurring 1 to 2 hours after oral administration.

The relative bioavailability of Labetalol Hydrochloride Tablets compared to an oral solution is 100%. The absolute bioavailability (fraction of drug reaching systemic circulation) of labetalol when compared to an IV infusion is 25%; this is due to extensive "first-pass" metabolism. There is a linear relationship between oral doses of 100 mg to 3,000 mg and peak plasma levels.

Effect of Food 

The absolute bioavailability of labetalol is increased when administered with food.

Distribution 

Labetalol has been shown to cross the placental barrier in humans. Labetalol is approximately 50% protein bound.

Elimination 

The plasma half-life of labetalol following oral administration is about 6 to 8 hours. Steady-state plasma levels of labetalol are reached by about the third day of dosing.

Metabolism

Metabolism of labetalol is mainly through conjugation to glucuronide metabolites.

Excretion 

Approximately 55% to 60% of a dose appears in the urine as conjugates or unchanged labetalol within the first 24 hours of dosing. These metabolites are present in plasma and are excreted in the urine and, via the bile, into the feces. Neither hemodialysis nor peritoneal dialysis removes a significant amount of labetalol hydrochloride from the general circulation (<1%).

Specific Populations

Patients with Renal or Hepatic Impairment

In patients with decreased hepatic or renal function, the elimination half-life of labetalol is not altered; however, the relative bioavailability in hepatically impaired patients is increased due to decreased "first pass" metabolism.

Drug Interaction Studies

Tricyclic Antidepressants 

In one survey, 2.3% of patients taking labetalol hydrochloride in combination with tricyclic antidepressants experienced tremor, as compared to 0.7% reported to occur with labetalol hydrochloride alone. The contribution of each of the treatments to this adverse reaction is unknown, but the possibility of a drug interaction cannot be excluded.

Cimetidine 

Cimetidine has been shown to increase the bioavailability of labetalol hydrochloride. Since this could be explained either by enhanced absorption or by an alteration of hepatic metabolism of labetalol hydrochloride, special care should be used in establishing the dose required for blood pressure control in such patients.

Long-term oral dosing studies with labetalol hydrochloride for 18 months in mice and for 2 years in rats showed no evidence of carcinogenesis. Studies with labetalol hydrochloride using dominant lethal assays in rats and mice and exposing microorganisms according to modified Ames tests showed no evidence of mutagenesis.

Labetalol Hydrochloride Tablets USP, 100 mg, White to off-white, biconvex, film coated tablets with “ET20” debossed on one side and nonfunctional scoring on the other side, bottles of 100 (NDC 71930-035-12) and bottles of 500 (NDC 71930-035-52).

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Tablets USP, 100 mg, White to off-white, biconvex, film coated tablets with “ET20” debossed on one side and nonfunctional scoring on the other side, bottles of 100 (NDC 71930-035-12) and bottles of 500 (NDC 71930-035-52)." }

Labetalol Hydrochloride Tablets USP, 200 mg, White to off-white, biconvex, film coated tablets with “ET21” debossed on one side and nonfunctional scoring on the other side, bottles of 100 (NDC 71930-036-12) and bottles of 500 (NDC 71930-036-52).

{ "type": "p", "children": [], "text": " Labetalol Hydrochloride Tablets USP, 200 mg, White to off-white, biconvex, film coated tablets with “ET21” debossed on one side and nonfunctional scoring on the other side, bottles of 100 (NDC 71930-036-12) and bottles of 500 (NDC 71930-036-52)." }

Labetalol Hydrochloride Tablets USP, 300 mg, White to off-white, biconvex, film coated tablets with “ET22” debossed on one side and nonfunctional scoring on the other side, bottles of 100 (NDC 71930-037-12) and bottles of 500 (NDC 71930-037-52). Storage Store Labetalol Hydrochloride Tablets, USP between 2° and 30°C (36° and 86°F).

{ "type": "p", "children": [], "text": " Labetalol Hydrochloride Tablets USP, 300 mg, White to off-white, biconvex, film coated tablets with “ET22” debossed on one side and nonfunctional scoring on the other side, bottles of 100 (NDC 71930-037-12) and bottles of 500 (NDC 71930-037-52).\n\nStorage\n Store Labetalol Hydrochloride Tablets, USP between 2° and 30°C (36° and 86°F)." }

{ "type": "ul", "children": [ "Advise patients to not interrupt or discontinue using Labetalol Hydrochloride Tablets without advice from their healthcare provider", "Advise patients to contact their healthcare provider about any signs or symptoms of impending cardiac failure or hepatic dysfunction [see Warnings and Precautions (5.3,5.8)]\n", "Inform patients or caregivers that there is a risk of hypoglycemia when Labetalol Hydrochloride Tablets is given to patients who are fasting or who are vomiting. Monitor for symptoms of hypoglycemia [see Warnings and Precautions (5.6)].  \n" ], "text": "" }

Manufactured for:

{ "type": "p", "children": [], "text": "Manufactured for:" }

Eywa-Hibrow Pharma 908 Oak Tree Road, Suite O South Plainfield, NJ 07080 Made in India Revised: 04/2025

{ "type": "p", "children": [], "text": " Eywa-Hibrow Pharma 908 Oak Tree Road, Suite O South Plainfield, NJ 07080\n Made in India\n Revised: 04/2025" }

NDC 71930-035-12

{ "type": "p", "children": [], "text": "NDC 71930-035-12" }

Labetalol Hydrochloride Tablets, USP

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Tablets, USP" }

100 mg

{ "type": "p", "children": [], "text": "100 mg" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

100 tablets

{ "type": "p", "children": [], "text": "100 tablets" }

Eywa-Hibrow Pharma

{ "type": "p", "children": [], "text": "Eywa-Hibrow Pharma" }

NDC 71930-036-12

{ "type": "p", "children": [], "text": "NDC 71930-036-12" }

Labetalol Hydrochloride Tablets, USP

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Tablets, USP" }

200 mg

{ "type": "p", "children": [], "text": "200 mg" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

100 tablets

{ "type": "p", "children": [], "text": "100 tablets" }

Eywa-Hibrow Pharma

{ "type": "p", "children": [], "text": "Eywa-Hibrow Pharma" }

NDC 71930-037-12

{ "type": "p", "children": [], "text": "NDC 71930-037-12" }

Labetalol Hydrochloride Tablets, USP

{ "type": "p", "children": [], "text": "Labetalol Hydrochloride Tablets, USP" }

300 mg

{ "type": "p", "children": [], "text": "300 mg" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

100 tablets

{ "type": "p", "children": [], "text": "100 tablets" }

Eywa-Hibrow Pharma

{ "type": "p", "children": [], "text": "Eywa-Hibrow Pharma" }