HIGHLIGHTS OF PRESCRIBING INFORMATION • Greater-than-first-degree heart block (4)

• Cardiogenic shock (4)

These highlights do not include all the information needed to use • Severe bradycardia (4)
LABETALOL HYDROCHLORIDE IN SODIUM CHLORIDE
INJECTION and LABETALOL HYDROCHLORIDE IN DEXTROSE ----------------------- WARNINGS AND PRECAUTIONS ---------------------­
INJECTION safely and effectively. See full prescribing information for • Exacerbation of heart failure: Avoid use. (5.3)
LABETALOL HYDROCHLORIDE. • Acute exacerbation of coronary artery disease upon cessation of therapy:
Do not abruptly discontinue. (5.4)
LABETALOL HYDROCHLORIDE IN SODIUM CHLORIDE injection,
• Non-allergic bronchospasm (e.g., chronic bronchitis and emphysema):
for intravenous use.
Avoid since it has not been studied. (5.5)
LABETALOL HYDROCHLORIDE IN DEXTROSE injection, for
• Masked hypoglycemia: Monitor glucose as beta blockers may mask
intravenous use.
symptoms of hypoglycemia or worsen hyperglycemia. (5.6)
Initial U.S. Approval: 1984
• Exacerbation of pheochromocytoma: Paradoxical increases in blood
--------------------------- INDICATIONS AND USAGE -------------------------- pressure may occur. (5.7)
Labetalol Hydrochloride (HCl) is a beta adrenergic blocker. Labetalol HCl in • Severe hepatocellular injury: Discontinue permanently for liver injury or
Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are jaundice (5.8)
indicated in severe hypertension, to lower blood pressure (1)
------------------------------ ADVERSE REACTIONS ----------------------------­
---------------------- DOSAGE AND ADMINISTRATION ---------------------­ Most common adverse events:
Administered as a slow continuous infusion at a rate of 2 mL/min to deliver 2 • Symptomatic postural hypotension. (6)
mg/min. (2.1) • Nausea13%, dizziness 9% (6)
--------------------- DOSAGE FORMS AND STRENGTHS -------------------- To report SUSPECTED ADVERSE REACTIONS, contact Hikma
Labetalol HCl in Sodium Chloride Injection in a single-dose bag: Pharmaceuticals USA Inc. at 1-877-845-0689, or FDA at 1-800-FDA-1088
• 100 mg/100 mL (1 mg/mL) (3) or www.fda.gov/medwatch. For product Inquiry call 1-877-845-0689.
• 200 mg/200 mL (1 mg/mL) (3)
------------------------------ DRUG INTERACTIONS ----------------------------­
• 300 mg/300 mL (1 mg/mL) (3)
• Beta blockers antagonize the bronchodilator effect of beta-receptor
Labetalol HCl in Dextrose Injection in a single-dose bag: agonists. (7.1)
• 200 mg/200 mL (1 mg/mL) (3) • Increase hypotension may occur with halothane anesthesia. (7.2)
• Nitroglycerin may result in additional hypotensive effects. (7.3)
------------------------------ CONTRAINDICATIONS ----------------------------­ See 17 for PATIENT COUNSELING INFORMATION
• Bronchial asthma (4)
• Overt cardiac failure (4) Revised: 11/2020

7.3 Nitroglycerin
FULL PRESCRIBING INFORMATION: CONTENTS* 7.4 Calcium Channel Blockers
1 INDICATIONS AND USAGE 7.5 Drug/Laboratory Test Interactions
2 DOSAGE AND ADMINISTRATION 8 USE IN SPECIFIC POPULATIONS
2.1 General Information 8.1 Pregnancy
2.2 Recommended Dosage 8.2 Lactation
3 DOSAGE FORMS AND STRENGTHS 8.3 Females and Males of Reproductive Potential
4 CONTRAINDICATIONS 8.4 Pediatric Use
5 WARNINGS AND PRECAUTIONS 8.5 Geriatric Use
5.1 Hypotension 10 OVERDOSAGE
5.2 Bradycardia 10.1 Signs and Symptoms of Overdose
5.3 Cardiac Failure 11 DESCRIPTION
5.4 Ischemic Heart Disease 12 CLINICAL PHARMACOLOGY
5.5 Reactive Airway Disease and Nonallergic Bronchospasm 12.1 Mechanism of Action
5.6 Use in Patients with Diabetes Mellitus and Hypoglycemia 12.2 Pharmacodynamics
5.7 Use in Patients with Pheochromocytoma 12.3 Pharmacokinetics
5.8 Hepatic Injury 13 NONCLINICAL TOXICOLOGY
5.9 Use in Patients at Risk of Severe Acute Hypersensitivity 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Reactions 16 HOW SUPPLIED/STORAGE AND HANDLING
5.10 Intraoperative Floppy Iris Syndrome (IFIS) 16.1 How Supplied
6 ADVERSE REACTIONS 16.2 Storage
6.1 Clinical Trial Experience 17 PATIENT COUNSELING INFORMATION
7 DRUG INTERACTIONS *Sections or subsections omitted from the full prescribing information are not
7.1 Bronchodilators listed
7.2 Anesthesia

Reference ID: 4699171

 FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are
indicated in severe hypertension, to lower blood pressure.

2 DOSAGE AND ADMINISTRATION

2.1 General Information

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. Parenteral drug products should
be inspected visually for particulate matter and discoloration prior to administration, whenever
solution and container permit. Do not use the content of the bag unless the solution is clear
(colorless to light yellow) and the seal is intact. Do not add any additional medications to the
bag.

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

2.2 Recommended Dosage

The recommended initial dosage is 2 mg/minute by continuous intravenous infusion, which is

2 mL/minute. Monitor blood pressure and adjust the dosage and duration of infusion
accordingly.

Once supine diastolic blood pressure has begun to rise, transition to oral labetalol HCl.

The usual intravenous dose is in the range of 50 to 200 mg. A total dose of up to 300 mg may be
required in some patients, but the safety of doses above 300 mg has not been established.

3 DOSAGE FORMS AND STRENGTHS

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are
available as a 1 mg/mL, preservative-free, clear, colorless to light yellow solution in single-dose
bags in the following configurations;

Diluent Labetalol Dose Volume

Sodium Chloride 100 mg 100 mL
Sodium Chloride 200 mg 200 mL
Sodium Chloride 300 mg 300 mL
Dextrose 100 mg 100 mL

Reference ID: 4699171

 4 CONTRAINDICATIONS

Labetalol HCl in Sodium Chloride Injection and Labetalol HCl in Dextrose Injection are
contraindicated in patients with:

• 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

5 WARNINGS AND PRECAUTIONS

5.1 Hypotension
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.
5.2 Bradycardia

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.
5.3 Cardiac Failure
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.
5.4 Ischemic Heart Disease

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.

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 5.5 Reactive Airway Disease and Nonallergic Bronchospasm

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.
5.6 Use in Patients with Diabetes Mellitus and Hypoglycemia

In patients with hypoglycemia, or diabetic patients (especially those with labile diabetes) who are
receiving insulin or other hypoglycemic agents, beta blockers may mask tachycardia occurring
with hypoglycemia, but other manifestations such as dizziness and sweating may not be masked.
Concomitant use of beta-blockers and antidiabetic agents can enhance the glucose-lowering
effect of antidiabetic agents. Monitor glycemic levels in patients receiving labetalol HCl
injection.
5.7 Use in Patients with Pheochromocytoma
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.
5.8 Hepatic Injury

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.
5.9 Use in Patients at Risk of Severe Acute Hypersensitivity Reactions

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.
5.10 Intraoperative Floppy Iris Syndrome (IFIS)

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

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 ophthalmologist to be prepared for possible modifications to the surgical technique, such as the
utilization of iris hooks, iris dilator rings, or viscoelastic substances.

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Hypotension [see Warnings and Precautions (5.1)]

• Bradycardia [see Warnings and Precautions (5.2)]
• Depression of myocardial contractility in patients with overt congestive heart failure [see
Warnings and Precautions (5.3)]
• Aggravation of angina [see Warnings and Precautions (5.4)]
• Significant decline in cardiac output following coronary bypass [see Warnings and
Precautions (5.3)]
• Bronchospasm in patients with reactive airway disease [see Warnings and Precautions
(5.5)]
• Paradoxical hypertensive responses in patients with pheochromocytoma [see Warnings
and Precautions (5.7)]
• Hepatic injury [see Warnings and Precautions (5.8)]
• Acute hypersensitivity reaction [see Warnings and Precautions (5.9)]
6.1 Clinical Trial Experience
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

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 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.

7 DRUG INTERACTIONS
7.1 Bronchodilators

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

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.
7.3 Nitroglycerin

Coadministration of labetalol HCl and nitroglycerine will have an additive effect in lowering
blood pressure. Additionally, labetalol HCl blunts the reflex tachycardia produced by

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 nitroglycerin. If labetalol is used in patients with angina pectoris on nitroglycerine, monitor
patients’ blood pressure and adjust labetalol HCl injection dose as needed. In these patients,
avoid initiating labetalol HCl tablets.
7.4 Calcium Channel Blockers

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.
7.5 Drug/Laboratory Test Interactions

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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

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

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 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.

8.2 Lactation

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

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 labetalol and any potential adverse effects on the breastfed infant from labetalol or from the
underlying maternal condition.

8.3 Females and Males of Reproductive Potential

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

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
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)].

10 OVERDOSAGE
10.1 Signs and Symptoms of Overdose

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.

11 DESCRIPTION

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

Reference ID: 4699171

 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.

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.

12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action

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 (ISA) activity detected. In animals, at doses
greater than those required for alpha- or beta-adrenergic blockade, a membrane stabilizing effect
has been demonstrated.
12.2 Pharmacodynamics

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

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 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.
12.3 Pharmacokinetics

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.

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 13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Labetalol HCl in Sodium Chloride Injection is a preservative-free, clear, colorless to light yellow
sterile solution that is 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:

Strength Package NDC Number

1 single-dose bag 0143-9363-01
100 mg/100 mL (1 mg/mL)
Box of 10 bags 0143-9363-10
preservative-free

1 single-dose bag 0143-9364-01

200 mg/200 mL (1 mg/mL)
Box of 10 bags 0143-9364-10
preservative-free
1 single-dose bag 0143-9365-01
300 mg/300 mL (1 mg/mL)
Box of 10 bags 0143-9365-10
preservative-free
Labetalol HCl in Dextrose Injection is a preservative-free, clear, colorless to light yellow sterile
solution that is 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:

Strength Package NDC Number

1 single-dose bag 0143-9366-01
200 mg/200 mL (1 mg/mL)
Box of 10 bags 0143-9366-10
preservative-free

16.2 Storage
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. DO
NOT REMOVE FROM OVERWRAP UNTIL READY TO USE.

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 17 PATIENT COUNSELING INFORMATION

• Advise patients to remain supine and to proceed gradually in becoming ambulatory

during and immediately following infusion (for up to 3 hours) of labetalol HCl injection.
• Inform patient to notify their healthcare provider if they experience symptoms of
hypotension.
• Advise patients to not interrupt or discontinue their labetalol HCl tablets without
discussing with their healthcare provider and report any signs or symptoms of impending
cardiac failure or hepatic dysfunction
Rx Only

Manufactured by
HIKMA FARMACÊUTICA (PORTUGAL), S.A.
Estrada do Rio da Mó, 8, 8A e 8B – Fervença – 2705-906 Terrugem SNT, PORTUGAL
Distributed by
Hikma Pharmaceuticals USA Inc.
Eatontown, NJ 07724
PIN539-WES/1

Reference ID: 4699171