labetalol Hydrochloride Injection, USP - VIAL Adverse Reactions

ADVERSE REACTIONS

Labetalol injection is usually well tolerated. 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 injection. 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 injection with the incidence per 100 patients as noted:

Cardiovascular System: Ventricular arrhythmia in 1.

Central and Peripheral Nervous Systems: Dizziness in 9; tingling of the scalp/skin 7; hypoesthesia (numbness) and vertigo, 1 each.

Gastrointestinal System: Nausea in 13; vomiting 4; dyspepsia and taste distortion, 1 each.

Metabolic Disorders: Transient increases in blood urea nitrogen and serum creatinine levels occurred in 8 of 100 patients; these were associated with drops in blood pressure, generally in patients with prior renal insufficiency.

Psychiatric Disorders: Somnolence/yawning in 3.

Respiratory System: Wheezing in 1.

Skin: Pruritus in 1.

The incidence of adverse reactions depends upon the dose of labetalol. The largest experience is with oral labetalol. Certain of the side effects increased with increasing oral dose as shown in the table below which depicts the entire U.S. therapeutic trials data base for adverse reactions that are clearly or possibly dose related.

Labetalol Daily Dose (mg)

200

300

400

600

800

900

1200

1600

2400

Number of Patients

522

181

606

608

503

117

411

242

175

Dizziness (%)

2

3

3

3

5

1

9

13

16

Fatigue

2

1

4

4

5

3

7

6

10

Nausea

<1

0

1

2

4

0

7

11

19

Vomiting

0

0

<1

<1

<1

0

1

2

3

Dyspepsia

1

0

2

1

1

0

2

2

4

Paresthesias

2

0

2

2

1

1

2

5

5

Nasal Stuffiness

1

1

2

2

2

2

4

5

6

Ejaculation Failure

0

2

1

2

3

0

4

3

5

Impotence

1

1

1

1

2

4

3

4

3

Edema

1

0

1

1

1

0

1

2

2

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 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.

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Adverse Reactions

ADVERSE REACTIONS

Labetalol injection is usually well tolerated. 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 injection. 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 injection with the incidence per 100 patients as noted:

Cardiovascular System: Ventricular arrhythmia in 1.

Central and Peripheral Nervous Systems: Dizziness in 9; tingling of the scalp/skin 7; hypoesthesia (numbness) and vertigo, 1 each.

Gastrointestinal System: Nausea in 13; vomiting 4; dyspepsia and taste distortion, 1 each.

Metabolic Disorders: Transient increases in blood urea nitrogen and serum creatinine levels occurred in 8 of 100 patients; these were associated with drops in blood pressure, generally in patients with prior renal insufficiency.

Psychiatric Disorders: Somnolence/yawning in 3.

Respiratory System: Wheezing in 1.

Skin: Pruritus in 1.

The incidence of adverse reactions depends upon the dose of labetalol. The largest experience is with oral labetalol. Certain of the side effects increased with increasing oral dose as shown in the table below which depicts the entire U.S. therapeutic trials data base for adverse reactions that are clearly or possibly dose related.

Labetalol Daily Dose (mg)

200

300

400

600

800

900

1200

1600

2400

Number of Patients

522

181

606

608

503

117

411

242

175

Dizziness (%)

2

3

3

3

5

1

9

13

16

Fatigue

2

1

4

4

5

3

7

6

10

Nausea

<1

0

1

2

4

0

7

11

19

Vomiting

0

0

<1

<1

<1

0

1

2

3

Dyspepsia

1

0

2

1

1

0

2

2

4

Paresthesias

2

0

2

2

1

1

2

5

5

Nasal Stuffiness

1

1

2

2

2

2

4

5

6

Ejaculation Failure

0

2

1

2

3

0

4

3

5

Impotence

1

1

1

1

2

4

3

4

3

Edema

1

0

1

1

1

0

1

2

2

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 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.

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