Humalog

Generic Name: Insulin Lispro
Class: Insulins
ATC Class: A10AB04
VA Class: HS501
Chemical Name: 28B-l-Lysine-29B-l-prolineinsulin (human)
Molecular Formula: C₂₅₇H₃₈₃N₆₅O₇₇S ₆
CAS Number: 133107-64-9

Introduction

Antidiabetic agent; a rapid-acting biosynthetic human insulin analog.^{1 2 8 13 51 145}

Uses for Humalog

Diabetes Mellitus

Used to control hyperglycemia in the management of diabetes mellitus.^{1 2 3 6 12 47 75 77 78}

In patients with type 1 diabetes mellitus, generally used in conjunction with an intermediate-acting or long-acting insulin preparation (i.e., isophane [NPH] insulin human, insulin lispro protamine [as the fixed combination Humalog Mix 75/25], insulin zinc [Lente], extended insulin human zinc [Ultralente]), to provide prandial glycemic control.^{1 73 74 76 77 78 79 81 96 144 145 159 160 161 165} In patients with type 2 diabetes mellitus, may be used without a longer-acting insulin when given with a sulfonylurea agent.^{1 158 159 160 161 165}

Patients likely to benefit from insulin lispro therapy include type 1 diabetics who desire a more flexible injection schedule, those with low glycosylated hemoglobin values, and patients with recent-onset type 1 diabetes mellitus who have some residual β-cell function to provide basal insulin levels between meals.^{6 12 56 59 74 77 78 79 81 144 145}

The effects of age, obesity, gender, and type of diabetes mellitus on glycemic response do not appear to differ in patients receiving insulin lispro versus insulin human.^{1 51}

Some clinicians suggest that patients who are well-controlled on conventional short-acting insulin preparations without frequent hypoglycemia should not be routinely switched to insulin lispro.^{74 144}

Humalog Dosage and Administration

General

• 
  

  Insulin lispro and insulin human are equipotent on a unit-for-unit basis with regard to glucose-lowering activity.^{1 2 3 7 9 12 19 47 51 59}

  
  


• 
  

  Any change in insulin should be made cautiously and only under medical supervision.¹ Changes in insulin strength, manufacturer, type (e.g., regular, NPH), species (animal, human), or method of manufacture (rDNA versus animal-source insulin) may necessitate a change in dosage.¹

  
  


• 
  

  Monitor patients through regular laboratory evaluations, including fasting blood (or plasma) glucose determinations, to assess therapeutic response and obtain the minimum effective dosage of insulin lispro.^{1 20 24} Whenever possible, patients should self-monitor blood glucose concentrations.^{1 5 19 22 51 60} Following initiation of insulin lispro therapy and dosage titration, determine glycosylated hemoglobin (hemoglobin A_1c [HbA_1c]) concentrations at intervals of approximately 3 months.^{22 24 144 145}

  
  

Transferring from Therapy with Other Insulins

• 
  

  Make any change in insulin preparation or dosage regimen with caution and only under medical supervision.^{1 19 51}

  
  


• 
  

  Not possible to clearly identify which patients will require a change in dosage when therapy with a different preparation is initiated.^{6 9 12 19 51}

  
  


• 
  

  When switching from insulin human (regular) in regimens consisting of multiple insulin doses, use the previous insulin (regular) dosage as the initial dosage of insulin lispro.^{1 72 74 147} Subsequent dosage adjustments may be required due to changes in insulin purity, strength, brand, type, species source, or method of manufacture.^{1 2 3 7 9 12 19 47 51 59} Adjustments may be needed with the first dose or over a period of several weeks.¹

  
  


• 
  

  When switching from insulin human (regular) in combination with a longer-acting insulin, dosage adjustment of the longer-acting insulin may be required.^{1 12 51 58 75 77 78 147 154}

  
  


• 
  

  Patients receiving intensive insulin therapy (≥3 insulin injections daily with dosage adjusted according to results of at least 4 daily blood glucose determinations, dietary intake, and anticipated exercise) will achieve greater postprandial glycemic control than those receiving conventional therapy because of the increased use of rapid- or short-acting insulin.^{6 9 22 59}

  
  


• 
  

  Patients who previously were inadequately controlled on conventional insulin therapy generally will require a smaller total daily insulin dosage when switched to an intensive insulin regimen.^{6 9 22 59}

  
  

Administration

Administer by sub-Q injection or continuous sub-Q infusion.¹

Do not administer insulin lispro in fixed combination with insulin lispro protamine IV.^a

To improve accuracy of dosing in pediatric patients, may be diluted to a ratio of 1:10 or 1:2 with the sterile diluent supplied by the manufacturer.¹

Sub-Q Injection

For solution and drug compatibility information, see Compatibility under Stability.

Administer by sub-Q injection immediately (i.e., within 15 minutes before or after a meal) using a conventional insulin syringe or an injection pen (e.g., Becton-Dickinson [B-D] Pen, Humalog Pen, Novo Nordisk’s NovoPen).^{1 19 155 156 157}

Generally administered in multiple daily doses in regimens that also include an intermediate- or long-acting insulin (e.g., NPH, Lente, Ultralente) given in the morning and/or evening to provide basal insulin needs.^{1 72 74}

Administer insulin lispro in fixed combination with insulin lispro protamine (Humalog Mix 75/25) twice daily within 15 minutes prior to the morning and evening meal.^{159 161}

Administer into abdominal wall, thigh, or upper arm.^g To avoid tissue damage, give the next injection at least 1/2 inch from the previous injection site.^g

Sub-Q Infusion

Administer by continuous sub-Q infusion using an external controlled-infusion device.¹ Recommended for use in Disetronic H-TRONplus V100 (with Disetronic 3.15 mL insulin reservoir), Disetronic D-TRON, or Disetronic D-TRONplus external infusion pumps with Disetronic Rapid infusion sets and in MiniMed model 506, 507, or 508 pumps with MiniMed Polyfin infusion sets.¹ Delivers rapid- or short-acting insulin at a basal rate continuously throughout the day, with patient-initiated delivery of insulin prior to meals.^{27 28}

Dosage

Dosage of insulin lispro is always expressed in USP units.^{1 19 20 22 23 24 38 62 63}

Pediatric Patients

Diabetes Mellitus

Sub-Q Injection

Individualize dosage; adjust dosage regularly based on blood glucose determinations.^{1 n} Usually, the total daily insulin requirement in children with type 1 diabetes mellitus ranges from 0.2–1 units/kg (generally 0.5–0.8 units/kg daily).^{22 28 47 z} Adolescents in a growth phase may require an initial insulin dosage of 1–1.5 units/kg daily.²⁸ No specific dosage recommendations by manufacturer.¹ When used as a preprandial treatment regimen in clinical trials, 26–64% of total insulin requirements have been provided by insulin lispro, with the remainder provided by an intermediate-acting or long-acting insulin.^{n o q t u}

Sub-Q Infusion

Individualize dosage; adjust dosage regularly based on blood glucose determinations.¹ Glucose monitoring is particularly important for patients receiving insulin via an external infusion pump.¹

No specific dosage recommendations by manufacturer.¹ In a clinical trial, preprandial administration of insulin lispro injection comprised approximately 66% of the total daily insulin dosage, with the remainder given as a basal infusion.^q

Adults

Diabetes Mellitus

Sub-Q Injection

Individualize dosage; adjust dosage regularly based on blood glucose determinations.¹ Usually, the total daily insulin requirements in patients with type 1 diabetes mellitus is 0.5–1 unit/kg.^h No specific dosage recommendations by manufacturer.¹ When used in a preprandial treatment regimen in clinical trials, 39–66% of total insulin requirements have been provided by insulin lispro, with the remainder provided by an intermediate-acting or long-acting insulin.^{147 i j k l r}

In patients with type 2 diabetes mellitus who are not controlled on intermediate-acting or long-acting insulin, some clinicians suggest initiating preprandial therapy with a short-acting or rapid-acting insulin, with the preprandial injection comprising 40–50% of the total insulin dosage.^p

Sub-Q Infusion

Individualize dosage; adjust dosage regularly based on blood glucose determinations.¹ Glucose monitoring is particularly important for patients receiving insulin via an external infusion pump.¹

No specific dosage recommendations by the manufacturer.¹ In patients with type 1 diabetes mellitus, preprandial administration of insulin lispro injection has been used in clinical trials, comprising approximately 21–46% of the total daily insulin dosage, with the remainder given as a basal infusion.^{168 m r s}

Therapy with Fixed-Combination Insulin Lispro and Insulin Lispro Protamine

Sub-Q Injection

Individualize dosage; adjust dosage regularly based on blood glucose determinations.^a

No specific dosage recommendations by the manufacturer.^a Initially, 0.3–0.5 units/kg daily given in 2 divided doses (before morning and evening meal) has been used in patients with type 2 diabetes mellitus.^{v y} Subsequent dosage has been titrated in increments of 2–4 units per injection per day every 2–3 days to achieve the targeted fasting blood glucose concentration.^{v y} Mean daily maintenance insulin dosage achieved was 0.46–0.66 units/kg.^{159 v w x y}

In patients with type 1 diabetes mellitus in a clinical trial, mean daily maintenance insulin dosage achieved was 0.64 units/kg.^x

Special Populations

Renal and Hepatic Impairment

Careful monitoring of blood glucose and dosage adjustment may be necessary.¹

Cautions for Humalog

Contraindications

• 
  

  Use of insulin lispro during episodes of hypoglycemia.¹

  
  


• 
  

  Known hypersensitivity to insulin lispro or any of its excipients.¹

  
  

Warnings/Precautions

Warnings

Formulation Considerations

Insulin lispro has a more rapid onset and shorter duration of action than insulin human (regular).¹ Patients with type 1 diabetes require a longer-acting insulin to maintain adequate nighttime and preprandial blood glucose control.^{1 74 76 77 78 79 81 144}

Hypoglycemia

Care should be taken in patients who are most at risk for the development of these effects, including patients who are fasting or those with defective counterregulatory responses (e.g., patients with autonomic neuropathy, adrenal or pituitary insufficiency, those receiving β-adrenergic blocking agents).

Rapid changes in serum glucose concentrations may precipitate manifestations of hypoglycemia, regardless of glucose concentrations.¹ Homeostatic responses become defective, and early warning signs of hypoglycemia may be diminished or absent in patients with long-standing type 1 diabetes mellitus, diabetic neuropathy,¹ and/or those receiving drugs such as β-adrenergic blocking agents that mask catecholamine-induced manifestations of hypoglycemia (e.g., tremors, palpitations).¹

Use intensive insulin therapy with caution in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes. Higher target blood glucose concentrations (e.g., fasting blood glucose concentrations of 140 mg/dL and 2-hour postprandial concentrations of 200–250 mg/dL) are advisable in these patients.

Sensitivity Reactions

Local reactions (e.g., erythema, pruritus, swelling) reported.¹ Generalized hypersensitivity reactions (e.g., rash, shortness of breath, wheezing, hypotension, tachycardia, and diaphoresis) reported less frequently; may be life-threatening.¹

Localized reactions and generalized myalgias reported with the use of m-cresol, an excipient in the formulation.¹

Insulin lispro is no more immunogenic than insulin human.^{12 14 15 17 18 51 52}

Weigh benefits versus risks in patients with a history of hypersensitivity to other insulins.⁵¹

General Precautions

Lipodystrophy

Atrophy or hypertrophy of subcutaneous fat tissue may occur at sites of frequent insulin injections.¹ Changing injection technique may reduce or prevent these effects.^g

Hypokalemia

Care should be taken in patients who are most at risk for the development of hypokalemia, such as those who are receiving potassium-lowering drugs.^a

Specific Populations

Pregnancy

Category B.¹

Lactation

Not known whether insulin lispro is distributed into milk, however, other insulins (e.g., insulin human) are distributed into milk.^{1 1} Caution if used in nursing women.¹ Adjustments in insulin lispro dosage and/or meal plans may be required.¹

Pediatric Use

Safety and efficacy of insulin lispro in fixed combination with insulin lispro protamine not established in children <18 years of age.¹⁶⁵

Insulin lispro has been used in children aged 3–18 years of age with type 1 diabetes mellitus,^{1 51 74} and preliminary data suggest no unusual effects of insulin lispro therapy in adolescents receiving the drug.^{74 118 144 145 149 150 151} Adjustment of basal insulin dosages may be required.¹

Geriatric Use

Safety of intensive insulin regimens in geriatric patients has been questioned. Increased incidence of hypoglycemia associated with intensive insulin therapy may increase the probability of strokes and heart attacks in such patients.

Hypoglycemic reactions may mimic a cerebrovascular accident.^d Patients with type 2 diabetes mellitus may be more vulnerable to serious consequences of hypoglycemia (e.g., fainting, seizures, falls, stroke, silent ischemia, MI, or sudden death) due to an increased incidence of macrovascular disease.

Response in patients ≥65 years of age does not appear to differ from that in younger adults.¹

Common Adverse Effects

Hypoglycemia.¹

Interactions for Humalog

Specific Drugs

Drugs That May Potentiate Hypoglycemic Effects

ACE inhibitors

Disopyramide

Fibrate derivatives

Fluoxetine

MAO inhibitors

Oral antidiabetic agents

Propoxyphene

Salicylates

Somatostatin derivatives (e.g., octreotide)

Sulfonamide anti-infectives

Drugs That May Antagonize Hypoglycemic Effects

Corticosteroids

Danazol

Diuretics

Estrogens and progestins (e.g., oral contraceptives)

Isoniazid

Phenothiazines

Somatropin

Sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline)

Thyroid hormones

Drugs That May Have a Variable Effect on Glycemic Control

Alcohol

β-Adrenergic blocking agents

Clonidine

Lithium salts

Pentamidine

Drugs That May Reduce or Eliminate Signs of Hypoglycemia (Sympatholytic Agents)

β-Adrenergic blocking agents

Clonidine

Guanethidine

Reserpine

Humalog Pharmacokinetics

Absorption

Bioavailability

Following sub-Q administration, more rapidly absorbed than soluble preparations of insulin human or insulins of animal origin.^{1 2 3 6 9 10 51 73 144 145 165}

Peak plasma insulin concentrations are higher and occur earlier with insulin lispro (at 30–90 minutes) than with insulin human (at 50–120 minutes).^{1 2 6 9 10 11 73 165}

Following sub-Q administration of the fixed combination of insulin lispro and insulin lispro protamine (Humalog Mix 75/25), peak serum insulin concentrations were observed at 30–240 minutes (median: 60 minutes).¹⁶⁵ More rapidly absorbed than the fixed combination of insulin human (regular) and isophane insulin human (Humulin 70/30).¹⁶⁵

Onset

Many factors can affect the onset, degree, and duration of insulin activity (e.g., injection technique, presence of insulin antibodies, site of injection, tissue blood supply, temperature, excipients in insulin formulations, and interindividual and intraindividual differences in response).^{1 19 47 74 83}

Following sub-Q injection of insulin lispro, onset generally ranges from 0.25–0.5 hours versus 0.5–1 hours for insulin human, respectively.^{1 3 9 51 73 74 83} Peak glycemic response for insulin lispro or insulin human occurs at 0.5–2.5 or 1–5 hours, respectively.^{1 3 9 51 73 74 83}

Duration

Following sub-Q administration, the duration of hypoglycemic action of insulin lispro is 3–6.5 hours compared with 6–10 hours for insulin human.^{47 51 73 74 83}

The duration of action of Humalog Mix 75/25 is similar to that of Humulin 70/30.¹⁶⁵

Food

Administer 15 minutes before or immediately after meals.^{1 72}

Special Populations

The presence of hepatic impairment does not affect the absorption in patients with type 2 diabetes mellitus.¹

Distribution

Not known whether insulin lispro is distributed into human milk; however, other insulins (e.g., insulin human) are distributed into milk.¹ Does not appear to cross the placenta in pregnant women with gestational diabetes.¹⁶⁴

Extent

The volume of distribution of insulin lispro reportedly is identical to that of insulin human and ranges from 0.26–0.36 L/kg.¹

Special Populations

Hepatic impairment does not affect the distribution in patients with type 2 diabetes mellitus.¹

Elimination

Metabolic fate has not been determined in humans.^{1 165} In animals, metabolism of insulin lispro is identical to that of insulin human.^{1 165}

Metabolism

Insulin is rapidly metabolized mainly in the liver and to a lesser extent in the kidneys and muscle tissue.^d

Half-life

1 or 1.5 hours for insulin lispro or insulin human, respectively.^{2 51}

Special Populations

Circulating insulin concentrations may be increased in patients with renal or hepatic failure.¹

Stability

Storage

Parenteral

Injection, for Sub-Q Use

With unopened vials, disposable injection pens, or cartridges of the drug that have not been placed in a delivery device, 2–8°C.^{1 19 156 165} Do not freeze; discard vial or cartridge if frozen.^{1 19 156 165}

With vials, pens, or cartridges of insulin lispro that cannot be refrigerated or vials, cartridges, and disposable injection pens that are in use, <30°C for up to 28 days.^{1 19 51 81 155} Protect from heat and light.^{1 155}

With disposable injection pens of insulin lispro in fixed combination with insulin lispro protamine (Humalog Mix 75/25 Pen) that are in use, room temperature for up to 10 days.^{160 165} Protect from light and excessive heat.^{160 165}

When insulin lispro is diluted with the sterile diluent for pediatric use, discard the diluted solution after 28 days when stored at 5°C or after 14 days when stored at 30°C.¹⁶⁵

Should not expose insulin lispro in the external infusion device to temperatures >37°C during administration.¹ Replace infusion sets (reservoir syringe, tubing, and catheter), the DisetronicD-TRON or DisetronicD-TRONplus cartridge adapter, and insulin lispro in the pump reservoir and select a new infusion site at least every 48 hours.¹ Should discard the 3-mL cartridges used in the DisetronicD-TRON or DisetronicD-TRONplus insulin pumps after 7 days, even if some drug still remains in the reservoir.¹

Simulated administration of insulin lispro by continuous sub-Q infusion in several external infusion pump systems (i.e., Disetronic H-TRON, Minimed Model 504 pumps) revealed no changes in the potency, purity, or physical stability of the drug when stored within each of these devices for 48 hours.^{51 81 146 163} However, precipitation of insulin lispro on infusion catheters (i.e., Silhouette, Soft-Set catheters) has been noted in several patients who were receiving insulin lispro via one of several external pump systems (i.e., Disetronic H-TRON V-100, Minimed 507C pumps).¹⁶⁷

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

When insulin lispro is mixed with a longer-acting insulin preparation, insulin lispro should be drawn into the syringe first in order to prevent precipitation or turbidity of the insulin lispro solution by the longer-acting insulin.¹ Insulin mixtures should not be administered IV.¹

Should not dilute or mix insulin lispro with any other insulin when administered via an external sub-Q controlled-infusion device (pump).¹

Drug Compatibility

Admixture Compatibility 1

Compatible
Extended human insulin zinc
Insulin, isophane human (recombinant DNA origin)

ActionsActions

• 
  

  Facilitates cellular uptake of glucose in muscle and other tissues, except the brain.^{c d} Stimulates protein synthesis and inhibits protein catabolism.^{1 d}

  
  


• 
  

  Inhibits output of glucose from the liver.^{9 c d} In the liver, insulin facilitates phosphorylation of glucose to glucose-6-phosphate which is converted to glycogen or further metabolized.^d Promotes the conversion of excess glucose into fat.¹

  
  


• 
  

  Stimulates lipogenesis and inhibits lipolysis and release of free fatty acids from adipose cells.^d

  
  


• 
  

  Promotes an intracellular shift of potassium and thereby appears to temporarily decrease elevated blood concentrations of this ion.^d

  
  

Advice to Patients

• 
  

  Importance of providing the patient with a copy of the manufacturer’s patient information.^{1 2 23 26}

  
  


• 
  

  Importance of providing instructions regarding insulin storage, dosage, and proper injection technique.^{1 e}

  
  


• 
  

  Importance of strict adherence to manufacturer’s instructions regarding assembly, administration, and care of specialized delivery systems, such as insulin pens.^{72 144 145 e}

  
  


• 
  

  Importance of changing insulin preparation or dosage with caution and only under medical supervision.^{1 19 51} Discuss potential for alterations in insulin requirements and need for additional monitoring of blood glucose concentrations in special situations (e.g., illness, concomitant agents that alter glycemic control, travel, emotional disturbances, or other stresses).

  
  


• 
  

  Advise patients of the risks and advantages of conventional and intensive insulin therapy.

  
  


• 
  

  Importance of administering insulin lispro sub-Q within 15 minutes before or immediately after a meal.¹

  
  


• 
  

  Advise patient not to smoke within 30 minutes after insulin injection, due to potential for decreased absorption of insulin.^e

  
  


• 
  

  Importance of carefully advising patients of the differences in action profiles between insulin lispro and insulin human (regular) during transfer from insulin human to insulin lispro.^{1 74} May be necessary to adjust the consumption and/or timing of snacks or exercise to avoid hypoglycemic episodes and/or prevent preprandial hyperglycemia.^{1 74}

  
  


• 
  

  Importance of regular self monitoring of blood glucose concentrations.^{1 e} Particular importance of frequent self monitoring of blood glucose concentrations in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes.

  
  


• 
  

  Provide instructions regarding adherence to meal planning, regular physical exercise, periodic HbA_1c monitoring, and management of hypoglycemia or hyperglycemia.^{1 e}

  
  


• 
  

  Importance of wearing a medical identification bracelet or pendant, carrying ample insulin supply and syringes on trips, and having carbohydrates (sugar or candy) on hand for emergency.^e

  
  


• 
  

  Importance of not changing the order of mixing insulins or the model or brand of syringe or needle without medical supervision.^{1 e} When mixing with long-acting insulin preparations, importance of drawing insulin lispro into the syringe first.^e

  
  


• 
  

  Importance of informing clinicians of the development of generalized hypersensitivity reactions (shortness of breath, hypotension, wheezing, whole body rash, tachycardia, diaphoresis).¹

  
  


• 
  

  Importance of patients being aware of symptoms of diabetic ketoacidosis and the need to monitor blood ketones if preprandial blood glucose concentrations repeatedly exceed 250–300 mg/dL or if they have an acute illness. Importance of contacting a physician if results of self-monitored blood glucose concentrations are consistently abnormal.

  
  


• 
  

  Inform patient that use of marijuana may increase insulin requirements.^e

  
  


• 
  

  Instruct patient on the appropriate measures for safe disposal of needles.^e

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Insulin Lispro (Recombinant DNA Origin)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	100 units/mL	Humalog (with cresol, glycerin and zinc oxide; available as 1.5-mL cartridge, 3-mL disposable delivery device, and 10-mL vial)	Lilly

Insulin Lispro Combinations (Recombinant DNA Origin)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Suspension, Sterile	Insulin Lispro 25 units/mL with Insulin Lispro Protamine 75 units/mL	Humalog Mix 75/25 (with m-cresol, glycerin, and zinc oxide; available as 3-mL delivery device)	Lilly

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

HumaLOG 100UNIT/ML Solution (LILLY): 10/$125.99 or 30/$339.97

HumaLOG 100UNIT/ML Solution (LILLY): 15/$215.99 or 45/$625.97

HumaLOG KwikPen 100UNIT/ML Solution (LILLY): 15/$225.99 or 45/$629.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Eli Lilly and Company. Humalog (insulin lispro, [rDNA origin]) injection prescribing information. Indianapolis, IN; 2004 Jun 2.

2. Howey DC, Bowsher RR, Brunelle RL et al. [Lys (B28), Pro (B29)]-human insulin: a rapidly absorbed analogue of human insulin. Diabetes. 1994; 43:396-402. [IDIS 326178] [PubMed 8314011]

3. Howey DC, Bowsher RR, Brunelle RL et al. [Lys (B28), Pro (B29)]–human insulin: effect of injection time on postprandial glycemia. Clin Pharmacol Ther. 1995; 58:459-69. [IDIS 358235] [PubMed 7586939]

4. Chance RE, Dimarchi RD, Frank BH et al; Eli Lilly and Company, assignee. Preparation of insulin with modified association and biological properties. European Patent Application patent 383472. 1990 Aug 22.

5. Burge MR, Castillo KR, Schade DS. Meal composition is a determinant of lispro-induced hypoglycemia in IDDM. Diabetes Care. 1997; 20:152-5. [IDIS 380425] [PubMed 9118763]

6. Pampanelli S, Torlone E, Lalli C et al. Improved postprandial metabolic control after subcutaneous injection of a short-acting insulin analog in IDDM of short duration with residual pancreatic β-cell function. Diabetes Care. 1995; 18:1452-9. [IDIS 355473] [PubMed 8722069]

7. Buelke-Sam J, Byrd RA, Hoyt JA et al. A reproductive and developmental toxicity study in CD rats of LY275585, [Lys(B28),Pro(B29)]-human insulin. J Am Coll Toxicol. 1994; 13:247-60.

8. Ciszak E, Beals JM, Frank BH et al. Role of C-terminal B-chain residues in insulin assembly: the structure of hexameric Lys^B28Pro^B29-human insulin. Structure. 1995; 3:615-22. [PubMed 8590022]

9. Torlone E, Fanelli C, Rambotti AM et al. Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM. Diabetologia. 1994; 37:713-20. [PubMed 7958544]

10. Betz JL. Fast-acting human insulin analogs: a promising innovation in diabetes care. Diabetes Educ. 1995; 21:195, 197-8, 200. [PubMed 7758386]

11. Trautmann ME. Effect of the insulin analogue [LYS (B28),PRO(B29)] on blood glucose control. Horm Metab Res. 1994; 26:588-90. [PubMed 7705764]

12. Pfützner A, Küstner E, Forst T et al for the German Insulin Lispro/IDDM Study Group. Intensive insulin therapy with insulin lispro in patients with type 1 diabetes reduces the frequency of hypoglycemic episodes. Exp Clin Endocrinol Diabetes. 1996; 104:25-30.

13. Brems DN, Alter LA, Beckage MJ et al. Altering the association properties of insulin by amino acid replacement. Protein Eng. 1992; 5:527-33. [PubMed 1438163]

14. DiMarchi RD, Chance RE, Long HB et al. Preparation of an insulin with improved pharmacokinetics relative to human insulin through consideration of structural homology with insulin-like growth factor I. Horm Res. 1994; 41(Suppl 2):93-6. [PubMed 8088710]

15. Jacobs MAJM, Salobir B, Popp-Snijders C et al. Counterregulatory hormone responses and symptoms during hypoglycaemia induced by porcine, human regular insulin, and Lys(B28), Pro(B29) human insulin analogue (insulin lispro) in healthy male volunteers. Diabetic Med. 1997; 14:248-57. [PubMed 9088775]

16. Zimmermann J. A 12-month chronic toxicity study of LY275585 (human insulin analog) administered subcutaneously to Fischer 344 rats. Diabetes. 1994; 43(Suppl 1):166A.

17. Zwickl CM, Smith HW, Zimmermann JL et al. Immunogenicity of biosynthetic human LysPro insulin compared to native-sequence human and purified porcine insulins in Rhesus monkeys immunized over a 6-week period. Arzneimittelforschung. 1995; 45:524-8. [PubMed 7779155]

18. Slieker LJ, Brooke GS, Chance RE et al. Insulin and IGF-I analogs: novel approaches to improved insulin pharmacokinetics. In: LeRoith D, Raizada MK eds. Current directions in insulin-like growth factor research. New York: Plenum Press; 1994:25-32.

19. American Diabetes Association. Insulin administration. Diabetes Care. 1997; 20(Suppl 1):S46-9.

20. European IDDM Policy Group 1993. Consensus guidelines for the management of insulin-dependent (type 1) diabetes. Diabetic Med. 1993; 10:990-1005. [PubMed 8306599]

21. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329:977-86. [IDIS 320201] [PubMed 8366922]

22. Campbell PJ, May ME. A practical guide to intensive insulin therapy. Am J Med Sci. 1995; 310:24-30. [IDIS 351605] [PubMed 7604835]

23. Ziegler O, Kolopp M, Louis J et al. Self-monitoring of blood glucose and insulin dose alteration in type 1 diabetes mellitus. Diabetes Res Clin Pract. 1993; 21:51-9. [PubMed 8253023]

24. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 1997; 2000:23(Suppl 1):S32-42.

25. Olefsky JM. Diabetes mellitus. In: Wyngaarden JB, Smith LH Jr, Bennett JC, eds. Cecil textbook of medicine. 19th ed. Philadelphia: WB Saunders Company; 1992:1291-1310.

26. Mazze RS, Etzwiler

Glycotuss-DM

Generic Name: dextromethorphan and guaifenesin (DEX troe me THOR fan and gwye FEN e sin)

Brand Names: Allfen DM, Altarussin DM, Aquatab DM, Benylin Expectorant, Drituss DM, Extuss LA, Fenesin DM IR, Glycotuss-DM, Guaifen DM, Mucinex Children's Cough, Mucinex DM, MucusRelief DM, Naldecon DX Liquigel, Relacon LAX, Respa-DM, Robitussin Cough & Congestion, Tussi-Bid, Tussi-Organidin DM NR, Vicks 44E

What is Glycotuss-DM (dextromethorphan and guaifenesin)?

Dextromethorphan is a cough suppressant. It affects the signals in the brain that trigger cough reflex.

Guaifenesin is an expectorant. It helps loosen congestion in your chest and throat, making it easier to cough out through your mouth.

The combination of dextromethorphan and guaifenesin is used to treat cough and chest congestion caused by the common cold, infections, or allergies.

Dextromethorphan will not treat a cough that is caused by smoking, asthma, or emphysema.

Dextromethorphan and guaifenesin may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Glycotuss-DM (dextromethorphan and guaifenesin)?

Do not give this medication to a child younger than 2 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body. Do not use any other over-the-counter cough or cold medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of one or more types of medicine. Read the label of any other medicine you are using to see if it contains dextromethorphan or guaifenesin. Dextromethorphan will not treat a cough that is caused by smoking, asthma, or emphysema.

What should I discuss with my healthcare provider before taking Glycotuss-DM (dextromethorphan and guaifenesin)?

Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body.

Ask a doctor or pharmacist if it is safe for you to take this medication if you have emphysema or chronic bronchitis.

FDA pregnancy category C. It is not known whether dextromethorphan and guaifenesin is harmful to an unborn baby. Before you take this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether this medication passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cold medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take Glycotuss-DM (dextromethorphan and guaifenesin)?

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 2 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Measure the liquid form of this medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time.

Dextromethorphan and guaifenesin granules should be sprinkled directly onto the tongue and swallowed right away.

Drink extra fluids to help loosen the congestion and lubricate your throat while you are taking this medication. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

If you need to have any type of surgery, tell the surgeon ahead of time if you have taken a cold medicine within the past few days.

Store this medicine at room temperature, away from heat, light, and moisture.

What happens if I miss a dose?

Since cough or cold medicine is usually taken only as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include feeling restless or nervous.

What should I avoid while taking Glycotuss-DM (dextromethorphan and guaifenesin)?

This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of this medication.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with cough or cold medicine can increase your risk of unpleasant side effects.

Do not use any other over-the-counter cough or cold medication without first asking your doctor or pharmacist. Dextromethorphan and guaifenesin are contained in many medicines available over the counter. If you take certain products together you may accidentally take too much of one or more types of medicine. Read the label of any other medicine you are using to see if it contains dextromethorphan or guaifenesin.

Glycotuss-DM (dextromethorphan and guaifenesin) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

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  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


• 
  

  confusion, hallucinations; or

  
  


• 
  

  slow, shallow breathing.

  
  

Less serious side effects may include:

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  dizziness;

  
  


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  headache;

  
  


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  skin rash or itching; or

  
  


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  nausea, vomiting, or stomach upset.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Glycotuss-DM (dextromethorphan and guaifenesin)?

Before taking this medication, tell your doctor if you are using any of the following drugs:

• 
  

  celecoxib (Celebrex);

  
  


• 
  

  cinacalcet (Sensipar);

  
  


• 
  

  darifenacin (Enablex);

  
  


• 
  

  imatinib (Gleevec);

  
  


• 
  

  quinidine (Quinaglute, Quinidex);

  
  


• 
  

  ranolazine (Ranexa);

  
  


• 
  

  ritonavir (Norvir);

  
  


• 
  

  sibutramine (Meridia);

  
  


• 
  

  terbinafine (Lamisil);

  
  


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  medicines to treat high blood pressure; or

  
  


• 
  

  an antidepressant such as amitriptyline (Elavil, Etrafon), bupropion (Wellbutrin, Zyban), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), imipramine (Janimine, Tofranil), paroxetine (Paxil), sertraline (Zoloft), and others.

  
  

This list is not complete and there may be other drugs that can interact with dextromethorphan and guaifenesin. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Glycotuss-DM resources

• Glycotuss-DM Side Effects (in more detail)
• Glycotuss-DM Use in Pregnancy & Breastfeeding
• Glycotuss-DM Drug Interactions
• Glycotuss-DM Support Group
• 0 Reviews for Glycotuss-DM - Add your own review/rating

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• Guaifenesin DM Elixir MedFacts Consumer Leaflet (Wolters Kluwer)


• Humibid CS MedFacts Consumer Leaflet (Wolters Kluwer)


• Mucinex DM Prescribing Information (FDA)


• Mucinex DM Maximum Strength Prescribing Information (FDA)


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• Scot-Tussin DM Liquid MedFacts Consumer Leaflet (Wolters Kluwer)


• Tussin DM Prescribing Information (FDA)

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• Cough
• Expectoration

Where can I get more information?

• Your pharmacist can provide more information about dextromethorphan and guaifenesin.

See also: Glycotuss-DM side effects (in more detail)

Uritact DS

Pronunciation: A-troe-peen/ben-ZOE-ik AS-id/hye-oh-SYE-a-meen/meth-EN-a-meen/METH-i-leen/FEN-ill sa-LI-si-late
Generic Name: Atropine/Benzoic Acid/Hyoscyamine/Methenamine/Methylene Blue/Phenyl Salicylate
Brand Name: Examples include Prosed/DS and Uritact DS

Uritact DS is used for:

Treating painful and irritating symptoms of the urinary tract due to urinary tract infections or diagnostic procedures.

Uritact DS is a urinary antiseptic, urinary acidifier, analgesic, and anticholinergic combination. It works by helping to kill bacteria in the urine, decreasing pain and inflammation, and reducing muscle spasms in the urinary tract. These actions work together to help relieve discomfort while urinating.

Do NOT use Uritact DS if:

• you are allergic to any ingredient in Uritact DS


• you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to aspirin, other salicylate medicines, or a nonsteroidal anti-inflammatory drug (NSAID) (eg, ibuprofen, naproxen, celecoxib)


• you have angle-closure glaucoma, problems with your esophagus, bowel motility problems, a blockage of your bladder or bowel, severe intestinal problems (eg, ulcerative colitis), severe bleeding, flu or chickenpox, myasthenia gravis, severe kidney problems, or you are severely dehydrated


• you are taking a sulfonamide (eg, sulfamethoxazole)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Uritact DS:

Some medical conditions may interact with Uritact DS. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have constipation, diarrhea, an infection of the stomach or bowel, a hiatal hernia, or stomach ulcers


• if you have nervous system problems, glucose-6-phosphate-dehydrogenase (G-6-PD) deficiency, gout, influenza, Kawasaki syndrome, rheumatic disease, open-angle glaucoma, risk factors for angle-closure glaucoma, kidney or liver problems, an enlarged prostate, bladder problems, or you are unable to urinate


• if you have a history of stroke or brain blood vessel problems (eg, aneurysm), an irregular heartbeat, heart blood vessel problems, congestive heart failure, heart valve problems, or other heart problems


• if you are on a low-salt diet

Some MEDICINES MAY INTERACT with Uritact DS. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticholinergics (eg, benztropine) because they may increase the risk of Uritact DS's side effects.


• Ketoconazole because it may decrease Uritact DS's effectiveness.


• Monoamine oxidase inhibitorss(MAOIs) or narcotic pain medicine (eg, codeine) because the risk of serious side effects may be increased


• Medicine for myasthenia gravis (eg, ambenonium), phenothiazines (eg, chlorpromazine), sulfonamides (eg, sulfamethoxazole), thiazide diuretics (eg, hydrochlorothiazide), or urinary alkalinizers (eg, sodium bicarbonate) because their effectiveness may be decreased by Uritact DS

This may not be a complete list of all interactions that may occur. Ask your health care provider if Uritact DS may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Uritact DS:

Use Uritact DS as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Uritact DS by mouth with or without food.


• Do not take an antacid or antidiarrheal medicine (eg, loperamide) within 1 hour before or after you take Uritact DS.


• Drinking extra fluids while you are taking Uritact DS is recommended. Check with your doctor for instructions.


• If you miss a dose of Uritact DS, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Uritact DS.

Important safety information:

• Uritact DS may cause dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Uritact DS with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do NOT take more than the recommended dose or use more often than prescribed without checking with your doctor.


• Uritact DS may discolor the urine or stools a blue-green color. This is normal and not a cause for concern.


• Uritact DS contains a salicylate. Salicylates have been linked to a serious illness called Reye syndrome. Do not give Uritact DS to a child or teenager who has the flu, chickenpox, or a viral infection. Contact your doctor with any questions or concerns.


• Use Uritact DS with caution in the ELDERLY; they may be more sensitive to its effects, especially excitement, agitation, drowsiness, and confusion.


• Uritact DS should not be used in CHILDREN younger than 6 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: It is not known if Uritact DS can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Uritact DS while you are pregnant. The medicine is found in breast milk. If you are or will be breast-feeding while you use Uritact DS, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Uritact DS:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Dry mouth; flushing; nausea; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blurred vision; difficulty urinating; dizziness; fast or irregular heartbeat.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Uritact DS side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Uritact DS:

Store Uritact DS between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Brief excursions at temperatures between 59 and 86 degrees F (15 and 30 degrees C) are permitted. . Store away from heat, moisture, and light. Do not store in the bathroom. Keep Uritact DS out of the reach of children and away from pets.

General information:

• If you have any questions about Uritact DS, please talk with your doctor, pharmacist, or other health care provider.


• Uritact DS is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Uritact DS. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Uritact DS resources

• Uritact DS Side Effects (in more detail)
• Uritact DS Use in Pregnancy & Breastfeeding
• Uritact DS Drug Interactions
• Uritact DS Support Group
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• Urinary Tract Infection

Labetalol

Generic Name: Labetalol hydrochloride

Dosage Form: injection
Labetalol Hydrochloride Injection, USP

(For IV Use Only)

SAGENT™

Rx only

DESCRIPTION

Labetalol hydrochloride injection, USP is 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 2-hydroxy-5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]benzamide monohydrochloride, and it has the following structure:

Labetalol HCl has the molecular 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 HCl is a white or off-white powder, soluble in water.

Labetalol hydrochloride injection is a clear, colorless to light yellow, aqueous, sterile, isotonic solution for intravenous (IV) injection. It has a pH range of 3.0 to 4.5. Each milliliter contains 5 mg of Labetalol HCl, 45 mg of anhydrous dextrose, 0.1 mg of edetate disodium; 0.8 mg of methylparaben and 0.1 mg of propylparaben as preservatives; and anhydrous citric acid and sodium hydroxide, as necessary, to bring the solution into the pH range.

CLINICAL PHARMACOLOGY

Labetalol HCl combines both selective, competitive, alpha1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta-blockade have been estimated to be approximately 1:3 and 1:7 following oral and IV administration, respectively. 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.

Pharmacodynamics

The capacity of Labetalol HCl 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 HCl'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 HCl contribute to a decrease in blood pressure in hypertensive patients. Labetalol HCl 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 HCl dosing.

Single oral doses of Labetalol HCl 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 HCl slightly prolonged A-V nodal conduction time and atrial effective refractory period with only small changes in heart rate. The effects on A-V nodal refractoriness were inconsistent.

Labetalol HCl 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.

Doses of Labetalol HCl that controlled hypertension did not affect renal function in mildly to severely hypertensive patients with normal renal function.

Due to the alpha1-receptor blocking activity of Labetalol HCl, blood pressure is lowered more in the standing than in the supine position, and symptoms of postural hypotension can occur. During dosing with IV Labetalol HCl, the contribution of the postural component should be considered when positioning the patients for treatment, and the patient should not be allowed to move to an erect position unmonitored until their ability to do so is established.

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 IV 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 IV 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.

Exacerbation of angina and, in some cases, myocardial infarction and ventricular dysrhythmias have been reported after abrupt discontinuation of therapy with beta-adrenergic blocking agents in patients with coronary artery disease. Abrupt withdrawal of these agents in patients without coronary artery disease has resulted in transient symptoms, including tremulousness, sweating, palpitation, headache, and malaise. Several mechanisms have been proposed to explain these phenomena, among them increased sensitivity to catecholamines because of increased numbers of beta receptors.

Although beta-adrenergic receptor blockade is useful in the treatment of angina and hypertension, there are also situations in which sympathetic stimulation is vital. For example, in patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. Beta-adrenergic blockade may worsen A-V block by preventing the necessary facilitating effects of sympathetic activity on conduction. Beta2-adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm, and it may also interfere with exogenous bronchodilators in such patients.

Pharmacokinetics and Metabolism

Following IV infusion of Labetalol, the elimination half-life is about 5.5 hours and the total body clearance is approximately 33 mL/min/kg. The plasma half-life of Labetalol following oral administration is about 6 to 8 hours. 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.

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

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 HCl from the general circulation (<1%).

INDICATIONS AND USAGE

Labetalol hydrochloride injection is indicated for control of blood pressure in severe hypertension.

CONTRAINDICATIONS

Labetalol hydrochloride injection is contraindicated in bronchial asthma, overt cardiac failure, greater-than-first-degree heart block, cardiogenic shock, severe bradycardia, other conditions associated with severe and prolonged hypotension, and in patients with a history of hypersensitivity to any component of the product (see WARNINGS).

Beta-blockers, even those with apparent cardioselectivity, should not be used in patients with a history of obstructive airway disease, including asthma.

WARNINGS

Hepatic Injury

Severe hepatocellular injury, confirmed by rechallenge in at least one case, occurs rarely with Labetalol therapy. The hepatic injury is usually reversible, but hepatic necrosis and death have been reported. Injury has occurred after both short- and long-term treatment and may be slowly progressive despite minimal symptomatology. Similar hepatic events have been reported with a related compound, dilevalol HCl, including two deaths. Dilevalol HCl is one of the four isomers of Labetalol HCl. Thus, for patients taking Labetalol, periodic determination of suitable hepatic laboratory tests would be appropriate. Laboratory testing should be done at the very first symptom or sign of liver dysfunction (e.g., pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness, or unexplained “flu-like” symptoms). If the patient has laboratory evidence of liver injury or jaundice, Labetalol should be stopped and not restarted.

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. Although beta-blockers should be avoided in overt congestive heart failure, if necessary, Labetalol HCl can be used with caution in patients with a history of heart failure who are well compensated.

Congestive heart failure has been observed in patients receiving Labetalol HCl. Labetalol HCl does not abolish the inotropic action of digitalis on heart muscle.

In Patients without a History of Cardiac Failure

In patients with latent cardiac insufficiency, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or be given a diuretic, and the response should be observed closely. If cardiac failure continues despite adequate digitalization and diuretic, therapy with Labetalol hydrochloride should be withdrawn (gradually, if possible).

Ischemic Heart Disease

Angina pectoris has not been reported upon Labetalol HCl discontinuation. However, following abrupt cessation of therapy with some beta-blocking agents in patients with coronary artery disease, exacerbations of angina pectoris and, in some cases, myocardial infarction have been reported. Therefore, such patients should be cautioned against interruption of therapy without the physician's advice. Even in the absence of overt angina pectoris, when discontinuation of Labetalol hydrochloride injection is planned, the patient should be carefully observed and should be advised to limit physical activity. If angina markedly worsens or acute coronary insufficiency develops, administration of Labetalol hydrochloride injection should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken.

Nonallergic Bronchospasm (e.g., Chronic Bronchitis and Emphysema)

Since Labetalol hydrochloride injection at the usual IV therapeutic doses has not been studied in patients with nonallergic bronchospastic disease, it should not be used in such patients.

Pheochromocytoma

Intravenous Labetalol HCl 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, use caution when administering Labetalol HCl to patients with pheochromocytoma.

Diabetes Mellitus and Hypoglycemia

Beta-adrenergic blockade may prevent the appearance of premonitory signs and symptoms (e.g., tachycardia) of acute hypoglycemia. This is especially important with labile diabetics. Beta-blockade also reduces the release of insulin in response to hyperglycemia; it may therefore be necessary to adjust the dose of antidiabetic drugs.

Major Surgery

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.

Several deaths have occurred when Labetalol hydrochloride injection was used during surgery (including when used in cases to control bleeding).

A synergism between Labetalol HCl and halothane anesthesia has been shown (see PRECAUTIONS: Drug Interactions).

Rapid Decreases of Blood Pressure

Caution must be observed when reducing severely elevated blood pressure. A number of adverse reactions, including cerebral infarction, optic nerve infarction, angina, and ischemic changes in the electrocardiogram, have been reported with other agents when severely elevated blood pressure was reduced over time courses of several hours to as long as 1 or 2 days. The desired blood pressure lowering should therefore be achieved over as long a period of time as is compatible with the patient's status.

PRECAUTIONS

General

Impaired Hepatic Function

Labetalol hydrochloride injection should be used with caution in patients with impaired hepatic function since metabolism of the drug may be diminished.

Intraoperative Floppy Iris Syndrome (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. The patient's ophthalmologist should be prepared for possible modifications to the surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances. There does not appear to be benefit of stopping alpha-1 blocker therapy prior to cataract surgery.

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 hydrochloride injection. Therefore, the patient's ability to tolerate an upright position should be established before permitting any ambulation.

Following Coronary Artery Bypass Surgery

In one uncontrolled study, patients with low cardiac indices and elevated systemic vascular resistance following intravenous Labetalol HCl experienced significant declines in cardiac output with little change in systemic vascular resistance. One of these patients developed hypotension following Labetalol treatment. Therefore, use of Labetalol HCl should be avoided in such patients.

High Dose Labetalol

Administration of up to 3 g/d as an infusion for up to 2 to 3 days has been anecdotally reported; several patients have experienced hypotension or bradycardia (see DOSAGE AND ADMINISTRATION ).

Jaundice or Hepatic Dysfunction (see WARNINGS).

Information for Patients

The following information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects. During and immediately following (for up to 3 hours) Labetalol hydrochloride injection, the patient should remain supine. Subsequently, the patient should be advised on how to proceed gradually to become ambulatory and should be observed at the time of first ambulation.

When the patient is started on Labetalol hydrochloride tablets following adequate control of blood pressure with Labetalol hydrochloride injection, appropriate directions for titration of dosage should be provided (see DOSAGE AND ADMINISTRATION).

As with all drugs with beta-blocking activity, certain advice to patients being treated with Labetalol HCl is warranted. While no incident of the abrupt withdrawal phenomenon (exacerbation of angina pectoris) has been reported with Labetalol HCl, dosing with Labetalol hydrochloride tablets should not be interrupted or discontinued without a physician's advice. Patients being treated with Labetalol hydrochloride tablets should consult a physician at any signs or symptoms of impending cardiac failure or hepatic dysfunction (see WARNINGS). Also, transient scalp tingling may occur, usually when treatment with Labetalol hydrochloride tablets is initiated (see ADVERSE REACTIONS).

Laboratory Tests

Routine laboratory tests are ordinarily not required before or after IV Labetalol HCl. In patients with concomitant illnesses, such as impaired renal function, appropriate tests should be done to monitor these conditions.

Drug Interactions

Since Labetalol hydrochloride injection may be administered to patients already being treated with other medications, including other antihypertensive agents, careful monitoring of these patients is necessary to detect and treat promptly any undesired effect from concomitant administration.

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

Drugs possessing beta-blocking properties can blunt the bronchodilator effect of beta-receptor agonist drugs in patients with bronchospasm; therefore, doses greater than the normal antiasthmatic dose of beta-agonist bronchodilator drugs may be required.

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

Synergism has been shown between halothane anesthesia and intravenously administered Labetalol HCl. During controlled hypotensive anesthesia using Labetalol HCl 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. The anesthesiologist should be informed when a patient is receiving Labetalol HCl.

Labetalol HCl blunts the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effect. If Labetalol HCl is used with nitroglycerin in patients with angina pectoris, additional antihypertensive effects may occur.

Care should be taken if Labetalol is used concomitantly with calcium antagonists of the verapamil type.

When drug products that are alkaline, such as furosemide, have been administered in combination with Labetalol, a white precipitate has been noted. Therefore, these drugs should not be administered in the same infusion line.

Risk of Anaphylactic Reaction

While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

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 HCl, a specific method, such as a high performance liquid chromatographic assay with solid phase extraction (e.g., J Chromatogr. 385:241,1987) should be employed in determining levels of catecholamines.

Labetalol HCl 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 Toxi-Lab A® (thin-layer chromatographic assay) and Emit-d.a.u.® (radioenzymatic assay). When patients being treated with Labetalol have a positive urine test for amphetamine using these techniques, confirmation should be made by using more specific methods, such as a gas chromatographic-mass spectrometer technique.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

Pregnancy

Teratogenic Effects - Pregnancy Category C

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 IV doses up to 1.7 times the MRHD revealed no evidence of drug-related harm to the fetus. There are no adequate and well-controlled studies in pregnant women. Labetalol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Hypotension, bradycardia, hypoglycemia, and respiratory depression have been reported in infants of mothers who were treated with Labetalol HCl for hypertension during pregnancy. 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.

Labor and Delivery

Labetalol HCl given to pregnant women with hypertension did not appear to affect the usual course of labor and delivery.

Nursing Mothers

Small amounts of Labetalol (approximately 0.004% of the maternal dose) are excreted in human milk. Caution should be exercised when Labetalol hydrochloride injection is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Adverse Reactions

Labetalol hydrochloride injection is usually well tolerated. Most adverse effects have been mild and transient and, in controlled trials involving 92 patients, did not require Labetalol HCl 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 hydrochloride 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 hydrochloride 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 in 7, hypoesthesia (numbness) and vertigo in 1 each.

Gastrointestinal System

Nausea in 13, vomiting in 4, dyspepsia and taste distortion in 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 HCl. The largest experience is with oral Labetalol HCl (see Labetalol HCl tablet product information for details). Certain of the side effects increased with increasing oral dose, as shown in the following table that 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
Paresthesia	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 HCl during investigational use and extensive foreign marketing experience.

Clinical Laboratory Tests

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

OVERDOSAGE

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. 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. The following additional measures should be employed if necessary: Excessive bradycardia—administer atropine or epinephrine. Cardiac failure—administer a digitalis glycoside and a diuretic. Dopamine or dobutamine may also be useful. Hypotension—administer vasopressors, e.g., norepinephrine. There is pharmacologic evidence that norepinephrine may be the drug of choice. Bronchospasm—administer epinephrine and/or an aerosolized beta2-agonist. Seizures—administer diazepam.

In severe beta-blocker overdose resulting in hypotension and/or bradycardia, glucagon has been shown to be effective when administered in large doses (5 to 10 mg rapidly over 30 seconds, followed by continuous infusion of 5 mg/hr that can be reduced as the patient improves).

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 IV LD50 in these species is 50 to 60 mg/kg.

DOSAGE AND ADMINISTRATION

Labetalol hydrochloride injection is intended for IV use in hospitalized patients. DOSAGE MUST BE INDIVIDUALIZED depending upon the severity of hypertension and the response of the patient during dosing.

Patients should always be kept in a supine position during the period of IV drug administration. A substantial fall in blood pressure on standing should be expected in these patients. The patient's ability to tolerate an upright position should be established before permitting any ambulation, such as using toilet facilities.

Either of two methods of administration of Labetalol hydrochloride injection may be used: a) repeated IV injection, or b) slow continuous infusion.

Repeated Intravenous Injection

Initially, Labetalol hydrochloride injection should be given in a 20 mg dose (which corresponds to 0.25 mg/kg for an 80 kg patient) by slow IV injection over a 2-minute period.

Immediately before the injection and at 5 and 10 minutes after injection, supine blood pressure should be measured to evaluate response. Additional injections of 40 or 80 mg can be given at 10-minute intervals until a desired supine blood pressure is achieved or a total of 300 mg of Labetalol HCl has been injected. The maximum effect usually occurs within 5 minutes of each injection.

Slow Continuous Infusion

Labetalol hydrochloride injection is prepared for continuous IV infusion by diluting the vial contents with commonly used IV fluids (see below). Examples of two methods of preparing the infusion solution are:

Add 40 mL of Labetalol hydrochloride injection to 160 mL of a commonly used IV fluid such that the resultant 200 mL of solution contains 200 mg of Labetalol HCl, 1 mg/mL. The diluted solution should be administered at a rate of 2 mL/min to deliver 2 mg/min.

Alternatively, add 40 mL of Labetalol hydrochloride injection to 250 mL of a commonly used IV fluid. The resultant solution will contain 200 mg of Labetalol HCl, approximately 2 mg/3 mL. The diluted solution should be administered at a rate of 3 mL/min to deliver approximately 2 mg/min.

The rate of infusion of the diluted solution may be adjusted according to the blood pressure response, at the discretion of the physician. To facilitate a desired rate of infusion, the diluted solution can be infused using a controlled administration mechanism, e.g., graduated burette or mechanically driven infusion pump.

Since the half-life of Labetalol is 5 to 8 hours, steady-state blood levels (in the face of a constant rate of infusion) would not be reached during the usual infusion time period. The infusion should be continued until a satisfactory response is obtained and should then be stopped and oral Labetalol HCl started (see below). The effective IV dose is usually in the range of 50 to 200 mg. A total dose of up to 300 mg may be required in some patients.

Blood Pressure Monitoring

The blood pressure should be monitored during and after completion of the infusion or IV injection. Rapid or excessive falls in either systolic or diastolic blood pressure during IV treatment should be avoided. In patients with excessive systolic hypertension, the decrease in systolic pressure should be used as an indicator of effectiveness in addition to the response of the diastolic pressure.

Initiation of Dosing with Labetalol Tablets

Subsequent oral dosing with Labetalol tablets should begin when it has been established that the supine diastolic blood pressure has begun to rise. The recommended initial dose is 200 mg, followed in 6 to 12 hours by an additional dose of 200 or 400 mg, depending on the blood pressure response. Thereafter, inpatient titration with Labetalol tablets may proceed as follows:

Inpatient Titration Instructions

*If needed, the total daily dose may be given in three divided doses.
Regimen	Daily Dose*
200 mg b.i.d.	400 mg
400 mg b.i.d.	800 mg
800 mg b.i.d.	1600 mg
1200 mg b.i.d.	2400 mg

The dosage of Labetalol tablets used in the hospital may be increased at 1-day intervals to achieve the desired blood pressure reduction.

For subsequent outpatient titration or maintenance dosing, see DOSAGE AND ADMINISTRATION in the Labetalol tablets Product Information for additional recommendations.

Compatibility with commonly used intravenous fluids

Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

Labetalol hydrochloride injection was tested for compatibility with commonly used IV fluids at final concentrations of 1.25 to 3.75 mg of Labetalol HCl per milliliter of the mixture. Labetalol hydrochloride injection was found to be compatible with and stable (for 24 hours refrigerated or at room temperature) in mixtures with the following solutions:

Ringer's Injection, USP

Lactated Ringer's Injection, USP

5% Dextrose and Ringer's Injection

5% Lactated Ringer's and 5% Dextrose Injection

5% Dextrose Injection, USP

0.9% Sodium Chloride Injection, USP

5% Dextrose and 0.2% Sodium Chloride Injection, USP

2.5% Dextrose and 0.45% Sodium Chloride Injection, USP

5% Dextrose and 0.9% Sodium Chloride Injection, USP

5% Dextrose and 0.33% Sodium Chloride Injection, USP.

Labetalol hydrochloride injection was NOT compatible with 5% sodium bicarbonate injection, USP. Care should be taken when administering alkaline drugs, including furosemide, in combination with Labetalol. Compatibility should be assured prior to administering these drugs together.

HOW SUPPLIED

Labetalol Hydrochloride Injection, USP is supplied as follows:

NDC	Labetalol Hydrochloride Injection, USP	Package Factor
	(5 mg per mL)
25021-300-20	100 mg per 20 mL Multi-Dose Vial	1 vial per carton
25021-300-40	200 mg per 40 mL Multi-Dose Vial	1 vial per carton

Storage Conditions

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Do not freeze.

Protect from light. Retain in carton until time of use.

LATEX-FREE

Sterile, Nonpyrogenic.

SAGENT™

Mfd. for SAGENT Pharmaceuticals

Schaumburg, IL 60195 (USA)

Made in India

©2011 Sagent Pharmaceuticals, Inc.

Revised: January 2011

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – VIAL LABEL

NDC 25021-300-20

Labetalol Hydrochloride Injection, USP 100 mg per 20 mL* (5 mg per mL*)

Rx only

20 mL Multi-Dose Vial

For IV Use Only

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – VIAL LABEL

NDC 25021-300-40

Labetalol Hydrochloride Injection, USP 200 mg per 40 mL* (5 mg per mL*)

Rx only

40 mL Multi-Dose Vial

For IV Use Only

Labetalol  Labetalol hydrochloride  injection

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 25021-300 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Labetalol Hydrochloride (Labetalol) Labetalol Hydrochloride 5 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength Anhydrous Dextrose 45 mg  in 1 mL Edetate Disodium 0.10 mg  in 1 mL Methylparaben 0.80 mg  in 1 mL Propylparaben 0.10 mg  in 1 mL Citric Acid Monohydrate   Sodium Hydroxide

Product Characteristics Color