SUMMARY PRODUCT INFORMATION 3 INDICATIONS AND CLINICAL USE 3 CONTRAINDICATIONS 4 WARNINGS AND PRECAUTIONS 4 ADVERSE REACTIONS 8 DRUG INTERACTIONS 9 DOSAGE AND ADMINISTRATION 12 OVERDOSAGE 14 ACTION AND CLINICAL PHARMACOLOGY 14 STORAGE AND STABILITY 15 DOSAGE FORMS, COMPOSITION AND PACKAGING 15

PART II: SCIENTIFIC INFORMATION 16

PHARMACEUTICAL INFORMATION 16 CLINICAL TRIALS 17 DETAILED PHARMACOLOGY 17 TOXICOLOGY 17 REFERENCES 19

PART III: CONSUMER INFORMATION. 21

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

INDICATIONS AND CLINICAL USE

DIAbETA(r) (glyburide) is indicated: DIAbETA(r) (glyburide) is indicated as an adjunct to proper dietary management, exercise and weight reduction to lower blood glucose in adult patients with type 2 diabetes whose hyperglycemia cannot be controlled by diet and exercise alone or when insulin therapy is not required.

Pediatrics (<18 years of age)

Safety and effectiveness of DIAbETA(r) (glyburide) has not been established. Use in patients under 18 years of age is not recommended (see WARNING AND PRECAUTIONS, Special Populations).

Geriatrics

Elderly with type 2 diabetes when treated with DIAbETA(r) (glyburide) are more prone to hypoglycemia (see WARNINGS AND PRECAUTIONS, Special Populations).

CONTRAINDICATIONS

During pregnancy, no oral antidiabetic agent should be given. Due to the possible excretion in human milk, the patient should discontinue nursing or discontinue taking the drug depending on the importance of the drug to the mother. If glyburide is discontinued, the patient should be transferred to insulin therapy.

WARNINGS AND PRECAUTIONS

Use of DIAbETA(r) must be viewed by both the physician and patient as a treatment in addition to diet and exercise and not as a substitute for proper dietary management, exercise and weight reduction or as a convenient mechanism for avoiding dietary restraint. Furthermore, loss of blood glucose control on diet and exercise alone may be transient, thus requiring only short-term administration of DIAbETA(r). As is necessary during treatment with any blood-glucose-lowering drug, the patient and the physician must be aware of the risk of hypoglycemia. In initiating treatment for type 2 diabetes, non-pharmacologic therapy (proper dietary management, exercise and weight reduction) should be emphasized as the initial form of treatment. Caloric restriction, weight loss and exercise are essential in the obese diabetic patient. Proper dietary management and exercise alone may be effective in controlling the blood glucose and symptoms of hyperglycemia. If non-pharmacologic therapy fails to reduce symptoms and/or blood glucose, the use of an oral sulfonylurea should be considered.

Careful selection of patients is important. It is recommended that response to sulfonylurea be measured as increased C-peptide. Those patients who do not respond with increased C-peptide will be less likely to show improvement. It is imperative that there be careful ongoing attention to diet, adherence to regular exercise, reduction of body weight in obese patients, careful adjustment of dosage, instruction of the patient on hypoglycemic reactions and their control as well as regular, thorough follow-up examinations. Cardiovascular risk factors should be identified. The effectiveness of any oral hypoglycemic drug, including DIAbETA(r), in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of the diabetes or to diminished responsiveness to the drug. This phenomenon, known as secondary failure, is distinctive of primary failure in which the drug is ineffective in an individual patient when given for the first time. Patients should therefore be monitored with regular clinical and laboratory evaluations, including blood glucose and glycosylated hemoglobin (AlC) determinations, to determine the minimum effective dosage and to detect primary failure (inadequate lowering of blood glucose concentrations at the maximum recommended dosage) or secondary failure (progressive deterioration in blood sugar control following an initial period of effectiveness). The rate of primary failure will vary greatly depending upon patient selection and adherence to diet and exercise. The etiology of secondary failure is multifactorial and may involve progressive b-cell failure as well as exogenous diabetogenic factors such as obesity, illness, drugs, or tachyphylaxis to the sulfonylurea.

Loss of control of blood glucose:

If loss of adequate blood glucose lowering response to sulfonylurea is detected, treatment must be reassessed.

When a patient stabilized on any diabetic regimen is exposed to stress such as illness during therapy, fever, trauma, infection, or surgery, a loss of glycemic control may occur. At such times, it may be necessary to adjust the dosage of DIAbETA(r) or consider discontinuation of DIAbETA(r) and administration of insulin.

Treatment of patients with glucose-6-phosphate dehydrogenase (G6PD)-deficiency with sulfonylurea agents can lead to hemolytic anemia. Since DIAbETA(r) belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD-deficiency and a nonsulfonylurea alternative should be considered.

Hypoglycemia, sometimes prolonged and even life-threatening, may occur as a result of the blood-glucose-lowering action of DIAbETA(r). Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes. Hepatic and/or renal disease, inadequate caloric intake, malnutrition and/or irregular meals, exercise without adequate caloric supplementation, debility, advanced age, patient non-compliance, when alcohol is ingested, certain disorders of thyroid function, adrenal or pituitary insufficiency, excessive glyburide dosage, treatment with glyburide in the absence of indication or concurrent use with other agents with blood glucose lowering potential (see Drug-Drug Interactions) may be predisposing factors. Oral hypoglycemic agents should be administered with caution to patients with Addison's disease. The manifestations of hypoglycemia include: flushing or pallor, chilliness, excessive hunger, trembling, headache, dizziness, nausea, vomiting, restlessness, aggressiveness, depression, speech disorders, aphasia, sensory and/or visual disturbances, helplessness, lassitude, shallow respiration or bradycardia. In more severe cases, the clinical symptoms of a stroke or coma appear. However, symptoms of hypoglycemia are not necessarily as typical as described above and sulphonylureas may cause insidious development of symptoms mimicking cerebrovascular insufficiency (e.g. disordered sleep, somnolence, impaired alertness and reactions, confusion, delirium, cerebral convulsions, paralytic symptoms or loss of consciousness). Signs of adrenergic counter-regulation to hypoglycemia include: sweating, damp skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris, and cardiac arrhythmias. However, these symptoms may be milder or absent in patients who develop hypoglycemia gradually, patients with autonomic neuropathy, elderly or patients who receive concurrent treatment with sympatholytic agents (e.g. beta blockers, clonidine, reserpine, guanethidine) (see Drug-Drug Interactions). Mild to moderate episodes of hypoglycemia can usually be treated with oral carbohydrates. Artificial sweeteners are ineffective in controlling hypoglycemia. The symptoms of hypoglycemia nearly always subside when hypoglycemia is corrected. Severe hypoglycemia, which may be prolonged and has occasionally been life-threatening, may occur and mimics acute CNS disorders. Signs of severe hypoglycemia can include disorientation, loss of consciousness, and seizures. Severe hypoglycemia, or a protracted episode, which can only be temporarily controlled by usual amounts of sugar requires in-patient hospital care.

Some literature studies have suggested an association between the use of sulfonylureas and the risk of cardiovascular adverse events including cardiovascular mortality, since these agents may potentially impair cardioprotective processes. Although, there is inconsistency in the literature regarding a definite conclusion for this association, a cautious approach is nevertheless warranted. All patients on sulfonylureas, particularly high risk patients with cardiovascular disease, should be closely monitored for cardiovascular complications.

The metabolism and excretion of sulfonylureas including DIAbETA(r) may be slowed in patients with impaired hepatic function (see Monitoring and Laboratory Tests below).

In patients with renal insufficiency, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions.

The use of DIAbETA(r) is contraindicated for women planning a pregnancy (see CONTRAINDICATIONS). Recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities. Experts, including the Canadian Diabetes Association and the Canadian Medical Association recommend that insulin be used during pregnancy to maintain glucose levels as close to normal as possible.

Nursing women:

The use of DIAbETA(r) is contraindicated in lactating women (see CONTRAINDICATION).

Pediatrics:

Safety and effectiveness of DIAbETA(r) (glyburide) has not been established. Use in patients under 18 years of age is not recommended.

Geriatrics:

Fasting blood glucose should be monitored periodically to determine therapeutic response. Glycosylated hemoglobin (HbA1C) should also be monitored, usually every 3 to 6 months, to more precisely assess long-term glycemic control. Hepatic function should be assessed before initiating therapy and periodically in patients with impaired hepatic function. In patients with impaired renal function, blood and urine glucose should be regularly monitored. Elderly patients (malnourished, with impaired hepatic, renal, or adrenal function) will require periodic monitoring and special care. Periodic assessment of cardiovascular, ophthalmic, hematologic, renal and hepatic status is recommended.

ADVERSE REACTIONS

Adverse Drug Reaction Overview

The most commonly occurring significant adverse event of sulfonylureas (including glyburide) is hypoglycemia (see WARNINGS AND PRECAUTIONS).

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

Less Common Clinical Trial Adverse Drug Reactions (<1%)

Endocrine and Metabolism:

Reduced radioactive iodine uptake by the thyroid gland has been reported with oral hypoglycemic therapy. Hepatic porphyria and disulfiram-like reactions have been observed in patients treated with oral hypoglycemic drugs. Elevation of liver enzyme levels has been reported very rarely in patients treated with glyburide. In isolated cases, impairment of liver function (e.g. cholestasis and jaundice) and hepatitis have been observed which can regress after withdrawal of the drug or may lead to life-threatening liver failure. Cases of hyponatremia have been reported with sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increased release of antidiuretic hormones. Although there have been no reports for DIAbETA(r), the syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported with certain other sulfonylureas, and it has been suggested that these sulfonylureas may augment the peripheral (antidiuretic) action of ADH and/or increased release of ADH.

Gastrointestinal:

Nausea, epigastric fullness and heartburn are common reactions. Vomiting, diarrhea, and abdominal pain have also been reported. These tend to be dose related and may disappear when dosage is reduced.

Hematologic:

Potentially life-threatening changes in the blood picture may occur. Rare cases of mild to severe thrombocytopenia which can manifest itself as purpura have been reported. Leukopenia, agranulocytosis, pancytopenia (which may be due to myelosuppression), erythrocytopenia, granulocytopenia, hemolytic anemia and aplastic anemia have been observed very rarely with DIAbETA(r) therapy. These reactions may be reversible following discontinuation of the sulphonylurea antidiabetic agent.

Sensitivity/Resistance:

Allergic and pseudoallergic skin reactions such as pruritus, erythema, urticaria, morbilliform, or maculopapular eruptions have been reported in a number of patients. These may subside on continued use of DIAbETA(r) (glyburide), but if they persist the drug should be discontinued. Mild reactions such as urticaria may very rarely develop into serious and life-threatening reactions including dyspnea, hypotension or shock. Porphyria cutanea tarda and photosensitivity reactions have been associated with the use of oral hypoglycemic drugs. Allergic vasculitis have been observed very rarely in patients receiving DIAbETA(r) and in some circumstances may be life-threatening. Cross-sensitivity to sulfonamides or their derivatives may occur in patients treated with oral sulphonylurea hypoglycemic agents.

Other:

Transient visual disturbances may occur at the commencement of treatment due to fluctuations in blood glucose levels.

DRUG INTERACTIONS

Weakening of the blood-glucose-lowering effect and, thus, raised blood glucose levels may occur when taking other drugs.

Patients who receive or discontinue certain medications while undergoing treatment with DIAbETA(r) may experience changes in blood glucose control.

In addition, the hypoglycaemic action of sulfonylureas is potentiated when used with insulin and other oral antidiabetics, which is not indicated.

Alertness and reactions may be impaired due to hypo- or hyperglycemia, especially when beginning or after altering treatment, or when DIAbETA(r) (glyburide) is not taken regularly. This may, for example, affect the ability to drive or to operate machinery. Both acute and chronic alcohol intake may potentiate or weaken the blood-glucose-lowering action of glyburide in an unpredictable fashion. Intolerance to alcohol (disulfiram-like reaction: flushing, sensation of warmth, giddiness, nausea, and occasionally tachycardia) may occur in patients treated with oral hypoglycemic drugs. These reactions can be prevented by avoiding the use of alcohol.

DOSAGE AND ADMINISTRATION

In diabetic subjects, there is no fixed dosage regimen for management of blood glucose levels. Individual determination of the minimum dose that will lower the blood glucose adequately should be made, aiming for glycemic targets as close to normal as possible and, in most people, as early as possible. Over a period of time, patients may become progressively less responsive to therapy with oral hypoglycemic agents because of deterioration of their diabetic state. Patients should therefore be monitored with regular clinical and laboratory evaluations, including blood glucose and glycosylated hemoglobin (AlC) measurements, to determine the minimum effective dosage and to detect primary failure or secondary failure (see WARNINGS AND PRECAUTIONS). Adjustment of glyburide dosage should be considered whenever factors predisposing the patient to the development of hypo- or hyperglycemia, such as illness, weight or life-style changes, are present (see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS). As an improvement in control of diabetes is, in itself, associated with higher insulin sensitivity, glyburide requirements may fall as treatment proceeds. To avoid hypoglycemia, timely dose reduction or cessation of DIAbETA(r) therapy must therefore be considered.

The initial dose is 5 mg daily (2.5 mg in patients over 60 years of age) administered with breakfast or a first meal and should be continued for 5 to 7 days. Depending on the response, the dosage should then be either increased or decreased by steps of 2.5 mg. The maximum daily dose of DIAbETA(r) is 20 mg (higher doses normally have no additional effect on control of metabolic state). Occasionally, control is maintained with 2.5 mg daily. The majority of cases can be controlled by 5 to 10 mg (1 to 2 tablets) daily given as a single dose during or immediately after breakfast. Patients who eat only a light breakfast should defer the first dose of the day until lunchtime. If more than 10 mg (2 tablets) daily is required, the excess should be taken with the evening meal. It is very important not to skip meals after the tablets have been taken.

There is no exact dosage relationship between DIAbETA(r) and other oral antidiabetic agents. Discontinue previous oral medication and start DIAbETA(r) 5 mg daily (2.5 mg in patients over 60 years of age). This also applies to patients changed over from the maximum dose of other oral antidiabetic medication. Determine maintenance dosage as in newly diagnosed diabetics. Consideration must be given to the potency and duration of action of the previous antidiabetic agent. A break from medication may be required to avoid any summation of effects entailing a risk of hypoglycemia.

If a change from insulin to DIAbETA(r) is contemplated in a patient with stable, mild, Type 2 diabetes, treatment with insulin should be discontinued for a period of two or three days to determine whether any therapy other than dietary regulation and exercise is needed. During this insulin-free interval, the patient's urine should be tested at least three times daily for glucose and ketone-bodies, and the results monitored carefully by a physician. The appearance of significant ketonuria accompanied by glucosuria within 12 - 24 hours after the withdrawal of insulin strongly suggests that the patient is ketosis-prone and precludes the change from insulin to DIAbETA(r).

The missed dose should be taken as soon as possible, unless it is almost time for the next dose. Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a larger dose. Measures for dealing with such mistakes (in particular forgetting a dose or skipping a meal) or in the event a dose cannot be taken at the prescribed time must be discussed and agreed between physician and patient beforehand. If it is discovered that too high a dose or an extra dose of DIAbETA(r) has been taken, a physician must be notified immediately.

OVERDOSAGE

Overdosage with sulfonylureas may result in hypoglycemia, but it should be noted that the dosage which causes hypoglycemia varies widely, and may be within the accepted therapeutic range in sensitive individuals. Discontinue medication and treat hypoglycemia by giving dextrose promptly and in sufficient quantity. The symptoms of hypoglycemia nearly always subside when blood glucose control is attained. However, some sulfonylurea-induced hypoglycemias may be refractory to treatment and susceptible to relapse, especially in elderly or malnourished patients. Patients must, therefore, remain under close observation. Continuous dextrose infusions for hours to days have been necessary.

ACTION AND CLINICAL PHARMACOLOGY

DIAbETA(r) appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which DIAbETA(r) lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs. In addition to its blood glucose lowering actions, DIAbETA(r) produces a mild diuresis by enhancement of renal free water clearance. Clinical experience to date indicates an extremely low incidence of disulfiram-like reactions in patients while taking DIAbETA(r).

Pharmacokinetics

Single-dose studies with DIAbETA(r) in normal subjects demonstrate significant absorption within one hour, peak drug levels at about four hours, and low but detectable levels at twenty- four hours. Mean serum levels of glyburide, as reflected by areas under the serum concentration- time curve, increase in proportion to corresponding increases in dose. Multiple-dose studies with DIAbETA(r) in diabetic patients demonstrate drug level concentration-time curves similar to single dose studies, indicating no build-up of drug in tissue depots. The decrease of glyburide in the serum of normal healthy individuals is biphasic, the terminal half-life being about 10 hours. In single-dose studies in fasting normal subjects, the degree and duration of blood glucose lowering is proportional to the dose administered and to the area under the drug level concentration-time curve. The blood glucose lowering effect persists for 24 hours following single morning doses in non-fasting diabetic patients. Under conditions of repeated administration in diabetic patients, however, there is no reliable correlation between blood drug levels and fasting blood glucose levels. A one-year study of diabetic patients treated with DIAbETA(r)showed no reliable correlation between administered dose and serum drug level. The major metabolite of DIAbETA(r) is the 4-trans-hydroxy derivative. A second metabolite, the 3-cis-hydroxy derivative, also occurs. These metabolites contribute no significant hypoglycemic action since they are only weakly active (1/400th and 1/40th, respectively, as glyburide) in rabbits. DIAbETA(r) is excreted as metabolites in the bile and urine, approximately 50% by each route. This dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine. Sulfonylurea drugs are extensively bound to serum proteins. Displacement from protein binding sites by other drugs may lead to enhanced hypoglycemic action. In vitro, the protein binding exhibited by DIAbETA(r) is predominantly non-ionic, whereas that of other sulfonylureas (chlorpropamide, tolbutamide, tolazamide) is predominantly ionic. Acidic drugs such as phenylbutazone, warfarin, and salicylates displace the ionic-binding sulfonylureas from serum proteins to a far greater extent than the non-ionic binding DIAbETA(r). It has not been shown that this difference in protein binding will result in fewer drug-drug interactions with DIAbETA(r) in clinical use.

STORAGE AND STABILITY

DIAbETA(r) should be stored between 15 and 30oC, and not beyond the expiry date indicated on the package.

DOSAGE FORMS, COMPOSITION AND PACKAGING

DIAbETA(r) (glyburide) 2.5 mg contains 2.5 mg glyburide. DIAbETA(r) (glyburide) 5.0 mg contains 5.0 mg glyburide. Each tablet also contains as non-medicinal ingredients: colloidal anhydrous silica, lactose monohydrate, magnesium stearate, starch (corn starch and pre- gelatinized corn starch) and talc. DIAbETA(r) (glyburide) 2.5 mg tablets are compressed white, flat round beveled tablets with code letter "LB" above and "G" below the breakline on one side and plain on the other. Available in cartons of 30 (2 x 15 blister pack). DIAbETA(r) (glyburide) 5.0 mg tablets are white, biplane, oblong tablets with a score line on both sides, "LDI" is engraved on each side of the score-line and inverted. The other face is plain. Available in cartons of 30 (2 x 15 blister pack) or HDPE bottles of 300 tablets.

Route of Administration	Dosage Form / Strength	Clinically Relevant Nonmedicinal Ingredients
Oral	Tablet 2.5 mg, 5 mg	Lactose monohydrate For a complete listing see Dosage Forms, Composition and Packaging section.

Proper name	Reference	Effect	Clinical comment
ACE-inhibitors	T	The hypoglycaemic action of sulfonylureas may be potentiated.	When these drugs are administered to a patient receiving DIAbETA (r) , the patient should be observed closely for hypoglycaemia. When these drugs are withdrawn from a patient receiving DIAbETA (r) , the patient should be observed closely for loss of glycemic control.
Anabolic steroids and androgens	T
Nonsteroidal anti- inflammatory drugs	T
Salicylates	T
Azapropazone	T
Chloramphenicol	T
Clarithromycin	C
Fibrates (clofibrate)	T
Coumarin derivatives	T
Cyclophosphamide	T
Proper name	Reference	Effect	Clinical comment
Disopyramide	T
Fenyramidol	T
Fenfluramine	T
Fluconazole,	T
Fluoxetine	T
Ifosfamide	T
Miconazole	T
Monoamine oxidase inhibitors	T
Oxyphenbutazone	T
Para-aminosalicylic acid	T
Pentoxifylline (high dose parenteral),	T
Phenylbutazone,	T
Probenecid,	T
Propranolol	T
Quinolones	T
Sulfonamides (e.g sulphaphenazole)	T
Sulphinpyrazone	T
Sympatholytic agents (e.g. beta-blockers, guanethidine)	T
Tetracyclines	T
Tuberculostatics.	T
Acetazolamide,	T	These drugs tend to produce hyperglycemia and may lead to loss of blood sugar control	When these drugs are administered to a patient receiving DIAbETA (r) , the patient should be observed closely for loss of glycemic control. When these drugs are withdrawn from a patient receiving DIAbETA (r) , the patient should be observed closely for hypoglycaemia.
Barbiturates	T
Corticosteroids	T
Diazoxide	T
Diuretics (thiazides, furosemide)	T
Epinephrine and other sympathomimetic agents	T
Glucagon	T
Laxatives (after protracted use)	T
Isoniazid	T
Nicotinic acid (in pharmacologic doses)	T
Estrogen and progestogen	T
Phenothiazines	T
Phenytoin	T
Rifampicin	T
Thyroid products	T
Proper name	Reference	Effect	Clinical comment
Sympatholytic drugs (such as beta-blockers, clonidine, guanethidine, and reserpine)	T		The signs of adrenergic counter- regulation to hypoglycemia may be reduced or absent in case of concomitant use with DIAbETA (r) .
H 2 -receptor antagonists, beta- blockers, clonidine or reserpine	T		Concurrent use with DIAbETA (r) may lead to either a potentiation or an attenuation of the blood- glucose-lowering effect
Barbiturates	T	Prolonged barbiturate action	To be used cautiously in patients receiving an oral hypoglycemic agent.
Coumarin derivatives	T	DIAbETA (r) may potentiate or weaken the effects of coumarin derivatives.
Cyclosporine	C	DIAbETA (r) may increase cyclosporine plasma level, with potentially increased toxicity.	Monitoring and dosage adjustment of cyclosporin are recommended when both drug are coadministered.
Bosentan	C	An increased incidence of elevated liver enzymes was observed in patients receiving DIAbETA (r) concomitantly with bosentan. Both DIAbETA (r) and bosentan inhibit the bile salt export pump, leading to intracellular accumulation of cytotoxic bile salts.	This combination should not be used.
Drugs containing alcohol	C	Both acute and chronic alcohol intake may potentiate or weaken the blood-glucose- lowering action of DIAbETA (r) in an unpredictable fashion.	Intolerance to alcohol (disulfiram-like reaction; flushing, sensation of warmth, giddiness, nausea, and occasionally tachycardia) may occur in patients treated with oral hypoglycemic drugs. Caution should be exercised with the concomitant use of alcohol- containing drugs.

Date of Revision:

Submission Control No.: 120676 s-a Version 3.0 dated

PART I: HEALTH PROFESSIONAL INFORMATION 3