Glyburide and Metformin (Glyburide / Metformin Hydrochloride) - Indications and Dosage

INDICATIONS AND USAGE

Glyburide and Metformin Hydrochloride Tablets are indicated as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus.

DOSAGE AND ADMINISTRATION

General Considerations

Patients should be retitrated when transferred from micronized glyburide tablets or other oral hypoglycemic agents (see PRECAUTIONS).

Dosage of Glyburide and Metformin Hydrochloride must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glyburide/2000 mg metformin. Glyburide and Metformin Hydrochloride should be given with meals and should be initiated at a low dose, with gradual dose escalation as described below, in order to avoid hypoglycemia (largely due to glyburide), to reduce GI side effects (largely due to metformin), and to permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient.

With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to Glyburide and Metformin Hydrochloride and to identify the minimum effective dose for the patient. Thereafter, HbA_1c should be measured at intervals of approximately 3 months to assess the effectiveness of therapy. The therapeutic goal in all patients with type 2 diabetes is to decrease FPG, PPG, and HbA_1c to normal or as near normal as possible. Ideally, the response to therapy should be evaluated using HbA_1c (glycosylated hemoglobin), which is a better indicator of long-term glycemic control than FPG alone.

No studies have been performed specifically examining the safety and efficacy of switching to Glyburide and Metformin Hydrochloride therapy in patients taking concomitant glyburide (or other sulfonylurea) plus metformin. Changes in glycemic control may occur in such patients, with either hyperglycemia or hypoglycemia possible. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring.

Glyburide and Metformin Hydrochloride in Patients with Inadequate Glycemic Control on Diet and Exercise

Recommended starting dose: 1.25 mg/250 mg once or twice daily with meals.

For patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone, the recommended starting dose of Glyburide and Metformin Hydrochloride is 1.25 mg/250 mg once a day with a meal. As initial therapy in patients with baseline HbA_1c >9% or an FPG >200 mg/dL, a starting dose of Glyburide and Metformin Hydrochloride 1.25 mg/250 mg twice daily with the morning and evening meals may be used. Dosage increases should be made in increments of 1.25 mg/250 mg per day every two weeks up to the minimum effective dose necessary to achieve adequate control of blood glucose. In clinical trials of Glyburide and Metformin Hydrochloride as initial therapy, there was no experience with total daily doses greater than 10 mg/2000 mg per day. Glyburide and Metformin Hydrochloride 5 mg/500 mg should not be used as initial therapy due to an increased risk of hypoglycemia.

Glyburide and Metformin Hydrochloride Use in Patients with Inadequate Glycemic Control on a Sulfonylurea and/or Metformin

Recommended starting dose: 2.5 mg/500 mg or 5 mg/500 mg twice daily with meals.

For patients not adequately controlled on either glyburide (or another sulfonylurea) or metformin alone, the recommended starting dose of Glyburide and Metformin Hydrochloride is 2.5 mg/500 mg or 5 mg/500 mg twice daily with the morning and evening meals. In order to avoid hypoglycemia, the starting dose of Glyburide and Metformin Hydrochloride should not exceed the daily doses of glyburide or metformin already being taken. The daily dose should be titrated in increments of no more than 5 mg/500 mg up to the minimum effective dose to achieve adequate control of blood glucose or to a maximum dose of 20 mg/2000 mg per day.

For patients previously treated with combination therapy of glyburide (or another sulfonylurea) plus metformin, if switched to Glyburide and Metformin Hydrochloride, the starting dose should not exceed the daily dose of glyburide (or equivalent dose of another sulfonylurea) and metformin already being taken. Patients should be monitored closely for signs and symptoms of hypoglycemia following such a switch and the dose of Glyburide and Metformin Hydrochloride should be titrated as described above to achieve adequate control of blood glucose.

Addition of Thiazolidinediones to Glyburide and Metformin Hydrochloride Therapy

For patients not adequately controlled on Glyburide and Metformin Hydrochloride, a thiazolidinedione can be added to Glyburide and Metformin Hydrochloride therapy. When a thiazolidinedione is added to Glyburide and Metformin Hydrochloride therapy, the current dose of Glyburide and Metformin Hydrochloride can be continued and the thiazolidinedione initiated at its recommended starting dose. For patients needing additional glycemic control, the dose of the thiazolidinedione can be increased based on its recommended titration schedule. The increased glycemic control attainable with Glyburide and Metformin Hydrochloride plus a thiazolidinedione may increase the potential for hypoglycemia at any time of day. In patients who develop hypoglycemia when receiving Glyburide and Metformin Hydrochloride and a thiazolidinedione, consideration should be given to reducing the dose of the glyburide component of Glyburide and Metformin Hydrochloride. As clinically warranted, adjustment of the dosages of the other components of the antidiabetic regimen should also be considered.

Specific Patient Populations

Glyburide and Metformin Hydrochloride is not recommended for use during pregnancy. The initial and maintenance dosing of Glyburide and Metformin Hydrochloride should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment requires a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of Glyburide and Metformin Hydrochloride to avoid the risk of hypoglycemia. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the elderly. (See WARNINGS.)

HOW SUPPLIED

Glyburide and Metformin Hydrochloride Tablets, USP are available as follows:

1.25 mg/250 mg —Each white to off-white, capsule-shaped, film coated tablet debossed with

2.5 mg/500 mg —Each yellow, capsule-shaped, film coated tablet debossed with

5 mg/500 mg — Each blue, capsule-shaped, film coated tablet debossed with

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

Dispense in a tight, light-resistant container as defined in the USP.

Manufactured by:
Actavis Pharma Manufacturing Pvt. Ltd.
Plot No. 101, 102, 107 & 108
SIDCO Pharmaceutical Complex
Alathur, Kanchipuram Dist – 603 110
Tamilnadu, India

Distributed by:
Actavis Elizabeth LLC
200 Elmora Avenue
Elizabeth, NJ 07207 USA

0065-01

Revised — March 2009

Micronase® is a registered trademark of Pharmacia & Upjohn Company.

Patient Package Insert

PHARMACIST – DETACH HERE
AND GIVE PATIENT INFORMATION SHEET TO PATIENT

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PATIENT INFORMATION ABOUT GLYBURIDE (micronized) AND METFORMIN HYDROCHLORIDE TABLETS, USP

Revised – March 2009

WARNING: A small number of people who have taken metformin hydrochloride have developed a serious condition called lactic acidosis. Properly functioning kidneys are needed to help prevent lactic acidosis. Most people with kidney problems should not take Glyburide and Metformin Hydrochloride tablets. (See Question Nos. 9-13.)

Q1. Why do I need to take Glyburide and Metformin Hydrochloride?

Your doctor has prescribed Glyburide and Metformin Hydrochloride to treat your type 2 diabetes. This is also known as non-insulin-dependent diabetes mellitus.

Q2. What is type 2 diabetes?

People with diabetes are not able to make enough insulin and/or respond normally to the insulin their body does make. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems including kidney damage, amputations, and blindness. Diabetes is also closely linked to heart disease. The main goal of treating diabetes is to lower your blood sugar to a normal level.

Q3. Why is it important to control type 2 diabetes?

The main goal of treating diabetes is to lower your blood sugar to a normal level. Studies have shown that good control of blood sugar may prevent or delay complications such as heart disease, kidney disease, or blindness.

Q4. How is type 2 diabetes usually controlled?

High blood sugar can be lowered by diet and exercise, by a number of oral medications, and by insulin injections. Before taking Glyburide and Metformin Hydrochloride you should first try to control your diabetes by exercise and weight loss. Even if you are taking Glyburide and Metformin Hydrochloride, you should still exercise and follow the diet recommended for your diabetes.

Q5. Does Glyburide and Metformin Hydrochloride work differently from other glucose-control medications?

Yes it does. The Glyburide and Metformin Hydrochloride product combines two glucose lowering drugs, glyburide and metformin. These two drugs work together to improve the different metabolic defects found in type 2 diabetes. Glyburide lowers blood sugar primarily by causing more of the body’s own insulin to be released, and metformin lowers blood sugar, in part, by helping your body use your own insulin more effectively. Together, they are efficient in helping you achieve better glucose control.

Q6. What happens if my blood sugar is still too high?

When blood sugar cannot be lowered enough by Glyburide and Metformin Hydrochloride your doctor may prescribe injectable insulin or take other measures to control your diabetes.

Q7. Can Glyburide and Metformin Hydrochloride cause side effects?

Glyburide and Metformin Hydrochloride, like all blood sugar-lowering medications, can cause side effects in some patients. Most of these side effects are minor. However, there are also serious, but rare, side effects related to Glyburide and Metformin Hydrochloride (see Q9 - Q13).

Q8. What are the most common side effects of Glyburide and Metformin Hydrochloride?

The most common side effects of Glyburide and Metformin Hydrochloride are normally minor ones such as diarrhea, nausea, and upset stomach. If these side effects occur, they usually occur during the first few weeks of therapy. Taking your Glyburide and Metformin Hydrochloride with meals can help reduce these side effects.

Less frequently, symptoms of hypoglycemia (low blood sugar), such as lightheadedness, dizziness, shakiness, or hunger may occur. The risk of hypoglycemic symptoms increases when meals are skipped, too much alcohol is consumed, or heavy exercise occurs without enough food. Following the advice of your doctor can help you to avoid these symptoms.

Q9. Are there any serious side effects that Glyburide and Metformin Hydrochloride can cause?

Glyburide and Metformin Hydrochloride rarely causes serious side effects. The most serious side effect that Glyburide and Metformin Hydrochloride can cause is called lactic acidosis.

Q10. What is lactic acidosis and can it happen to me?

Lactic acidosis is caused by a build-up of lactic acid in the blood. Lactic acidosis associated with metformin is rare and has occurred mostly in people whose kidneys were not working normally. Lactic acidosis has been reported in about one in 33,000 patients taking metformin over the course of a year. Although rare, if lactic acidosis does occur, it can be fatal in up to half the cases.

It’s also important for your liver to be working normally when you take Glyburide and Metformin Hydrochloride. Your liver helps remove lactic acid from your bloodstream.

Your doctor will monitor your diabetes and may perform blood tests on you from time to time to make sure your kidneys and your liver are functioning normally.

There is no evidence that Glyburide and Metformin Hydrochloride causes harm to the kidneys or liver.

Q11. Are there other risk factors for lactic acidosis?

Your risk of developing lactic acidosis from taking Glyburide and Metformin Hydrochloride is very low as long as your kidneys and liver are healthy. However, some factors can increase your risk because they can affect kidney and liver function. You should discuss your risk with your physician.

You should not take Glyburide and Metformin Hydrochloride if:

You have chronic kidney or liver problems

You have congestive heart failure which is treated with medications, e.g.,digoxin (Lanoxin®) or furosemide (Lasix®)

You drink alcohol excessively (all the time or short-term “binge” drinking)

You are seriously dehydrated (have lost a large amount of body fluids)

You are going to have certain x-ray procedures with injectable contrast agents

You are going to have surgery

You develop a serious condition such as a heart attack, severe infection, or a stroke

You are ≥ 80 years of age and have NOT had your kidney function tested

Q12. What are the symptoms of lactic acidosis?

Some of the symptoms include: feeling very weak, tired or uncomfortable; unusual muscle pain, trouble breathing, unusual or unexpected stomach discomfort, feeling cold, feeling dizzy or lightheaded, or suddenly developing a slow or irregular heartbeat.

If you notice these symptoms, or if your medical condition has suddenly changed, stop taking Glyburide and Metformin Hydrochloride tablets and call your doctor right away. Lactic acidosis is a medical emergency that must be treated in a hospital.

Q13. What does my doctor need to know to decrease my risk of lactic acidosis?

Tell your doctor if you have an illness that results in severe vomiting, diarrhea, and/or fever, or if your intake of fluids is significantly reduced. These situations can lead to severe dehydration, and it may be necessary to stop taking Glyburide and Metformin Hydrochloride temporarily.

You should let your doctor know if you are going to have any surgery or specialized x-ray procedures that require injection of contrast agents. Glyburide and Metformin Hydrochloride therapy will need to be stopped temporarily in such instances.

Q14. Can I take Glyburide and Metformin Hydrochloride with other medications?

Remind your doctor that you are taking Glyburide and Metformin Hydrochloride when any new drug is prescribed or a change is made in how you take a drug already prescribed. Glyburide and Metformin Hydrochloride may interfere with the way some drugs work and some drugs may interfere with the action of Glyburide and Metformin Hydrochloride.

Q15. What if I become pregnant while taking Glyburide and Metformin Hydrochloride?

Tell your doctor if you plan to become pregnant or have become pregnant. As with other oral glucose-control medications, you should not take Glyburide and Metformin Hydrochloride during pregnancy.

Usually your doctor will prescribe insulin while you are pregnant. As with all medications, you and your doctor should discuss the use of Glyburide and Metformin Hydrochloride if you are nursing a child.

Q16. How do I take Glyburide and Metformin Hydrochloride?

Your doctor will tell you how many Glyburide and Metformin Hydrochloride tablets to take and how often. This should also be printed on the label of your prescription. You will probably be started on a low dose of Glyburide and Metformin Hydrochloride and your dosage will be increased gradually until your blood sugar is controlled.

Q17. Where can I get more information about Glyburide and Metformin Hydrochloride?

This leaflet is a summary of the most important information about Glyburide and Metformin Hydrochloride. If you have any questions or problems, you should talk to your doctor or other healthcare provider about type 2 diabetes as well as Glyburide and Metformin Hydrochloride and its side effects. There is also a leaflet (package insert) written for health professionals that your pharmacist can let you read.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Manufactured by:
Actavis Pharma Manufacturing Pvt. Ltd.
Plot No. 101, 102, 107 & 108
SIDCO Pharmaceutical Complex
Alathur, Kanchipuram Dist – 603 110
Tamilnadu, India

Distributed by:
Actavis Elizabeth LLC
200 Elmora Avenue
Elizabeth, NJ 07207 USA

Revised – March 2009