FORTAMET^® (metformin hydrochloride)
Extended-Release Tablets

Rx only

FORTAMET^® (metformin hydrochloride) Extended-Release Tablets contain an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride (N, N-dimethylimidodicarbonimidic diamide hydrochloride) is a member of the biguanide class of oral antihyperglycemics and is not chemically or pharmacologically related to any other class of oral antihyperglycemic agents. The empirical formula of metformin hydrochloride is C₄H₁₁N₅•HCl and its molecular weight is 165.63. Its structural formula is:

Metformin hydrochloride is a white to off-white crystalline powder that is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68.

FORTAMET^® Extended-Release Tablets are designed for once-a-day oral administration and deliver 500 mg or 1000 mg of metformin hydrochloride. In addition to the active ingredient metformin hydrochloride, each tablet contains the following inactive ingredients: candellila wax, cellulose acetate, hypromellose, magnesium stearate, polyethylene glycols (PEG 400, PEG 8000), polysorbate 80, povidone, sodium lauryl sulfate, synthetic black iron oxides, titanium dioxide, and triacetin.

FORTAMET^® was developed as an extended-release formulation of metformin hydrochloride and designed for once-a-day oral administration using the patented single-composition osmotic technology (SCOT™). The tablet is similar in appearance to other film-coated oral administered tablets but it consists of an osmotically active core formulation that is surrounded by a semipermeable membrane. Two laser drilled exit ports exist in the membrane, one on either side of the tablet. The core formulation is composed primarily of drug with small concentrations of excipients. The semipermeable membrane is permeable to water but not to higher molecular weight components of biological fluids. Upon ingestion, water is taken up through the membrane, which in turn dissolves the drug and excipients in the core formulation. The dissolved drug and excipients exit through the laser drilled ports in the membrane. The rate of drug delivery is constant and dependent upon the maintenance of a constant osmotic gradient across the membrane. This situation exists so long as there is undissolved drug present in the core tablet. Following the dissolution of the core materials, the rate of drug delivery slowly decreases until the osmotic gradient across the membrane falls to zero at which time delivery ceases. The membrane coating remains intact during the transit of the dosage form through the gastrointestinal tract and is excreted in the feces.

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances, seePRECAUTIONS) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting plasma insulin levels and day-long plasma insulin response may actually decrease.

FORTAMET^® (metformin hydrochloride) Extended-Release Tablets, used as a once per day monotherapy, are indicated as an adjunct to diet and exercise to lower blood glucose. FORTAMET^® can be used concomitantly with a sulfonylurea or insulin to improve glycemic control in adults. FORTAMET^® is indicated in patients 17 years of age and older as either monotherapy or in combination therapy.

FORTAMET^® is contraindicated in patients with:

• Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels ≥1.5 mg/dL [males], ≥1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see WARNINGS and PRECAUTIONS).
• Congestive heart failure requiring pharmacologic treatment.
• Known hypersensitivity to metformin.
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

FORTAMET^® should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function (see also PRECAUTIONS).

Lactic Acidosis:

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with FORTAMET^® (metformin hydrochloride) Extended-Release Tablets; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/ L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 μg/mL are generally found.

The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/ surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking FORTAMET^® (metformin hydrochloride) Extended-Release Tablets and by use of the minimum effective dose of FORTAMET^®. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. FORTAMET^® treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, FORTAMET^® should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, FORTAMET^® should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking FORTAMET^®, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, FORTAMET^® should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS).

The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). FORTAMET^® should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of FORTAMET^®, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.

Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking FORTAMET^® do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling (see also PRECAUTIONS).

Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).

Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking FORTAMET^®, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery (see also CONTRAINDICATIONS and PRECAUTIONS).

Patients should be informed of the potential risks and benefits of FORTAMET^® and of alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of blood glucose, glycosylated hemoglobin, renal function, and hematologic parameters.

The risks of lactic acidosis, its symptoms, and conditions that predispose to its development, as noted in the WARNINGS and PRECAUTIONS sections, should be explained to patients. Patients should be advised to discontinue FORTAMET^® immediately and to promptly notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual somnolence, or other nonspecific symptoms occur. Once a patient is stabilized on any dose level of FORTAMET^®, gastrointestinal symptoms, which are common during initiation of metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.

Patients should be counseled against excessive alcohol intake, either acute or chronic, while receiving FORTAMET^®.

FORTAMET^® alone does not usually cause hypoglycemia, although it may occur when FORTAMET^® is used in conjunction with oral sulfonylureas and insulin. When initiating combination therapy, the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members (see Patient Information Printed Below).

Patients should be informed that FORTAMET^® must be swallowed whole and not chewed, cut, or crushed, and that the inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet (see Patient Information).

Response to all diabetic therapies should be monitored by periodic measurements of fasting blood glucose and glycosylated hemoglobin levels, with a goal of decreasing these levels toward the normal range. During initial dose titration, fasting glucose can be used to determine the therapeutic response. Thereafter, both glucose and glycosylated hemoglobin should be monitored. Measurements of glycosylated hemoglobin may be especially useful for evaluating long-term control (see also DOSAGE AND ADMINISTRATION).

Initial and periodic monitoring of hematologic parameters (e.g., hemoglobin/hematocrit and red blood cell indices) and renal function (serum creatinine) should be performed, at least on an annual basis. While megaloblastic anemia has rarely been seen with immediate-release metformin therapy, if this is suspected, Vitamin B₁₂ deficiency should be excluded.

Long-term carcinogenicity studies with metformin have been performed in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1500 mg/kg/day, respectively. These doses are both approximately four times the maximum recommended human daily dose of 2000 mg based on body surface area comparisons. No evidence of carcinogenicity with metformin was found in either male or female mice. Similarly, there was no tumorigenic potential observed with metformin in male rats. There was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg/day.

There was no evidence of mutagenic potential of metformin in the following in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse micronucleus test were also negative.

Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg/day, which is approximately three times the maximum recommended human daily dose based on body surface area comparisons.

Studies in lactating rats show that metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted in nursing mothers. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If FORTAMET^® is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.

No pediatric clinical studies have been conducted with FORTAMET^®. The safety and effectiveness of immediate-release metformin for the treatment of type 2 diabetes have been established in pediatric patients ages 10 to 16 years (studies have not been conducted in pediatric patients below the age of 10 years). Use of immediate-release metformin in this age group is supported by evidence from adequate and well-controlled studies of immediate-release metformin in adults with additional data from a controlled clinical study in pediatric patients ages 10-16 years with type 2 diabetes, which demonstrated a similar response in glycemic control to that seen in adults (see CLINICAL PHARMACOLOGY: Pediatric Clinical Studies). In this study, adverse effects were similar to those described in adults (see ADVERSE REACTIONS: Pediatric Patients). A maximum daily dose of 2000 mg of immediate-release metformin is recommended.

The safety and efficacy of FORTAMET^® has not been evaluated in pediatric patients.

Of the 389 patients who received FORTAMET^® in controlled Phase III clinical studies, 26.5% [103/389] were 65 years and older. No overall differences in effectiveness or safety were observed between these patients and younger patients.

Controlled clinical studies of immediate-release metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and younger patients. Metformin is known to be substantially excreted by the kidney and because of the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, immediate-release metformin should only be used in patients with normal renal function (see CONTRAINDICATIONS, WARNINGS, and CLINICAL PHARMACOLOGY: Pharmacokinetics). Because aging is associated with reduced renal function, immediate-release metformin should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of immediate-release metformin (see also WARNINGS and DOSAGE AND ADMINISTRATION).

In the controlled clinical studies of FORTAMET^® in patients with type 2 diabetes, a total of 424 patients received FORTAMET^® therapy (up to 2500 mg/day) and 430 patients received immediate-release metformin. Adverse reactions reported in ≥5% of the FORTAMET^® or immediate-release metformin patients are uled in Table 6. These pooled results show that the most frequently reported adverse reactions in the FORTAMET^® group were infection, diarrhea, and nausea. Similar incidences of these adverse reactions were seen in the immediate-release metformin group.

The most frequent adverse events thought to be related to FORTAMET^® were diarrhea, nausea, dyspepsia, flatulence, and abdominal pain. The frequency of dyspepsia was 4.2% in the FORTAMET^® group compared to 5.1% in the immediate-release group, the frequency of flatulence was 3.5% in the FORTAMET^® group compared to 3.7% in the immediate-release group, and the frequency of abdominal pain was 3.3% in the FORTAMET^® group compared to 4.4% in the immediate-release group.

In the controlled studies, 4.7% of patients treated with FORTAMET^® and 4.9% of patients treated with immediate-release metformin were discontinued due to adverse events.

Immediate-Release Metformin Phase III Clinical Studies

In a U.S. double-blind clinical study of immediate-release metformin in patients with type 2 diabetes, a total of 141 patients received immediate-release metformin therapy (up to 2550 mg per day) and 145 patients received placebo. Adverse reactions reported in greater than 5% of the immediate-release metformin patients, and that were more common in immediate-release metformin than placebo-treated patients, are uled in Table 7.

Diarrhea led to discontinuation of study medication in 6% of patients treated with immediate-release metformin. Additionally, the following adverse reactions were reported in ≥1.0 - ≤5.0% of immediate-release metformin patients and were more commonly reported with immediate-release metformin than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation.

No pediatric clinical studies have been conducted with FORTAMET^®. In clinical trials with immediate-release metformin in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.

Hypoglycemia has not been seen even with ingestion of up to 85 grams of immediate-release metformin, although lactic acidosis has occurred in such circumstances (see WARNINGS). Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin over-dosage is suspected.

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with FORTAMET^® or any other pharmacologic agent. Dosage of FORTAMET^® must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily dose. The maximum recommended daily dose of FORTAMET^® Extended-Release Tablets in adults is 2500 mg.

FORTAMET^® should be taken with a full glass of water once daily with the evening meal. FORTAMET^® should be started at a low dose, with gradual dose escalation, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

During treatment initiation and dose titration (see Recommended Dosing Schedule), fasting plasma glucose should be used to determine the therapeutic response to FORTAMET^® and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of FORTAMET^®, either when used as monotherapy or in combination with sulfonylurea or insulin.

Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and secondary failure, i.e., loss of an adequate blood glucose lowering response after an initial period of effectiveness.

Short-term administration of FORTAMET^® may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

The usual starting dose of FORTAMET^® (metformin hydrochloride) Extended-Release Tablets is 1000 mg taken with a full glass of water once daily with the evening meal, although 500 mg may be utilized when clinically appropriate. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2500 mg once daily with the evening meal (see CLINICAL PHARMACOLOGY, Clinical Studies).

In randomized trials, patients currently treated with immediate-release metformin were switched to FORTAMET^®. Results of this trial suggest that patients receiving immediate-release metformin treatment may be safely switched to FORTAMET^® once daily at the same total daily dose, up to 2500 mg once daily. Following a switch from immediate-release metformin to FORTAMET^®, glycemic control should be closely monitored and dosage adjustments made accordingly (see CLINICAL PHARMACOLOGY, Clinical Studies).

FORTAMET^® (metformin hydrochloride) Extended-Release Tablets are supplied as biconvex-shaped, film-coated extended-release tablets containing 500 mg or 1000 mg of metformin hydrochloride.

NDC 59630-574-60: 500 mg extended-release, white-colored tablets imprinted with Andrx logo and 574 on one side: bottles of 60.

NDC 59630-575-60: 1000 mg extended-release, white-colored tablets imprinted with Andrx logo and 575 on one side: bottles of 60.

Store at 20-25°C (68-77°F) Excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled Room Temperature]. Keep tightly closed (protect from moisture). Protect from light. Avoid excessive heat and humidity.

Distributed by:
Sciele™ Pharma, Inc.
Atlanta, GA 30328

Manufactured by:
Watson Laboratories - Florida
Ft. Lauderdale, FL 33314

Rx only

Q1. Why do I need to take FORTAMET^®?

Your doctor has prescribed FORTAMET^® to treat your type 2 diabetes, a condition in which blood sugar (blood glucose) is elevated. There are two types of diabetes. FORTAMET^® is indicated for the most common type, known as type 2 diabetes.

Q2. Why is it important to control type 2 diabetes?

Type 2 diabetes has multiple possible complications, including blindness, kidney failure, and circulatory and heart problems. Lowering your blood sugar to a normal level may prevent or delay these complications.

Q3. 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. Your doctor may recommend that you try lifestyle modifications such as improved diet and exercise before initiating drug treatment for type 2 diabetes. Each patient will be treated individually by his or her physician, and should follow all treatment recommendations.

Q4. Does FORTAMET^® work differently from other glucosecontrol medications?

Yes. FORTAMET^®, as well as other formulations of metformin, lowers the amount of sugar in your blood by controlling how much sugar is released by the liver. FORTAMET^® (metformin hydrochloride) does not cause your body to produce more insulin. FORTAMET^® rarely causes hypoglycemia (low blood sugar) and it does not usually cause weight gain when taken alone. However, if you do not eat enough, if you take other medications to lower blood sugar, or if you drink alcohol, you can develop hypoglycemia. Specifically, when FORTAMET^® is taken together with a sulfonylurea or with insulin, hypoglycemia and weight gain are more likely to occur.

Q5. What happens if my blood sugar is still too high?

If your blood sugar is high, consult your physician. When blood sugar cannot be lowered enough by either FORTAMET^® (metformin hydrochloride) Extended-Release Tablets or a sulfonylurea, the two medications can be effective when taken together. Other alternatives involve switching to other oral antidiabetic drugs (e.g., alpha glucoside inhibitors or glitazones). FORTAMET^® may be stopped and replaced with other drugs and/or insulin. If you are unable to maintain your blood sugar with diet, exercise and glucose-control medications taken orally, then your doctor may prescribe injectable insulin to control your diabetes.

Q6. Why should I take FORTAMET^® in addition to insulin if I am already on insulin alone?

Adding FORTAMET^® to insulin can help you better control your blood sugar while reducing the insulin dose and possibly reducing your weight.

Q7. Can FORTAMET^® cause side effects?

FORTAMET^®, like all blood sugar-lowering medications, can cause side effects in some patients. Most of these side effects are minor and will go away after you've taken FORTAMET^® for a while. However, there are also serious but rare side effects related to FORTAMET^® (see below).

Q8. What kind of side effects can FORTAMET^® cause?

If side effects occur, they usually occur during the first few weeks of therapy. They are normally minor ones such as diarrhea, nausea, abdominal pain and upset stomach. FORTAMET^® is generally taken with meals, which reduce these side effects.

Although these side effects are likely to go away, call your doctor if you have severe discomfort or if these effects last for more than a few weeks. Some patients may need to have their doses lowered or stop taking FORTAMET^®, either temporarily or permanently. You should tell your doctor if the problems come back or start later on during the therapy.

WARNING: A rare number of people who have taken metformin have developed a serious condition called lactic acidosis. Properly functioning kidneys are needed to help prevent lactic acidosis. You should not take FORTAMET^® if you have impaired kidney function, as measured by a blood test (see Q9-13).

Q9. Are there any serious side effects that FORTAMET^® can cause?

FORTAMET^® rarely causes serious side effects. The most serious side effect that FORTAMET^® 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 is also important for your liver to be working normally when you take FORTAMET^®. Your liver helps to 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 FORTAMET^® causes harm to the kidneys or liver.

Q11. Are there other risk factors for lactic acidosis?

Your risk of developing lactic acidosis from taking FORTAMET^® 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 FORTAMET^® if:

• You have some forms of 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, within a few days, certain x-ray tests 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 or older 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 FORTAMET^® 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 generally reduced. These situations can lead to severe dehydration, and it may be necessary to stop taking FORTAMET^® 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. FORTAMET^® therapy will need to be stopped temporarily in such instances.

Q14. Can I take FORTAMET^® with other medications?

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

Q15. What if I become pregnant while taking FORTAMET^®?

Tell your doctor if you plan to become pregnant or have become pregnant. As with other oral glucose-control medications, you should not take FORTAMET^® during pregnancy. Usually your doctor will prescribe insulin while you are pregnant.

Q16. How do I take FORTAMET^®?

FORTAMET^® tablets should not be cut, crushed, or chewed and should be taken whole with a full glass of water once daily with the evening meal. Occasionally, the inactive ingredients of FORTAMET^® may be eliminated as a soft mass in your stool that may look like the original tablet; this is not harmful and will not effect the way FORTAMET^® works to control diabetes. FORTAMET^® should be taken once a day with food. You will be started on a low dose of FORTAMET^® and your dosage will be increased gradually until your blood sugar is controlled.

Q17. Where can I get more information about FORTAMET^®?

This leaflet is a summary of the most important information about FORTAMET^®. If you have any questions or problems, you should talk to your doctor or other healthcare provider about type 2 diabetes as well as FORTAMET^® and its side effects.

Distributed by:
Sciele™ Pharma, Inc.
Atlanta, GA 30328

Manufactured by:
Watson Laboratories - Florida
Ft. Lauderdale, FL 33314

www.Fortamet.com

FORT-PI-04 Rev. 02/07             74200207

U.S. patent numbers 6,495,162; 6,866,866; 6,790,459; 6,099,859 - additional patents pending.