Walmet

Contraindications

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What is the most important information I should know about Walmet?

Walmet extended-release tablets are contraindicated in patients with:

1. 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.

2. Known hypersensitivity to Walmet.

3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

Diabetic ketoacidosis should be treated with insulin.

Walmet extended-release tablets 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.

Undesirable effects

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What are the possible side effects of Walmet?

In worldwide clinical trials over 900 patients with type 2 diabetes have been treated with Walmet extended-release tablets in placebo- and active-controlled studies. In placebo-controlled trials, 781 patients were administered Walmet extended-release tablets and 195 patients received placebo. Adverse reactions reported in greater than 5% of the Walmet extended-release tablets patients, and that were more common in Walmet extended-release tablets- than placebo-treated patients, are listed in Table 10.

*Reactions that were more common in Walmet extended-release tablets than placebo-treated patients.

Diarrhea led to discontinuation of study medication in 0.6% of patients treated with Walmet extended-release tablets. Additionally, the following adverse reactions were reported in ≥1.0% - ≤5.0% of Walmet extended-release tablets patients and were more commonly reported with Walmet extended-release tablets than placebo: abdominal pain, constipation, distention abdomen, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance.

Therapeutic indications

GLUCOPHAGE (Walmet) Tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus.

GLUCOPHAGE XR (Walmet) Extended-Release Tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Walmet is an oral diabetes medicine that helps control blood sugar levels.

Walmet is for people with type 2 diabetes. Walmet is sometimes used in combination with insulin or other medications, but it is not for treating type 1 diabetes.

Walmet may also be used for purposes not listed in this medication guide.

Name of the medicinal product

Qualitative and quantitative composition

Walmet is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Walmet may induce weight loss and is the drug of choice for obese NIDDM patients. Use of Walmet is associated with modest weight loss. When used alone, Walmet does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Walmet should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Walmet decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Walmet may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus Walmet was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and Walmet is appropriate.

Special warnings and precautions for use

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

• An extra patient leaflet is available with Walmet. Talk to your pharmacist if you have questions about this information.
• Take Walmet by mouth with the evening meal unless your doctor tells you otherwise.
• Swallow Walmet whole. Do not break, crush, or chew before swallowing.
• Take Walmet on a regular schedule to get the most benefit from it. Taking Walmet at the same time each day will help you remember to take it.
• Continue to take Walmet even if you feel well. Do not miss any doses.
• If you miss a dose of Walmet, 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 Walmet.

Diabetes mellitus, type 2: Management of type 2 diabetes mellitus when hyperglycemia cannot be managed with diet and exercise alone.

Note: If not contraindicated and if tolerated, Walmet is the preferred initial pharmacologic agent for type 2 diabetes management (ADA 2020).

Data from multiple meta-analyses of randomized controlled trials with varying degrees of heterogeneity (primarily in patients with schizophrenia and schizoaffective disorder) support the use of Walmet in promoting modest weight loss and preventing weight gain associated with second-generation antipsychotics in adult patients

Dosage (Posology) and method of administration

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with GLUCOPHAGE or GLUCOPHAGE XR or any other pharmacologic agent. Dosage of GLUCOPHAGE or GLUCOPHAGE XR must be individualized on the basis of both effectiveness and tolerance, while not exceeding the maximum recommended daily doses. The maximum recommended daily dose of GLUCOPHAGE is 2550 mg in adults and 2000 mg in pediatric patients (10-16 years of age); the maximum recommended daily dose of GLUCOPHAGE XR in adults is 2000 mg. GLUCOPHAGE should be given in divided doses with meals while GLUCOPHAGE XR should generally be given once daily with the evening meal.

GLUCOPHAGE or GLUCOPHAGE XR 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, fasting plasma glucose should be used to determine the therapeutic response to GLUCOPHAGE or GLUCOPHAGE XR and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately 3 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 GLUCOPHAGE or GLUCOPHAGE XR, 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 GLUCOPHAGE or GLUCOPHAGE XR may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

GLUCOPHAGE XR tablets must be swallowed whole and never crushed or chewed.

Occasionally, the inactive ingredients of GLUCOPHAGE XR will be eliminated in the feces as a soft, hydrated mass.

In general, clinically significant responses are not seen at doses below 1500 mg per day. However, a lower recommended starting dose and gradually increased dosage is advised to minimize gastrointestinal symptoms.

The usual starting dose of GLUCOPHAGE Tablets is 500 mg twice a day or 850 mg once a day, given with meals. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For those patients requiring additional glycemic control, GLUCOPHAGE may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given 3 times a day with meals.

The usual starting dose of GLUCOPHAGE XR (Walmet) Extended-Release Tablets is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on GLUCOPHAGE XR 2000 mg once daily, a trial of GLUCOPHAGE XR 1000 mg twice daily should be considered. If higher doses of Walmet are required, GLUCOPHAGE should be used at total daily doses up to 2550 mg administered in divided daily doses, as described above.

In a randomized trial, patients currently treated with GLUCOPHAGE were switched to GLUCOPHAGE XR. Results of this trial suggest that patients receiving GLUCOPHAGE treatment may be safely switched to GLUCOPHAGE XR once daily at the same total daily dose, up to 2000 mg once daily. Following a switch from GLUCOPHAGE to GLUCOPHAGE XR, glycemic control should be closely monitored and dosage adjustments made accordingly.

The usual starting dose of GLUCOPHAGE is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses. Safety and effectiveness of GLUCOPHAGE XR in pediatric patients have not been established.

When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to GLUCOPHAGE or GLUCOPHAGE XR, no transition period generally is necessary. When transferring patients from chlorpropamide, care should be exercised during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.

If patients have not responded to 4 weeks of the maximum dose of GLUCOPHAGE or GLUCOPHAGE XR monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing GLUCOPHAGE or GLUCOPHAGE XR at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for Walmet plus glyburide (glibenclamide).

With concomitant GLUCOPHAGE or GLUCOPHAGE XR and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. In a clinical trial of patients with type 2 diabetes and prior failure on glyburide, patients started on GLUCOPHAGE 500 mg and glyburide 20 mg were titrated to 1000/20 mg, 1500/20 mg, 2000/20 mg, or 2500/20 mg of GLUCOPHAGE and glyburide, respectively, to reach the goal of glycemic control as measured by FPG, HbA1c, and plasma glucose response. However, attempts should be made to identify the minimum effective dose of each drug to achieve this goal. With concomitant GLUCOPHAGE or GLUCOPHAGE XR and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken.

If patients have not satisfactorily responded to 1 to 3 months of concomitant therapy with the maximum dose of GLUCOPHAGE or GLUCOPHAGE XR and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without GLUCOPHAGE or GLUCOPHAGE XR.

The current insulin dose should be continued upon initiation of GLUCOPHAGE or GLUCOPHAGE XR therapy. GLUCOPHAGE or GLUCOPHAGE XR therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of GLUCOPHAGE or GLUCOPHAGE XR should be increased by 500 mg after approximately 1 week and by 500 mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2500 mg for GLUCOPHAGE and 2000 mg for GLUCOPHAGE XR. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and GLUCOPHAGE or GLUCOPHAGE XR. Further adjustment should be individualized based on glucose-lowering response.

GLUCOPHAGE or GLUCOPHAGE XR are not recommended for use in pregnancy. GLUCOPHAGE is not recommended in patients below the age of 10 years. GLUCOPHAGE XR is not recommended in pediatric patients (below the age of 17 years).

The initial and maintenance dosing of GLUCOPHAGE or GLUCOPHAGE XR should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of GLUCOPHAGE or GLUCOPHAGE XR.

Monitoring of renal function is necessary to aid in prevention of lactic acidosis, particularly in the elderly.

GLUCOPHAGE 500 mg tablets are round, white to off-white, film-coated tablets debossed with “BMS 6060” around the periphery of the tablet on one side and “500” debossed across the face of the other side.

GLUCOPHAGE 850 mg tablets are round, white to off-white, film-coated tablets debossed with “BMS 6070” around the periphery of the tablet on one side and “850” debossed across the face of the other side.

GLUCOPHAGE 1000 mg tablets are white, oval, biconvex, film-coated tablets with “BMS 6071” debossed on one side and “1000” debossed on the opposite side and with a bisect line on both sides.

GLUCOPHAGE XR 500 mg tablets are white to off-white, capsule shaped, biconvex tablets, with “BMS 6063” debossed on one side and “500” debossed across the face of the other side.

GLUCOPHAGE XR 750 mg tablets are capsule shaped, biconvex tablets, with “BMS 6064” debossed on one side and “750” debossed on the other side. The tablets are pale red and may have a mottled appearance.

Store at 20°-25° C (68°-77° F); excursions permitted to 15°-30° C (59°-86° F).

Dispense in light-resistant containers.

Distributed by: Bristol-Myers Squibb Company, Princeton, NJ 08543 USA. Revised: June 2015

Interaction with other medicinal products and other forms of interaction

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What other drugs will affect Walmet?

In a single-dose interaction study in type 2 diabetes patients, coadministration of Walmet and glyburide did not result in any changes in either Walmet pharmacokinetics or pharmacodynamics. Decreases in glyburide AUC and Cmax were observed, but were highly variable. The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain;">Sulfonylurea Therapy in Adult Patients).

A single-dose, Walmet-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by coadministration. Furosemide increased the Walmet plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in Walmet renal clearance. When administered with Walmet, the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance.