Bigomet SR

Bigomet SR 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. Bigomet SR may induce weight loss and is the drug of choice for obese NIDDM patients. Use of Bigomet SR is associated with modest weight loss. When used alone, Bigomet SR 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. Bigomet SR 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. Bigomet SR decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Bigomet SR may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus Bigomet SR hydrochloride was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and Bigomet SR is appropriate.

In maturity onset (non-insulin-dependent) obese diabetics and juvenile diabetics in whom diet alone has failed as monotherapy or in combination with insulin, glitazones or sulfonylureas. Also as an adjunct to diet and exercise to improve glycemic control in patients with type-2 diabetes.

Glitazones are used in combination with Bigomet SR HCl when glycemic control is poor on Bigomet SR HCl monotherapy and maximum tolerated dose (preferable) of Bigomet SR HCl has been tried. The combination of glitazone plus Bigomet SR HCl is preferred to glitazone plus sufonylurea, particularly for obese patients.

Bigomet SR is used to treat high blood sugar levels that are caused by a type of diabetes mellitus or sugar diabetes called type 2 diabetes. With this type of diabetes, insulin produced by the pancreas is not able to get sugar into the cells of the body where it can work properly. Using Bigomet SR alone, with a type of oral antidiabetic medicine called a sulfonylurea, or with insulin, will help to lower blood sugar when it is too high and help restore the way you use food to make energy.

Many people can control type 2 diabetes with diet and exercise. Following a specially planned diet and exercise will always be important when you have diabetes, even when you are taking medicines. To work properly, the amount of Bigomet SR you take must be balanced against the amount and type of food you eat and the amount of exercise you do. If you change your diet or exercise, you will want to test your blood sugar to find out if it is too low. Your doctor will teach you what to do if this happens.

Bigomet SR does not help patients does not help patients who have insulin-dependent or type 1 diabetes because they cannot produce insulin from their pancreas gland. Their blood glucose is best controlled by insulin injections.

Bigomet SR is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, Bigomet SR is used in certain patients with the following medical conditions:

• Polycystic ovary syndrome.

There is no fixed dosage regimen for the management of hyperglycemia in patients with type 2 diabetes with Bigomet SR or Bigomet SR XR or any other pharmacologic agent. Dosage of Bigomet SR or Bigomet SR 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 Bigomet SR is 2550 mg in adults and 2000 mg in pediatric patients (10-16 years of age); the maximum recommended daily dose of Bigomet SR XR in adults is 2000 mg.

Bigomet SR should be given in divided doses with meals while Bigomet SR XR should generally be given once daily with the evening meal. Bigomet SR or Bigomet SR 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 Bigomet SR or Bigomet SR 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 Bigomet SR or Bigomet SR 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 Bigomet SR or Bigomet SR XR may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.

Bigomet SR XR tablets must be swallowed whole and never crushed or chewed. Occasionally, the inactive ingredients of Bigomet SR XR will be eliminated in the feces as a soft, hydrated mass.

Recommended Dosing Schedule

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 Bigomet SR 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, Bigomet SR 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 Bigomet SR XR (Bigomet SR hydrochloride) 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 Bigomet SR XR 2000 mg once daily, a trial of Bigomet SR XR 1000 mg twice daily should be considered. If higher doses of Bigomet SR are required, Bigomet SR 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 Bigomet SR were switched to Bigomet SR XR. Results of this trial suggest that patients receiving Bigomet SR treatment may be safely switched to Bigomet SR XR once daily at the same total daily dose, up to 2000 mg once daily. Following a switch from Bigomet SR to Bigomet SR XR, glycemic control should be closely monitored and dosage adjustments made accordingly.

Pediatrics

The usual starting dose of Bigomet SR 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 Bigomet SR XR in pediatric patients have not been established.

Transfer From Other Antidiabetic Therapy

When transferring patients from standard oral hypoglycemic agents other than chlorpropamide to Bigomet SR or Bigomet SR 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.

Concomitant Bigomet SR or Bigomet SR XR and

Oral Sulfonylurea Therapy in Adult Patients

If patients have not responded to 4 weeks of the maximum dose of Bigomet SR or Bigomet SR XR monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing Bigomet SR or Bigomet SR 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 Bigomet SR plus glyburide (glibenclamide).

With concomitant Bigomet SR or Bigomet SR 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 Bigomet SR 500 mg and glyburide 20 mg were titrated to 1000/20 mg, 1500/20 mg, 2000/20 mg, or 2500/20 mg of Bigomet SR 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 Bigomet SR or Bigomet SR 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 Bigomet SR or Bigomet SR XR and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without Bigomet SR or Bigomet SR XR.

Concomitant Bigomet SR or Bigomet SR XR and Insulin Therapy in Adult Patients

The current insulin dose should be continued upon initiation of Bigomet SR or Bigomet SR XR therapy. Bigomet SR or Bigomet SR XR therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of Bigomet SR or Bigomet SR 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 Bigomet SR and 2000 mg for Bigomet SR 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 Bigomet SR or Bigomet SR XR. Further adjustment should be individualized based on glucose-lowering response.

Specific Patient Populations

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

The initial and maintenance dosing of Bigomet SR or Bigomet SR 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 Bigomet SR or Bigomet SR XR.

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

See also:
What is the most important information I should know about Bigomet SR?

Bigomet SR® is 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 Bigomet SR.
3. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

Bigomet SR® 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.

WARNINGS

Lactic Acidosis:

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to Bigomet SR accumulation during treatment with Bigomet SR® (Bigomet SR 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 Bigomet SR is implicated as the cause of lactic acidosis, Bigomet SR plasma levels >5 μg/mL are generally found.

The reported incidence of lactic acidosis in patients receiving Bigomet SR 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 Bigomet SR® (Bigomet SR hydrochloride) Extended-Release Tablets and by use of the minimum effective dose of Bigomet SR®. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Bigomet SR® 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, Bigomet SR® 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, Bigomet SR® 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 Bigomet SR®, since alcohol potentiates the effects of Bigomet SR hydrochloride on lactate metabolism. In addition, Bigomet SR® should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure.

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. Bigomet SR® should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood Bigomet SR levels may be useful. Once a patient is stabilized on any dose level of Bigomet SR®, 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 Bigomet SR® 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.

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 Bigomet SR®, the drug should be discontinued immediately and general supportive measures promptly instituted. Because Bigomet SR 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 Bigomet SR. Such management often results in prompt reversal of symptoms and recovery.

Use Bigomet SR extended-release tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

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

Use: Labeled Indications

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, Bigomet SR is the preferred initial pharmacologic agent for type 2 diabetes management (ADA 2020).

Off Label Uses

Antipsychotic-induced weight gain

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 Bigomet SR in promoting modest weight loss and preventing weight gain associated with second-generation antipsychotics in adult patients

See also:
What other drugs will affect Bigomet SR?

Drug Interactions (Clinical Evaluation Of Drug Interactions Conducted With Immediate-Release Bigomet SR)

Glyburide

In a single-dose interaction study in type 2 diabetes patients, co-administration of Bigomet SR and glyburide did not result in any changes in either Bigomet SR 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.

Furosemide

A single-dose, Bigomet SR-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by co-administration. Furosemide increased the Bigomet SR plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in Bigomet SR renal clearance. When administered with Bigomet SR, 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. No information is available about the interaction of Bigomet SR and furosemide when co-administered chronically.

Nifedipine

A single-dose, Bigomet SR-nifedipine drug interaction study in normal healthy volunteers demonstrated that co-administration of nifedipine increased plasma Bigomet SR Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Tmax and half-life were unaffected. Nifedipine appears to enhance the absorption of Bigomet SR. Bigomet SR had minimal effects on nifedipine.

Cationic Drugs

Cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with Bigomet SR by competing for common renal tubular transport systems. Such interaction between Bigomet SR and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, Bigomet SR-cimetidine drug interaction studies, with a 60% increase in peak Bigomet SR plasma and whole blood concentrations and a 40% increase in plasma and whole blood Bigomet SR AUC. There was no change in elimination half-life in the single-dose study. Bigomet SR had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of Bigomet SR® and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.

Other

Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Bigomet SR®, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving Bigomet SR®, the patient should be observed closely for hypoglycemia.

In healthy volunteers, the pharmacokinetics of Bigomet SR and propranolol, and Bigomet SR and ibuprofen were not affected when coadministered in single-dose interaction studies.

Bigomet SR is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid, as compared to the sulfonylureas, which are extensively bound to serum proteins.

See also:
What are the possible side effects of Bigomet SR?

During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite which resolve spontaneously in most cases.

In a US double-blind clinical study of Bigomet SR in patients with type 2 diabetes, a total of 141 patients received Bigomet SR therapy (up to 2550 mg/day) and 145 patients received placebo. Adverse reactions reported in >5% of the Bigomet SR patients, and that was more common in Bigomet SR than placebo-treated patients, are listed in Table 2.

Diarrhea led to discontinuation of study medication in 6% of patients treated with Bigomet SR. Additionally, the following adverse reactions were reported in >1% to <5% of Bigomet SR patients and were more commonly reported with Bigomet SR than placebo: Abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, increased sweating, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation.

In worldwide clinical trials, over 900 patients with type 2 diabetes have been treated with Bigomet SR extended-release tablet in placebo- and active-controlled studies. In placebo-controlled trials, 781 patients were administered Bigomet SR extended-release tablet and 195 patients received placebo. Adverse reactions reported in >5% of the Bigomet SR extended-release tablet patients and that were more common in Bigomet SR extended-release tablet than placebo treated patients, are listed in Table 3.

Diarrhea led to discontinuation of study medication in 0.6% of patients treated with Bigomet SR extended-release tablet. Additionally, the following adverse reactions were reported in >1% to <5% of Bigomet SR extended-release tablet patients and were more commonly reported with Bigomet SR extended-release tablet than placebo: Abdominal pain, constipation, abdomen distention, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance.

In clinical trials with Bigomet SR in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.

Other reported adverse events with use of Bigomet SR are: Skin reactions eg, erythema, pruritus and urticaria; isolated reports of liver function tests abnormalities or hepatitis resolving upon Bigomet SR discontinuation; lactic acidosis; decrease of vitamin B12 absorption with decrease of serum levels during long-term use of Bigomet SR, consideration of such etiology is recommended if a patient presents with megaloplastic anaemia.