"The U.S. Food and Drug Administration today approved Trulicity (dulaglutide), a once-weekly subcutaneous injection to improve glycemic control (blood sugar levels), along with diet and exercise, in adults with type 2 diabetes.
Type 2 diabet"...
Glucovance (glyburide and metformin)
In double-blind clinical trials involving GLUCOVANCE (glyburide and metformin) as initial therapy or as second-line therapy, a total of 642 patients received GLUCOVANCE (glyburide and metformin) , 312 received metformin therapy, 324 received glyburide therapy, and 161 received placebo. The percent of patients reporting events and types of adverse events reported in clinical trials of GLUCOVANCE (glyburide and metformin) (all strengths) as initial therapy and second-line therapy are listed in Table 6.
Table 6: Most Common Clinical Adverse Events ( > 5%) in Double-Blind Clinical Studies of GLUCOVANCE (glyburide and metformin) Used as Initial or Second-Line Therapy
|Adverse Event||Number (%) of Patients|
|Upper respiratory infection||22 (13.7)||57 (17.6)||51 (16.3)||111(17.3)|
|Diarrhea||9(5.6)||20 (6.2)||64 (20.5)||109 (17.0)|
|Headache||17(10.6)||37(11.4)||29 (9.3)||57 (8.9)|
|Nausea/vomiting||10 (6.2)||17 (5.2)||38 (12.2)||49 (7.6)|
|Abdominal pain||6(3.7)||10(3.1)||25 (8.0)||44 (6.9)|
In a controlled clinical trial of rosiglitazone versus placebo in patients treated with GLUCOVANCE (glyburide and metformin) (n=365), 181 patients received GLUCOVANCE (glyburide and metformin) with rosiglitazone and 184 received GLUCOVANCE (glyburide and metformin) with placebo.
Edema was reported in 7.7% (14/181) of patients treated with rosiglitazone compared to 2.2% (4/184) of patients treated with placebo. A mean weight gain of 3 kg was observed in rosiglitazone-treated patients.
Disulfiram-like reactions have very rarely been reported in patients treated with glyburide tablets.
In controlled clinical trials of GLUCOVANCE (glyburide and metformin) there were no hypoglycemic episodes requiring medical intervention and/or pharmacologic therapy; all events were managed by the patients. The incidence of reported symptoms of hypoglycemia (such as dizziness, shakiness, sweating, and hunger), in the initial therapy trial of GLUCOVANCE (glyburide and metformin) are summarized in Table 7.
The frequency of hypoglycemic symptoms in patients treated with GLUCOVANCE (glyburide and metformin) 1.25 mg/250 mg was highest in patients with a baseline HbA1c < 7%, lower in those with a baseline HbAic of between 7% and 8%, and was comparable to placebo and metformin in those with a baseline HbA1c > 8%. For patients with a baseline HbAic between 8% and 11% treated with GLUCOVANCE (glyburide and metformin) 2.5 mg/500 mg as initial therapy, the frequency of hypoglycemic symptoms was 30% to 35%. As second-line therapy in patients inadequately controlled on sulfonylurea alone, approximately 6.8% of all patients treated with GLUCOVANCE (glyburide and metformin) experienced hypoglycemic symptoms. When rosiglitazone was added to GLUCOVANCE (glyburide and metformin) therapy, 22% of patients reported 1 or more fingerstick glucose measurements ≤ 50 mg/dL compared to 3.3% of placebo-treated patients. All hypoglycemic events were managed by the patients and only 1 patient discontinued for hypoglycemia. (See PRECAUTIONS: General: Addition of Thiazolidinediones to GLUCOVANCE (glyburide and metformin) Therapy.)
The incidence of gastrointestinal (GI) side effects (diarrhea, nausea/vomiting, and abdominal pain) in the initial therapy trial are summarized in Table 7. Across all GLUCOVANCE (glyburide and metformin) trials, GI symptoms were the most common adverse events with GLUCOVANCE (glyburide and metformin) and were more frequent at higher dose levels. In controlled trials, < 2% of patients discontinued GLUCOVANCE (glyburide and metformin) therapy due to GI adverse events.
Table 7: Treatment Emergent Symptoms of Hypoglycemia or Gastrointestinal
Adverse Events in a Placebo- and Active-Controlled Trial of GLUCOVANCE (glyburide and metformin) as Initial
| Glyburide Tablets
| Metformin Tablets
| GLUCOVANCE (glyburide and metformin)
1.25 mg/250 mg Tablets
| GLUCOVANCE (glyburide and metformin)
2.5 mg/500 mg Tablets
|Mean Final Dose||0 mg||5.3 mg||1317 mg||2.78 mg/557 mg||4.1 mg/824 mg|
|Number (%) of patients with symptoms of hypoglycemia||5(3.1)||34(21.3)||5(3.1)||18(11.4)||61 (37.7)|
|Number (%) of patients with gastrointestinal adverse events||39 (24.2)||38 (23.8)||69 (43.3)||50(31.6)||62 (38.3)|
In postmarketing reports cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; GLUCOVANCE (glyburide and metformin) should be discontinued if this occurs.
Read the Glucovance (glyburide and metformin) Side Effects Center for a complete guide to possible side effects
Glucovance (glyburide and metformin)
These drugs include 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 GLUCOVANCE (glyburide and metformin) , the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving GLUCOVANCE (glyburide and metformin) , the patient should be observed closely for hypoglycemia. Metformin 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 sulfonylureas, which are extensively bound to serum proteins.
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including nonsteroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta-adrenergic blocking agents. When such drugs are administered to a patient receiving GLUCOVANCE (glyburide and metformin) , the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving GLUCOVANCE (glyburide and metformin) , the patient should be observed closely for loss of blood glucose control.
A possible interaction between glyburide and ciprofloxacin, a fluoroquinolone antibiotic, has been reported, resulting in a potentiation of the hypoglycemic action of glyburide. The mechanism for this interaction is not known.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known.
A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by coadministration. Furosemide increased the metformin plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in metformin renal clearance. When administered with metformin, 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 metformin and furosemide when coadministered chronically.
A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin 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 metformin. Metformin had minimal effects on nifedipine.
Cationic drugs (eg, 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 metformin by competing for common renal tubular transport systems. Such interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, metformin-cimetidine drug interaction studies, with a 60% increase in peak metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics. Although such interactions remain theoretical (except for cimetidine), careful patient monitoring and dose adjustment of GLUCOVANCE (glyburide and metformin) and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.
In healthy volunteers, the pharmacokinetics of metformin and propranolol and metformin and ibuprofen were not affected when coadministered in single-dose interaction studies.
Read the Glucovance Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 1/11/2011
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