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قرص glucophage xr
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Generic name: METFORMIN HYDROCHLORIDE 500mgDosage form: tablet, extended release
See also:
Medically reviewed by Drugs.com. Last updated on Jan 14, 2019.
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.قرص glucophage xr
During treatment initiation and dose titration (see Recommended Dosing Schedule), 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. (See Patient Information printed below.)
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 (metformin hydrochloride) 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 (metformin 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 GLUCOPHAGE XR 2000 mg once daily, a trial of GLUCOPHAGE XR 1000 mg twice daily should be considered. If higher doses of metformin are required, GLUCOPHAGE should be used at total daily doses up to 2550 mg administered in divided daily doses, as described above. (See CLINICAL PHARMACOLOGY: Clinical Studies.)
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 (see CLINICAL PHARMACOLOGY: Clinical Studies).
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 metformin 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 (see CLINICAL PHARMACOLOGY: Clinical Studies). 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. (See Package Insert of the respective sulfonylurea.)
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. (See WARNINGS.)
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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طبقه دارویی: داروی خوراکی کاهنده قند خون
شکل دارو: قرص روکشدار (Film-Coated Tablets)
ترکیبات دارو: هر قرص گلومت پیوسته رهش 500 و 1000 میلیگرم به ترتیب حاوی 500 و 1000 میلیگرم متفورمین هیدروکلراید است.
مکانیسم عمل: متفورمین با کاهش مقاومت به انسولین در بافتهای محیطی، کاهش تولید گلوکز در کبد و کاهش باز جذب گلوکز در روده باعث کنترل قند خون میشود.
دوزاژ و نحوه تجویز: دوز شروع متفورمین پیوسته رهش 500 میلیگرم یکبار در روز و حداکثر دوز آن 2000 میلیگرم یکبار در روز است. این دارو همراه با غذا (وعده شام) مصرف میشود.
توجه : در بیماران مبتلابه مشکلات کلیوی متفورمین نیاز به تعدیل دوز دارد. در نارسایی شدید کلیوی این دارو منع مصرف دارد.قرص glucophage xr
موارد مصرف: متفورمین در درمان دیابت نوع 2 در کنار ورزش و رژیم غذایی به کار میرود.
گلومت XR (متفورمین هیدروکلراید پیوسته رهش)
گلومت XR در درمان دیابت نوع دو (دیابت غیر وابسته به انسولین) استفاده میشود. افراد مبتلابه دیابت نوع 2 قادر به تولید کافی انسولین نیستند و یا بهطور طبیعی به انسولین تولیدشده در بدنشان پاسخ نمیدهند. وقتی این اتفاق میافتد، قند (گلوکز) خون بالا میرود. این موضوع میتواند منجر به مشکلات جدی پزشکی مانند آسیب به کلیه، قطع عضو و نابینایی شود. همچنین دیابت با بیماریهای قلبی رابطه مستقیمی دارد. هدف اصلی در درمان دیابت، کاهش قند خون شما در جهت رسیدن به سطح طبیعی است.
قند خون بالا میتواند توسط رژیم و ورزش، داروهای خوراکی و همچنین انسولین کاهش یابد. در کنار مصرف گلومت XR سعی کنید که بهوسیله ورزش و کاهش وزن، دیابت خود را کنترل کنید. درحالیکه داروهای دیابت خود را مصرف میکنید، به ورزش ادامه دهید و رژیم غذایی توصیهشده برای دیابت را دنبال کنید. مطالعات نشان دادهاند که کنترل خوب قند خون میتواند عوارض دیابت را متوقف کند یا به تأخیر بی اندازد.
این دارو به کنترل قند خون شما به طرق مختلف کمک میکند که شامل موارد زیر است: 1) کمک به بدن برای پاسخگویی بهتر به انسولینی که بهصورت طبیعی تولید میشود. 2) کاهش میزان قند ساختهشده در کبد شما و 3) کاهش میزان قندی که در روده باز جذب میگردد. گلومت XR باعث تولید انسولین بیشتر در بدن شما نمیشود. به همین دلیل، هنگامیکه بهتنهایی مصرف میشود، بهندرت باعث ایجاد هیپوگلیسمی (افت قند خون) میشود و معمولاً سبب افزایش وزن نمیشود. زمانی که با یک سولفونیل اوره یا انسولین مصرف میشود، احتمال ایجاد هیپوگلیسمی یا افزایش وزن بیشتر میشود. اگر باردار هستید یا قصد بارداری دارید، به پزشک خود پیش از مصرف این دارو اطلاع دهید. همچنین اگر کودک خود را شیر میدهید، باید پزشک خود را در مورد مصرف این دارو در جریان بگذارید.
دوز شروع متفورمین پیوسته رهش 500 میلیگرم یکبار در روز و حداکثر دوز آن 2000 میلیگرم یکبار در روز است. این دارو همراه با غذا (وعده شام) مصرف میشود.
توجه: در بیماران مبتلابه مشکلات کلیوی متفورمین نیاز به تعدیل دوز دارد. در نارسایی شدید کلیوی این دارو منع مصرف دارد.
گلومت XR بهطور مؤثری در کودکان 10 تا 16 سال مبتلابه دیابت نوع دو سبب کاهش سطح گلوکز شده است. درحالیکه هیچ مطالعهای از این دارو در کودکان زیر 10 سال صورت نگرفته است. گلومت XR در ترکیب با سایر داروهای خوراکی کنترل قند یا انسولین در کودکان موردمطالعه قرار نگرفته است. اگر سؤالی در مورداستفاده از گلومت XR در کودکان دارید، با پزشک خود مشورت کنید.
در مورد مقدار و زمان مصرف دارو، پزشک اطلاعات لازم را به شما میدهد. احتمالاً شما باید با دوز پایین مصرف دارو را شروع کنید. پزشک شما ممکن است دوز را کمکم افزایش دهد تا قند خون شما بهتر کنترل گردد. گلومت XR حتماً باید با وعده غذایی مصرف شود. پزشک شما ممکن است به همراه گلومت XR از داروهای دیگر برای کنترل قند خون شما استفاده کند. این داروها ممکن است شامل انسولین نیز باشد. مصرف گلومت XR با انسولین ممکن است به شما در کنترل بهتر قند خون کمک کند.
ورزش و رژیم غذایی خود را ادامه دهید و قند خون خود را بهطور منظم در هنگام مصرف گلومت XR اندازهگیری کنید. پزشک دیابت با آزمایشهای دورهای عملکرد کلیه و کبد شما را ارزیابی میکند. توجه داشته باشید که گلومت XR بههیچعنوان سبب آسیب به کلیهها و کبد نمیشود.
گلومت XR باید بلعیده شود و هرگز خردشده یا جویده نشود. گاهی اوقات مواد غیرفعال در گلومت XR میتوانند بهصورت یک توده نرم از طریق مدفوع شما دفع شوند که ممکن است شبیه قرص اصلی باشند. این موضوع اصلاً خطرناک نیست و تأثیری بر عملکرد این دارو بر کنترل دیابت شما نخواهد داشت.
متفورمین؛ ماده فعال در گلومت XR در کسانی که از قبل سابقه مشکلات کلیوی داشتهاند میتواند منجر به یک بیماری جدی به نام اسیدوز لاکتیک شود. اسیدوز لاکتیک یک شرایط اورژانسی است و حتماً باید بیمار در بیمارستان درمان شود.علائم زیر ممکن است نشانههایی از اسیدوز لاکتیک باشد. درصورتیکه آنها را تجربه کردید حتماً با پزشک خود مشورت کنید:
تلفن : ۴۴۵۲۲۴۵۱ ( ۲۱ ۹۸+ )
فکس : ۴۴۵۰۴۷۸۷ ( ۲۱ ۹۸+ )
آدرس کارخانه داروسازی عبیدی: تهران، کیلومتر ۸ بزرگراه شهید لشگری (جاده مخصوص کرج)، بلوار عبیدی، پلاک ۷۲
داروسازی دکتر عبیدی
www.abidipharma.ir
گروه کوبل دارو
www.cobeldarou.com
کلاب دیابت عبیدی تحت عنوان Abidi Diabetes Master Class جهت بهروز کردن مداوم دانش پزشکان درگیر در درمان دیابت با حمایت گروه خبرهای از اساتید فوق تخصص غدد و متابولیسم دانشگاههای تهران، شهید بهشتی و ایران از 21 خرداد سال 1394 در تهران تشکیل گردیده و تا کنون بیش از 40 کلاس در شهرهای مختلف ایران برگزار شده است.
در کشور ما حدود ۵ میلیون بیمار دیابتی وجود دارد که فقط نیمی از آنها از بیماری خود آگاه هستند.
عوارض جدی دیابت نظیر مشکلات قلبی – عروقی و کلیوی میتوانند منجر به ناتوانی و مرگ و میر شوند.
بزرگترین هدف واحد دیابت داروسازی دکتر عبیدی داشتن راهحلهای مناسب برای مدیریت بیماری در بیماران مبتلا به دیابت نوع ۲ میباشد.
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Updated
May 31, 2018
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Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions (5.1)].قرص glucophage xr
Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see Dosage and Administration (2.3), (2.7), Contraindications (4), Warnings and Precautions (5.1)].
If metformin-associated lactic acidosis is suspected, immediately discontinue GLUCOPHAGE or GLUCOPHAGE XR and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1)].
GLUCOPHAGE is a biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. (1) GLUCOPHAGE XR is a biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1)
Adult Dosage for GLUCOPHAGE:
Adult Dosage for GLUCOPHAGE XR:
Pediatric Dosage for GLUCOPHAGE:
Renal Impairment:
o Do not use in patients with eGFR below 30 mL/minute/1.73 m2 (2.3) o Initiation is not recommended in patients with eGFR between 30-45 mL/minute/1.73 m2 (2.3) o Assess risk/benefit of continuing if eGFR falls below 45 mL/minute/1.73 m2(2.3) o Discontinue if eGFR falls below 30 mL/minute/1.73 m2 (2.3)
Discontinuation for Iodinated Contrast Imaging Procedures:
GLUCOPHAGE/GLUCOPHAGE XR may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures (2.4)
For GLUCOPHAGE/GLUCOPHAGE XR, the most common adverse reactions (>5.0%) are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 5/2018
GLUCOPHAGE is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus.GLUCOPHAGE XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
GLUCOPHAGE
GLUCOPHAGE XR
Assess renal function prior to initiation of GLUCOPHAGE/GLUCOPHAGE XR and periodically thereafter.
GLUCOPHAGE/GLUCOPHAGE XR is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2.
Initiation of GLUCOPHAGE/GLUCOPHAGE XR in patients with an eGFR between 30 – 45 mL/minute/1.73 m2 is not recommended.
In patients taking GLUCOPHAGE/GLUCOPHAGE XR whose eGFR later falls below 45 mL/min/1.73 m2, assess the benefit risk of continuing therapy.
Discontinue GLUCOPHAGE/GLUCOPHAGE XR if the patient’s eGFR later falls below 30 mL/minute/1.73 m2 [see Warnings and Precautions (5.1) ]
Discontinue GLUCOPHAGE/GLUCOPHAGE XR at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart GLUCOPHAGE/GLUCOPHAGE XR if renal function is stable.
قرص glucophage xr
GLUCOPHAGE is available as:
GLUCOPHAGE XR is available as:
GLUCOPHAGE and GLUCOPHAGE XR are contraindicated in patients with:
There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; metformin plasma levels were generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk.
If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of GLUCOPHAGE/GLUCOPHAGE XR. In GLUCOPHAGE/GLUCOPHAGE XR treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions). Hemodialysis has often resulted in reversal of symptoms and recovery.Educate patients and their families about the symptoms of lactic acidosis and, if these symptoms occur, instruct them to discontinue GLUCOPHAGE/GLUCOPHAGE XR and report these symptoms to their healthcare provider.For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below:
The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Clinical recommendations based upon the patient’s renal function include [see Dosage and Administration (2.1) andClinical Pharmacology (12.3)]
In GLUCOPHAGE clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B12 levels was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, may be associated with anemia but appears to be rapidly reversible with discontinuation of GLUCOPHAGE or vitamin B12 supplementation. Certain individuals (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B12 levels. Measure hematologic parameters on an annual basis and vitamin B12 at 2 to 3 year intervals in patients on GLUCOPHAGE/GLUCOPHAGE XR and manage any abnormalities [see Adverse Reactions (6.1)].
Insulin and insulin secretagogues (e.g., sulfonylurea) are known to cause hypoglycemia. GLUCOPHAGE/GLUCOPHAGE XR may increase the risk of hypoglycemia when combined with insulin and/or an insulin secretagogue. Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with GLUCOPHAGE/GLUCOPHAGE XR [see Drug Interactions (7)].
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with GLUCOPHAGE/GLUCOPHAGE XR.
The following adverse reactions are also discussed elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
GLUCOPHAGE In a U.S. clinical trial of GLUCOPHAGE in patients with type 2 diabetes mellitus, a total of 141 patients received GLUCOPHAGE up to 2550 mg per day. Adverse reactions reported in greater than 5% of GLUCOPHAGE treated patients and that were more common than in placebo-treated patients, are listed in Table 1.
Diarrhea led to discontinuation of GLUCOPHAGE in 6% of patients. Additionally, the following adverse reactions were reported in ≥1% to ≤5% of GLUCOPHAGE treated patients and were more commonly reported with GLUCOPHAGE than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation.In GLUCOPHAGE clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B12 levels was observed in approximately 7% of patients. Pediatric Patients In clinical trials with GLUCOPHAGE in pediatric patients with type 2 diabetes mellitus, the profile of adverse reactions was similar to that observed in adults. GLUCOPHAGE XR In placebo-controlled trials, 781 patients were administered GLUCOPHAGE XR. Adverse reactions reported in greater than 5% of the GLUCOPHAGE XR patients, and that were more common in GLUCOPHAGE XR- than placebo-treated patients, are listed in Table 2.
Diarrhea led to discontinuation of GLUCOPHAGE XR in 0.6% of patients. Additionally, the following adverse reactions were reported in ≥1.0% to ≤5.0% of GLUCOPHAGE XR patients and were more commonly reported with GLUCOPHAGE XR than placebo: abdominal pain, constipation, distention abdomen, dyspepsia/heartburn, flatulence, dizziness, headache, upper respiratory infection, taste disturbance.
The following adverse reactions have been identified during post approval use of metformin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.
Table 3 presents clinically significant drug interactions with GLUCOPHAGE/GLUCOPHAGE XR.
Clinical Impact:
Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with GLUCOPHAGE/GLUCOPHAGE XR may increase the risk for lactic acidosis.
Consider more frequent monitoring of these patients.
Topiramate, zonisamide, acetazolamide or dichlorphenamide.
Clinical Impact:
Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology (12.3)].
Intervention:
Consider the benefits and risks of concomitant use with GLUCOPHAGE/GLUCOPHAGE XR.
Examples:
Ranolazine, vandetanib, dolutegravir, and cimetidine.
Clinical Impact:
Alcohol is known to potentiate the effect of metformin on lactate metabolism.
Intervention:
Warn patients against excessive alcohol intake while receiving GLUCOPHAGE/GLUCOPHAGE XR.
Clinical Impact:
Coadministration of GLUCOPHAGE/GLUCOPHAGE XR with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia.
Intervention:
Patients receiving an insulin secretagogue or insulin may require lower doses of the insulin secretagogue or insulin.
Clinical Impact:
Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control.
Intervention:
When such drugs are administered to a patient receiving GLUCOPHAGE/GLUCOPHAGE XR, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving GLUCOPHAGE/GLUCOPHAGE XR, observe the patient closely for hypoglycemia.
Examples:
Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid.
Risk Summary Limited data with GLUCOPHAGE/GLUCOPHAGE XR in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data]. There are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy [see Clinical Considerations].
No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during the period of organogenesis at doses up to 2- and 5- times, respectively, a 2550 mg clinical dose, based on body surface area [see Data].
The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes mellitus with an HbA1C >7 and has been reported to be as high as 20–25% in women with a HbA1C >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Poorly-controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
Data Human Data Published data from post-marketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. However, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups.
Animal Data Metformin hydrochloride did not adversely affect development outcomes when administered to pregnant rats and rabbits at doses up to 600 mg/kg/day. This represents an exposure of about 2 and 5 times a 2550 mg clinical dose based on body surface area comparisons for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin.
Risk Summary Limited published studies report that metformin is present in human milk [see Data]. However, there is insufficient information to determine the effects of metformin on the breastfed infant and no available information on the effects of metformin on milk production. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GLUCOPHAGE/GLUCOPHAGE XR and any potential adverse effects on the breastfed child from GLUCOPHAGE/GLUCOPHAGE XR or from the underlying maternal condition.
Data Published clinical lactation studies report that metformin is present in human milk which resulted in infant doses approximately 0.11% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.13 and 1. However, the studies were not designed to definitely establish the risk of use of metformin during lactation because of small sample size and limited adverse event data collected in infants.
Discuss the potential for unintended pregnancy with premenopausal women as therapy with GLUCOPHAGE/GLUCOPHAGE XR may result in ovulation in some anovulatory women.
GLUCOPHAGE The safety and effectiveness of GLUCOPHAGE for the treatment of type 2 diabetes mellitus have been established in pediatric patients 10 to 16 years old. Safety and effectiveness of GLUCOPHAGE have not been established in pediatric patients less than 10 years old.
Use of GLUCOPHAGE in pediatric patients 10 to 16 years old for the treatment of type 2 diabetes mellitus is supported by evidence from adequate and well-controlled studies of GLUCOPHAGE in adults with additional data from a controlled clinical study in pediatric patients 10 to 16 years old with type 2 diabetes mellitus, which demonstrated a similar response in glycemic control to that seen in adults [see Clinical Studies (14.1)]. In this study, adverse reactions were similar to those described in adults. A maximum daily dose of 2000 mg of GLUCOPHAGE is recommended. [See Dosage and Administration (2.2)]
GLUCOPHAGE XR Safety and effectiveness of GLUCOPHAGE XR in pediatric patients have not been established.
Controlled clinical studies of GLUCOPHAGE/GLUCOPHAGE XR did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients [see Warnings and Precautions (5.1)].
Metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. GLUCOPHAGE/GLUCOPHAGE XR is contraindicated in severe renal impairment, patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2 [see Dosage and Administration (2.3), Contraindications (4), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)].
Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. GLUCOPHAGE/GLUCOPHAGE XR is not recommended in patients with hepatic impairment [see Warnings and Precautions (5.1)].
Overdose of metformin hydrochloride has occurred, including ingestion of amounts greater than 50 grams. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.1)]. 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 overdosage is suspected.
GLUCOPHAGE/GLUCOPHAGE XR contain the antihyperglycemic agent metformin, which is a biguanide, in the form of monohydrochloride. The chemical name of metformin hydrochloride is N,N-dimethylimidodicarbonimidic diamide hydrochloride. The structural formula is as shown below:
Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C4H11N5 • HCl and a molecular weight of 165.63. It 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.GLUCOPHAGE tablets contain 500 mg, 850 mg, or 1000 mg of metformin hydrochloride, which is equivalent to 389.93 mg, 662.88 mg, 779.86 mg metformin base, respectively. Each tablet contains the inactive ingredients povidone and magnesium stearate. In addition, the coating for the 500 mg and 850 mg tablets contains hypromellose and the coating for the 1000 mg tablet contains hypromellose and polyethylene glycol.
GLUCOPHAGE XR contains 500 mg or 750 mg of metformin hydrochloride, which is equivalent to 389.93 mg, 584.90 mg metformin base, respectively.GLUCOPHAGE XR 500 mg tablets contain the inactive ingredients hypromellose, microcrystalline cellulose, sodium carboxymethyl cellulose, and magnesium stearate.GLUCOPHAGE XR 750 mg tablets contain the inactive ingredients hypromellose, sodium carboxymethyl cellulose, magnesium stearate and iron oxide pigment red.
Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.
Absorption The absolute bioavailability of a GLUCOPHAGE 500 mg tablet given under fasting conditions is approximately 50% to 60%. Studies using single oral doses of GLUCOPHAGE 500 to 1500 mg and 850 to 2550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. At usual clinical doses and dosing schedules of GLUCOPHAGE, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 μg/mL.
Following a single oral dose of GLUCOPHAGE XR, Cmax is achieved with a median value of 7 hours and a range of 4 to 8 hours. Peak plasma levels are approximately 20% lower compared to the same dose of GLUCOPHAGE, however, the extent of absorption (as measured by AUC) is comparable to GLUCOPHAGE.
At steady state, the AUC and Cmax are less than dose proportional for GLUCOPHAGE XR within the range of 500 to 2000 mg administered once daily. Peak plasma levels are approximately 0.6, 1.1, 1.4 and 1.8 mcg/mL for 500, 1000, 1500, and 2000 mg once-daily doses, respectively. The extent of metformin absorption (as measured by AUC) from GLUCOPHAGE XR at a 2000 mg once-daily dose is similar to the same total daily dose administered as GLUCOPHAGE tablets 1000 mg twice daily. After repeated administration of GLUCOPHAGE XR, metformin did not accumulate in plasma.
Effect of food: Food decreases the extent of absorption and slightly delays the absorption of metformin, as shown by approximately a 40% lower mean peak plasma concentration (Cmax), a 25% lower area under the plasma concentration versus time curve (AUC), and a 35-minute prolongation of time to peak plasma concentration (Tmax) following administration of a single 850 mg tablet of GLUCOPHAGE with food, compared to the same tablet strength administered fasting.Although the extent of metformin absorption (as measured by AUC) from the GLUCOPHAGE XR tablet increased by approximately 50% when given with food, there was no effect of food on Cmax and Tmax of metformin. Both high and low fat meals had the same effect on the pharmacokinetics of GLUCOPHAGE XR.
Distribution The apparent volume of distribution (V/F) of metformin following single oral doses of GLUCOPHAGE 850 mg averaged 654 ± 358 L. Metformin is negligibly bound to plasma proteins. Metformin partitions into erythrocytes, most likely as a function of time.MetabolismIntravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Elimination Renal clearance (see Table 4) is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.
Specific Populations
Renal Impairment In patients with decreased renal function the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased (see Table 3) [See Dosage and Administration (2.3), Contraindications (4), Warnings and Precautions (5.1) and Use in Specific Populations (8.6)] Hepatic Impairment No pharmacokinetic studies of metformin have been conducted in patients with hepatic impairment [See Warnings and Precautions (5.1) and Use in Specific Populations (8.7)]
Geriatrics Limited data from controlled pharmacokinetic studies of GLUCOPHAGE in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged, and Cmax is increased, compared to healthy young subjects. It appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see Table 4). [See Warnings and Precautions (5.1) and Use in Specific Populations (8.5)]
Subject Groups: GLUCOPHAGE dosea
(number of subjects)
Cmaxb
(mcg/mL)
Tmaxc
(hrs)
Renal Clearance
(mL/min)
a All doses given fasting except the first 18 doses of the multiple dose studies b Peak plasma concentration c Time to peak plasma concentration d Combined results (average means) of five studies: mean age 32 years (range 23-59 years) e Kinetic study done following dose 19, given fasting f Elderly subjects, mean age 71 years (range 65-81 years) g CLcr = creatinine clearance normalized to body surface area of 1.73 m2
Pediatrics After administration of a single oral GLUCOPHAGE 500 mg tablet with food, geometric mean metformin Cmax and AUC differed less than 5% between pediatric type 2 diabetic patients (12-16 years of age) and gender- and weight-matched healthy adults (20-45 years of age), all with normal renal function.
Gender Metformin pharmacokinetic parameters did not differ significantly between normal subjects and patients with type 2 diabetes mellitus when analyzed according to gender (males=19, females=16).
Race No studies of metformin pharmacokinetic parameters according to race have been performed.
Drug Interactions In Vivo Assessment of Drug Interactions
Dose of Metformin*
* All metformin and coadministered drugs were given as single doses † AUC = AUC(INF) ‡ Ratio of arithmetic means§ At steady state with topiramate 100 mg every 12 hours and metformin 500 mg every 12 hours; AUC = AUC0-12h
Coadministered Drug
Dose of Coadministered Drug*
Dose of Metformin*
* All metformin and coadministered drugs were given as single doses† AUC = AUC(INF) unless otherwise noted‡ Ratio of arithmetic means, p-value of difference <0.05§ AUC(0-24 hr) reported¶ Ratio of arithmetic means
Long-term carcinogenicity studies 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 3 times the maximum recommended human daily dose of 2550 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 a 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 2 times the maximum recommended human daily dose of 2550 mg based on body surface area comparisons.
Adult Clinical Studies A double-blind, placebo-controlled, multicenter US clinical trial involving obese patients with type 2 diabetes mellitus whose hyperglycemia was not adequately controlled with dietary management alone (baseline fasting plasma glucose [FPG] of approximately 240 mg/dL) was conducted. Patients were treated with GLUCOPHAGE (up to 2550 mg/day) or placebo for 29 weeks. The results are presented in Table 7.
* Not statistically significant
Mean baseline body weight was 201 lbs and 206 lbs in the GLUCOPHAGE and placebo arms, respectively. Mean change in body weight from baseline to week 29 was -1.4 lbs and -2.4 lbs in the GLUCOPHAGE and placebo arms, respectively.
A 29-week, double-blind, placebo-controlled study of GLUCOPHAGE and glyburide, alone and in combination, was conducted in obese patients with type 2 diabetes mellitus who had failed to achieve adequate glycemic control while on maximum doses of glyburide (baseline FPG of approximately 250 mg/dL). Patients randomized to the combination arm started therapy with GLUCOPHAGE 500 mg and glyburide 20 mg. At the end of each week of the first 4 weeks of the trial, these patients had their dosages of GLUCOPHAGE increased by 500 mg if they had failed to reach target fasting plasma glucose. After week 4, such dosage adjustments were made monthly, although no patient was allowed to exceed GLUCOPHAGE 2500 mg. Patients in the GLUCOPHAGE only arm (metformin plus placebo) discontinued glyburide and followed the same titration schedule. Patients in the glyburide arm continued the same dose of glyburide. At the end of the trial, approximately 70% of the patients in the combination group were taking GLUCOPHAGE 2000 mg/glyburide 20 mg or GLUCOPHAGE 2500 mg/glyburide 20 mg. The results are displayed in Table 8.
Comb
(n=213)
Glyb
(n=209)
GLU
(n=210)
Glyb vs Comb
GLU vs Comb
GLU vs Glyb
250.5
-63.5
247.5
13.7
253.9
-0.9
NS*
0.001
NS*
0.001
NS*
0.025
8.8
-1.7
8.5
0.2
8.9
-0.4
NS*
0.001
NS*
0.001
0.007
0.001
* Not statistically significant
Mean baseline body weight was 202 lbs, 203 lbs, and 204 lbs in the GLUCOPHAGE/glyburide, glyburide, and GLUCOPHAGE arms, respectively. Mean change in body weight from baseline to week 29 was 0.9 lbs, -0.7 lbs, and -8.4 lbs in the GLUCOPHAGE/glyburide, glyburide, and GLUCOPHAGE arms, respectively.
Pediatric Clinical Studies
A double-blind, placebo-controlled study in pediatric patients aged 10 to 16 years with type 2 diabetes mellitus (mean FPG 182.2 mg/dL), treatment with GLUCOPHAGE (up to 2000 mg/day) for up to 16 weeks (mean duration of treatment 11 weeks) was conducted. The results are displayed in Table 9.
Placebo
(n=36)
a Pediatric patients mean age 13.8 years (range 10-16 years)
Mean baseline body weight was 205 lbs and 189 lbs in the GLUCOPHAGE and placebo arms, respectively. Mean change in body weight from baseline to week 16 was -3.3 lbs and -2.0 lbs in the GLUCOPHAGE and placebo arms, respectively.
A 24-week, double-blind, placebo-controlled study of GLUCOPHAGE XR, taken once daily with the evening meal, was conducted in patients with type 2 diabetes mellitus who had failed to achieve glycemic control with diet and exercise. Patients entering the study had a mean baseline HbA1c of 8.0% and a mean baseline FPG of 176 mg/dL. The treatment dose was increased to 1500 mg once daily if at Week 12 HbA1c was 7.0% but <8.0% (patients with HbA1c 8.0% were discontinued from the study). At the final visit (24-week), mean HbA1c had increased 0.2% from baseline in placebo patients and decreased 0.6% with GLUCOPHAGE XR.A 16-week, double-blind, placebo-controlled, dose-response study of GLUCOPHAGE XR, taken once daily with the evening meal or twice daily with meals, was conducted in patients with type 2 diabetes mellitus who had failed to achieve glycemic control with diet and exercise. The results are shown in Table 10.
500 mg
Once
Daily
1000 mg
Once
Daily
1500 mg
Once
Daily
2000 mg
Once
Daily
1000 mg
Once
Daily
Placebo
a All comparisons versus Placebo
Mean baseline body weight was 193 lbs, 192 lbs, 188 lbs, 196 lbs, 193 lbs and 194 lbs in the GLUCOPHAGE XR 500 mg, 1000 mg, 1500 mg, and 2000 mg once daily, 1000 mg twice daily and placebo arms, respectively. Mean change in body weight from baseline to week 16 was -1.3 lbs, -1.3 lbs, -0.7 lbs, -1.5 lbs, -2.2 lbs and -1.8 lbs, respectively.
A 24-week, double-blind, randomized study of GLUCOPHAGE XR, taken once daily with the evening meal, and GLUCOPHAGE, taken twice daily (with breakfast and evening meal), was conducted in patients with type 2 diabetes mellitus who had been treated with GLUCOPHAGE 500 mg twice daily for at least 8 weeks prior to study entry. The results are shown in Table 11.
1000 mg
Once Daily
1500 mg
Once Daily
a n=68
Mean baseline body weight was 210 lbs, 203 lbs and 193 lbs in the GLUCOPHAGE 500 mg twice daily, and GLUCOPHAGE XR 1000 mg and 1500 mg once daily arms, respectively. Mean change in body weight from baseline to week 24 was 0.9 lbs, 1.1 lbs and 0.9 lbs, respectively.
NDC 0087-6060-10
Store at 20°–25°C (68°–77°F); excursions permitted to 15°–30°C (59°–86°F). [See USP Controlled Room Temperature]Dispense in light-resistant containers.
Advise the patient to read the FDA-approved patient labeling (Patient Information). Lactic Acidosis: Explain the risks of lactic acidosis, its symptoms, and conditions that predispose to its development. Advise patients to discontinue GLUCOPHAGE/GLUCOPHAGE XR immediately and to promptly notify their healthcare provider if unexplained hyperventilation, myalgias, malaise, unusual somnolence or other nonspecific symptoms occur. Counsel patients against excessive alcohol intake and inform patients about importance of regular testing of renal function while receiving GLUCOPHAGE/GLUCOPHAGE XR. Instruct patients to inform their doctor that they are taking GLUCOPHAGE/GLUCOPHAGE XR prior to any surgical or radiological procedure, as temporary discontinuation may be required [see Warnings and Precautions (5.1)].
Hypoglycemia: Inform patients that hypoglycemia may occur when GLUCOPHAGE/GLUCOPHAGE XR is coadministered with oral sulfonylureas and insulin. Explain to patients receiving concomitant therapy the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development [see Warnings and Precautions (5.3)].
Vitamin B12 Deficiency: Inform patients about importance of regular hematological parameters while receiving GLUCOPHAGE/GLUCOPHAGE XR [see Warnings and Precautions (5.2)].
Females of Reproductive Age: Inform females that treatment with GLUCOPHAGE/GLUCOPHAGE XR may result in ovulation in some premenopausal anovulatory women which may lead to unintended pregnancy [see Use in Specific Populations (8.3)].
GLUCOPHAGE XR Administration Information: Inform patients that GLUCOPHAGE XR must be swallowed whole and not crushed, cut, or chewed, and that the inactive ingredients may occasionally be eliminated in the feces as a soft mass that may resemble the original tablet.
Distributed by:Bristol-Myers Squibb CompanyPrinceton, NJ 08543 USAGLUCOPHAGE® is a registered trademark of Merck Santé S.A.S., a subsidiary of Merck KGaA of Darmstadt, Germany, licensed to Bristol-Myers Squibb Company.
3976400 1397294Rev May 2018
PATIENT INFORMATION GLUCOPHAGE ® [gloo-kō-fahzh] (metformin hydrochloride) Tablets and GLUCOPHAGE ® XR [gloo-kō-fahzh X-R](metformin hydrochloride) Extended-Release Tablets
Read the Patient Information that comes with GLUCOPHAGE and GLUCOPHAGE XR before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or treatment. What is the most important information I should know about GLUCOPHAGE and GLUCOPHAGE XR? Serious side effects can happen in people taking GLUCOPHAGE or GLUCOPHAGE XR, including:
Lactic Acidosis. Metformin hydrochloride, the medicine in GLUCOPHAGE and GLUCOPHAGE XR, can cause a rare, but serious, side effect called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital. Stop taking GLUCOPHAGE or GLUCOPHAGE XR and call your healthcare provider right away if you get any of the following symptoms of lactic acidosis:
You have a higher chance of getting lactic acidosis if you:
What are GLUCOPHAGE and GLUCOPHAGE XR?
Who should not take GLUCOPHAGE or GLUCOPHAGE XR?
Some conditions increase your chance of getting lactic acidosis, or cause other problems if you take either of these medicines. Most of the conditions listed below can increase your chance of getting lactic acidosis.
Do not take GLUCOPHAGE or GLUCOPHAGE XR if you:
What should I tell my healthcare provider before taking GLUCOPHAGE or GLUCOPHAGE XR?
Before taking GLUCOPHAGE or GLUCOPHAGE XR, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
Can GLUCOPHAGE or GLUCOPHAGE XR be used in children?
GLUCOPHAGE has been shown to effectively lower glucose levels in children (ages 10-16 years) with type 2 diabetes. GLUCOPHAGE has not been studied in children younger than 10 years old. GLUCOPHAGE has not been studied in combination with other oral glucose-control medicines or insulin in children. If you have any questions about the use of GLUCOPHAGE in children, talk with your doctor or other healthcare provider.GLUCOPHAGE XR has not been studied in children.
How should I take GLUCOPHAGE or GLUCOPHAGE XR?
What should I avoid while taking GLUCOPHAGE or GLUCOPHAGE XR?
Do not drink a lot of alcoholic drinks while taking GLUCOPHAGE or GLUCOPHAGE XR. This means you should not binge drink for short periods, and you should not drink a lot of alcohol on a regular basis. Alcohol can increase the chance of getting lactic acidosis.
What are the side effects of GLUCOPHAGE and GLUCOPHAGE XR?
Call your doctor right away if you have any of the following symptoms, which could be signs of lactic acidosis:
Most people who have had lactic acidosis with metformin have other things that, combined with the metformin, led to the lactic acidosis. Tell your doctor if you have any of the following, because you have a higher chance for getting lactic acidosis with GLUCOPHAGE or GLUCOPHAGE XR if you:
Common side effects of GLUCOPHAGE and GLUCOPHAGE XR include diarrhea, nausea, and upset stomach. These side effects generally go away after you take the medicine for a while. Taking your medicine with meals can help reduce these side effects. Tell your doctor if the side effects bother you a lot, last for more than a few weeks, come back after they’ve gone away, or start later in therapy. You may need a lower dose or need to stop taking the medicine for a short period or for good.About 3 out of every 100 people who take GLUCOPHAGE or GLUCOPHAGE XR have an unpleasant metallic taste when they start taking the medicine. It lasts for a short time.
GLUCOPHAGE and GLUCOPHAGE XR rarely cause hypoglycemia (low blood sugar) by themselves. However, hypoglycemia can happen if you do not eat enough, if you drink alcohol, or if you take other medicines to lower blood sugar.
How should I store GLUCOPHAGE and GLUCOPHAGE XR? Store GLUCOPHAGE and GLUCOPHAGE XR at 68°F to 77°F (20°C to 25°C). Keep GLUCOPHAGE and GLUCOPHAGE XR and all medicines out of the reach of children.
General information about the use of GLUCOPHAGE and GLUCOPHAGE XR If you have questions or problems, talk with your doctor or other healthcare provider. You can ask your doctor or pharmacist for the information about GLUCOPHAGE and GLUCOPHAGE XR that is written for healthcare professionals. Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use GLUCOPHAGE or GLUCOPHAGE XR for a condition for which it was not prescribed. Do not share your medicine with other people.
What are the ingredients of GLUCOPHAGE and GLUCOPHAGE XR?
Active ingredients of GLUCOPHAGE: metformin hydrochloride.
Inactive ingredients in each tablet of GLUCOPHAGE: povidone and magnesium stearate. In addition, the coating for the 500 mg and 850 mg tablets contain hypromellose and the coating for the 1000 mg tablet contains hypromellose and polyethylene glycol.
Active ingredients of GLUCOPHAGE XR: metformin hydrochloride.
Inactive ingredients in each tablet of GLUCOPHAGE XR 500 mg: sodium carboxymethyl cellulose, hypromellose, microcrystalline cellulose, and magnesium stearate.
Inactive ingredients in each tablet of GLUCOPHAGE XR 750 mg: sodium carboxymethyl cellulose, hypromellose, and magnesium stearate.
What is type 2 diabetes? Type 2 diabetes is a condition in which your body does not make enough insulin, and the insulin that your body produces does not work as well as it should. Your body can also make too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems.
The main goal of treating diabetes is to lower your blood sugar to a normal level.
High blood sugar can be lowered by diet and exercise, and by certain medicines when necessary.
Talk to your healthcare provider about how to prevent, recognize, and take care of low blood sugar (hypoglycemia), high blood sugar (hyperglycemia), and problems you have because of your diabetes.
GLUCOPHAGE® is a registered trademark of Merck Santé S.A.S., a subsidiary of Merck KGaA of Darmstadt, Germany, licensed to Bristol-Myers Squibb Company.
Other brands listed are the trademarks of their respective owners.
Distributed by:Bristol-Myers Squibb CompanyPrinceton, NJ 08543 USA3976400 1397294Rev May 2018
—————————————– REPRESENTATIVE PACKAGING
See How Supplied section for a complete list of available packages of GLUCOPHAGE and GLUCOPHAGE XR.
100 TabletsNDC 0087-6060-05
GLUCOPHAGE®(metformin hydrochloride) TabletsRx only500 mgBristol-Myers Squibb
100 TabletsNDC 0087-6070-05GLUCOPHAGE® (metformin hydrochloride) TabletsRx only850 mgBristol-Myers Squibb
100 TabletsNDC 0087-6071-11GLUCOPHAGE® (metformin hydrochloride) TabletsRx only1000 mgBristol-Myers Squibb
100 TabletsNDC 0087-6063-13GLUCOPHAGE®XR(metformin HCl) Extended-Release Tablets500 mgRx onlyBristol-Myers Squibb
100 TabletsNDC 0087-6064-13GLUCOPHAGE®XR(metformin HCl) Extended-Release Tablets750 mgRx onlyBristol-Myers Squibb
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