Metformin - Glucophage - Renal Dosing
Usual starting dose: 500mg po bid or 850 mg po qd. Dosage increases should be made in increments of 500 mg weekly or 850 mg q2 weeks, up to a total of 2000 mg per day, given in divided doses. (Maximum: 2550mg/day). Glucophage XR: Starting dose: 500 mg qd with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg daily with the evening meal. Contraindicated: Males with a serum creatinine > 1.5 mg/dl or females >1.4 mg/dl. Also patients with an abnormal creatinine clearance (~ <60-70 ml/min). National Institutes of Health, U.S. National Library of Medicine, DailyMed Database. Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates. A local search option of this data can be found here . The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinicaljudgment. Neither GlobalRPh Inc. nor any other party involved in thepreparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. Readthe disclaimer Continue reading >>
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As you were browsing PracticeUpdate, something about your browser made us think you were a bot. There are a few reasons this might happen: You're a power user moving through this website with super-human speed. You've disabled JavaScript in your web browser. A third-party browser plugin, such as Ghostery or NoScript, is preventing JavaScript from running. Additional information is available in this . After completing the CAPTCHA below, you will immediately regain access to PracticeUpdate. You reached this page when attempting to access from 35.226.183.143 on 2018-01-06 18:18:13 UTC. Trace: 8d3497e3-c874-476e-b444-70710053403c via f142fe30-0da7-428a-92b2-8a74e399b4ec Continue reading >>
Nice Guidance - Metformin In Type 2 Diabetes - General Practice Notebook
NICE guidance - metformin in type 2 diabetes start metformin treatment in a person who is overweight or obese (tailoring the assessment of body-weight-associated risk according to ethnic group ) and whose blood glucose is inadequately controlled by lifestyle interventions (nutrition and exercise) alone metformin should be considered as an option for first-line glucose-lowering therapy for a person who is not overweight metformin should be continued if blood glucose control remains or becomes inadequate and another oral glucose-lowering medication is added the dose of metformin should be stepped up gradually over weeks to minimise risk of gastro-intestinal (GI) side effects. Consider a trial of extended-absorption metformin tablets where GI tolerability prevents continuation of metformin therapy in adults with type 2 diabetes, review the dose of metformin if the estimated glomerular filtration rate (eGFR) is below 45 ml/minute/1.73m2: Stop metformin if the eGFR is below 30 ml/minute/1.73m2 Prescribe metformin with caution for those at risk of a sudden deterioration in kidney function and those at risk of eGFR falling below 45ml/minute/1.73m2 benefits of metformin therapy should be discussed with a person with mild to moderate liver dysfunction or cardiac impairment so that: due consideration can be given to the cardiovascular-protective effects of the drug (1) an informed decision can be made on whether to continue or stop the metformin Continue reading >>
Metformin In The Treatment Of Adults With Type 2 Diabetes Mellitus
INTRODUCTION Two classes of oral hypoglycemic drugs directly improve insulin action: biguanides (only metformin is currently available) and thiazolidinediones (TZDs). In the absence of contraindications, metformin is considered the first choice for oral treatment of type 2 diabetes (table 1). A 2006 consensus statement from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), updated regularly, proposed that metformin therapy (in the absence of contraindications) be initiated, concurrent with lifestyle intervention, at the time of diabetes diagnosis [1-3]. The pharmacology, efficacy, and side effects of metformin for the treatment of diabetes will be reviewed here. A general discussion of initial treatment of type 2 diabetes and the role of metformin in the prevention of diabetes, in the treatment of polycystic ovary syndrome, and in gestational diabetes are reviewed separately. Continue reading >>
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Metformin In Chronic Kidney Disease: Time For A Rethink
Go to: The Case Against Metformin The main problem with metformin is its association with LA. Lactic acidosis is defined as an arterial lactate of > 5 mmol/L and a blood pH ≤ 7.35 (1,2). There are two forms of LA. Type A is anaerobic LA caused by lactate overproduction in order to regenerate adenosine triphosphate (ATP) in the absence of oxygen, and is usually seen in the presence of circulatory collapse, e.g. heart failure, sepsis, and shock. Type B, the aerobic version, is caused by underutilization of lactate due to impaired removal by oxidation or gluconeogenesis, and is the type seen in liver disease, diabetes, cancer, and alcohol and metformin intoxication. Combinations of Type A & B are possible. The therapeutic trough level for metformin is 0.7 (0.3-1.0) mg/L (3) (for μmol/L, multiply by 7.75). The pragmatic upper therapeutic limit is 5 mg/L (4). There is no doubt that metformin in toxic doses is a cause of LA. In rats, plasma lactate begins to rise if the metformin concentration is > 20 mg/L (5). Intentional metformin overdose usually leads to hyperlactemia (6), and often to LA. This can be fatal in cases with plasma metformin > 50 mg/L (7). Some cases are accompanied by a raised creatinine. Since the most common symptom of metformin intoxication is vomiting and diarrhea, it is possible that the reduced renal function is caused by prerenal dehydration and/or circulatory collapse. Metformin is renally excreted (8,9), with a clearance approximately linearly correlated to glomerular filtration rate (GFR). There are thus two situations where metformin intoxication can occur: failure to reduce the dose in the presence of CKD, and acute uremia. It is possible that a vicious cycle can develop with acute uremia causing metformin accumulation leading to vomiting, deh Continue reading >>
Metformin Contraindications
The biguanide metformin (dimethylbiguanide) was initially introduced for use in the treatment of type 2 diabetes mellitus in the late 1950s. Today this drug is considered to be the first-choice agent and the “gold standard” for most people with type 2 diabetes. It has been estimated that the annual number of people receiving prescriptions for metformin worldwide is more than 120 million. The efficacy and benefits of metformin treatment in type 2 diabetes have been confirmed by large-scale studies and recognized by many consensus statements. Still, a large list of contraindications may increase the incidence of serious adverse effects, which precludes many patients from taking metformin. Intolerance and contraindications to metformin Three particular contraindications to the use of metformin have been suggested. They include renal impairment with elevated serum creatine levels (i.e. more than 136 mmol/l in men and 124 mmol/l in women) or abnormal creatinine clearance, congestive heart failure requiring pharmacologic treatment and advanced age (more than 80 years of age). Renal impairment represents a contraindication to metformin usage due to the increased risk of lactic acidosis (a form of metabolic acidosis due to the inadequate clearance of lactic acid from the blood). Although lactic acidosis linked to metformin is a rare condition, with an estimated prevalence of one to five cases per 100 000 population, it has a reported mortality of 30-50%. However, recent studies have suggested that metformin can be used safely, unless the estimated glomerulal filtration rate (the volume of fluid that is filtered from the capillaries of the glomeruli into the kidney tubules per unit time) falls below 30 ml/min, with a dose reduction advised at 45 ml/min. Congestive heart fail Continue reading >>
Metformin In Patients With Type 2 Diabetes And Kidney Disease
Go to: Abstract Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies d Continue reading >>
Prescribing In Renal Disease
The appropriate prescribing of many drugs depends on knowledge of the patient's total renal function, which is proportional to their body mass. The Cockcroft-Gault method of calculating creatinine clearance takes into account the patient's weight. The recently introduced estimated glomerular filtration rate, which is now routinely reported with biochemistry test results, is useful for screening for renal disease, but is unsuitable for calculating doses as it does not take into account the patient's size. Both are unreliable at extremes of weight. The list of medications that need dosage adjustment according to renal function is long, but includes commonly prescribed drugs such as antivirals, hypoglycaemic drugs (metformin, sulfonylureas, insulin), spironolactone and allopurinol. Introduction The clearance of many drugs and their metabolites depends on adequate renal function. Renal clearance is especially important for some drugs where the gap between efficacy and toxicity is narrow. Doses of these drugs need careful adjustment if they are prescribed for patients with impaired renal function. Some drugs also have the potential to cause renal toxicity. This is particularly likely to occur in patients who already have some degree of renal impairment, although other factors can increase the risk. Estimating renal function An accurate estimation of renal function, or glomerular filtration rate (GFR), requires sophisticated techniques that are unsuitable for routine or repeated use. In practice, the serum creatinine concentration is used for day-to-day assessment of renal function. It has limitations, but it remains a robust and practical parameter for most clinical situations. Serum creatinine The serum creatinine concentration has important limitations when used for estima Continue reading >>
In Brief: New Recommendations For Use Of Metformin In Renal Impairment
The FDA has required labeling changes that replace serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) as the parameter used to determine the appropriateness of treatment with the biguanide metformin (Glucophage, and others) in patients with renal impairment. These changes will allow more patients with mild to moderate renal impairment to receive metformin, which is generally the first drug prescribed for treatment of type 2 diabetes. Metformin was previously contraindicated in women with a SCr level ≥1.4 mg/dL and in men with a SCr level ≥1.5 mg/dL, but use of SCr as a surrogate indicator tends to underestimate renal function in certain populations (e.g., younger patients, men, black patients, patients with greater muscle mass). The calculation of eGFR takes into account age, race, and sex, as well as SCr level, providing a more accurate assessment of kidney function. A literature review summarized in an FDA Drug Safety Communication concluded that, based on eGFR, metformin is safe to use in patients with mild renal impairment and in some patients with moderate renal impairment.1 The eGFR should be calculated before patients begin treatment with metformin and at least annually thereafter. Metformin is now contraindicated in patients with an eGFR <30 mL/min/1.73 m2, and starting treatment with the drug in patients with an eGFR between 30 and 45 mL/min/1.73 m2 is not recommended. If the eGFR falls below 45 mL/min/1.73 m2 in a patient already taking metformin, the benefits and risks of continuing treatment should be assessed. Metformin should be not be administered for 48 hours after an iodinated contrast imaging procedure in patients with an eGFR <60 mL/min/1.73 m2 or a history of liver disease, alcoholism, or heart failure, or in those receiving Continue reading >>
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Fda Drug Safety Communication: Fda Revises Warnings Regarding Use Of The Diabetes Medicine Metformin In Certain Patients With Reduced Kidney Function
[ 4-8-2016 ] The U.S. Food and Drug Administration (FDA) is requiring labeling changes regarding the recommendations for metformin-containing medicines for diabetes to expand metformin’s use in certain patients with reduced kidney function. The current labeling strongly recommends against use of metformin in some patients whose kidneys do not work normally. We were asked1,2 to review numerous medical studies regarding the safety of metformin use in patients with mild to moderate impairment in kidney function,3-14 and to change the measure of kidney function in the metformin drug labeling that is used to determine whether a patient can receive metformin. We have concluded our review, and are requiring changes to the labeling of all metformin-containing medicines to reflect this new information. Health care professionals should follow the latest recommendations when prescribing metformin-containing medicines to patients with impaired kidney function. Patients should talk to their health care professionals if they have any questions or concerns about taking metformin. Metformin-containing medicines are available by prescription only and are used along with diet and exercise to lower blood sugar levels in patients with type 2 diabetes. When untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. Metformin-containing medicines are available as single-ingredient products and also in combination with other drugs used to treat diabetes (see FDA Approved metformin-containing Medicines). The current drug labeling strongly recommends against metformin use in some patients whose kidneys do not work normally because use of metformin in these patients can increase the risk of developing a serious and potentially dead Continue reading >>
Fda Issues Guidance For Metformin Use In Renal Impairment
Chris Tanski received his PharmD from the University at Buffalo School of Pharmacy and Pharmaceutical Sciences and is now working as a clinical staff pharmacist for Pinnacle Health in Harrisburg, Pennsylvania. He entered the field of hospital pharmacy directly from school, and he was one of the first to pilot a decentralized pharmacist role in the hospital. His other notable work contributions include working on palliative projects and transition of care for COPD patients. Chris was an editor and contributor to a film theory blog, a sketch comedy writer throughout pharmacy school, and he has a significant amount of experience writing drug information papers on neurology and infectious disease topics for both school and work. The FDA has issued new guidance for the use of the first-line diabetes drug metformin in patients with renal impairment. Metformin was approved by the FDA in 1994 for the management of type 2 diabetes. Since its approval, its labeling has warned of a contraindication in elevated serum creatinine (>1.5 mg/dL for males, >1.4 mg/dL for females) due to a risk of lactic acidosis secondary to metformin accumulation.1 Other risk factors for lactic acidosis include contrast dye exposure within 48 hours, chronic or excessive alcohol intake, dehydration, sepsis, acute congestive heart failure, and age. This absolute contraindication was based on clinical trials of an older biguanide called phenformin, which showed a greater risk of lactic acidosis associated with significant mortality and was subsequently pulled off the market in 1977.2 Although phenformin is no longer available in the United States, it’s still available in European and South American markets. Notably, the incidence of lactic acidosis associated with metformin is as low as 0.03 cases per 10 Continue reading >>
Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency
ADVANTAGES OF METFORMIN There is some evidence that early treatment with metformin is associated with reduced cardiovascular morbidity and total mortality in newly diagnosed type 2 diabetic patients (4). However, the data come from a small subgroup of a much larger trial. In contrast, despite multiple trials of intensive glucose control using a variety of glucose-lowering strategies, there is a paucity of data to support specific advantages with other agents on cardiovascular outcomes (5–7). In the original UK Prospective Diabetes Study (UKPDS), 342 overweight patients with newly diagnosed diabetes were randomly assigned to metformin therapy (8). After a median period of 10 years, this subgroup experienced a 39% (P = 0.010) risk reduction for myocardial infarction and a 36% reduction for total mortality (P = 0.011) compared with conventional diet treatment. Similar benefits were not observed in those randomly assigned to sulfonylurea or insulin. In an 8.5-year posttrial monitoring study, after participants no longer were randomly assigned to their treatments, individuals originally assigned to metformin (n = 279) continued to demonstrate a reduced risk for both myocardial infarction (relative risk 33%, P = 0.005) and total mortality (relative risk 27%, P = 0.002) (9). The latter results are even more impressive when one considers that HbA1c levels in all initially randomly assigned groups had converged within 1 year of follow-up. Unlike sulfonylureas, thiazolidinediones, and insulin, metformin is weight neutral (10), which makes it an attractive choice for obese patients. Furthermore, the management of type 2 diabetes can be complicated by hypoglycemia, which can seriously limit the pursuit of glycemic control. Here, too, metformin has advantages over insulin and some Continue reading >>
Using Metformin In The Presence Of Renal Disease
Using metformin in the presence of renal disease Using metformin in the presence of renal disease BMJ 2015; 350 doi: (Published 14 April 2015) Cite this as: BMJ 2015;350:h1758 Tahseen A Chowdhury, consultant in diabetes, M Magdi Yaqoob, professor in clinical nephrology 1Departments of Diabetes and Nephrology, Barts and the London School of Medicine and Dentistry, London E1 1BB, UK. Correspondence to: T Chowdhury Tahseen.Chowdhury{at}bartshealth.nhs.uk Current guidelines are too restrictive, and many patients who could benefit are missing out In January, the electronic Medicines Compendium (eMC) updated the Summary of Product Characteristics for Glucophage (metformin), approved by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). The summary states that Metformin may be used in patients with moderate renal impairment, stage 3a (creatinine clearance [CrCl] 45-59 mL/min or estimated glomerular filtration rate [eGFR] 45-59 mL/min/1.73 m2) only in the absence of other conditions that may increase the risk of lactic acidosis . . . If CrCl or eGFR fall <45 mL/min or <45 mL/min/1.73 m2 respectively, metformin must be discontinued immediately.1 This is reiterated in the patient information leaflet. Interestingly, the summary for generic metformin states that Renal failure or renal dysfunction (creatinine clearance <60 ml/min) is a contraindication to use. In the face of burgeoning levels of type 2 diabetes and associated renal disease, we believe that this restriction is too conservative and will deny an important drug to many thousands of people with diabetes who Continue reading >>
Metformin Use In Renal Impairment Extended
For patients with a creatinine clearance of 45–59ml/min or an eGFR of 45–59ml/min/1.73m2, the initial dose of metformin is 500mg or 850mg once daily in the morning with food. The maximum daily dose is 1g in two divided doses with monitoring of renal function every 3–6 months. This change to the prescribing information reflects the advice given in the NICE clinical guideline on the management of type II diabetes, namely that metformin can be used with caution in patients with renal impairment but the dose should be reviewed if the patient's eGFR drops below 45ml/min/1.73m2 and treatment discontinued if the eGFR drops below 30ml/min/1.73m2. The metformin drug entry in MIMS has been updated to reflect the current Glucophage SPCs. The MIMS drug listings for products containing metformin in combination with other drugs (eg, dipeptidyl peptidase 4 inhibitors, SGLT2 inhibitors, pioglitazone) will be updated when the updated SPCs become available. Prescribers should refer to the product SPCs to check if a combination product is suitable for an individual patient with renal impairment. Follow MIMS on Twitter Continue reading >>
Changes In Metformin Use In Chronic Kidney Disease
Go to: Fear of LA Metformin is chemically similar to phenformin, but has a different mechanism of action. Although the fear of LA remains, no absolute definitive causal relationship has been proven beyond doubt. Many reported cases of metformin-associated LA (MALA) did not measure metformin levels, whereas in others levels were not high, suggesting ‘metformin coincident lactic acidosis’ [9]. In 1998, Misbin et al. reported that after starting to use metformin, rates of LA in the USA were no different from prior to the approval of metformin [10]. Many reported cases of LA had multiple risk factors besides renal failure. Since DM2 is a risk factor, it is thought that many such cases may have been just from DM2. The putative risk factors for LA described in the literature include old age, decreased cardiac output, respiratory failure or hypoxic conditions, ethanol intoxication, fasting and decreased hepatic function. In a nested case–control analysis that included 50 048 patients, six patients were identified with active use of metformin and LA. Out of those, five patients had sepsis and signs of end-organ damage, suggesting that LA most frequently occurs in acutely worsening clinical scenarios [11]. Continue reading >>
