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Metformin Contraindications Liver

Metformin - Oral, Glucophage

Metformin - Oral, Glucophage

are allergic to dapagliflozin or any of the ingredients in FARXIGA. Symptoms of a serious allergic reaction may include skin rash, raised red patches on your skin (hives), swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing. If you have any of these symptoms, stop taking FARXIGA and contact your healthcare provider or go to the nearest hospital emergency room right away have severe kidney problems or are on dialysis. Your healthcare provider should do blood tests to check how well your kidneys are working before and during your treatment with FARXIGA Dehydration (the loss of body water and salt), which may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). You may be at a higher risk of dehydration if you have low blood pressure; take medicines to lower your blood pressure, including water pills (diuretics); are 65 years of age or older; are on a low salt diet, or have kidney problems Ketoacidosis occurred in people with type 1 and type 2 diabetes during treatment with FARXIGA. Ketoacidosis is a serious condition which may require hospitalization and may lead to death. Symptoms may include nausea, tiredness, vomiting, trouble breathing, and abdominal pain. If you get any of these symptoms, stop taking FARXIGA and call your healthcare provider right away. If possible, check for ketones in your urine or blood, even if your blood sugar is less than 250 mg/dL Kidney problems. Sudden kidney injury occurred in people taking FARXIGA. Talk to your doctor right away if you reduce the amount you eat or drink, or if you lose liquids; for example, from vomiting, diarrhea, or excessive heat exposure Serious urinary tract infections (UTI), some that lead to hospitalization, occu Continue reading >>

Metformin

Metformin

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 PRECAUTIONS). 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, CONTRAINDICATIONS, and PRECAUTIONS). If Metformin-associated lactic acidosis is suspected, immediately discontinue Metformin and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see PRECAUTIONS). Table 1: Select Mean (±S.D.) Metformin Pharmacokinetic Parameters Following Single or Multiple Oral Doses of Metformin Hydrochloride Tablets Subject Groups: Metformin hydrochloride tablets dose* (number of subjects) Cmax† (mcg/mL) Tmax‡ (hrs) Renal Clearance (mL/min) * All doses given fasting except the first 18 doses of the multiple dose studies † Peak plasma concentration ‡ Time to peak plasma concentration § Co Continue reading >>

Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk

Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk

Abstract Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (< 10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the resu Continue reading >>

Metformin - General Practice Notebook

Metformin - General Practice Notebook

Metformin is a biguanide oral hypoglycaemic which suppresses appetite. Metformin is first-line drug treatment for overweight patients with type 2 diabetes (1) in whom diet and exercise treatments have failed. The principle advantage of metformin treatment is that glycaemic control is improved but with significantly less weight gain than when sulphonylureas are used (2). Metformin is contraindicated if there is liver, kidney or heart failure, or in patients with a very high alcohol intake because of the perceived risk of serious lactic acidosis. however studies by Salpeter et al concluded that the use of metformin in type 2 diabetes does not increase the risk for fatal or non-fatal lactic acidosis or increase in blood lactate concentrations compared with placebo or other hypoglycaemic treatments (3,4) a commentary in the Evidence Based Medicine journal concerning this study stated...'in contrast to phenformin, no credible evidence exists that metformin increases the risk for lactic acidosis beyond what would be expected from underlying diseases' (5) this gap between evidence and prescribing guidelines makes management decisions difficult for the clinician - a clinician must therefore make decisions in the context of evidence, his or her own clinical experience and expertise in this area, prescribing guidelines and the summary of product characteristics review the dose of metformin if the serum creatinine exceeds 130 micromol/litre or the estimated glomerular filtration rate (eGFR) is below 45 ml/minute/1.73-m2. stop the metformin if the serum creatinine exceeds 150 micromol/litre or the eGFR is below 30 ml/minute/1.73-m2 The summary of product characteristics should be consulted before prescribing this drug. Prescribers' Journal (2000), 40 (1), 38-48 Continue reading >>

Metformin‐associated Lactic Acidosis In A Patient With Liver Disease

Metformin‐associated Lactic Acidosis In A Patient With Liver Disease

Sir, Metformin is an orally active biguanide, and was found to reduce mortality and complications in obese diabetic patients in the UK Prospective Diabetes Study.1 As a result, the drug is widely used as first‐line therapy for patients with obesity and type 2 diabetes. We would like to remind prescribers of a rare, but commonly fatal complication of metformin therapy in patients with liver or renal disease. A 40‐year‐old Gujerati man was admitted through accident and emergency. On admission, little history was available from the patient, and no corroborative history was available, apart from the fact that he was diabetic and on metformin. He was short of breath at rest, with oxygen saturation of 84% on air, and had a Glasgow Coma Score of 13/15. Capillary blood glucose was 1.7 mmol/l. Arterial blood gas analysis on 60% oxygen revealed severe metabolic acidosis: pH 6.62, pCO2 8.3 kPa, pO2 47.8 kPa, base excess −31.2, bicarbonate 6.4 mmol/l, anion gap 37 mmol/l. Serum lactate was extremely high at >20 mmol/l. He had a low urea of 2.4 mmol/l, normal creatinine of 63 µmol/l, a raised aspartate transaminase (110 IU/l, NR 10–50), bilirubin (64 µmol/l, NR 2–17) and alkaline phosphatase (323 IU/l, NR 40–135). He had a macrocytic anaemia (haemoglobin 9.7 g/dl, NR 13.0–17.0; MCV 99.0 fl, NR 76.0–96.0), and deranged clotting (PT 30 s, control 12 s; KPTT 65 s, control 35 s), but normal platelet count (152×109/l, NR 135–450). Hypoglycaemia was confirmed by a venous plasma glucose of 1.9 mmol/l. On review of his medical notes, he had been diagnosed with type 2 diabetes 3 years prior to admission. He had not been seen at diabetic clinic for over 2 years, when his diabetes was well controlled with metformin 850 mg twice daily. Eighteen months previously, he was a Continue reading >>

Metformin

Metformin

Metformin may rarely cause a serious, life-threatening condition called lactic acidosis. Tell your doctor if you have kidney disease. Your doctor will probably tell you not to take metformin. Also, tell your doctor if you are over 65 years old and if you have ever had a heart attack; stroke; diabetic ketoacidosis (blood sugar that is high enough to cause severe symptoms and requires emergency medical treatment); a coma; or heart or liver disease. Taking certain other medications with metformin may increase the risk of lactic acidosis. Tell your doctor if you are taking acetazolamide (Diamox), dichlorphenamide (Keveyis), methazolamide, topiramate (Topamax, in Qsymia), or zonisamide (Zonegran). Tell your doctor if you have recently had any of the following conditions, or if you develop them during treatment: serious infection; severe diarrhea, vomiting, or fever; or if you drink much less fluid than usual for any reason. You may have to stop taking metformin until you recover. If you are having surgery, including dental surgery, or any major medical procedure, tell the doctor that you are taking metformin. Also, tell your doctor if you plan to have any x-ray procedure in which dye is injected, especially if you drink or have ever drunk large amounts of alcohol or have or have had liver disease or heart failure. You may need to stop taking metformin before the procedure and wait 48 hours to restart treatment. Your doctor will tell you exactly when you should stop taking metformin and when you should start taking it again. If you experience any of the following symptoms, stop taking metformin and call your doctor immediately: extreme tiredness, weakness, or discomfort; nausea; vomiting; stomach pain; decreased appetite; deep and rapid breathing or shortness of breath; dizzi Continue reading >>

Metformin-induced Hepatotoxicity

Metformin-induced Hepatotoxicity

Metformin is the first choice oral antidiabetic drug for type 2 diabetes and currently the most consumed. Although gastrointestinal intolerance is frequent, metformin-induced hepatotoxicity is rare. Fewer than 10 cases have been reported (1). In all of those cases, metformin was associated with concomitant intake of other potentially hepatotoxic drugs. We present what we feel may be the first documented case of hepatotoxicity due to metformin with no other drug interference. A 61-year-old man was admitted to the hospital with a 3-day history of painless jaundice. He had no history of liver disease or toxic habits and denied previous consumption of drugs or herbal products, but had been taking metformin (1,700 mg/day for 6 weeks) after being diagnosed with type 2 diabetes. Laboratory tests showed a mixed pattern of liver damage (total bilirubin 2.9 mg/dL, direct bilirubin 2.4 mg/dL, aspartate aminotransferase [AST] 290 units/L [≤40], alanine aminotransferase [ALT] 861 units/L [≤35], γ-glutamyltransferase [GGT] 861 units/L [≤35], and alkaline phosphatase [ALP] 622 units/L [≤120]). International normalized ratio and eosinophil counts were normal. Diagnostic work-up ruled out viral hepatitis A, B, and C, as well as autoimmune and metabolic liver disease (negative antinuclear antibodies, anti-mitochondrial antibodies, smooth muscle antibodies, anti-liver/kidney microsomal antibodies; normal ceruloplasmin, α-1 antitrypsin, copper). Abdominal ultrasound and cholangio-MRI showed no pathological findings. The patient refused a liver biopsy. After stopping metformin, the patient's clinical condition progressively improved and liver enzymes normalized in 30 days. He was discharged with only recommendations to modify his lifestyle. Six weeks after discharge, the patient a Continue reading >>

Metformin

Metformin

Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes,[4][5] particularly in people who are overweight.[6] It is also used in the treatment of polycystic ovary syndrome.[4] Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes.[7][8] It is not associated with weight gain.[8] It is taken by mouth.[4] Metformin is generally well tolerated.[9] Common side effects include diarrhea, nausea and abdominal pain.[4] It has a low risk of causing low blood sugar.[4] High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses.[10] It should not be used in those with significant liver disease or kidney problems.[4] While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes.[4][11] Metformin is in the biguanide class.[4] It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues.[4] Metformin was discovered in 1922.[12] French physician Jean Sterne began study in humans in the 1950s.[12] It was introduced as a medication in France in 1957 and the United States in 1995.[4][13] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[14] Metformin is believed to be the most widely used medication for diabetes which is taken by mouth.[12] It is available as a generic medication.[4] The wholesale price in the developed world is between 0.21 and 5.55 USD per month as of 2014.[15] In the United States, it costs 5 to 25 USD per month.[4] Medical uses[edit] Metformin is primarily used for type 2 diabetes, but is increasingly be Continue reading >>

Metformin In The Treatment Of Adults With Type 2 Diabetes Mellitus

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 >>

Metformin Contraindications

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-induced Hepatotoxicity

Metformin-induced Hepatotoxicity

Metformin is the first choice oral antidiabetic drug for type 2 diabetes and currently the most consumed. Although gastrointestinal intolerance is frequent, metformin-induced hepatotoxicity is rare. Fewer than 10 cases have been reported (1). In all of those cases, metformin was associated with concomitant intake of other potentially hepatotoxic drugs. We present what we feel may be the first documented case of hepatotoxicity due to metformin with no other drug interference. A 61-year-old man was admitted to the hospital with a 3-day history of painless jaundice. He had no history of liver disease or toxic habits and denied previous consumption of drugs or herbal products, but had been taking metformin (1,700 mg/day for 6 weeks) after being diagnosed with type 2 diabetes. Laboratory tests showed a mixed pattern of liver damage (total bilirubin 2.9 mg/dL, direct bilirubin 2.4 mg/dL, aspartate aminotransferase [AST] 290 units/L [≤40], alanine aminotransferase [ALT] 861 units/L [≤35], γ-glutamyltransferase [GGT] 861 units/L [≤35], and alkaline phosphatase [ALP] 622 units/L [≤120]). International normalized ratio and eosinophil counts were normal. Diagnostic work-up ruled out viral hepatitis A, B, and C, as well as autoimmune and metabolic liver disease (negative antinuclear antibodies, anti-mitochondrial antibodies, smooth muscle antibodies, anti-liver/kidney microsomal antibodies; normal ceruloplasmin, α-1 antitrypsin, copper). Abdominal ultrasound and cholangio-MRI showed no pathological findings. The patient refused a liver biopsy. After stopping metformin, the patient's clinical condition progressively improved and liver enzymes normalized in 30 days. He was discharged with only recommendations to modify his lifestyle. Six weeks after discharge, the patient a Continue reading >>

The Role Of Metformin In The Management Of Nafld

The Role Of Metformin In The Management Of Nafld

Copyright © 2012 Angela Mazza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Its prevalence ranges 10–24% in the general population, reaching 60–95% and 28–55% in obese and diabetic patients, respectively. Although the etiology of NAFLD is still unclear, several lines of evidences have indicated a pathogenetic role of insulin resistance in this disorder. This concept has stimulated several clinical studies where antidiabetic drugs, such as insulin sensitizers including metformin, have been evaluated in insulin-resistant, NAFLD patients. These studies indicate that metformin might be of benefit in the treatment of NAFLD, also in nondiabetic patients, when associated to hypocaloric diet and weight control. However, the heterogeneity of these studies still prevents us from reaching firm conclusions about treatment guidelines. Moreover, metformin could have beneficial tissue-specific effects in NAFLD patients irrespective of its effects as insulin sensitizer. 1. Introduction Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. It includes a broad spectrum of liver alterations, ranging from pure steatosis to cirrhosis, through nonalcoholic steatohepatitis (NASH). NAFLD is characterized by liver damage and functional impairment similar to those observed in alcoholic liver disease although occurring in patients who do not drink or drink only a moderate amount of alcohol [1]. Although the pathogenesis of the disorder is not fully clarified, insulin resistance is widel Continue reading >>

Metformin Benefits Patients Historically Kept From Using It

Metformin Benefits Patients Historically Kept From Using It

Metformin Benefits Patients Historically Kept From Using It Metformin treatment in patients with type 2 diabetes who have historical contraindications to the drug's use is associated with improved clinical outcomes, new research shows. Matthew J Crowley, MD, from Durham Veteran's Affairs Medical Center and Duke University, Durham, North Carolina, and colleagues published the results of their systematic review of 17 observational studies online January 3 in the Annals of Internal Medicine. The evidence, albeit limited to observational data, suggests metformin is associated with reduced all-cause mortality in patients with type 2 diabetes with chronic kidney disease (CKD), congestive heart failure (CHF), and chronic liver disease (CLD) with hepatic impairment. Metformin also appears to reduce CHF admissions in patients with moderate CKD and CHF and to lower hypoglycemia risk in patients with CKD. Metformin has been recommended as first-line therapy for type 2 diabetes by professional diabetes societies in the United States and Europe for more than a decade, and that recommendation has just been reaffirmed by the American College of Physicians in guidelines that were also published online January 3 in the Annals of Internal Medicine. The renewed support comes on the heels of emerging data demonstrating that prior concerns about lactic acidosis in patients with moderate CKD, CHF, or CLD have been largely unfounded. The US Food and Drug Administration (FDA) removed CHF as a contraindication to metformin use in 2006. Moreover, in April 2016, the agency revised its CKD warning to restrict metformin use only in patients with severe CKD (estimated glomerular filtration rate [eGFR] <30 mL/minute per 1.73 m2), thereby allowing it for those with moderate CKD (3060 mL/minute per 1. Continue reading >>

Clinical Outcomes Of Metformin Use In Populations With Chronic Kidney Disease, Congestive Heart Failure, Or Chronic Liver Disease: A Systematic Review

Clinical Outcomes Of Metformin Use In Populations With Chronic Kidney Disease, Congestive Heart Failure, Or Chronic Liver Disease: A Systematic Review

Abstract Background: Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. Purpose: To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment. Data Sources: MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Study Selection: English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. Data Extraction: 2 reviewers abstracted data and independently rated study quality and strength of evidence. Data Synthesis: On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF. Limitations: Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. Conclusion: Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key c Continue reading >>

Fortamet

Fortamet

FORTAMET® (metformin hydrochloride) Extended-Release Tablets DESCRIPTION FORTAMET® (metformin hydrochloride) Extended-Release Tablets contain an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride (N, Ndimethylimidodicarbonimidic diamide hydrochloride) is a member of the biguanide class of oral antihyperglycemics and is not chemically or pharmacologically related to any other class of oral antihyperglycemic agents. The empirical formula of metformin hydrochloride is C4H11N5•HCl and its molecular weight is 165.63. Its structural formula is: Metformin hydrochloride is a white to off-white crystalline powder that 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. FORTAMET® Extended-Release Tablets are designed for once-a-day oral administration and deliver 500 mg or 1000 mg of metformin hydrochloride. In addition to the active ingredient metformin hydrochloride, each tablet contains the following inactive ingredients: candellila wax, cellulose acetate, hypromellose, magnesium stearate, polyethylene glycols (PEG 400, PEG 8000), polysorbate 80, povidone, sodium lauryl sulfate, synthetic black iron oxides, titanium dioxide, and triacetin. FORTAMET® meets USP Dissolution Test 5. System Components And Performance FORTAMET® was developed as an extended-release formulation of metformin hydrochloride and designed for once-a-day oral administration using the patented single-composition osmotic technology (SCOT™). The tablet is similar in appearance to other film-coated oral administered tablets but it consists of an osmotically active core formulation that is surrounded by a semipermeable membra Continue reading >>

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