Invokana
Invokana (canagliflozin) is one of several drugs that belong to a class of Type 2 diabetes medications called sodium-glucose cotransporter 2 (SGLT2) inhibitors. Invokana and SGLT2s control blood sugar by causing excess sugar to leave the body in urine. In March 2013, the U.S. Food and Drug Administration (FDA) approved Johnson & Johnson’s (J&J) Invokana as the first drug in its class. Then, in 2014, the FDA approved Invokamet (canagliflozin and metformin) and, in 2016, Invokamet XR (canagliflozin and metformin extended release). The Invokana family of medications made more than $1.4 billion for J&J in 2016, according to annual reports. Studies show the drug is effective at controlling blood sugar, but since the FDA approved the drug it has also released several safety communications and warnings. Serious side effects of Invokana include diabetic ketoacidosis, kidney injury, urinary tract infections and cardiovascular problems. How Invokana Works While many drugs treat Type 2 diabetes by increasing insulin or insulin sensitivity, Invokana works by stopping the kidneys from reabsorbing glucose. It acts by inhibiting a special protein in the kidney called SGLT2 that is responsible for reabsorbing 90 percent of the glucose in the kidneys. Instead of reabsorbing the sugar, the kidneys secrete it, and it leaves the body during urination. This results in lowered levels of glucose in the blood. Side Effects of Invokana In clinical studies, people who took Invokana suffered a number of common side effects. Researchers gathered data from 1,667 patients with Type 2 diabetes who took Invokana for about 24 weeks. The average age was 56 years and about 2 percent were older than 75. About half of the participants were male and 72 percent of all participants were white. Certain side Continue reading >>
Should Fda Change Metformin's Black Box Warning?
Diabetes experts are building a case to lift restrictions on using metformin in patients with moderate chronic kidney disease. Two groups of researchers who have separately filed citizens petitions with the FDA have published studies in JAMA journals in the past few weeks showing a lack of evidence for metformin-associated lactic acidosis -- a severe complication that prompted the FDA to warn against the drug's use in CKD patients when it came on the market 20 years ago. Silvio Inzucchi, MD, and Kasia Lipska, MD, MHS, of Yale, published a review in the Dec. 24/31 issue of JAMA concluding that most observational data -- there are no randomized controlled trials -- confirm the "overall safety profile" of metformin in mild-to-moderate CKD patients. And James Flory, MD, of Weill Cornell, and Sean Hennessy, PharmD, PhD, of the University of Pennsylvania, reported in a research letter in the Jan. 5 issue of the Archives of Internal Medicine, that nearly 1 million patients who have diabetes and CKD could be taking metformin but aren't. Both groups have asked the FDA to lift its black box warning that limits prescribing in CKD patients based on serum creatinine levels (1.5 mg/dL or above for men, 1.4 mg/dL for women), and asks the agency to use eGFR cutoffs instead -- typically, at 30 mL/min, where several professional societies and other international regulators draw the line. How the Black Box Came to Be When the FDA approved metformin in 1994, it slapped on the black box warning about lactic acidosis because of a similar problem with another biguanide, phenformin. This cousin to metformin was withdrawn from the market in 1977 because of an increased risk of lactic acidosis. Since metformin is also renally cleared, the agency was concerned that metabolism of the drug could co Continue reading >>
Metformin Use Being Limited?
Current black box warning may be overstating the kidney risk. Metformin—the blockbuster drug utilized as the primary agent to treat patients with type 2 diabetes—may potentially be hindered in usage due to its current prescribing grounds. Despite its establishment as the first-line therapy for type 2 diabetes, about one-half of the patients currently in the United States do not take it. A major proponent of this is its current labeling, which expresses unjustifiable concerns about its use for treatment in those with mild to moderate renal insufficiency. The current label carries a contraindication against use of metformin when serum creatinine levels exceed 1.4mg/dL in women or 1.5mg/dL in men. Over the past few years, clinicians throughout the country have come to an overwhelming consensus that the US Food and Drug Administration (FDA) labeling for metformin could be more lenient and also that it can be expressed in the more precise estimated glomerular filtration rates (eGFRs), rather than serum creatinine. The FDA’s initial rationale behind the label was due to resilient evidence that phenformin caused lactic acidosis (another biguanide which has been removed from the US market). Metformin is cleared from the body via the kidneys and for patients with significant renal failure, there were increasing concerns that metformin could potentially build up to relatively high levels that could leave patients to have lactic acidosis. There is now an overwhelming two decades’ worth of research and evidence showing no serious increased risks for lactic acidosis in patients with mild-to-moderately impaired renal function. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have furthermore supported the removal of restric Continue reading >>
![Metformin Use In Patients With Historical Contraindications Or Precautions [internet].](https://diabetestalk.net/images/.jpg)
Metformin Use In Patients With Historical Contraindications Or Precautions [internet].
This appendix explains both the original and updated US Food and Drug Administration's safety warnings in relation to the use of metformin. Go to: Original ALERT: U.S. Boxed Warning for Lactic Acidosis Lactic acidosis is a rare but serious metabolic complication that can occur because of metformin accumulation during treatment with metformin; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (5 mmol/L or more), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels of 5 mcg/mL or more are generally found. The reported incidence of lactic acidosis in patients receiving metformin is very low (approximately 0.03 cases per 1,000 patient-years, with approximately 0.015 fatal cases per 1,000 patient-years). In more than 20,000 patient-years' exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal function impairment, including intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure (CHF) requiring pharmacologic management, in particular those with unstable or acute CHF who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfun Continue reading >>
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 >>
Fda Reversal On Metformin Should Save More Lives
For decades, the FDA stood by its black box warning that Type II diabetics with kidney impairment should not take metformin, the first-line oral treatment for the diabetes. But last year, after reviewing years’ worth of evidence pointing to the overall safety in kidney patients, the agency finally lifted this restriction. This reversal is great news, as metformin is the only drug that effectively treats high blood sugar while preventing the eye, kidney, heart, and nerve problems associated with the disease. It also decreases death rates, the ultimate goal of any long-term Type II diabetes treatment, and in fact, any medical treatment at all. Of course, metformin also has its roots in natural medicine as it derived originally from the ancient European folk remedy called French lilac (known in the U.S. as “goat’s rue”). But I recently came across a headline in the medical news that seemed to stir up unnecessary questions. The headline asked, “Is metformin safe for patients with chronic kidney disease?” Whenever the mainstream raises questions about metformin, I have found them to be largely misdirected. I suspect they are part of an effort by big pharma to convince physicians to prescribe new, more dangerous, more expensive diabetes drugs that haven’t been proven over the long-term. Still, I wanted to know more about the new concerns kidney specialists seemed to be raising, so I read the entire article. Back in the late 20th century, when metformin (then called Glucophage) first entered the U.S. market, there was a firestorm over the idea that it could cause lactic acidosis. Of course, there was no evidence at the time that metformin actually did cause this condition. The concerns stemmed from problems with a related drug, phenformin, and its association wit Continue reading >>
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The Fda Revises Restrictions On Metformin Use In Kidney Impairment
Aschenbrenner, Diane S. MS, RN The Food and Drug Administration is requiring manufacturers of metformin and metformin-containing drugs to revise their labeling to indicate that metformin may be safely used in some patients with mild-to-moderate renal dysfunction. Nurses should regularly assess patients’ estimated glomerular filtration rate to confirm that renal function remains adequate to support metformin therapy. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Continue reading >>
Support Article
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 >>
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 >>
Metformin, Black Box Warnings, And Radiologic Studies
Pharmacists at Good Samaritan Hospital in Los Angeles, California, set out to determine the compliance rate of prescribers following metformin’s black box warning and the rate of patients developing lactic acidosis and/or contrast-induced nephropathy (CIN). Metformin’s black box warning states that it should be temporarily discontinued before an intravascular radiocontrast study, withheld for 48 hours after the procedure, and reinstituted only after an evaluation of renal function shows that it has resumed normal functioning. After conducting a retrospective cohort study, the researchers determined that prescribers did not consistently follow the black box warning to discontinue the drug – it was continued in 69.7% of cases. The researchers found that although no patients developed lactic acidosis, 9.1% (3 of 33) developed CIN. They concluded that pharmacists can contribute to patient safety by educating prescribers about the need to adhere to the black box warning, as well as screening for high-risk patients. The researchers presented their findings at the 49th Midyear meeting of the American Society of Health-System Pharmacists. --Stephanie Vaccaro Reference: 1. Ly B, Choi J, Eto K. Use of metformin in patients undergoing radiologic studies involving intravenous iodinated contrast media: evaluating compliance with black box warning. Presented at: 49th Midyear meeting of the American Society of Health-System Pharmacists. December 8, 2014; Anaheim, CA. Poster presentation. Continue reading >>
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Metformin Warnings
For several years now, metformin has been recommended as the first-line drug for Type 2 diabetes by the American Diabetes Association (ADA). As we noted in a post last month, metformin is the most widely prescribed diabetes drug in the world due to its effectiveness, low cost, and low risk of hypoglycemia compared with many other oral drugs and insulin. But to get approval in the United States in 1994, metformin had to overcome safety concerns about lactic acidosis. This rare but extremely serious side effect was found to be too common in a drug related to metformin, phenformin, which was withdrawn from the U.S. market as a result in 1977. So since it was first sold in the United States in 1995, metformin has carried a black box warning — the strongest type of warning that the Food and Drug Administration (FDA) can require on a drug label — about the risk of lactic acidosis. Specifically, this warning states that anyone with chronic kidney disease should not take metformin if their serum creatinine level is equal to or above 1.5 mg/dl for men or 1.4 mg/dl for women. Serum creatinine is often used as a marker of kidney function. In theory, people with reduced kidney function may be at greater risk for lactic acidosis as a side effect from metformin, since the drug is broken down by the kidneys. But two separate teams of researchers recently came to the conclusion that the FDA’s black box warning on metformin is too severe, and that millions of people with both diabetes and kidney disease might be missing out on the drug’s benefits as a result. These studies were described in an article published last week by MedPage Today. In a research review published last month by the Journal of the American Medical Association, one group of researchers concluded that the risk Continue reading >>
Label: Metformin Hydrochloride- Metformin Hydrochloride Tablet, Extended Release
BOXED WARNING(What is this?) WARNINGS WARNING: LACTIC ACIDOSIS 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 hydrochloride extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see PRECAUTIONS). Close Continue reading >>
Glucophage (metformin) Is The First Choice Medicine To Control Your Blood Sugar And Lower The Risk Of Death From Diabetes, Although A Few People May Not Tolerate The Stomach Side Effects.
Our bottom line Glucophage (metformin) is the first choice medicine to control your blood sugar and lower the risk of death from diabetes, although a few people may not tolerate the stomach side effects. Improves sugar control and lowers A1c levels as much as 2%. One of the few diabetes medicines that lowers the risk of death from diabetes-related complications. Rarely causes low blood sugar. Often causes stomach upset, like diarrhea, nausea, gas, or stomach cramping. Usually not a good choice for people with kidney problems. Your doctor will tell you if Glucophage (metformin) is right for you to take. Excessive or chronic alcohol use can increase the risk of a dangerous side effect. Glucophage (metformin) is an anti-diabetic drug. It lowers the amount of sugar your body makes or absorbs, and allows your body use the existing insulin better. Sign up and get Pill Talk, the latest in health & medicine news from Iodine What to expect when you take Glucophage (metformin) for Type 2 diabetes Effectiveness Source: FDA product label and Iodine pharmacists Where we got our data » Higher risk if: › Kidney problems › Liver problems › Congestive heart failure › Using contrast dye for procedures › Surgery › Alcohol use Glucophage (metformin) can cause this rare life-threatening condition. Your doctor will check your kidneys and liver before you start. Symptoms include deep and rapid breathing, nausea, vomiting, and stomach pain. This is a medical emergency and you should get help right away. You're more likely to get this if you already have kidney problems. Glucophage (metformin) should be stopped 48 hours before and after surgery or any imaging procedure needing contrast dye. This is a black box warning. The FDA requires this warning when there is a significant risk Continue reading >>
Metformin (glucophage): Drug Whys
Generic name: Metformin (multiple manufacturers) Common U.S. brand names: Glucophage (Bristol-Myers Squibb, USA) Popularity: Sixteenth most commonly prescribed drug between 2002-2006 (U.S.) Class: Antidiabetic Treatment Uses — For treatment of Type 2 diabetes mellitus (DM) when drug therapy is necessary. Metformin is the first drug of choice for Type 2 diabetics. In obese patients, unlike some other antidiabetic agents, it is not associated with weight gain and actually promotes weight loss. May afford better glycemic control when used as an adjunct to insulin therapy in Type 1 DM. Beneficial for preventing development of gestational diabetes in women with insulin resistance or polycystic ovary syndrome (PCOS). In combination with carbohydrate-modified diet, metformin has been used to help nondiabetic, hyperinsulinemic, obese women and adolescents achieve and sustain long-term weight loss. In combination with other agents, metformin reduces a variety of symptoms in adolescents with hyperinsulinemic hypersecretion of ovarian androgens. In PCOS, metformin has increased return of normal menses and ovulation in obese women and is being studied for treatment of infertility. Metformin is not effective for prevention of DM in high-risk patients, in prevention of fibrosis (progressive damage) in non-alcoholic fatty liver, or in reducing fat deposits in HIV patients taking protease inhibitors. In maturity onset diabetes of the young (MODY) — an inherited genetic mutation — metformin performs significantly worse at controlling disease than gliclazide (a different type of antidiabetic agent). Diabetes is relatively common: 20.8 million Americans — 7 percent of the total population — have it. Treatment for diabetes is evolving rapidly and will continue to progress with th Continue reading >>
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 >>
