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Fda Metformin Black Box Warning

Farxiga - Dosage, Interactions, Fda Warnings & Studies

Farxiga - Dosage, Interactions, Fda Warnings & Studies

Farxiga (dapagliflozin) belongs to a class of drugs called sodium-glucose cotransporter 2 (SGLT2) inhibitors. It effectively treats Type 2 diabetes by excreting extra sugar in the urine. But medical studies and FDA safety communications link SGLT2 inhibitors to diabetic ketoacidosis, kidney problems and bladder cancer. Related Drugs: Farxiga (dapagliflozin), Invokamet (canagliflozin and metformin), Jardiance (empagliflozin), Glyxambi (empagliflozin and linagliptin) Manufacturer: Bristol-Myers Squibb Company SIDE EFFECTS & RISKS: Bladder cancer, ketoacidosis and acute kidney injury AstraZeneca and Bristol-Myers Squibbs Farxiga (dapagliflozin) is an oral Type 2 diabetes medication that belongs to a class called sodium-glucose cotransporter 2 (SGLT2) inhibitors. It was the second drug approved in this class. Originally approved in 2014, Farxiga controls blood sugar by preventing the kidneys from reabsorbing sugar and releasing it into the blood. The excess sugar then leaves the body through the urine. Also in 2014, the U.S. Food & Drug Administration approved Xigduo XR, an extended release formula that combines dapagliflozin and metformin. Did you experience complications after taking Farxiga? Each year, more people receive prescriptions for Farxiga. In 2016 alone, AstraZeneca reported $835 million in revenue from the drug. While Farxiga is effective at controlling blood-sugar levels, studies also link it to a number of serious side effects. The FDA released several safety communications warning patients and doctors that Farxiga and other SGLT2 inhibitors may lead to potentially fatal conditions. While the most common side effect found in studies is female yeast infections, FDA warnings and recent studies link Farxiga to side effects that can be fatal . According to FDA r Continue reading >>

Metformin Warnings

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 >>

Metformin Use Being Limited?

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 >>

Fda Reversal On Metformin Should Save More Lives

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 >>

Metformin: Are You Taking This Common Type 2 Medication? Here’s What You Need To Know

Metformin: Are You Taking This Common Type 2 Medication? Here’s What You Need To Know

For the treatment of Type 2 diabetes, most of the time, the first course of treatment is to try and control it with diet and exercise. However, if your blood sugar levels are still high despite these lifestyle changes, your doctor may recommend starting you on Metformin. Here is what you should know. What Is Metformin? Metformin is prescribed to patients with Type 2 diabetes, mainly to those patients who are insulin resistant and overweight. Metformin is an oral medication that is manufactured by Bristol-Myers Squibb Company. It was approved in 1994, by the Food and Drug Administration (FDA). Metformin is under the class of diabetes drugs known as biguanide and is sold under the brand names Fortamet, Glucophage, Glucophage XR, Glumetza and Riomet. Glucophage is dispensed as an immediate-release tablet, while Fortamet, Glucophage XR and Glumetza are released as extended-release tablets and Riomet is dispensed as an oral solution. Metformin is prescribed in doses of 500 milligrams, 850 milligrams and 1,000 milligrams, with 500 milligrams being the most common dosage. Metformin may be used in conjunction with diet and exercise or it may be used with other diabetes medications, like Competact or Janumet. What Else is Metformin Used For? Besides Type 2 diabetes, Metformin is also to treat other conditions as well, including Polycystic Ovary Syndrome (PCOS), obesity, Insulin Resistance Syndrome and female infertility. How Does Metformin Work? Metformin works in three ways. First, it stops glucose from forming in your liver. Second, it reduces the amount of sugar that your intestines absorb. Third, it improves your body’s insulin sensitivity. I advise reading the following articles: What is Metformin FDA Black Box Warning? The Food and Drug Administration (FDA) has placed a 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 >>

Should Fda Change Metformin's Black Box Warning?

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, Black Box Warnings, And Radiologic Studies

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 >>

Glyburide And Metformin Hydrochloride

Glyburide And Metformin Hydrochloride

WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here . See full prescribing information for complete Boxed Warning. Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with glyburide and metformin hydrochloride tablets; 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), 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 >5 mcg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 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 insufficiency, in Continue reading >>

What Everyone With Type 2 Diabetes Should Know

What Everyone With Type 2 Diabetes Should Know

Nearly 20 million Americans have type 2 diabetes, also known as adult-onset diabetes, a condition where a person’s body does not respond well to sugar or store it properly. Diabetes can cause many very serious health problems, including kidney disease, blindness, amputation and, most notably, heart disease. Diabetes can even increase your risk of developing cancer. These health problems that are caused by diabetes are more dangerous than the diabetes itself. Diabetes is becoming more and more common, and is estimated to affect more than 9% of the U.S. population in 2014.[1] The fact that people often take diabetes medication for many years, has meant that a diabetes drug can make a lot of money for a pharmaceutical company. As a result, many drugs to treat diabetes have come on the market in the last several years. But unfortunately, it’s not clear if the new drugs are better than the old ones – in fact, all the newer drugs have serious safety concerns (see below for more details). There is also uncertainty about the best way to treat diabetes, especially among older adults. Recent studies suggest that using drugs to keep blood sugar very tightly controlled in type 2 diabetes patients, especially older adults, may not always be beneficial. If blood sugar gets too low, this can cause serious health problems in older adults. And the benefits of tight blood sugar control are likely to only help younger people. In other words, older adults may be less likely to benefit, and more likely to be harmed, by the traditional guidelines for blood sugar (glucose). Medical experts are now starting to change their recommendations by relaxing blood sugar level goals for older adults. New Warnings about Drugs Containing Saxagliptin and Alogliptin In April 2016, the FDA issued a wa Continue reading >>

Invokana

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 >>

Metformin Use In Patients With Historical Contraindications Or Precautions [internet].

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 >>

Fda: Boxed Warning: Amputation Risk For Canagliflozin

Fda: Boxed Warning: Amputation Risk For Canagliflozin

Post-marketing trial data show doubled rates compared to placebo. Based on new data from two large clinical trials, the FDA has concluded that the type 2 diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR) causes an increased risk of leg and foot amputations. FDA is requiring new warnings, including the most prominent Boxed Warning, to be added to the canagliflozin drug labels to describe this risk. Final results from two clinical trials – the CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus) – showed that leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with placebo, which is an inactive treatment. Amputations of the toe and middle of the foot were the most common; however, amputations involving the leg, and below and above the knee also occurred. Some patients had more than one amputation, some involving both limbs. The CANVAS trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to: 5.9 out of every 1,000 patients treated with canagliflozin 2.8 out of every 1,000 patients treated with placebo The CANVAS-R trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to: 7.5 out of every 1,000 patients treated with canagliflozin 4.2 out of every 1,000 patients treated with placebo The differences were statistically significant. CANVAS was the FDA-required study investigating cardiovascular outcomes; CANVAS-R assessed renal endpoints. Lower-limb infections, gangrene, diabetic foot ulcers, and ischemia were the most common precipitating factors for amputati Continue reading >>

Relaxed Renal Guidelines For Metformin

Relaxed Renal Guidelines For Metformin

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Aging Is Officially A Disease

Aging Is Officially A Disease

The search for eternal life isnt new, but how far weve come from the Holy Grail, the Fountain of Youth and the hidden valley of Shangri-La, is truly a sign of the times. Today, the crossroads meet between the natural tendency to find an easy way out, and the seductive promise of profits. The quest is on for how to put longevity in a pill. CLASSIFYING AGE AS A DISEASE MEANS INSURANCE COMPANIES WILL COVER TREATMENT. THE FDA JUST PAVED THE WAY. Two years ago, investigators convinced the FDA to green light a human lifespan study of Metformin, a drug currently used as first-line treatment for blood sugar control in type 2 diabetes, and off-label for polycystic ovary syndrome, weight control and cancer prevention. If successful, Metformin will be the first drug to be FDA-approved for the indication of aging, but it wont be the last. With a potential audience of 7 billion people worldwide, pharmaceutical companies will race to fund clinical trials for discovery of new, more expensive drugs. High levels of blood sugar and insulin are important factors in degenerative disorders, cardiovascular disease, cancer, and aging. Metformin lowers blood sugar, which in turn, lowers insulin levels and insulin resistance. The drug intrigues researchers because its protective effect on aging goes beyond the power to control sugar and insulin. EVERYTHING METFORMIN CAN AND MIGHT DO FOR HEALTHY AGING CAN BE ACHIEVED WITH LIFESTYLE CHOICES. The TAME Study (Targeting Aging With Metformin) began in 2016, aiming to enroll 3,000 seniors, ages 70 - 80, and study them for 5 - 7 years. Study subjects can have or be at risk for any or all of 3 common aging conditions: cancer, heart disease, and dementia. The question is whether Metformin can delay or prevent cancer, heart disease, cognitive impairment, Continue reading >>

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