Metformin Overdosage
Metformin is a biguanide used to treat type 2 diabetes mellitus and most commonly prescribed oral hypoglycemic agent. Metformin is now also used to treat polycystic ovary syndrome and some malignancies. Despite a good safety profile in a majority of patients with diabetes, the risk of metformin-associated lactic acidosis is genuine when safety guidelines are ignored. Overdoses with metformin are rare, but may result in serious consequences. Case reports and small case series of serious toxicity from metformin overdosage can be found in the medical literature, often with the portrayal of extracorporeal methods for the management of the subsequent severe lactic acidosis. Lactic acidosis can defined as a metabolic acidosis with a blood pH less than 7.35 and a serum lactate more than 2 mmol per liter. It can occur either with therapeutic metformin dosing (which is rare) or in overdose situations. 0.03 cases of lactic acidosis per 1000 patient-years occur within therapeutic dosing, with a majority of these cases among patients that have contraindications to metformin (such as renal insufficiency). In overdose situations, lactic acidosis is seen much more habitually, even though the precise incidence is unclear. Lactic acidosis has been observed in 1.6% of metformin exposures reported to poison control centers; nevertheless, merely 10% of these exposures were due to deliberate overdoses. The incidence of metformin-associated lactic acidosis was 12.8% in a review of poison control center inquiries from Germany. The minimum reported lethal dose was found in a 42 year-old patient who had a blood metformin level of 188 µg/ml (e.g. therapeutic range level is usually between 0.5–2.5 µg/ml). Although the intake of 35 g of metformin has shown to be lethal, the maximum reported to Continue reading >>
1322: Prolonged Hemodialysis-an Antidote For Metformin Induced Lactic Acidosis
Introduction: A 60 year old Hispanic man with Type 2 diabetes mellitus and on Metformin was brought to the Emergency Department with vomiting and diarrhea of two days duration. On physical examination, he was noted to be hypothermic, hypotensive and confused. Laboratory work-up revealed severe life threatening high anion gap metabolic acidosis,hyperlactatemia and markedly elevated creatinine of 9 mg/dl (normal 0.6-1.2 mg/dl) without prior laboratory data. Patient was intubated, vasopressor and sodium bicarbonate intravenous drips initiated and arrangement made for urgent hemodialysis based on a high index of suspicion for metformin poisoning. After 4 hours of hemodialysis, there was marked improvement in the laboratory parameters post hemodialysis. He was given another session of hemodialysis with the same hemodialysis prescription next day for 6 hours with further improvement. Initial metformin levels were found to be 46 mg/l (therapeutic levels < 2 mg/l),later confirming the diagnosis. On the 3rd day, renal function started to improve with further reduction of serum metformin level to 1.5 mg/l. He was extubated on day 5 and subsequently discharged after making a complete recovery.Lactic acidosis is a rare and potentially lethal complication of metformin therapy. It is seen in 6.3 cases per 100,000 patients on treatment(1). It can be a consequence of acute overdose or secondary to impaired metformin renal clearance. Most of the patients with metformin induced lactic acidosis have other co-morbidities like cardiopulmonary or severe renal or liver disease. Volume depletion, use of drugs that interfere with renal autoregulation like angiotensin converting enzyme Inhibitors and nonsteroidal anti-inflammatory drugs can be contributory factors. The mechanism of action is th Continue reading >>
Poisoning - Hypoglycaemic Agent - Kids Health Wa (pmh Ed Guidelines)
Oral hypoglycaemic agents are used for type II diabetes mellitus (non-insulin dependent diabetes) Sulfonylurea agents increase pancreatic insulin secretion and are the most important cause of hypoglycaemic toxicity Modified-release preparations may delay onset of symptoms for up to 8-18 hours Metformin is a biguanide agent that acts by decreasing carbohydrate absorption from the gut, increasing glucose uptake in peripheral tissues in the presence of insulin, and reducing hepatic gluconeogenesis The thiazolidinedione agents act at a nuclear receptor to improve insulin sensitivity in adipose tissues, skeletal muscles and the liver. Minimal information is available regarding overdose. The sulfonylurea agents may cause prolonged and profound life-threatening hypoglycaemia after accidental paediatric ingestion or deliberate self-poisoning Large overdoses may require treatment for several days A single tablet in a toddler has the potential to cause life-threatening hypoglycaemia. The onset of hypoglycaemia may be delayed up to 18 hours after ingestion. Admission for a minimum of 12- 24 hours is indicated for blood glucose monitoring. Discharge from hospital should only occur in the daylight hours. Metformin ingestion is not associated with hypoglycaemia in normal patients, but may cause life-threatening lactic acidosis in large overdoses or in the presence of renal or cardiac failure, or when there are co-ingestants which impair renal perfusion. Haemodialysis resolves the acidosis as well as removing metformin from the blood Nausea and vomiting may occur in smaller overdoses Asymptomatic patients following accidental exposure to metformin do not require referral to hospital, decontamination or investigation Children who have taken an unintentional ingestion of up to 1700 mg Continue reading >>
Overdose Of Oral Antidiabetic Medications And Insulin
Overdose of Oral Antidiabetic Medications and Insulin Authors: Diana Strasburger, MD, RDMS, Attending Physician, Department of Emergency Medicine, Advocate Christ Medical Center, Oak Lawn, IL. Janna H. Villano, MD, Resident Physician, Department of Emergency Medicine, Advocate Christ Medical Center, Oak Lawn, IL. Peer Reviewer: Gina Piazza, DO, Associate Professor of Emergency Medicine, Georgia Health Sciences University, Augusta, GA. — Sandra M. Schneider, MD, Editor Treating the hypoglycemia and metabolic derangements caused by antidiabetic medications, especially in massive overdose, are dynamic as new agents are introduced. Emergency physicians should know potential pitfalls in order to effectively and safely manage these patients, avoiding rebound hypoglycemia and premature discharge without appropriate monitoring. This article will review the clinical presentation and management of toxicity from commercially available antidiabetic agents in the United States, including oral hypoglycemic agents such as sulfonylureas and oral antihyperglycemic agents such as biguanides, as well as novel antidiabetic agents and insulin. Introduction Diabetes mellitus (DM) is an ever-increasing epidemic facing the current health care system. Its prevalence is increasing worldwide from an estimated 30 million in 1985 to 150 million in 2000, 171 million in 2007, and an anticipated 366 million in 2030.1,2 Medications used to treat diabetes are diverse, and often patients use multiple classes of medications to obtain euglycemia. Oral preparations can be divided into two categories based on their pharmacodynamics and effect or lack of an effect on insulin: hypoglycemic agents such as sulfonylureas and meglitinides; and antihyperglycemic agents such as biguanides, alpha-glucosidase inhibi Continue reading >>
Toxicology Brief: Metformin Overdose In Dogs And Cats
Unlike the sulfonylurea medications (e.g. glyburide or glipizide), metformin does not increase pancreatic insulin secretion and, thus, even in overdose situations, does not cause substantial hypoglycemia. In people, acute ingestions of up to 85 g1,133 mg/kg for the average 165-lb (75-kg) persondid not result in hypoglycemia.11 However, in individuals with pre-existing malnutrition, with a history of excessive exercise coupled with inadequate food intake, or taking other glucose-lowering drugs concurrently, hypoglycemia may occur.1,8 While life-threatening lactic acidosis was a frequent adverse effect in people taking phenformin, an association between lactic acidosis and metformin used therapeutically or in cases of acute overdoses is rare. Lactic acidosis is usually associated with long-term use,6 and once it develops, it has been associated with a 50% to 75% mortality rate.4 Lactic acidosis in people receiving metformin has occurred primarily in diabetic patients with significant renal insufficiency. Additionally, patients with congestive heart failure who require pharmacologic management for hypoperfusion and hypoxemia are at increased risk of lactic acidosis. The threat of lactic acidosis increases with the extent of renal dysfunction and the patient's age.9 These conditions can result in decreased renal clearance of the drug, and, consequently, lactic acidosis can occur. The postulated mechanism is that metformin causes decreased hepatic production of glucose from lactate (via the Cori cycle). The net result is decreased conversion of lactate to glucose and subsequent lactic acidosis.2,8,9 No minimum toxic metformin dose for the development of lactic acidosis is established in people. In one case report, a 15-year-old healthy girl ingested 38.25 g (550 mg/kg) of m Continue reading >>
Prime Pubmed | [methylene Blue Stopped Metformin-associated Lactic Acidosis And Refractory Vasodilatation
Hjer, Jonas, et al. "[Methylene Blue Stopped Metformin-associated Lactic Acidosis and Refractory Vasodilatation]." Lakartidningen, vol. 110, no. 42, 2013, pp. 1865-6. Hjer J, Westerbergh J, Edfeldt-Ugarph M, et al. [Methylene blue stopped metformin-associated lactic acidosis and refractory vasodilatation]. Lakartidningen. 2013;110(42):1865-6. Hjer, J., Westerbergh, J., Edfeldt-Ugarph, M., & Johansson, A. (2013). [Methylene blue stopped metformin-associated lactic acidosis and refractory vasodilatation]. Lakartidningen, 110(42), pp. 1865-6. Hjer J, et al. [Methylene Blue Stopped Metformin-associated Lactic Acidosis and Refractory Vasodilatation]. Lakartidningen. 2013;110(42):1865-6. PubMed PMID: 24294656. * Article titles in AMA citation format should be in sentence-case TY - JOURT1 - [Methylene blue stopped metformin-associated lactic acidosis and refractory vasodilatation].AU - Hjer,Jonas,AU - Westerbergh,Jenny,AU - Edfeldt-Ugarph,Malin,AU - Johansson,Asa,PY - 2013/12/4/entrezPY - 2013/12/4/pubmedPY - 2014/1/31/medlineSP - 1865EP - 6JF - LakartidningenJO - LakartidningenVL - 110IS - 42SN - 0023-7205UR - - - PRIMEDP - Unbound MedicineER - Continue reading >>
Metformin Overdose
Tweet Save As with any medication, it is possible to overdose on metformin. Some of the effects of a metformin overdose may include low blood sugar or lactic acidosis. Symptoms of low blood sugar include blurred vision, shakiness, and extreme hunger. Some symptoms of lactic acidosis can include an irregular heartbeat, trouble breathing, and feeling tired. There are some treatment options for a metformin overdose, including dialysis or using a sugar solution to increase blood sugar levels. Metformin Overdose: An Overview Metformin (Glucophage®) is a prescription medication that has been licensed to treat type 2 diabetes. As with all medicines, it is possible to take too much metformin. Effects of a metformin overdose will vary depending on a number of factors, including how much metformin was taken and whether it was taken with any other medicines, alcohol, and/or drugs. If you happen to overdose on metformin, seek medical attention immediately. Symptoms of a Metformin Overdose The effects of a metformin overdose may include: Possible symptoms of low blood sugar include: Sweating Shakiness Extreme hunger Dizziness Cold sweats Blurry vision. More severe low blood sugar symptoms include: Changes in behavior, such as irritability Loss of coordination Difficulty speaking Confusion Loss of consciousness Coma Lactic acidosis symptoms include: Feeling tired or weak Muscle pain Trouble breathing Abdominal pain (or stomach pain) Feeling cold Dizziness or lightheadedness A slow or irregular heartbeat Loss of life. Tweet Our free DiscountRx savings card can help you and your family save money on your prescriptions. This card is accepted at all major chain pharmacies, nationwide. Enter your name and email address to receive your free savings card. Treatment for a Metformin Overdose Continue reading >>
Metformin Overview
Metformin is a prescription medication used to treat type 2 diabetes. Metformin belongs to a group of drugs called biguanides, which work by helping your body respond better to the insulin it makes naturally, decreasing the amount of sugar your liver makes, and decreasing the amount of sugar your intestines absorb. This medication comes in tablet, extended-release tablet, and liquid forms. It is taken up to 3 times daily, depending on which form you are taking. Swallow extended-release tablets whole. Common side effects of metformin include diarrhea, nausea, and upset stomach. Metformin is a prescription medication used to treat type 2 diabetes. This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information. Metformin may be found in some form under the following brand names: Serious side effects have been reported including: Lactic Acidosis. In rare cases, metformin can cause a serious side effect called lactic acidosis. This is caused by a buildup of lactic acid in your blood. This build-up can cause serious damage. Lactic acidosis caused by metformin is rare and has occurred mostly in people whose kidneys were not working normally. Lactic acidosis has been reported in about one in 33,000 patients taking metformin over the course of a year. Although rare, if lactic acidosis does occur, it can be fatal in up to half the people who develop it. It is also important for your liver to be working normally when you take metformin. Your liver helps remove lactic acid from your blood. Make sure you tell your doctor before you use metformin if you have kidney or liver problems. You should also stop using metformin and call your doctor right away if you have signs of lactic acidosis. Lactic acidosis is a medical emergency that must be treate Continue reading >>
Metformin - National Library Of Medicine Hsdb Database
For more information, search the NLM HSDB database. IDENTIFICATION AND USE: Metformin is antihyperglycemic, not hypoglycemic agent. It does not cause insulin release from the pancreas and does not cause hypoglycemia, even in large doses. HUMAN EXPOSURE AND TOXICITY: Metformin is believed to work by inhibiting hepatic glucose production and increasing the sensitivity of peripheral tissue to insulin. It does not stimulate insulin secretion, which explains the absence of hypoglycemia. Metformin also has beneficial effects on the plasma lipid concentrations and promotes weight loss. Accumulation of metformin may occur in patients with renal impairment, and such accumulation rarely can result in lactic acidosis, a serious, potentially fatal metabolic disease. Lactic acidosis constitutes a medical emergency requiring immediate hospitalization and treatment; lactic acidosis is characterized by elevated blood lactate concentrations, decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. Lactic acidosis also may occur in association with a variety of pathophysiologic conditions, including diabetes mellitus, and whenever substantial tissue hypoperfusion and hypoxemia exist. Approximately 50% of cases of metformin-associated lactic acidosis have been reported to be fatal. No evidence of mutagenicity or chromosomal damage was observed in in vitro test systems, including human lymphocytes assay. ANIMAL STUDIES: No evidence of carcinogenic potential was seen in a 104-week study in male and female rats receiving metformin hydrochloride dosages up to and including 900 mg/kg daily or in a 91-week study in male and female mice receiving metformin hydrochloride at dosages up to and including 1500 mg/kg daily. Cancer preventive e Continue reading >>
Toxicology Case Of The Month: Oral Hypoglycaemic Overdose
Toxicology case of the month: oral hypoglycaemic overdose J Soderstrom, L Murray, M Little, Sir Charles Gairdner Hospital, Perth, WA, Australia L Murray, F F S Daly, M Little, University of Western Australia, Perth, WA, Australia L Murray, F F S Daly, M Little, New South Wales Poison Information Centre, New Children's Hospital, Westmead, NSW, Australia F F S Daly, Royal Perth Hospital, Perth, WA, Australia Copyright 2006 Emergency Medicine Journal. This article has been cited by other articles in PMC. A teenager ingests 375 mg of glipizide and 14.5 g of melformin intentionally in a small country town. She presents to the local medical facility with symptoms and signs of hypoglycaemia. Using a risk assessment based approach, the management of suiphonylurea and metformin overdose is discussed. Sulphonylurea overdose invariably results in profound hypoglycaemia that requires resuscitation with IV dextrose and the use of octreotide as an antidote. Metfonnin overdose rarely causes problems. Keywords: glipizide, hypoglycaemia, lactic acidosis, metformin, overdose This is the first in a series of cases presented by the Western Australian Toxicology Service. The cases are selected for their relevance to emergency medicine practice and emphasise the importance of risk assessment in formulating a coherent management plan for the acutely poisoned patient (boxes 1 and 2). These principles were discussed in depth in the introductory article for this series. 1 A 15 year old female presents to the hospital of a small remote town 2600 km north east of Perth. Some 4 h ago, following a family dispute, she ingested all of her diabetic father's medications. Her family are unable to account for 755 mg glipizide and 29500 mg metformin tablets. On arrival, she is vomiting and appears anxious Continue reading >>
The Toxicology Takedown #2 January 2015
The Toxicology Takedown #2 January 2015 A 15-Year-old female presents to the hospital 4 hours after ingestion of her diabetic fathers medication following a family dispute. Her family is unable to account for 75 x 5 mg glipizide and 29 x 500 mg metformin tablets. On arrival, she is vomiting and appears anxious and slightly sweaty with Glasgow Coma Score of 14/15. Her vital signs are pulse rate 90 bpm, blood pressure 110/75 mmHg, respiratory rate 18/min, and temperature of 36.8 C. A bedside blood glucose level is 54 mg/dl. Whats the immediate threat to life for this patient? Whats the mechanism of action of sulfonylurea medications, and how is it problematic in the management in toxicity? What are the antidotes for sulfonylurea toxicity? Whats concerning about metformin toxicity? What is the name of the syndrome that can develop in overdose and how it is managed? With respect to the ingestion of a potentially toxic amount of sulfonylureas, the immediate threat to life for this patient is hypoglycemia with potential progression to seizures and coma. This patient requires an IV line and administration of a bolus of 50 ml of 50% dextrose solution for correction of hypoglycemia and administration of another medication of minimize recurrent hypoglycemia. Glipizide is one of many sulfonylurea oral hypoglycemic agents. It exerts its effect by stimulating insulin release from the beta islet cells of the pancreas. All sulfonylureas inhibit ATP-sensitive K+ channels. This inhibition increases the membrane potential and depolarizes the cell. A subsequent influx of extracellular calcium ions through voltage-dependent calcium channels Occurs. An increase in the free intracellular calcium level is the signal, or second messenger, that triggers exocytosis and the release of insulin. F Continue reading >>
Toxicology Of Oral Antidiabetic Medications
Toxicology of Oral Antidiabetic Medications Am J Health Syst Pharm.2006;63(10):929-938. In 1996, the Food and Drug Administration approved the labeling for metformin (dimethylbiguanide), the only biguanide currently available in the United States. Phenformin, the other previously available biguanide, was withdrawn from the market in 1977 because of an association with lactic acidosis. Buformin, another biguanide, is not available in the United States. The complex of mechanisms of action of metformin is multifaceted but appears to include delayed glucose absorption, increased intestinal glucose utilization, increased intestinal lactate production, inhibition of hepatic gluconeogenesis, decreased lipid oxidation, decreased free fatty acid concentration, and increased peripheral insulin-related glucose uptake.[ 70 ] Metformin absorption is incomplete, with 20-30% found in the feces. Oral bioavailability is 40-60%, depending on the dose ingested, with greater doses producing lower bioavailability.[ 71 ] The reduced bioavailability may result from the drug binding by the intestinal wall.[ 72 ] The rate of absorption is slower than the rate of elimination, which makes absorption a rate-limiting step in the elimination half-life.[ 73 , 74 ] Absorption, in therapeutic doses, is expected to be complete in 6 hours. In an overdose situation involving massive doses, absorption may be prolonged. About 90% of the absorbed metformin is eliminated through the kidneys within the first 24 hours in patients with normal renal function.[ 72 ] Metformin has no metabolites. Metformin is the second most commonly prescribed oral antidiabetic medication in both monotherapy and combination therapy.[ 11 ] In 2004, metformin had the highest number of reports to U.S. poison control centers and the Continue reading >>
Metformin-related Acidosis In A Woman While Performing Haj: A Conservative Approach Ansari Rs, Mady Af, Qutub Ho, Althomaly E, Alzayer Za, Moulana Aa - Saudi J Kidney Dis Transpl
Metformin is a biguanide that enhances the release of glucose from the liver and the insulin effect on peripheral tissues thus decreasing the blood glucose. The most serious sideeffect of metformin is lactic acidosis due to inhibition of hepatic gluconeogenesis and/or reduction of conversion of lactic acid, pyruvic acid or alanine to glucose. The yearly incidence of lactic acidosis in previous reports was less than five episodes in every 100,000 treated individuals. Still, there is no particular antidote for metformin-induced lactic acidosis and its treatment mainly involves the correction of acidemia. [1] Considerable efficacy has been observed in the use of hemodialysis to treat the metformin-induced lactic acidosis. Hemodialysis application is currently recommended in patients with severe metabolic acidosis (pH < 7.1) and renal failure. It has been shown that plasma metformin concentrations are only slightly increased when the estimated glomerular filtration rate is 30 mL/ min/1.73 m2. [2] We present a case of successful management of metformin-associated metabolic acidosis, treated simply with intravenous sodium bicarbonate and aggressive hydration and intensive monitoring. Our aim in presenting this article is to demonstrate that even normal doses of metformin can induce severe acidosis. A 55-year-old woman with type 2 diabetes mellitus presented to the emergency department (ED) with altered level of consciousness. The patient was on metformin 500 mg three times a day. Her respiratory rate was 30 breaths/min, non-invasive blood pressure was 90/50 mm Hg, heart rate was 90 beats/min and temperature was 37C. The physical exam was otherwise unremarkable. The laboratory investigations [Table 1] on admission revealed plasma creatinine: 12.72 mg/dL, blood urea nitrogen: Continue reading >>
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 Litfl Life In The Fast Lane Medical Blog
Metformin rarely causes hypoglycaemia but it can cause a profound lactic acidosis in overdose and in patients with renal failure. Used therapeutically to inhibit glucogenogenesis and stimulate peripheral glucose uptake, in toxic doses it causes a profound lactaemia. All the mechanisms are unclear but it is in part due to the inhibition of gluconeogenesis (which lactate is required). Therefore in healthy individuals there is some build up of lactate, this is normally excreted in the urine but at impaired renal function or an acute overdose there is excess lactate. It is not metabolised and excretion relies solely on renal excretion A lactic acidosis in the context of therapeutic metformin has a high mortality rate and an underlying cause (sepsis) needs to be managed Metformin overdose is usually benign but doses > 10 grams are concerning Lactic acidosis will occur in these individuals who are susceptible (renal, cardiac, respiratory failure) or in patients who have ingested co-ingestants or are on medications that impair cardiac and renal function Severe lactic acidosis usually manifests with non-specific symptoms several hours later but can progress to coma, shock and death Children: Unintentional ingestion of up to 1700mg is benign. Hypoglycaemia, if present can be managed with dextrose . Severe acidosis and hyperkalaemia may require the administration of sodium bicarbonate (1 2 mmol/kg). However, it is likely the patient is already hyperventilating to compensate for the metabolic acidosis, haemodialysis is the ultimate priority. If in a patient on therapeutic metformin, stop further administration and seek the underlying cause for their deterioration (sepsis, acute kidney injury) Screening: 12 lead ECG, BSL, Paracetamol level 50 grams of charcoal to the co-operative Continue reading >>
