Pharmacology And Toxicology: Treatment Of Poisons - Metformin Intoxication
Pharmacology and Toxicology: Treatment of Poisons - Metformin Intoxication Pharmacology and Toxicology: Treatment of Poisons - Metformin Intoxication Does this patient have metformin intoxication? Since its introduction to the US market in 1995, the biguinide, metformin has become one of the most prescribed oral hypoglycemics. It is now considered the first line agent to treat type 2 diabetes. Because of its similarity to the drug another biguinide, phenformin, there was concern that it might increase the risk of lactic acidosis as was seen in phenformin. This delayed its release in the United States and led to a number of safety studies in the 1990s. One such study compared the incidence of lactic acidosis in patients treated with metformin and found that among the 7,227 patients followed on metformin, there were no incidents of lactic acidosis reported. Following its introduction, there have been a number of comparative studies with other oral agents for diabetes showing that metformin has a superior safety profile and excellent efficacy. As per the manufacturer, metformin is contraindicated in patients with chronic kidney disease. This is defined as a creatinine 1.4 mg/dL in women and 1.5 mg/dL in men. There have been a number of studies in patients with diabetes and chronic kidney disease that show that metformin remains a very safe medication and a number of authors have argued that its use should no longer be restricted in chronic kidney disease. Other authors have argued that for consistency sake alone, metformin should be restricted by a creatinine clearance estimate as it is with most medications whose clearance depends on renal function rather than a serum creatinine. For the time being, this author recommends following the restricted use of metformin as desc Continue reading >>
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- Is Metformin an Effective Treatment for Type 2 Diabetes?
Uses Metformin is used with a proper diet and exercise program and possibly with other medications to control high blood sugar. It is used in patients with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke. Metformin works by helping to restore your body's proper response to the insulin you naturally produce. It also decreases the amount of sugar that your liver makes and that your stomach/intestines absorb. How to use Metformin HCL Read the Patient Information Leaflet if available from your pharmacist before you start taking metformin and each time you get a refill. If you have any questions, consult your doctor or pharmacist. Take this medication by mouth as directed by your doctor, usually 1-3 times a day with meals. Drink plenty of fluids while taking this medication unless otherwise directed by your doctor. The dosage is based on your medical condition, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). To reduce your risk of side effects (such as upset stomach), your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Take this medication regularly in order to get the most benefit from it. Remember to use it at the same times each day. If you are already taking another diabetes drug (such as chlorpropamide), follow your doctor's directions carefully for stopping/continuing the old drug and starting metformin. Check your blood sugar regularly a Continue reading >>
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 >>
The Full Story Pills to treat diabetes are among the most dangerous medicines small children get into. A child who swallows even one of these pills must go the emergency room and usually must be admitted to the hospital for at least a day. There are several types of diabetes pills, called "oral hypoglycemics", to treat Type 2 diabetes. Some names are glipizide, glyburide, and chlorpropamide, though there are many others. Some act by increasing insulin release from the pancreas. Others make it easier for cells to use glucose. All act to lower blood sugar; this is the intended effect in someone with diabetes. For young children, there is no safe dose of these drugs. Even one pill can cause a child's blood sugar to drop dangerously low, causing seizures, coma, or death. These effects may not occur for twenty-four hours and can last up to three days. This means that a child who seems fine at bedtime can have seizures during the night unless he or she is being monitored closely. Use the webPOISONCONTROL® online tool for guidance or call Poison Control immediately at 1-800-222-1222 if a child swallows a diabetes pill (or any medicine). Poison Control will tell you exactly what to do, and will guide you every step of the way. If a child does need emergency treatment, Poison Control will work with paramedics and the emergency room staff to be sure that all of the right treatment is carried out. Pills to treat diabetes should be stored in their original containers. Lock them up where children cannot see or reach them. If a child swallows even one pill, take it seriously! Don't wait to see what might happen. Use the webPOISONCONTROL online tool for guidance or call Poison Control right away. Rose Ann Gould Soloway, RN, BSN, MSEd, DABAT emerita Clinical Toxicologist References Bu Continue reading >>
Metformin Feels Like Death In A Pill..
Registration is fast, simple and absolutely free so please,join our community todayto contribute and support the site. This topic is now archived and is closed to further replies. Well let's just say I was prepared for the stomach problems as most of you have talked about. However it has been absolutely horrid! I started my 2000mg of metformin yesterday, 1000 in the am and the rest at dinner. All I can say is oh my god! To think I felt sick before I was on meds, this just is horrible! Non stop bathroom trips, throwing up all night and this morning. My blood sugar is higher than before, probably because I can not stay hydrated. Called my dr and asked if I could start the normal dose and she won't let me lower it because my bs is too high, and made an appointment for tomorrow to check my sugar and go from there. I really do not know what to do at this point. I am missing so much work in the past week. At this point I would rather just deal with the high sugar symptoms! Sorry to hear you're having so much problems with the metformin...i'm surprised your doctor didn't start you off at the 500 mg twice daily dose the progressively increase it ---though he/she probably started you out higher as your blood sugars were so high at diagnosis. If you are taking the regular strength as opposed to the extended release pills, you might consider cutting the pills in half and spacing out your doses...say 1/2 at breakfast, 1/2 at lunch, 1/2 at dinner and 1/2 at bedtime...you'd still be getting the same TOTAL dose, just spaced differently. This might help with the symptoms, then when/if your body adjusts to the medicine, you can start just taking 2 WHOLE pills/day as directed. I did this for awhile when I was on the metformin, to stabilize my blood sugar readings. I never took more than Continue reading >>
Metformin, marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. Limited evidence suggests metformin may prevent the cardiovascular disease and cancer complications of diabetes. It is not associated with weight gain. It is taken by mouth. Metformin is generally well tolerated. Common side effects include diarrhea, nausea and abdominal pain. It has a low risk of causing low blood sugar. High blood lactic acid level is a concern if the medication is prescribed inappropriately and in overly large doses. It should not be used in those with significant liver disease or kidney problems. While no clear harm comes from use during pregnancy, insulin is generally preferred for gestational diabetes. Metformin is in the biguanide class. It works by decreasing glucose production by the liver and increasing the insulin sensitivity of body tissues. Metformin was discovered in 1922. French physician Jean Sterne began study in humans in the 1950s. It was introduced as a medication in France in 1957 and the United States in 1995. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Metformin is believed to be the most widely used medication for diabetes which is taken by mouth. It is available as a generic medication. The wholesale price in the developed world is between 0.21 and 5.55 USD per month as of 2014. In the United States, it costs 5 to 25 USD per month. Medical uses Metformin is primarily used for type 2 diabetes, but is increasingly be Continue reading >>
Toxicology Brief: Metformin Overdose In Dogs And Cats
Metformin is an antihyperglycemic prescription medication labeled for the treatment of noninsulin-dependent (type 2) diabetes mellitus in people. Metformin belongs to the biguanide group of oral antidiabetic agents and is the only biguanide currently available in the United States. Other biguanides, such as phenformin and buformin, were withdrawn from the U.S. market because of their higher risk of serious adverse effects (increased risk of lactic acidosis).1 Metformin has also been studied in cats as a potential treatment for diabetes mellitus.2,3 Most cases of metformin toxicosis reported to the ASPCA Animal Poison Control Center (APCC) involve dogs that have ingested their owners' medication. Metformin is available in single-ingredient preparations as well as in combination with other antidiabetic agents. Under the trade name Glucophage (Bristol-Myers Squibb) and in several generic formulations, metformin is available as tablets containing 500, 850, or 1,000 mg of metformin hydrochloride. Glucophage XR, the extended-release formulation, contains 500 or 750 mg of metformin hydrochloride. Two other metformin-only products available in the United States are Riomet (Ranbaxy Pharmaceuticals), a liquid oral formulation containing 500 mg/5 ml of metformin hydrochloride, and Fortamet (First Horizon Pharmaceutical) 500- or 1,000-mg extended-release tablets. MECHANISM OF ACTION AND PHARMACOKINETICS Biguanides are thought to lower postprandial glucose concentrations in diabetic patients by increasing glucose uptake and decreasing glucose production. Although the precise mechanisms by which metformin exerts its antihyperglycemic effects are not entirely certain, they are largely attributed to a reduction in hepatic gluconeogenesis, a decrease in intestinal glucose absorption, an Continue reading >>
Mala: Metformin-associated Lactic Acidosis
By Charles W. O’Connell, MD Introduction Metformin is a first-line agent for type 2 diabetes mellitus often used as monotherapy or in combination with oral diabetic medications. It is a member of the biguanide class and its main intended effect is expressed by the inhibition of hepatic gluconeogenesis. In addition, metformin increases insulin sensitivity, enhances peripheral glucose utilization and decreases glucose uptake in the gastrointestinal tract. Phenformin, a previously used biguanide, as withdrawn from the market in the 1970’s due its association with numerous cases of lactic acidosis. Metformin is currently used extensively in the management of diabetes and is the most commonly prescribed biguanide worldwide. The therapeutic dosage of metformin ranges from 850 mg to a maximum of 3000 mg daily and is typically divided into twice daily dosing. It is primarily used in the treatment of diabetes but has been used in other conditions associated with insulin resistance such as polycystic ovarian syndrome. MALA is a rare but well reported event that occurs with both therapeutic use and overdose states. Case presentation A 22-year-old female presents to the Emergency Department after being found alongside a suicide note by her family. She was thought to have taken an unknown, but large amount of her husband’s metformin. She arrives at the ED nearly 10 hours after ingestion. She was agitated, but conversant. She reports having nausea and vague feelings of being unwell and is very distraught over the state of her critically ill husband. She has some self-inflicted superficial lacerations over her left anterior forearm. Her vital assigns upon arrival were: T 98.9 degrees Fahrenheit, HR initially 140 bpm which improved to 110 bpm soon after arrival, BP 100/50, RR 22, Continue reading >>
Ph 6.68surviving Severe Metformin Intoxication
Metformin, a widely used anti-diabetic agent of the biguanide family, although generally safe, 1 , 2 , 3 , 4 holds the risk of developing a potentially lethal acidosis. 5 , 6 The association between lactic acidosis and metformin is well-established but rarely seen in patients taking this medication. 7 Its elimination relies solely on kidneys excretion, 8 so its accumulation is feasible in just two circumstances: renal failure (RF) and acute overdosage. At normal dosage, a toxic accumulation of drug requires time after the development of RF, due to metformin high clearance. About 90% of the drug is eliminated by glomerular filtration and tubular secretion (serum half-life of 1.55 h). Moreover, RF is itself associated with acidosis as it impairs kidneys ability to excrete protons. Acute intoxication on the other hand is a viable option in those cases where renal function is normal and can correlate with a psychiatric disorder. The mechanism thought to be responsible for lactic acidosis is suppression of gluconeogenesis forming lactate, pyruvate, glycerol and amino acids leading to lactate accumulation, 9 a risk that is increased by either chronic or acute RF (ARF). Usually hyperlactatemia is the most common finding leaving lactic acidosis for the most severe intoxications. A 47-year-old, apparently previously fit, non-insulin-dependent diabetic male was brought to the Emergency Department for hypoglycemia, agitation and hyperventilation. Ambulance crew found blood glucose level at 1.33 mmol/l (24 mg/dl) and administered 20 ml of 33% glucose solution followed by other 250 ml at 5%. At the arrival in the Emergency Room, the patient was confused and agitated with no signs of respiratory distress or shock. Arterial blood gases (ABG) and laboratory tests are summarized in Tab Continue reading >>
Fatal Metformin Overdose Presenting With Progressive Hyperglycemia
Go to: CASE REPORT A 29-year-old man ingested metformin in a suicide attempt. The patient consumed the entire remaining contents of his father’s prescription metformin bottle that originally contained 100 tablets of 850 mg each. The father stated that the bottle had contained at least three-quarters of its original contents, putting the ingested dose between 64 and 85 grams. The patient also consumed ethanol, but denied any other co-ingestants. The parents discovered the overdose around 6:30 a.m., about 5 ½ hours post-ingestion, when the patient began complaining of vomiting, diarrhea, thirst, abdominal pain and bilateral leg pain. Paramedics were called, who found the patient to be agitated with a fingerstick glucose level of 180 mg/dL. The patient had a history of psychosis and depression, including prior suicide attempts by drug ingestion. He was not taking any prescribed medications, having discontinued olanzapine and sertraline several months earlier. The patient had no personal history of diabetes, despite the family history of type II diabetes in his father, who was taking no other anti-diabetic medications than metformin. The patient admitted to daily ethanol and tobacco use, but denied any current or past use of illicit drugs. He had no surgical history or known allergies. Vital signs on arrival to the Emergency Department (ED) were temperature of 35.2°C (rectal), pulse of 113 beats/min, blood pressure of 129/59 mmHg, respirations at 28 breaths/min with 100% saturation via pulse oximetry on room air. The patient was awake and oriented x4, but agitated and slightly confused (GCS=14). Pupils were equal and reactive at 4mm and the oral mucous membranes were dry. Other than tachycardia, the heart and lung exams were unremarkable. The abdomen was mildly tender t Continue reading >>
Metformin-induced Lactic Acidosis: No One Left Behind
Abstract Metformin is a safe drug when correctly used in properly selected patients. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. The term metformin-induced lactic acidosis refers to cases that cannot be explained by any major risk factor other than drug accumulation, usually due to renal failure. Treatment consists of vital function support and drug removal, mainly achieved by renal replacement therapy. Despite dramatic clinical presentation, the prognosis of metformin-induced lactic acidosis is usually surprisingly good. In the previous issue of Critical Care, Friesecke and colleagues demonstrate that the survival rate of patients with severe lactic acidosis due to metformin accumulation can be strikingly higher than expected based on the initial clinical evaluation . Metformin is nowadays the first-line drug of choice for the treatment of adults with type 2 diabetes . This drug is the sixth most frequently prescribed in the USA (> 50 million prescriptions in 2009) and is taken by almost 1.5% of the Italian population [3, 4]. Metformin is a safe drug when correctly used in properly selected patients. In particular, no cases of lactic acidosis (a relatively common side effect of other biguanide compounds) were reported in 347 trials with 70,490 patient-years of metformin use . Real life can differ from research settings, however, and lactic acidosis has been repeatedly, although rarely, observed in patients treated with metformin. The number of inquiries to the Swedish Poison Information Centre for metformin intoxication has increased 10 times during the past decade, with 25 cases of severe lactic acidosis reported in 2007 and 2008 . According to the American Association of Poison Control Centers, metform Continue reading >>
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Hemodialysis In Metformin Poisoning
Extracorporeal Treatment fo Metformin Poisoning: Systematic Review and Recommendations From the Extracorporeal Treatments in Poisoning Workshop. Calello DP et al.Crit Care Med 2015 Apr 9 [Epub ahead of print] Metformin is now the oral drug most commonly prescribed to treat non-insulin-dependent diabetes in the United States. The drug is large eliminated by the kidneys. Toxicity presents with severe lactic acidosis, and can occur when decreasing renal function causes accumulation of therapeutic doses, or in the case of acute deliberate overdose. According to some reports metformin poisoning, though rare, is associated with a mortality rate of 30%. Metformin is a small molecule that is not protein-bound, making it amenable to dialysis despite having an appreciable volume of distribution (1-5 L/kg.) This paper, from the Extracorporeal Treatments in Poisoning (ExTRIP) Workgroup , aimed to review systematically literature relevant to the use of extracorporeal methods to treat metformin poisoning, and present recommendations for using such methods. The authors identified 175 relevant articles, including case reports and observation studies. Unfortunately, as in this groups previous papers regarding different poisons, the quality of the evidence was so poor that all of their recommendations were rated 1D (1=strong recommendation, D=very low level of evidence). As weve pointed out in discussing the groups earlier papers, this makes their conclusions opinions rather than evidence-based recommendations. However, given the expertise and experience of members of the group, their opinions must be reckoned with. The paper concludes that metformin is dialyzable and that extracorporeal treatment (ECTR) is recommended in severe metformin poisoning. Specific suggested indications are as Continue reading >>
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 Poisoning: A Complex Presentation
Metformin poisoning: A complex presentation We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Metformin poisoning: A complex presentation Manish Jagia, Salah Taqi, and Mahmud Hanafi The objective of this case report is to highlight presentation, complications and treatment of metformin poisoning. Patient after ingestion of 45gms of metformin developed colicky abdominal pain, severe tachypnea and vomiting. He developed severe lactic acidosis, cardiac arrest, pancreatitis and hemolytic anemia which was treated with charcoal, sodium bicarbonate, early initiation of high volume continuous veno-venous hemofiltration and supportive therapy. Metformin poisoning is a rare presentation and we discuss course of events in the management of metformin poisoning and its associated complications. Keywords: Cardiac arrest, haemolytic anemia, lactic acidosis, metformin poisoning, pancreatitis Metformin is a biguanide oral hypoglycemic agent used for non-insulin dependent diabetes mellitus (NIDDM). Metformin poisoning can cause fatal complications like severe lactic acidosis, haemolytic anemia and pancreatitis. Early diagnosis can result in successful outcome. Here, we report a case having good recovery despite metformin induced complications and cardiac arrest. A 36-year-old man presented in the Emergency Department after ingestion of 45 g metformin. He presented with colicky abdominal pain, severe tachypnoea and vomiting. He had history of NIDDM Continue reading >>
Tennessee Poison Center - 03-23-17 How Does Metformin Differ From Other Oral Hypoglycemic Drugs? - Vanderbilt Health Nashville, Tn
03-23-17 How does Metformin differ from other oral hypoglycemic drugs? 03-23-17 How does Metformin differ from other oral hypoglycemic drugs? How does Metformin differ from other oral hypoglycemic drugs? Metformin is a biguanide agent and the drug-of-choice for the treatment of newly diagnosed type-2 diabetes mellitus, making it one of the most widely prescribed medications in the world. With over half a century of clinical experience, metformin is generally recognized as safe with the most frequent adverse effects being gastrointestinal (i.e. nausea, indigestion, abdominal cramps/bloating, diarrhea). Metformin acts to reduce hepatic glucose production, reduce intestinal glucose absorption, and increase skeletal muscle glucose uptake and utilization. Because it does not affect the release of insulin or other pancreatic hormones, metformin is rarely associated with hypoglycemia. Metformin impairs mitochondrial respiration and inhibits the conversion of lactate to pyruvate. This results in both an increased production and decreased elimination of lactate with a subsequent acidosis known as metformin-associated lactic acidosis (MALA). MALA is a serious but rare complication of metformin therapy (less than 10 events per 100,000 patient-years of exposure) with a mortality rate that approaches 50%. MALA as a result of therapeutic use is typically due to an acute event that affects the patients ability to excrete metformin (i.e. acute kidney injury) coupled with risk factors that increase lactate production and/or retention (see table below). Small changes in hydration, renal function, plasma metformin concentrations, and tissue oxygenation often lead into a positive feedback loop that worsens the lactic acidosis. Acute metformin overdose is the most frequent cause of MALA. S Continue reading >>