text:
Maki.vc
Published in Maki.vc
Fintech watchlist for 2021
Fintech is one of the fastest-growing industries, and it has all the possibilities to revolutionize more than just the way we handle money. Maki.vc's Paavo Räisänen and Thomas Bacon discuss the latest trends in fintech and what type of fintech Maki's on the lookout for.
As the Covid-19 crisis has…
·Jan 18, 2021
Maki House grows — new recruits to build founder platform and boost market insights
Reetta Heiskanen and Thomas Bacon.
Maki.vc's team has grown with two new recruits, with Thomas Bacon joining as the fund's new Investment Analyst and Reetta Heiskanen appointed as the new Platform and Marketing Manager. The recruits further strengthen and build Maki.vc's market insights, brand and founder platform.
Thomas is Brexit's gift to the Nordics and…
Ultimate.ai secured a $20M funding: "There rarely is benefit of having Finnish as a first language, but it has been useful when building our AI"
Maki.vc's portfolio company Ultimate.ai, the company building the world's leading virtual customer service agent just raised a €20M Series A round. We sat down with ultimate.ai CO-founders, CEO Reetu Kainulainen and COO Sarah Al-Hussaini to discuss how they have managed to attract talent in their fast-growing team and the impressive…
IQM just raised €39M — "We want to deliver our first commercial quantum computer in 2021"
The Finnish quantum computing company IQM has just raised €39 million in Series A funding — . The fast-growing startup has already managed to recruit some of the best talent in this niche market, and today, they already have one of the world's largest quantum hardware team. Maki.vc …
Europe can no longer risk being sidelined in the quantum race
Quantum technology is the industry of tomorrow, and Europe has great potential to become it's global leader. Maki.vc Partner Ilkka Kivimäki explains why now is as good a time as ever to start investing in European quantum companies.
Within the next 10 years we might have a machine that has…
Marjo Miettinen — Notes from Board Rooms
We sat down with Marjo Miettinen, seasoned tech executive, business owner, and one of our Maki House LPs to discuss one the most important assets of an entrepreneur – the company board. Marjo has been part of leadership at Ensto (a global family business in smart electrical solutions that employs…
Why I'm betting on the long-term growth of esports
Miika Huttunen is the CEO of Slush, a global movement spanning a range of activities on a mission to create and help the next generation of groundbreaking entrepreneurs. First and foremost, however, he is an avid gamer who has followed esports actively since 2003. …
5 Lessons to Start Revenue-driven Marketing
How do you build a marketing function from scratch? What should you focus on and how do you make marketing measurable and grow your revenue? Lidia Lüttin is the CMO at Happeo, a social intranet with over 300,000 users and engagement rates comparable to popular social media platforms. Before Happeo…
Hold on to talent — what your startup needs to be doing to retain great people
Founders have been drilled the importance of making the right hires, and recruitment is a priority at every growing startup. However, firms often start focusing on retention too late, and founding teams end up learning the hard — and painful — way round. Julia Hämäläinen, Inklusiiv COO and Ex-Global HR…
Keeping Your House Clean — How to Prepare Your Company for Raising Funding
You've developed your product, gathered a winning team, set up your business model, and now you're confident you have what it takes to attract outside funding. All that's standing between your company and millions is a well-crafted pitch, right?
Wrong. There are a lot of legal steps startups can't afford…
Making history? We champion the entrepreneurs rewriting the future.


HIGHEST QUALITY / EASY INSTALL VIDEO INSTRUCTIONS / FAST SHIPPING WORLD-WIDE!
This is your opportunity to purchase (1) Full Set of High Quality Cast Replacement Pieces to fix your 2003-2010 BMW X3 DOOR LOCKS. Our kit includes all internal lock pieces needed to fix your jammed, non-working door lock. This is the perfect set for the common 'spinning barrel' door lock problem which impedes your ability to lock and unlock your BMW's door. Save yourself the dreaded trip to the mechanic or dealership and repair the problem easily yourself!
Retaining Clip - Is an important piece that secures all the lock components together.
Lock Shaft - The key feature is a "cross" shaped top. This cross fits into the door lock actuator and signals the vehicle to unlock the door when turned.
Spring - Allows the lock to retract and return to the center position.
U-Shaped Middle Plate - Attaches the lock mechanism to the spring and shaft. Two slightly different pieces are provided (driver, passenger) Because this is the most commonly defective OEM piece, we have made this replacement part in very high durability to last!
Base plate - This part's function is to secure all the components in place. It fits on the bottom of the mechanism and does not rotate.


text:
You are here: Home | Ponzi Scheme | Man who bilked elderly gets
Man who bilked elderly gets
Saturday June 28, 2003 Scientology
The Arizona Republic, June 28, 2003
http://www.azcentral.com/
Carol Sowers, The Arizona Republic
A former Carefree man who pleaded guilty to spending elderly investors' money on planes, luxury cars, and jewels was sentenced Friday to 17 1/2 years in prison.
Benjamin Franklin Cook III, 55, who has been jailed since October 1999, agreed to plead guilty to three theft counts in exchange for the dismissal of more than 30 other charges.
Admitting that "mistakes had been made," Cook asked for probation so he could try to repay about 300 investors more than $43 million he collected between Jan 1, 1998, and March 15, 1999.
But Judge Greg Martin of Maricopa County Superior Court wasn't buying it.
"If this isn't an aggravated case, I don't know what is," he told Cook, who once lived on a 10-acre spread in Carefree. "This is so much money and the fraud is so gross, there just has to be a major sanction against you."
Cook's Dennel Financial Limited collapsed after a nearly three-year investigation by the U.S. Securities and Exchange Commission, the Arizona Corporation Commission, the U.S. Customs Service and state Attorney General's Office. Prosecutors said Cook promised to sink investors' money into a secretive European Bank Trading Program but spent it on two planes, a 31-foot cabin cruiser, jewels and fat commissions for top salesmen, including a BMW.
Lawrence Warfield, a certified public accountant appointed as the receiver in the Cook case, testified Friday that the money was never invested and the type of foreign investment Cook promised "doesn't exist."
Warfield's seizure and sale of Cook's home and other assets netted about $15 million. That includes the $1.5 million Cook donated to the Church of Scientology, which handed over the money as part of a civil suit.
About $12.5 million has been returned to investors, many of whom wrote Martin, telling him that Cook robbed them of their retirement money.
Still, Cook has many supporters. Leroy Robinson of Chandler, who sold Cook his two planes, said in an interview that he invested $400,000 and was getting regular interest payments of $2,000 a month until Dennel Financial was shut down.
"If he ever gets out of this, I'd invest with him again," he said.
But Martin said he wasn't convinced that Cook's supporters understood that they were being paid by the money Cook took from new investors.
"I feel for them," Martin said of Cook's supporters.
Topics: Ponzi Scheme, Scientology
This post was last updated: Wednesday, November 12, 2014 at 7:41 AM, Central European Time (CET)
An Opus Dei priest defends self-punishment of the body
Scientology centre planned in Manchester, UK
Bogus Scientology pamphlets irk Dallas mayor
Newspaper continues series of exposés of Scientology cult
Scientology: SP profiles
Spiritual symbiosis: A surprising one

redpajama_set_name: RedPajamaCommonCrawl


Rehm, M., Notten, A., Glott, R., Hagemann, P., Seibold, B., Bijlsma, L., u. a.. (2013). Open Education Case Studies – A Variety of Shades and Formats. In Openness and Education (Bd. 1-1, Bd. 1). Bingley, United Kingdom: Emerald Group Publishing Limited.


Sead Kolasinac looks set to come in for his first Premier League start of the season against Liverpool after taking a full part in training on Friday.
With Nacho Monreal expected to miss out once again , Unai Emery may be forced to field Kolasinac slightly ahead of schedule to bring some balance to the troublesome left-back position.
Emery has had to use Granit Xhaka on the left side of his defence in recent weeks while both Monreal and Kolasinac have been in the treatment room nursing hamstring injuries.
But the prospect of the Switzerland international facing Mo Salah this weekend at the Emirates has had fans fearing the worse, so the timely return of Kolasinac will be a big boost to Arsenal as they look to end Liverpool's unbeaten start to the Premier League season.
The other big decision facing Emery is at right-back. Hector Bellerin was forced off with a thigh injury against Crystal Palace last weekend but he did train on Friday, so Emery has to decide whether to risk the Spaniard or play the experienced Stephan Lichtsteiner.
Sokratis is expected to miss out with an ankle problem so Rob Holding and Shkodran Mustafi will continue in the heart of defence.
With Kolasinac expected to start , Xhaka will be able to move back into the midfield to partner Lucas Torreira in front of the back four. Mesut Ozil will then play in the advanced No.10 role supporting the front three.
Henrikh Mkhitaryan is pushing for a start but Emery is expected to stick with an attack of Pierre-Emerick Aubameyang, Alex Iwobi and Alexandre Lacazette.
Expected Arsenal XI vs Liverpool : Leno, Bellerin, Mustafi, Holding, Kolasinac, Torreira, Xhaka, Ozil, Aubameyang, Iwobi, Lacazette.


text:
What's happened since the launch of the 'Changing Young Lives' appeal? - Fylde Coast YMCA Y:Active
We believe that by building a School facility the YMCA will be able to continue changing young people's lives through outdoor education an experience that they cannot get in mainstream educational settings. Learn more about the impact of YMCA Lakeside on children and young people by clicking here.
How has the public reacted to our appeal?
The response of the public to our appeal has been hugely encouraging. We have received a grand total of £1630 in public donations through Justgiving and our other ways to donate.
If you would like to donate directly to our appeal click here.
Learn more about fundraising events held across Fylde, Wyre and Cumbria that raised funds our appeal in the past three months
YMCA Poulton Phil Versus Phil Challenge
YMCA Poulton organised the Phil Versus Phil challenge, the event was a week long series of gym challenges. Two teams were drawn together randomly from entrants and they had to complete a series of random challenges and beat the other teams time. The event encouraged people to get active while raising £116 for the appeal, bringing us a step closer to achieving our target.
YMCA Lakeside Lectures
Two of YMCA Lakesides respected instructors gave lectures and held a raffle with prizes donated by local businesses. Fiona Weatherall spoke of her experience sea kayaking around New Zealand's North Island and Mike Margeson spoke of his experience high altitude climbing with teenagers in Bolivia, the lectures had a great response and turnout. The YMCA Lakeside team raised £900 for the appeal a fantastic achievement and we would like to thank our speakers for sharing their experiences.
Zumbathon
Zumba enthusiasts did what they do best by moving, dancing and raising funds at the Zumbathon held at YMCA St. Annes. The event was very successful due to the hard work of our Zumba instructors, a high turnout and lots of fun was had. The event raised over £1000 from ticket sales and a raffle with prizes kindly donated by local businesses. The funds were split between the 'Changing Young Lives' appeal and the R.N.L.I Shannon appeal with £526 being donated to each.
In the past three months we have raised £3,172 for the 'Changing Young Lives' appeal.
You may be asking yourself 'how can I get involved?'
Look no further, the 'Changing Young Lives' appeal has an ambitious target of £100,000 raised from public donations and fundraising events because we believe in the value of outdoor education for young people across the North West.
Take a look at the get involved section of our website for ways you can get involved in the appeal such as, becoming a fundraiser, donating to the appeal through Justgiving, donating your time at one of our events, promoting our events at your workplace or attending one or all of our events!


Glyburide and metformin hydrochloride tablets, USP contain two oral antihyperglycemic drugs used in the management of type 2 diabetes, glyburide and metformin hydrochloride.
Glyburide, USP is an oral antihyperglycemic drug of the sulfonylurea class. The chemical name for glyburide is 1-[[p-[2-(5-chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclo-hexylurea. Glyburide, USP is a white to off-white crystalline compound with a molecular formula of C23H28ClN3O5S and a molecular weight of 494.00. The structural formula is represented below.
Glyburide and metformin hydrochloride tablets, USP are available for oral administration in tablets containing 1.25 mg glyburide, USP with 250 mg metformin hydrochloride, USP, 2.5 mg glyburide, USP with 500 mg metformin hydrochloride, USP and 5 mg glyburide, USP with 500 mg metformin hydrochloride, USP. In addition, each tablet contains the following inactive ingredients: ammonio methacrylate copolymer (type B), croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, povidone, sodium hydroxide, sorbic acid, titanium dioxide and triacetin. The 2.5 mg/500 mg tablet also contains: black iron oxide, D&C Yellow #10 Aluminum Lake, and yellow iron oxide. The 5 mg/500 mg tablet also contains: black iron oxide, FD&C Blue #2/Indigo Carmine Aluminum Lake, and FD&C Yellow #6/Sunset Yellow FCF Aluminum Lake.
The glyburide and metformin hydrochloride product combines glyburide and metformin hydrochloride, two antihyperglycemic agents with complementary mechanisms of action, to improve glycemic control in patients with type 2 diabetes.
Glyburide appears to lower blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which glyburide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in patients with type 2 diabetes, the blood glucose-lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs.
Metformin hydrochloride is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
In bioavailability studies of glyburide and metformin hydrochloride 2.5 mg/500 mg and 5 mg/500 mg, the mean area under the plasma concentration versus time curve (AUC) for the glyburide component was 18% and 7%, respectively, greater than that of the Micronase® brand of glyburide coadministered with metformin. The glyburide component of glyburide and metformin HCl, therefore, is not bioequivalent to Micronase®. The metformin component of glyburide and metformin is bioequivalent to metformin coadministered with glyburide.
Following administration of a single glyburide and metformin hydrochloride 5 mg/500 mg tablet with either a 20% glucose solution or a 20% glucose solution with food, there was no effect of food on the Cmax and a relatively small effect of food on the AUC of the glyburide component. The Tmax for the glyburide component was shortened from 7.5 hours to 2.75 hours with food compared to the same tablet strength administered fasting with a 20% glucose solution. The clinical significance of an earlier Tmax for glyburide after food is not known. The effect of food on the pharmacokinetics of the metformin component was indeterminate.
Single-dose studies with Micronase® (Glyburide) tablets in normal subjects demonstrate significant absorption of glyburide within one hour, peak drug levels at about four hours, and low but detectable levels at 24 hours. Mean serum levels of glyburide, as reflected by areas under the serum concentration-time curve, increase in proportion to corresponding increases in dose. Bioequivalence has not been established between glyburide and metformin hydrochloride combination product and single-ingredient glyburide products.
The absolute bioavailability of a 500 mg metformin hydrochloride tablet given under fasting conditions is approximately 50% to 60%. Studies using single oral doses of metformin tablets of 500 mg and 1500 mg, and 850 mg to 2550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. Food decreases the extent of and slightly delays the absorption of metformin, as shown by approximately a 40% lower peak concentration and a 25% lower AUC in plasma and a 35-minute prolongation of time to peak plasma concentration following administration of a single 850 mg tablet of metformin with food, compared to the same tablet strength administered fasting. The clinical relevance of these decreases is unknown.
Sulfonylurea drugs are extensively bound to serum proteins. Displacement from protein binding sites by other drugs may lead to enhanced hypoglycemic action. In vitro, the protein binding exhibited by glyburide is predominantly non-ionic, whereas that of other sulfonylureas (chlorpropamide, tolbutamide, tolazamide) is predominantly ionic. Acidic drugs, such as phenylbutazone, warfarin, and salicylates, displace the ionic-binding sulfonylureas from serum proteins to a far greater extent than the non-ionic binding glyburide. It has not been shown that this difference in protein binding results in fewer drug-drug interactions with glyburide tablets in clinical use.
The apparent volume of distribution (V/F) of metformin following single oral doses of 850 mg averaged 654±358 L. Metformin is negligibly bound to plasma proteins. Metformin partitions into erythrocytes, most likely as a function of time. At usual clinical doses and dosing schedules of metformin, steady-state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 mcg/mL. During controlled clinical trials, maximum metformin plasma levels did not exceed 5 mcg/mL, even at maximum doses.
The decrease of glyburide in the serum of normal healthy individuals is biphasic; the terminal half-life is about 10 hours. The major metabolite of glyburide is the 4-trans-hydroxy derivative. A second metabolite, the 3-cis-hydroxy derivative, also occurs. These metabolites probably contribute no significant hypoglycemic action in humans since they are only weakly active (1/400th and 1/40th as active, respectively, as glyburide) in rabbits. Glyburide is excreted as metabolites in the bile and urine, approximately 50% by each route. This dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine.
Multiple-dose studies with glyburide in patients with type 2 diabetes demonstrate drug level concentration-time curves similar to single-dose studies, indicating no build-up of drug in tissue depots.
No pharmacokinetic studies have been conducted in patients with hepatic insufficiency for either glyburide or metformin (see PRECAUTIONS).
No information is available on the pharmacokinetics of glyburide in patients with renal insufficiency.
In patients with decreased renal function the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased (see Table 1; also, see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).
There is no information on the pharmacokinetics of glyburide in elderly patients.
Limited data from controlled pharmacokinetic studies of metformin in healthy elderly subjects suggest that total plasma clearance is decreased, the half-life is prolonged, and Cmax is increased, when compared to healthy young subjects. From these data, it appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see Table 1; also see WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).
After administration of a single oral metformin hydrochloride 500 mg tablet with food, geometric mean metformin Cmax and AUC differed <5% between pediatric type 2 diabetic patients (12 to 16 years of age) and gender- and weight-matched healthy adults (20 to 45 years of age), all with normal renal function.
After administration of a single oral glyburide and metformin hydrochloride tablet with food, dose-normalized geometric mean glyburide Cmax and AUC in pediatric patients with type 2 diabetes (11 to 16 years of age, n=28, mean body weight of 97 kg) differed <6% from historical values in healthy adults.
There is no information on the effect of gender on the pharmacokinetics of glyburide.
Metformin pharmacokinetic parameters did not differ significantly in subjects with or without type 2 diabetes when analyzed according to gender (males = 19, females = 16). Similarly, in controlled clinical studies in patients with type 2 diabetes, the antihyperglycemic effect of metformin was comparable in males and females.
No information is available on race differences in the pharmacokinetics of glyburide.
No studies of metformin pharmacokinetic parameters according to race have been performed. In controlled clinical studies of metformin in patients with type 2 diabetes, the antihyperglycemic effect was comparable in whites (n=249), blacks (n=51), and Hispanics (n=24).
In a 20-week, double-blind, multicenter U.S. clinical trial, a total of 806 drug-naive patients with type 2 diabetes, whose hyperglycemia was not adequately controlled with diet and exercise alone (baseline fasting plasma glucose [FPG] <240 mg/dL, baseline hemoglobin A1c [HbA1c] between 7% and 11%), were randomized to receive initial therapy with placebo, 2.5 mg glyburide, 500 mg metformin, glyburide and metformin hydrochloride 1.25 mg/250 mg, or glyburide and metformin hydrochloride 2.5 mg/500 mg. After four weeks, the dose was progressively increased (up to the eight-week visit) to a maximum of 4 tablets daily as needed to reach a target FPG of 126 mg/dL. Trial data at 20 weeks are summarized in Table 2.
Treatment with glyburide and metformin hydrochloride resulted in significantly greater reduction in HbA1c and postprandial plasma glucose (PPG) compared to glyburide, metformin, or placebo. Also, glyburide and metformin hydrochloride therapy resulted in greater reduction in FPG compared to glyburide, metformin, or placebo, but the differences from glyburide and metformin did not reach statistical significance.
Changes in the lipid profile associated with glyburide and metformin hydrochloride treatment were similar to those seen with glyburide, metformin, and placebo.
The double-blind, placebo-controlled trial described above restricted enrollment to patients with HbA1c <11% or FPG <240 mg/dL. Screened patients ineligible for the first trial because of HbA1c and/or FPG exceeding these limits were treated directly with glyburide and metformin hydrochloride 2.5 mg/500 mg in an open-label, uncontrolled protocol. In this study, three out of 173 patients (1.7%) discontinued because of inadequate therapeutic response. Across the group of 144 patients who completed 26 weeks of treatment, mean HbA1c was reduced from a baseline of 10.6% to 7.1%. The mean baseline FPG was 283 mg/dL and was reduced to 164 and 161 mg/dL after 2 and 26 weeks, respectively. The mean final titrated dose of glyburide and metformin hydrochloride was 7.85 mg/1569 mg (equivalent to approximately three glyburide and metformin hydrochloride 2.5 mg/500 mg tablets per day).
In a 16-week, double-blind, active-controlled U.S. clinical trial, a total of 639 patients with type 2 diabetes not adequately controlled (mean baseline HbA1c 9.5%, mean baseline FPG 213 mg/dL) while being treated with at least one-half the maximum dose of a sulfonylurea (e.g., glyburide 10 mg, glipizide 20 mg) were randomized to receive glyburide (fixed dose, 20 mg), metformin (500 mg), glyburide and metformin hydrochloride 2.5 mg/500 mg, or glyburide and metformin hydrochloride 5 mg/500 mg. The doses of metformin and glyburide and metformin hydrochloride were titrated to a maximum of four tablets daily as needed to achieve FPG <140 mg/dL. Trial data at 16 weeks are summarized in Table 3.
After 16 weeks, there was no significant change in the mean HbA1c in patients randomized to glyburide or to metformin therapy. Treatment with glyburide and metformin hydrochloride at doses up to 20 mg/2000 mg per day resulted in significant lowering of HbA1c, FPG, and PPG from baseline compared to glyburide or metformin alone.
In a 24-week, double-blind, multicenter U.S. clinical trial, patients with type 2 diabetes not adequately controlled on current oral antihyperglycemic therapy (either monotherapy or combination therapy) were first switched to open label glyburide and metformin hydrochloride 2.5 mg/500 mg tablets and titrated to a maximum daily dose of 10 mg/2000 mg. A total of 365 patients inadequately controlled (HbA1c >7.0% and ≤10%) after 10 to 12 weeks of a daily glyburide and metformin hydrochloride dose of at least 7.5 mg/1500 mg were randomized to receive add-on therapy with rosiglitazone 4 mg or placebo once daily. After eight weeks, the rosiglitazone dose was increased to a maximum of 8 mg daily as needed to reach a target mean daily glucose of 126 mg/dL or HbA1c <7%. Trial data at 24 weeks or the last prior visit are summarized in Table 4.
For patients who did not achieve adequate glycemic control on glyburide and metformin hydrochloride, the addition of rosiglitazone, compared to placebo, resulted in significant lowering of HbA1c and FPG.
Glyburide and metformin hydrochloride tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Severe renal impairment (eGFR below 30 mL/min/1.73m2) (see WARNINGS and PRECAUTIONS).
Known hypersensitivity to metformin hydrochloride or glyburide.
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.
If metformin-associated lactic acidosis is suspected, immediately discontinue glyburide and metformin hydrochloride tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended (see PRECAUTIONS).
The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups (Diabetes 19 (Suppl. 2):747-830, 1970).
UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 g per day) had a rate of cardiovascular mortality approximately 2½ times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and benefits of glyburide and of alternative modes of therapy.
Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.
There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypotension and resistant bradyarrhythmias have occurred with severe acidosis.
Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate:pyruvate ratio; metformin plasma levels were generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk.
If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of glyburide and metformin hydrochloride. In glyburide and metformin hydrochloride treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions). Hemodialysis has often resulted in reversal of symptoms and recovery.
Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur instruct them to discontinue glyburide and metformin hydrochloride tablets and report these symptoms to their healthcare provider.
Renal Impairment - The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment.
Before initiating glyburide and metformin hydrochloride, obtain an estimated glomerular filtration rate (eGFR).
Glyburide and metformin hydrochloride is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 (see CONTRAINDICATIONS).
Initiation of glyburide and metformin hydrochloride is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m2.
Obtain an eGFR at least annually in all patient taking glyburide and metformin hydrochloride. In patients at risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently.
In patients taking glyburide and metformin hydrochloride whose eGFR falls below 45 mL/min/1.73 m2, assess the benefit and risk of continuing therapy.
Drug Interactions -The concomitant use of glyburide and metformin hydrochloride with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation. Consider more frequent monitoring of patients.
Age 65 or Greater - The risk of metformin-associated lactic acidosis increases with the patient's age because elderly patients have a greater likelihood of having hepatic, renal, or cardiac impairment than younger patients. Assess renal function more frequently in elderly patients.
Radiologic Studies with Contrast - Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and the occurrence of lactic acidosis. Stop glyburide and metformin hydrochloride at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a history of hepatic impairment, alcoholism or heart failure, or in patients who will be administered intra-arterial iodinated contrast. Reevaluate eGFR 48 hours after the imaging procedure, and restart glyburide and metformin hydrochloride if renal function is stable.
Surgery and Other Procedures - Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment. glyburide and metformin hydrochloride should be temporarily discontinued while patients have restricted food and fluid intake.
Hypoxic States - Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia). Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may cause prerenal azotemia. When such an event occurs, discontinue glyburide and metformin hydrochloride.
Excessive Alcohol Intake—Alcohol is known to potentiate the effect of metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving glyburide and metformin hydrochloride.
Hepatic Impairment—Patients with hepatic impairment have developed cases of metformin-associated lactic acidosis. This may be due to impaired lactate clearance resulting in higher lactate blood levels. Therefore, avoid use of glyburide and metformin hydrochloride in patients with clinical or laboratory evidence of hepatic disease.
The glyburide component of glyburide and metformin HCl tablets is not bioequivalent to Micronase®. In addition, it has been reported that bioavailability studies have demonstrated that micronized glyburide tablets 3 mg provide serum glyburide concentration that are not bioequivalent to those from nonmicronized glyburide tablets 5 mg. Therefore, patients should be retitrated when transferred from micronized glyburide tablets or other oral hypoglycemic agents.
Glyburide and metformin hydrochloride is capable of producing hypoglycemia or hypoglycemic symptoms, therefore, proper patient selection, dosing, and instructions are important to avoid potential hypoglycemic episodes. The risk of hypoglycemia is increased when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents or ethanol. Renal or hepatic insufficiency may cause elevated drug levels of both glyburide and metformin hydrochloride, and the hepatic insufficiency may also diminish gluconeogenic capacity, both of which increase the risk of hypoglycemic reactions. Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs.
Treatment of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia. Because glyburide and metformin hydrochloride belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD deficiency and a non-sulfonylurea alternative should be considered. In postmarketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.
In controlled clinical trials with metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum vitamin B12, without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely associated with anemia and appears to be rapidly reversible with discontinuation of metformin or vitamin B12 supplementation. Measurement of hematologic parameters on an annual basis is advised in patients on metformin and any apparent abnormalities should be appropriately investigated and managed (see PRECAUTIONS: Laboratory Tests).
Certain individuals (those with inadequate vitamin B12 or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B12 levels. In these patients, routine serum vitamin B12 measurements at 2- to 3-year intervals may be useful.
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glyburide and metformin hydrochloride or any other antidiabetic drug.
Patients receiving glyburide and metformin hydrochloride in combination with a thiazolidinedione may be at risk for hypoglycemia.
Weight gain was seen with the addition of rosiglitazone to glyburide and metformin hydrochloride, similar to that reported for thiazolidinedione therapy alone.
When a thiazolidinedione is used in combination with glyburide and metformin hydrochloride, periodic monitoring of liver function tests should be performed in compliance with the labeled recommendations for the thiazolidinedione.
Patients should be informed of the potential risks and benefits of glyburide and metformin hydrochloride and alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions, a regular exercise program, and regular testing of blood glucose, glycosylated hemoglobin, renal function, and hematologic parameters.
The risks of lactic acidosis associated with metformin therapy, its symptoms, and conditions that predispose to its development, as noted in the WARNINGS and PRECAUTIONS sections, should be explained to patients. Patients should be advised to discontinue glyburide and metformin hydrochloride immediately and promptly notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual somnolence, or other nonspecific symptoms occur. Once a patient is stabilized on any dose level of glyburide and metformin hydrochloride, gastrointestinal symptoms, which are common during initiation of metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.
The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members.
Periodic fasting blood glucose (FBG) and HbA1c measurements should be performed to monitor therapeutic response.
Initial and periodic monitoring of hematologic parameters (e.g., hemoglobin/hematocrit and red blood cell indices) and renal function (serum creatinine) should be performed, at least on an annual basis. While megaloblastic anemia has rarely been seen with metformin therapy, if this is suspected, vitamin B12 deficiency should be excluded.
Instruct patients to inform their doctor that they are taking glyburide and metformin hydrochloride prior to any surgical or radiological procedure, as temporary discontinuation of glyburide and metformin hydrochloride may be required until renal function has been confirmed to be normal (see PRECAUTIONS).
Certain drugs tend to produce hyperglycemia and may lead to loss of blood glucose control. These drugs include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving glyburide and metformin hydrochloride, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving glyburide and metformin hydrochloride, the patient should be observed closely for hypoglycemia. Metformin is negligibly bound to plasma proteins and is, therefore, less likely to interact with highly protein-bound drugs such as salicylates, sulfonamides, chloramphenicol, and probenecid as compared to sulfonylureas, which are extensively bound to serum proteins.
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs, including nonsteroidal anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta-adrenergic blocking agents. When such drugs are administered to a patient receiving glyburide and metformin hydrochloride, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving glyburide and metformin hydrochloride, the patient should be observed closely for loss of blood glucose control.
An increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan. Therefore concomitant administration of glyburide and metformin hydrochloride and bosentan is contraindicated.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known.
Colesevelam: Concomitant administration of colesevelam and glyburide resulted in reductions in glyburide AUC and Cmax of 32% and 47%, respectively. The reductions in glyburide AUC and Cmax were 20% and 15%, respectively, when administered 1 hour before, and not significantly changed (-7% and 4%, respectively) when administered 4 hours before colesevelam.
A single-dose, metformin-furosemide drug interaction study in healthy subjects demonstrated that pharmacokinetic parameters of both compounds were affected by coadministration. Furosemide increased the metformin plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in metformin renal clearance. When administered with metformin, the Cmax and AUC of furosemide were 31% and 12% smaller, respectively, than when administered alone, and the terminal half-life was decreased by 32%, without any significant change in furosemide renal clearance. No information is available about the interaction of metformin and furosemide when coadministered chronically.
A single-dose, metformin-nifedipine drug interaction study in normal healthy volunteers demonstrated that coadministration of nifedipine increased plasma metformin Cmax and AUC by 20% and 9%, respectively, and increased the amount excreted in the urine. Tmax and half-life were unaffected. Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine.
Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transport-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the accumulation of metformin and the risk for lactic acidosis. Consider the benefits and risks of concomitant use. Such interaction between metformin and oral cimetidine has been observed in normal healthy volunteers in both single- and multiple-dose, metformin-cimetidine drug interaction studies, with a 60% increase in peak metformin plasma and whole blood concentrations and a 40% increase in plasma and whole blood metformin AUC. There was no change in elimination half-life in the single-dose study. Metformin had no effect on cimetidine pharmacokinetics.
Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with glyburide and metformin hydrochloride may increase the risk for lactic acidosis. Consider more frequent monitoring of these patients.
Alcohol is known to potentiate the effects of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving glyburide and metformin hydrochloride.
No animal studies have been conducted with the combined products in glyburide and metformin hydrochloride. The following data are based on findings in studies performed with the individual products.
Studies in rats with glyburide alone at doses up to 300 mg/kg/day (approximately 145 times the maximum recommended human daily [MRHD] dose of 20 mg for the glyburide component of glyburide and metformin hydrochloride based on body surface area comparisons) for 18 months revealed no carcinogenic effects. In a two-year oncogenicity study of glyburide in mice, there was no evidence of treatment-related tumors.
There was no evidence of mutagenic potential of glyburide alone in the following in vitro tests: Salmonella microsome test (Ames test) and in the DNA damage/alkaline elution assay.
Long-term carcinogenicity studies were performed with metformin alone in rats (dosing duration of 104 weeks) and mice (dosing duration of 91 weeks) at doses up to and including 900 mg/kg/day and 1500 mg/kg/day, respectively. These doses are both approximately four times the MRHD dose of 2000 mg of the metformin component of glyburide and metformin hydrochloride based on body surface area comparisons. No evidence of carcinogenicity with metformin alone was found in either male or female mice. Similarly, there was no tumorigenic potential observed with metformin alone in male rats. There was, however, an increased incidence of benign stromal uterine polyps in female rats treated with 900 mg/kg/day of metformin alone.
There was no evidence of a mutagenic potential of metformin alone in the following in vitro tests: Ames test (S. typhimurium), gene mutation test (mouse lymphoma cells), or chromosomal aberrations test (human lymphocytes). Results in the in vivo mouse micronucleus test were also negative.
Fertility of male or female rats was unaffected by metformin alone when administered at doses as high as 600 mg/kg/day, which is approximately three times the MRHD dose of the metformin component of glyburide and metformin hydrochloride based on body surface area comparisons.
There are no adequate and well-controlled studies in pregnant women with glyburide and metformin hydrochloride or its individual components. No animal studies have been conducted with the combined products in glyburide and metformin hydrochloride. The following data are based on findings in studies performed with the individual products.
Reproduction studies were performed in rats and rabbits at doses up to 500 times the MRHD dose of 20 mg of the glyburide component of glyburide and metformin hydrochloride based on body surface area comparisons and revealed no evidence of impaired fertility or harm to the fetus due to glyburide.
Metformin alone was not teratogenic in rats or rabbits at doses up to 600 mg/kg/day. This represents an exposure of about two and six times the MRHD dose of 2000 mg of the metformin component of glyburide and metformin hydrochloride based on body surface area comparisons for rats and rabbits, respectively. Determination of fetal concentrations demonstrated a partial placental barrier to metformin.
Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. It is not recommended that glyburide and metformin hydrochloride be used during pregnancy. However, if it is used, glyburide and metformin hydrochloride should be discontinued at least two weeks before the expected delivery date (see Pregnancy: Teratogenic Effects: Pregnancy Category B).
Although it is not known whether glyburide is excreted in human milk, some sulfonylurea drugs are known to be excreted in human milk. Studies in lactating rats show that metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted in nursing mothers. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue glyburide and metformin hydrochloride, taking into account the importance of the drug to the mother. If glyburide and metformin hydrochloride is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
The safety and efficacy of glyburide and metformin hydrochloride was evaluated in an active-controlled, double-blind, 26-week randomized trial involving a total of 167 pediatric patients (ranging from 9 to 16 years of age) with type 2 diabetes. Glyburide and metformin hydrochloride was not shown statistically to be superior to either metformin or glyburide with respect to reducing HbA1c from baseline (see Table 5). No unexpected safety findings were associated with glyburide and metformin hydrochloride in this trial.
Of the 642 patients who received glyburide and metformin hydrochloride in double-blind clinical studies, 23.8% were 65 and older while 2.8% were 75 and older. Of the 1302 patients who received glyburide and metformin hydrochloride in open-label clinical studies, 20.7% were 65 and older while 2.5% were 75 and older. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients (see also WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).
In double-blind clinical trials involving glyburide and metformin hydrochloride as initial therapy or as second-line therapy, a total of 642 patients received the combination product glyburide and metformin hydrochloride, 312 received metformin therapy, 324 received glyburide therapy, and 161 received placebo. The percent of patients reporting events and types of adverse events reported in clinical trials of glyburide and metformin hydrochloride (all strengths) as initial therapy and second-line therapy are listed in Table 6.
In a controlled clinical trial of rosiglitazone versus placebo in patients treated with glyburide and metformin hydrochloride (n=365), 181 patients received glyburide and metformin hydrochloride with rosiglitazone and 184 received glyburide and metformin hydrochloride with placebo.
Edema was reported in 7.7% (14/181) of patients treated with rosiglitazone compared to 2.2% (4/184) of patients treated with placebo. A mean weight gain of 3 kg was observed in rosiglitazone-treated patients.
Disulfiram-like reactions have very rarely been reported in patients treated with glyburide tablets.
In controlled clinical trials of glyburide and metformin hydrochloride there were no hypoglycemic episodes requiring medical intervention and/or pharmacologic therapy; all events were managed by the patients. The incidence of reported symptoms of hypoglycemia (such as dizziness, shakiness, sweating, and hunger), in the initial therapy trial of glyburide and metformin hydrochloride are summarized in Table 7. The frequency of hypoglycemic symptoms in patients treated with glyburide and metformin hydrochloride 1.25 mg/250 mg was highest in patients with a baseline HbA1c <7%, lower in those with a baseline HbA1c of between 7% and 8%, and was comparable to placebo and metformin in those with a baseline HbA1c >8%. For patients with a baseline HbA1c between 8% and 11% treated with glyburide and metformin hydrochloride 2.5 mg/500 mg as initial therapy, the frequency of hypoglycemic symptoms was 30% to 35%. As second-line therapy in patients inadequately controlled on sulfonylurea alone, approximately 6.8% of all patients treated with glyburide and metformin hydrochloride experienced hypoglycemic symptoms. When rosiglitazone was added to glyburide and metformin hydrochloride therapy, 22% of patients reported one or more fingerstick glucose measurements ≤50 mg/dL compared to 3.3% of placebo-treated patients. All hypoglycemic events were managed by the patients and only one patient discontinued for hypoglycemia (see PRECAUTIONS: General: Addition of Thiazolidinediones to Glyburide and Metformin Hydrochloride Therapy).
The incidence of gastrointestinal (GI) side effects (diarrhea, nausea/vomiting, and abdominal pain) in the initial therapy trial are summarized in Table 7. Across all glyburide and metformin hydrochloride trials, GI symptoms were the most common adverse events with glyburide and metformin hydrochloride and were more frequent at higher dose levels. In controlled trials, <2% of patients discontinued glyburide and metformin hydrochloride therapy due to GI adverse events.
Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; the drug should be discontinued if this occurs. Liver function abnormalities, including isolated transaminase elevations, have been reported.
Allergic skin reactions, eg, pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions, occur in 1.5% of glyburide-treated patients. These may be transient and may disappear despite continued use; if skin reactions persist, the drug should be discontinued.
The following adverse reactions have been identified during post-approval use. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Allergic: Angioedema, arthralgia, myalgia, and vasculitis have been reported.
Dermatologic: Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.
Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, which occasionally may present as purpura, hemolytic anemia, aplastic anemia, and pancytopenia, have been reported with sulfonylureas.
Metabolic: Hepatic porphyria reactions have been reported with sulfonylureas; however, these have not been reported with glyburide. Disulfiram-like reactions have been reported very rarely with glyburide. Cases of hyponatremia have been reported with glyburide and all other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone.
Other Reactions: Changes in accommodation and/or blurred vision have been reported with glyburide and other sulfonylureas. These are thought to be related to fluctuation in glucose levels.
Overdosage of sulfonylureas, including glyburide tablets, can produce hypoglycemia. Mild hypoglycemic symptoms, without loss of consciousness or neurological findings, should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger.
Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours, since hypoglycemia may recur after apparent clinical recovery.
Overdose of metformin hydrochloride has occurred, including ingestion of amounts >50 g. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases (see WARNINGS). Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.
Dosage of glyburide and metformin hydrochloride must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glyburide/2000 mg metformin. Glyburide and metformin hydrochloride should be given with meals and should be initiated at a low dose, with gradual dose escalation as described below, in order to avoid hypoglycemia (largely due to glyburide), to reduce GI side effects (largely due to metformin), and to permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient.
With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to glyburide and metformin hydrochloride and to identify the minimum effective dose for the patient. Thereafter, HbA1c should be measured at intervals of approximately 3 months to assess the effectiveness of therapy. The therapeutic goal in all patients with type 2 diabetes is to decrease FPG, PPG, and HbA1c to normal or as near normal as possible. Ideally, the response to therapy should be evaluated using HbA1c (glycosylated hemoglobin), which is a better indicator of long-term glycemic control than FPG alone.
No studies have been performed specifically examining the safety and efficacy of switching to glyburide and metformin hydrochloride therapy in patients taking concomitant glyburide (or other sulfonylurea) plus metformin. Changes in glycemic control may occur in such patients, with either hyperglycemia or hypoglycemia possible. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring.
Recommended starting dose: 1.25 mg/250 mg once or twice daily with meals.
For patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone, the recommended starting dose of glyburide and metformin hydrochloride is 1.25 mg/250 mg once a day with a meal. As initial therapy in patients with baseline HbA1c >9% or an FPG >200 mg/dL, a starting dose of glyburide and metformin hydrochloride 1.25 mg/250 mg twice daily with the morning and evening meals may be used. Dosage increases should be made in increments of 1.25 mg/250 mg per day every two weeks up to the minimum effective dose necessary to achieve adequate control of blood glucose. In clinical trials of glyburide and metformin hydrochloride as initial therapy, there was no experience with total daily doses >10 mg/2000 mg per day. Glyburide and metformin hydrochloride 5 mg/500 mg should not be used as initial therapy due to an increased risk of hypoglycemia.
Recommended starting dose: 2.5 mg/500 mg or 5 mg/500 mg twice daily with meals.
For patients not adequately controlled on either glyburide (or another sulfonylurea) or metformin alone, the recommended starting dose of glyburide and metformin hydrochloride is 2.5 mg/500 mg or 5 mg/500 mg twice daily with the morning and evening meals. In order to avoid hypoglycemia, the starting dose of glyburide and metformin hydrochloride should not exceed the daily doses of glyburide or metformin already being taken. The daily dose should be titrated in increments of no more than 5 mg/500 mg up to the minimum effective dose to achieve adequate control of blood glucose or to a maximum dose of 20 mg/2000 mg per day.
For patients previously treated with combination therapy of glyburide (or another sulfonylurea) plus metformin, if switched to glyburide and metformin hydrochloride, the starting dose should not exceed the daily dose of glyburide (or equivalent dose of another sulfonylurea) and metformin already being taken. Patients should be monitored closely for signs and symptoms of hypoglycemia following such a switch and the dose of glyburide and metformin hydrochloride should be titrated as described above to achieve adequate control of blood glucose.
For patients not adequately controlled on glyburide and metformin hydrochloride, a thiazolidinedione can be added to glyburide and metformin hydrochloride therapy. When a thiazolidinedione is added to glyburide and metformin hydrochloride therapy, the current dose of glyburide and metformin hydrochloride can be continued and the thiazolidinedione initiated at its recommended starting dose. For patients needing additional glycemic control, the dose of the thiazolidinedione can be increased based on its recommended titration schedule. The increased glycemic control attainable with glyburide and metformin hydrochloride plus a thiazolidinedione may increase the potential for hypoglycemia at any time of day. In patients who develop hypoglycemia when receiving glyburide and metformin hydrochloride and a thiazolidinedione, consideration should be given to reducing the dose of the glyburide component of glyburide and metformin hydrochloride. As clinically warranted, adjustment of the dosages of the other components of the antidiabetic regimen should also be considered.
When colesevelam is coadministered with glyburide, maximum plasma concentration and total exposure to glyburide is reduced. Therefore, glyburide and metformin hydrochloride should be administered at least 4 hours prior to colesevelam.
Assess renal function prior to initiation of glyburide and metformin hydrochloride and periodically thereafter.
Glyburide and metformin hydrochloride is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2.
Initiation of glyburide and metformin hydrochloride in patients with an eGFR between 30 to 45 mL/min/1.73 m2 is not recommended.
In patients taking glyburide and metformin hydrochloride whose eGFR later falls below 45 mL/min/1.73 m2, assess the benefit risk of continuing therapy.
Discontinue glyburide and metformin hydrochloride if the patient's eGFR later falls below 30 mL/min/1.73 m2 (see WARNINGS and PRECAUTIONS.).
Discontinue glyburide and metformin hydrochloride at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m2; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart glyburide and metformin hydrochloride if renal function is stable.
Glyburide and metformin hydrochloride is not recommended for use during pregnancy. The initial and maintenance dosing of glyburide and metformin hydrochloride should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment requires a careful assessment of renal function.
1.25 mg/250 mg —Each white to off-white, capsule-shaped, film coated tablet imprinted with and 751 on one side and plain on the other side contains 1.25 mg of glyburide, USP and 250 mg of metformin hydrochloride, USP. Tablets are supplied in bottles of 100 (NDC 0115-1648-01) and 500 (NDC 0115-1648-02).
2.5 mg/500 mg —Each yellow, capsule-shaped, film coated tablet imprinted with and 752 on one side and plain on the other side contains 2.5 mg of glyburide, USP and 500 mg of metformin hydrochloride, USP. Tablets are supplied in bottles of 100 (NDC 0115-1649-01) and 500 (NDC 0115-1649-02).
5 mg/500 mg — Each blue, capsule-shaped, film coated tablet imprinted with and 753 on one side and plain on the other side contains 5 mg of glyburide, USP and 500 mg of metformin hydrochloride, USP. Tablets are supplied in bottles of 100 (NDC 0115-1650-01) and 500 (NDC 0115-1650-02).
Store at temperatures up to 25°C (77°F) [See USP Controlled Room Temperature].
Q1. Why do I need to take Glyburide and Metformin Hydrochloride Tablets?
Your doctor has prescribed glyburide and metformin hydrochloride tablets to treat your type 2 diabetes. This is also known as non-insulin-dependent diabetes mellitus.
Q2. What is type 2 diabetes?
People with diabetes are not able to make enough insulin and/or respond normally to the insulin their body does make. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems, including kidney damage, amputations, and blindness. Diabetes is also closely linked to heart disease. The main goal of treating diabetes is to lower your blood sugar to a normal level.
Q3. Why is it important to control type 2 diabetes?
The main goal of treating diabetes is to lower your blood sugar to a normal level. Studies have shown that good control of blood sugar may prevent or delay complications, such as heart disease, kidney disease, or blindness.
Q4. How is type 2 diabetes usually controlled?
High blood sugar can be lowered by diet and exercise, a number of oral medications, and insulin injections. Before taking glyburide and metformin hydrochloride tablets you should first try to control your diabetes by exercise and weight loss. Even if you are taking glyburide and metformin hydrochloride tablets, you should still exercise and follow the diet recommended for your diabetes.
Q5. Does Glyburide and Metformin Hydrochloride tablets work differently from other glucose-control medications?
Yes, it does. The glyburide and metformin hydrochloride product combines two glucose-lowering drugs, glyburide and metformin. These two drugs work together to improve the different metabolic defects found in type 2 diabetes. Glyburide lowers blood sugar primarily by causing more of the body's own insulin to be released, and metformin lowers blood sugar, in part, by helping your body use your own insulin more effectively. Together, they are efficient in helping you to achieve better glucose control.
Q6. What happens if my blood sugar is still too high?
When blood sugar cannot be lowered enough by glyburide and metformin hydrochloride tablets your doctor may prescribe injectable insulin or take other measures to control your diabetes.
Q7. Can Glyburide and Metformin Hydrochloride tablets cause side effects?
Glyburide and metformin hydrochloride tablets, like all blood sugar-lowering medications, can cause side effects in some patients. Most of these side effects are minor. However, there are also serious, but rare, side effects related to glyburide and metformin hydrochloride tablets (see Q9 to Q13).
Q8. What are the most common side effects of Glyburide and Metformin Hydrochloride tablets?
The most common side effects of glyburide and metformin hydrochloride tablets are normally minor ones such as diarrhea, nausea, and upset stomach. If these side effects occur, they usually occur during the first few weeks of therapy. Taking your glyburide and metformin hydrochloride tablets with meals can help reduce these side effects.
Less frequently, symptoms of hypoglycemia (low blood sugar), such as lightheadedness, dizziness, shakiness, or hunger may occur. The risk of hypoglycemic symptoms increases when meals are skipped, too much alcohol is consumed, or heavy exercise occurs without enough food. Following the advice of your doctor can help you to avoid these symptoms.
Q9. Are there any serious side effects that Glyburide and Metformin Hydrochloride tablets can cause?
People who have a condition known as glucose-6-phosphate dehydrogenase (G6PD) deficiency and who take glyburide and metformin hydrochloride tablets may develop hemolytic anemia (fast breakdown of red blood cells). G6PD deficiency usually runs in families. Tell your doctor if you or any members of your family have been diagnosed with G6PD deficiency before you start taking glyburide and metformin hydrochloride tablets.
Glyburide and metformin hydrochloride tablets rarely causes serious side effects. The most serious side effect that glyburide and metformin hydrochloride tablets can cause is called lactic acidosis.
Q10. What is lactic acidosis and can it happen to me?
Metformin, one of the medicines in glyburide and metformin hydrochloride tablets can cause a rare but serious condition called lactic acidosis (a buildup of an acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital.
Q11. Are there other risk factors for lactic acidosis?
The best way to keep from having a problem with lactic acidosis from metformin is to tell your doctor if you have any of the problems in the list above. Your doctor may decide to stop your glyburide and metformin hydrochloride tablets for a while if you have any of these things.
Q12. What are the symptoms of lactic acidosis?
Q13. What does my doctor need to know to decrease my risk of lactic acidosis?
are going to get an injection of dye or contrast agents for an x-ray procedure. Glyburide and metformin hydrochloride tablets may need to be stopped for a short time. Talk to your doctor about when you should stop glyburide and metformin hydrochloride tablets and when you should start glyburide and metformin hydrochloride tablets again. See "What is the most important information I should know about glyburide and metformin hydrochloride tablets?"
Q14. Can I take Glyburide and Metformin Hydrochloride Tablets with other medications?
Remind your doctor that you are taking glyburide and metformin hydrochloride tablets when any new drug is prescribed or a change is made in how you take a drug already prescribed. Glyburide and metformin hydrochloride tablets may interfere with the way some drugs work and some drugs may interfere with the action of glyburide and metformin hydrochloride.
Do not take glyburide and metformin hydrochloride tablets if you are taking bosentan used for pulmonary arterial hypertension (PAH), which is high blood pressure in the vessels of the lungs.
Q15. What if I become pregnant while taking Glyburide and Metformin Hydrochloride Tablets?
Tell your doctor if you plan to become pregnant or have become pregnant. As with other oral glucose-control medications, you should not take glyburide and metformin hydrochloride tablets during pregnancy.
Usually your doctor will prescribe insulin while you are pregnant. As with all medications, you and your doctor should discuss the use of glyburide and metformin hydrochloride tablets if you are nursing a child.
Q16. How do I take Glyburide and Metformin Hydrochloride Tablets?
Your doctor will tell you how many glyburide and metformin hydrochloride tablets to take and how often. This should also be printed on the label of your prescription. You will probably be started on a low dose of glyburide and metformin hydrochloride tablets and your dosage will be increased gradually until your blood sugar is controlled.
Q17. Where can I get more information about Glyburide and Metformin Hydrochloride Tablets?
This leaflet is a summary of the most important information about glyburide and metformin hydrochloride tablets. If you have any questions or problems, you should talk to your doctor or other healthcare provider about type 2 diabetes as well as glyburide and metformin hydrochloride tablets and their side effects. For additional information about glyburide and metformin hydrochloride tablets, call Actavis at 1-800-432-8534. There is also a leaflet (prescribing information) written for health professionals that your pharmacist can let you read.


Doing neat installations is what we do best. No need to spoil your premise with un-tidy cables. Our cameras are also very user friendly and can be monitored from your mobile device without any issues.
Feel free to contact us for you next camera installation.


text:
Stainland Road, Stainland, Halifax, HX4 9HU
Bowling Green Primary School
Curriculum and Learning
Reading and Phonics Scheme
Learning Ladders
Letters and News
Staff and Governors
PREVENT Strategy
The Department for Education have recently reinforced the need "to create and enforce a clear and rigorous expectation on all schools to promote the fundamental British values of democracy, the rule of law, individual liberty and mutual respect and tolerance of those with different faiths and beliefs."
The Government set out its definition of British values in the 2011 Prevent Strategy, and these values have been reiterated more recently.
At Bowling Green Primary School, we recognise the importance of teaching our pupils mutual respect for those of different or of no faith, and the shared values of Christianity and other major world faiths.
Our Religious Education programme includes the Calderdale/Kirklees agreed syllabus and focuses on the three faiths of Christianity, Islam and Judaism.
Within our school, British Values pervade much of what do on a daily basis, largely through what could be deemed the 'hidden curriculum'. This is where the school's ethos influences more abstract areas of personal development such as forming and maintain relationships, self-esteem and patterns of behaviour - all of which are considered crucial to prepare our children for life in modern Britain.
Our mission statement of 'Achieving Together' reinforces this ethos - our aims and values are:
To provide a safe and secure place to learn
To provide a happy, caring and welcoming environment in which all work together
To encourage self-esteem, independence and emotional intelligence
To provide a variety of fun, stimulating, quality learning experiences which enable all learners to reach their full potential
To provide a balanced, broad and differentiated curriculum, which is equally accessible to all, and which encourages learners to develop knowledge, skills and understanding
To value and respect all, in our community and beyond
To encourage perseverance and a positive attitude to learning
To encourage healthy, safe life choices
To build strong effective relationships with all in our community
To create firm foundations for the future, as individuals and citizens.
We also offer regular activities and opportunities to our pupils which promote British Values in a more explicit and deliberate way. Click on each link below to find out more...
© 2019 Bowling Green Primary School.
School website created using School Jotter, a Webanywhere product. [Administer Site]


Dancing professionally seems to be a family affair for soon-to-be NAISDA graduates and sisters Amy and Emily Flannery. The duo concluded their studies at NAISDA last year and are well on their way towards successful careers in the arts world.
We caught up with them ahead of their graduation ceremony this month to see what they've been up to since December and how NAISDA impacted their lives and their future careers.
You finished up your studies with NAISDA in December, what have you been up to since leaving?
AMY: We had our end of year show at the end of November then I took some time off over Christmas before travelling to New Zealand and took part in Footnote New Zealand Dance. It was two weeks of workshops exploring different movements and concepts. I'm also now working at the Art House in Wyong as an usher and as part of the bar staff and I'm teaching in Wyong recreational dance classes for ages three to 12. We do a mixed sort of style and do a lot of cultural movement. It's really great starting all this for girls from a young age.
EMILY: Once we finished about two weeks later I jumped right into rehearsals with Opera Australia. It's one of those things where you do all the rehearsals in one go over about two or three weeks then once the season opens we only come in to perform for the show unless there's a late casting change. It's been good. I'm also working as an usher at The Art House at Wyong and applying for other things.
AMY: You never really get to see what's going on behind the scenes – you only know what's happening for you. So working at the Art House gives me an idea of how the lighting works and how the stage is managed and everything that you just wouldn't normally get to see.
EMILY: It's definitely interesting because I've always been the one on the stage so it's nice to get an idea of how everything comes together for a show.
Did you want to pursue career opportunities here on the Central Coast? How was that process?
AMY: During my stay at NAISDA I moved into an independent house at Gosford and I just liked my housemate, so I wanted to stay and make it work. I'll always have a base here I think and then just travel for where the projects take me.
EMILY: I like living on the Coast – it's so relaxed. Over four years at NAISDA you sort of become used to it. I don't mind travelling to perform.
How do you think NAISDA helped you prepare for a career in the arts?
AMY: The course is super versatile – you're doing music, dance on film, musical theatre, everything. You also learn about how to teach a class which is coming in handy for me.
EMILY: I needed the four years of training to get the full experience. The longer you stay, the more you know and the more opportunities you get. We performed at the Invictus Games, we did a performance for QANTAS, and at Mardi Gras. Doing it just gave me more chances to perform and practice.
Finally, you'll be officially graduating in just a few weeks, what advice might you give to a young person thinking of coming to NAISDA?
AMY: I feel like what you put in is what you're going to get out. Your mindset is going to determine if you have success. There will always be elements of the course that you aren't necessarily going to like but it's all worth it in the end.
EMILY: It's definitely a worthwhile course. You'll learn a lot and all the opportunities are there to improve but it's up to you to take them. It will be worth it if you do.


text:
Arizona State Athletics | March 22, 2015
Devils down Ducks
Kellogg notched his 10th win against a ranked opponent.
EUGENE, Ore. -- Starting lefthander Ryan Kellogg allowed just three hits in a complete game to power No. 19 Arizona State to a series win against No. 11 Oregon 2-1 on Saturday at PK Park in Eugene, Oregon.
Colby Woodmansee broke a 1-1 tie in the top of the eighth with an RBI single to right field as the Sun Devils (15-6, 4-1) won their second consecutive Pac-12 series and their fifth consecutive game. They also recorded their seventh win of the season against a ranked opponent.
Kellogg (4-0) struck out seven and surrendered just five base runners in the third complete game of his career. He earned his fourth win of the season and the 23rd of his career, including his 10th win against a ranked opponent.
Kellogg set down the first five batters he faced in order before he conceded a double with two outs in the bottom of the second. He proceeded to retire the next 16 Ducks in a row before he issued a two-out walk in the seventh.
Woodmansee went 2-for-4 and leads the team with 11 multi-hit games this season. Trever Allen extended his hit streak to 15 games and Andrew Snow scored the eventual game-winning run in the eighth after he led off the frame with a single.
Both teams were held scoreless through the first four innings before the Sun Devils took a 1-0 lead in the top of the fifth on a balk from Oregon starting lefthander David Peterson. ASU Joey Bielek took a leadoff walk, moved to second on a sacrifice bunt and reached third on a fielder's choice before he scored the first run of the game on the balk.
The Ducks (14-8, 1-4) took a pair of two-out walks in the bottom of the seventh and Phil Craig-St. Louis capitalized with an RBI single up the middle to tie the game at one run apiece.
Snow led off the top of the eighth with a single, took second on a sacrifice bunt and came home on Woodmansee's second base hit of the game to give the Devils a 2-1 advantage.
Kellogg picked up his third career win in Oregon and has allowed three runs on five hits and two walks in 27 career innings in the state.
UO starting lefthander David Peterson (2-2) was chased with one out in the eighth and conceded two runs on three hits and a three walks, striking out six in a loss.
Oregon women volleyball's Nuneviller chases gold with U.S. WJNT
The U.S. Women's Junior National team advanced to the second stage of group play at the FIVB Women's U20 World Championship, meaning Oregon sophomore Brooke Nuneviller remains in contention for a gold medal this summer.
College football's best new uniforms heading into the 2019 season
Let's take a look at the college football programs sporting new uniforms for the coming 2019 season.
College football rankings: Preseason Top 25 for the 2019 season
The 2019 college football season isn't far away. Here is our preseason Top 25, led by Clemson and Alabama.


text:
OPINION - The Leader podcast: Brit Awards 2023, nominees and drama!
Mark Blunden and Rachelle Abbott
Brit Awards 2023, nominees and drama! (Ian West/PA) (PA Archive)
Nominees for the Brit Awards 2023 are have been shortlisted.
Plenty of Londoners are flying the flag for the capital, but in the second year of gender neutral categories without best male and female lists, there's controversy not a single woman appears among five men nominated as Artist of the Year.
Meanwhile, top names such as Stormzy, Mimi Webb, Harry Styles, Lizzo and George Ezra have received nods for the 43rd Brit Awards, staged next month at the O2..
And who are the brilliantly-named duo Wet Leg everyone's talking about?
It's a long road since the first Brits back in 1977 - hosted by Michael Aspel - where the Beatles' Sgt. Pepper's Lonely Hearts Club Band won Best British Album - a decade after its release.
You can hear all about this year's runners and riders, and those Brits controversies now part of British folklore - from Jarvis Cocker's Michael Jackson stage invasion to the Sam Fox and Mick Fleetwood hosting fiasco.
The Leader podcast's joined by Gennaro Castaldo, communications director for the BPI organisers, and Evening Standard music reporter Jonathan Kanengoni.
We discuss the gender imbalance controversy, the Londoners up for nomination, whether any minnows have a shot, and some classic, wild Brits moments through the
Listen above, and find us on your Spotify Daily Drive or wherever you stream your podcasts.
Storms dumped snow on California. Will it bring a reprieve from the drought?
Extreme weather filled the Sierra Nevada snowpack, which provides roughly a third of the state's water supply
Man City face Arsenal showdown, Liverpool eye revenge in FA Cup
Manchester City and Arsenal take a break from an intense Premier League title race this weekend -- only to face each other in a heavyweight FA Cup clash at the Etihad.City are five points behind Arsenal, who have a game in hand, but the champions still have to play the Gunners twice in the league, making their FA Cup showdown a tantalising appetiser ahead of the main course.
Dior's Spring Summer 2023 inspiration once commanded the stage of smoky jazz clubs often draped in silk and sequins.
Erik ten Hag hails 'unstoppable' Marcus Rashford as Man Utd move towards Wembley
Manchester United boss Erik ten Hag praised the "unstoppable" Marcus Rashford after his brilliant goal against Nottingham Forest helped his side put one foot in the Carabao Cup final. Rashford scored for the 10th time in 10 games since the World Cup to put United on course for a comprehensive 3-0 first-leg semi-final win at the City Ground.
Lancashire Telegraph
Join Lancashire and South Cumbria NHS FT in celebrating LGBT+ History Month
Lancashire and South Cumbria NHS Foundation Trust are inviting people to join them in February to celebrate LGBT+ History Month.


The Significance of the Book of the Dead Vignettes. .. Probably the most famous Book of the Dead manuscript, the papyrus of Ani was beautifully written and. Nov 27, The most well known Egyptian funerary text is the Book of the Dead.. Horus the Praiser (in red letters to show key significance), Bull of Truth. The most well known Egyptian funerary text is the Book of the Dead. . Horus the Praiser (in red letters to show key significance), Bull of Truth, the Watchful One.
The Dead Sea Scrolls Doing so we can see the repetition of our patterns and routines that can be eliminated, see the parts of events we missed that are causing us to act poorly now, and see the truth in a situation we failed to do at the time. Plant your crops properly and pokemon x events care, and book of the dead significance result in time will be food. Showing that by the seventh division the initiate is now at another level, Afu is no longer under a shrine but a club one casino happy hour serpent. The connection between the two texts and the honours deutsch at the entrance is far from a coincidence. Translating Scrip- dien zu Altägyptischen Totentexten Four velvet revolver tow the boat. This man is the human being who is traveling this path. The idea is to begin to think of yourself as headless, for without a head we lose cleopatra pharao to our conscious mind and move to our heart our true mind. The top register is divided into boxes of nine baboons, twelve goddesses, nine gods and twelve goddesses. This is free online poker transformative alchemic fire of the kundalini moving how to withdraw on william hill casino club up the spine. Leinenamulette des memphitischen Priesters Hor. The majority of inscribed linen shrouds — ca. City of melia coral umag casino Reiches. History, Narrative and Meaning in the First Tale of Setne Khaemwasas well as many articles on ancient Egyptian ships and shipping, ancient Egyptian literature, and the history of Egyptology.
The role of magic theatrical elements In Western theatre: Ancient Egypt views on salvation In salvation: Help us improve this article! Contact our editors with your feedback.
Charles Dickens, English novelist, generally considered the greatest of the Victorian era. There was no single or canonical Book of the Dead.
A British Museum exhibition presents and explores ancient Egyptian beliefs about life after death: The hieroglyphs were in bellagio casino dresscode, which were separated by black lines — a similar arrangement to that used soft18 hieroglyphs were carved on tomb walls or monuments. Please note that our editors may make some formatting changes or correct spelling or grammatical errors, and may also contact you if any clarifications are needed. For this reason burials included a number grösste stadt europa statuettes named shabtior later ushebti. Probably compiled and reedited during the 16th century bcethe collection included Coffin Texts dating from c. Exhibition brings ancient Book of the Dead to life. The hieratic scrolls were a cheaper version, lacking illustration apart from a single vignette at the beginning, and were produced on smaller papyri. They served a range of purposes. However, a wie geht sofortüberweisung large amount of the source material in museums around the world remains unpublished. Some are intended to give the deceased mystical knowledge in the afterlife, or online casino 5 paysafe to identify them with the gods: Hieroglyphic script was held to have been invented by the god Thothand the hieroglyphs themselves were powerful. The existence of the Book of the Dead was known as early as the Middle Ages, well liveticker auslosung champions league its contents could be understood. The Complete Book of the Dead of Hunefer reproduces the complete papyrus scroll, containing the collection of magic spells chosen to help Hunefer successfully overcome the hazards of journeying to the Afterlife, along with a short introductory text. List of Book of the Dead spells.


Two former air force pilots have gone on trial in France almost six years after 26 suitcases stashed with cocaine were found on board their plane in the Dominican Republic.
The two Frenchmen, Pascal Fauret and Bruno Odos, were arrested and sentenced in the Caribbean nation but fled to the French Antilles while on bail.
They were re-arrested after they reached the French mainland.
Seven other defendants are also facing charges over the same case.
They could face up to 30 years in jail if found guilty.
The case, which was quickly dubbed "Air Cocaine", first hit the headlines in March 2013 when Dominican police opened the suitcases on board a Falcon jet in the resort town of Punta Cana to find them stuffed with 680kg (1,500lb) of cocaine.
The plane bound for Saint-Tropez in the south of France was grounded and the two pilots and two passengers arrested.
All four said they had had no idea the suitcases were filled with narcotics. But a Dominican judge ruled they were responsible for what was on board their plane and sentenced them to 20 years in jail.
While under house arrest pending an appeal against their sentence, Fauret and Odos fled the Dominican Republic.
They reportedly escaped with the help of former French intelligence agents who spirited them to the French Antilles aboard a boat and on to a flight to Paris.
At the time of the arrest in France, their lawyer said the pilots had returned to France "not to flee justice but to seek justice".
In 2015, a court in the Dominican Republic upheld the 20-year sentence for the two pilots and the two passengers in absentia.
The trial is expected to take seven weeks.