WARNINGS
Lactic Acidosis:
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with FORTAMET® (metformin hydrochloride) Extended-Release Tablets; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/ L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 μg/mL are generally found.
The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/ surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking FORTAMET® (metformin hydrochloride) Extended-Release Tablets and by use of the minimum effective dose of FORTAMET®. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. FORTAMET® treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, FORTAMET® should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, FORTAMET® should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking FORTAMET®, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, FORTAMET® should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS).
The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient's physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). FORTAMET® should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of FORTAMET®, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.
Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking FORTAMET® do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling (see also PRECAUTIONS).
Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).
Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking FORTAMET®, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery (see also CONTRAINDICATIONS and PRECAUTIONS).
|
| |
FORTAMET SUMMARY
FORTAMET⢠(metformin hydrochloride) Extended-Release Tablets contain an oral antihyperglycemic drug used in the management of type 2 diabetes.
FORTAMET⢠(metformin hydrochloride) Extended-Release Tablets, used as a once per day monotherapy, are indicated as an adjunct to diet and exercise to lower blood glucose. FORTAMET⢠can be used concomitantly with a sulfonylurea or insulin to improve glycemic control in adults. FORTAMET⢠is indicated in patients 17 years of age and older as either monotherapy or in combination therapy.
|
|
NEWS HIGHLIGHTSMedia Articles Related to Fortamet (Metformin)
Metformin for Obesity in Children: Questions Still Remain
Source: Medscape Pediatrics Headlines [2017.06.13]
Metformin improved body mass index in nondiabetic obese prepubertal -- but not pubertal -- children, a new study has found.
Medscape Medical News
Metformin No Help for Atherosclerosis in T1D
Source: MedPage Today Endocrinology [2017.06.13]
(MedPage Today) -- Findings don't support metformin in long-standing type 1 diabetes
REMOVAL: Mixed Data on CV Benefits of Metformin in Type 1 Diabetes
Source: Medscape Diabetes & Endocrinology Headlines [2017.06.12]
Results from REMOVAL trial suggest possible cardiovascular benefit, but minimal effect on glucose lowering, in type 1 diabetes patients at increased cardiovascular risk.
Medscape Medical News
Metformin shows promise as a potential treatment for fragile X syndrome
Source: Autism News From Medical News Today [2017.05.15]
New study shows that treatment with the common type 2 diabetes drug metformin improves social, behavioral, and neuron deficits in mouse model of fragile X.
Is it safe to use metformin during pregnancy?
Source: Pregnancy / Obstetrics News From Medical News Today [2017.05.12]
Metformin is commonly prescribed for managing type 2 diabetes. Although it effectively lowers blood sugar, is it safe for women to take during pregnancy?
Published Studies Related to Fortamet (Metformin)
Anagliptin and sitagliptin as add-ons to metformin for patients with type 2
diabetes: a 24-week, multicentre, randomized, double-blind, active-controlled,
phase III clinical trial with a 28-week extension. [2015]
We conducted a 24-week, multicentre, double-blind, randomized study with a
28-week extension to compare the efficacy and safety of anagliptin and
sitagliptin as an add-on to metformin in patients with type 2 diabetes. Patients
inadequately controlled on metformin were randomized to either anagliptin (100 mg
twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88)...
Effect of combination therapy with repaglinide and metformin hydrochloride on
glycemic control in Japanese patients with type 2 diabetes mellitus. [2014]
exercise... CONCLUSIONS: Combination therapy with repaglinide and metformin resulted in an
Lipid profiling reveals different therapeutic effects of metformin and glipizide
in patients with type 2 diabetes and coronary artery disease. [2014]
CONCLUSIONS: Our findings revealed the differential therapeutic effects of
Metformin for non-diabetic patients with coronary heart disease (the CAMERA
study): a randomised controlled trial. [2014]
diabetes... INTERPRETATION: Metformin had no effect on cIMT and little or no effect on
The effect of metformin on apoptosis in a breast cancer presurgical trial. [2013]
presurgical trial... CONCLUSION: Overall, we found no significant modulation of apoptosis by
Clinical Trials Related to Fortamet (Metformin)
A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Metformin [Completed]
The purpose of this study is to assess the effect of multiple doses of isavuconazole on the
pharmacokinetics of a single dose of metformin. Safety and tolerability of isavuconazole
will be assessed alone and in combination with metformin.
Crossover Study to Evaluate the Comparative Bioavailability of Two Fixed Dose Combination Tablet Formulations of Extended Release Metformin and Extended Release Glimepiride in Health Volunteers [Terminated]
This is a an open-label, randomized, single dose, four-way crossover, multi-stage study
enrolling 20 healthy adult male and female subjects per part. This study consists of two
separate parts (Part A and B) with each part comprising four treatment periods. Each subject
will participate in all four treatment periods per part; Subjects may not enrol in both
Parts A and B.
This study is being conducted to compare the pharmacokinetics (PK) of two extended release
fixed dose combinations (FDC) oral formulations of metformin and glimepiride at two doses,
500mg/1mg and 1000mg/2mg, with each FDC formulation to be administered orally as a single
dose and compared with the commercially available formulations of metformin extended release
(XR) (GLUCOPHAGE ™ Sustained Release [SR]) and glimepiride immediate release (IR) (AMARYL
™).
Part A of study will evaluate the bioavailability of a formulation comprising a film coated
tablet containing release controlling polymers; and Part B will evaluate the bioavailability
of a formulation comprising a tablet coated with release controlling polymers.
In each part there will be 4 treatment periods. During each period, subjects will be
randomized sequentially to receive a single dose of a reference treatment of 500 mg
metformin XR / 1 mg glimepiride IR; and a reference treatment of 1000 mg metformin XR / 2 mg
glimepiride IR; and an FDC tablet containing 500 mg metformin XR and 1 mg glimepiride XR;
and an FDC tablet containing 1000 mg metformin XR and 2 mg glimepiride XR. Serial PK sampling
for up to 36 hours and safety assessments will be performed. Each period will be separated
by a washout period of at least 5 days and a follow-up visit will occur 14 days after the
last dose of study drug.
A Study Comparing the Amount of Metformin and After Taking a Combination Tablet vs. Separate Tablets [Completed]
Reducing Antipsychotic-Induced Weight Gain in Children With Metformin [Recruiting]
Recent but limited short term studies have shown that Metformin can slow down weight gain in
obese children and in children with psychotropic-induced weight gain, two distinct pediatric
populations that are at risk for obesity related co-morbid conditions. The purpose of this
study is to conduct a long term prospective pilot cohort study to investigate the use of
Metformin to prevent or decrease weight gain in two cohorts of children: 1) children with
psychotropic induced weight gain on Metformin and 2) children with BMI above the 95th
percentile on Metformin. Both study populations will be enrolled in a lifestyle weight
management program
Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants [Completed]
|
|
|
|
Page last updated: 2017-06-13
|
