Biografia metformina

7/28/2019 Biografia metformina

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Pronunciation

(met FOR min)

Generic Available (U.S.)

Yes: Excludes solution

Index Terms

Metformin Hydrochloride

Brand Names: U.S.

Fortamet

Glucophage

Glucophage XR

Glumetza

Riomet

Brand Names: Canada Apo-Metformin

Ava-Metformin

CO Metformin

Dom-Metformin

Glucophage

Glumetza

Glycon

JAMP-Metformin

JAMP-Metformin Blackberry Med-Metformin

Mylan-Metformin

Novo-Metformin

Nu-Metformin

PHL-Metformin

PMS-Metformin

PRO-Metformin

Q-Metformin

RAN-Metformin

ratio-Metformin

Riva-Metformin

Sandoz-Metformin FC

Pharmacologic Category

Antidiabetic Agent, Biguanide

Pharmacologic Category Synonyms


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Biguanide

Oral Hypoglycemic Agent, Biguanide

Use: Labeled Indications

Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM) when hyperglycemia

cannot be managed with diet and exercise alone.

Use: Unlabeled

Gestational diabetes mellitus (GDM); polycystic ovary syndrome (PCOS); prevention of type 2

diabetes mellitus

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal studies; therefore, metformin is classified as

pregnancy category B. Metformin has been found to cross the placenta in concentrations which

may be comparable to those found in the maternal plasma. Pharmacokinetic studies suggest that

clearance of metformin may be increased during pregnancy and dosing may need adjusted in some

women when used during the third trimester.Fetal, neonatal, and maternal outcomes have been

evaluated following maternal use of metformin for the treatment of GDM and type 2 diabetes.

Available information suggests that metformin use during pregnancy may be safe as long as good

glycemic control is maintained; however, many studies used metformin during the second or third

trimester only. Maternal hyperglycemia can be associated with adverse effects in the fetus,

including macrosomia, neonatal hyperglycemia, and hyperbilirubinemia; the risk of congenitalmalformations is increased when the Hb A1c is above the normal range. Diabetes can also be

associated with adverse effects in the mother. Poorly-treated diabetes may cause end-organ

damage that may negatively affect obstetric outcomes. Physiologic glucose levels should be

maintained prior to and during pregnancy to decrease the risk of adverse events in the mother and

the fetus. Until additional safety and efficacy data are obtained, the use of oral agents is generally

not recommended as routine management of GDM or type 2 diabetes mellitus during pregnancy.

Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.Metformin has also

been evaluated for the treatment of PCOS, a syndrome which may exhibit oligomenorrhea and, in

some women, hyperinsulinemia. It is not recommended as first-line therapy; when used to treatinfertility related to PCOS, current guidelines restrict the use of metformin to women with glucose

intolerance. Because ovulation rates will likely improve in women with PCOS who are taking

metformin, appropriate contraceptive measures should be discussed in women who are not

attempting to conceive.

Lactation


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Enters breast milk/not recommended

Breast-Feeding Considerations

Low amounts of metformin (generally 1% of the weight-adjusted maternal dose) are excreted into

breast milk. Breast-feeding is not recommended by the manufacturer. Because breast milk

concentrations of metformin stay relatively constant, avoiding nursing around peak plasma

concentrations in the mother would not be helpful in reducing metformin exposure to the infant.

Growth and development were not affected in infants born to mothers with PCOS and who took

metformin while breast-feeding.

Contraindications

Hypersensitivity to metformin or any component of the formulation; renal disease or renal

dysfunction (serum creatinine 1.5 mg/dL in males or 1.4 mg/dL in females) or abnormal creatinine

clearance from any cause, including shock, acute myocardial infarction, or septicemia; acute or

chronic metabolic acidosis with or without coma (including diabetic ketoacidosis)

Note: Temporarily discontinue in patients undergoing radiologic studies in which intravascular

iodinated contrast media are utilized.

Warnings/Precautions

Boxed warnings:

Lactic acidosis: See Concerns related to adverse effects below.

Concerns related to adverse effects:

Cardiovascular mortality: Administration of oral antidiabetic drugs has been reported to be

associated with increased cardiovascular mortality; metformin does not appear to share this risk.

Lactic acidosis:[U.S. Boxed Warning]: Lactic acidosis is a rare, but potentially severe

consequence of therapy with metformin. Lactic acidosis should be suspected in any patient with

diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis.

Discontinue metformin in clinical situations predisposing to hypoxemia, including conditions such as

cardiovascular collapse, respiratory failure, acute myocardial infarction, acute congestive heart

failure, and septicemia. The risk of accumulation and lactic acidosis increases with the degree of

impairment of renal function.

Disease-related concerns:


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Heart failure: Use caution in patients with congestive heart failure requiring pharmacologic

management, particularly in patients with unstable or acute heart failure; risk of lactic acidosis may

be increased secondary to hypoperfusion.

Hepatic impairment: Avoid use in patients with impaired liver function due to potential for lactic

acidosis.

Renal impairment: Metformin is substantially excreted by the kidney; patients with renal function

below the limit of normal for their age should not receive therapy. Use of concomitant medications

that may affect renal function (ie, affect tubular secretion) may also affect metformin disposition.

Metformin should be withheld in patients with dehydration and/or prerenal azotemia.

Stress-related states: It may be necessary to discontinue metformin and administer insulin if the

patient is exposed to stress (fever, trauma, infection, surgery).

Special populations:

Elderly: Metformin should not be initiatedin patients 80 years of age unless normal renal function

is confirmed.

Dosage form specific issues:

Extended release tablet: Insoluble tablet shell (Glumetza 1000 mg tablet) may remain intact and

be visible in the stool. Other extended released tablets (Fortamet, Glucophage XR, Glumetza

500 mg) may appear in the stool as a soft mass resembling the tablet.

Other warnings/precautions:

Ethanol use: Instruct patients to avoid excessive acute or chronic ethanol use; ethanol may

potentiate metformin's effect on lactate metabolism.

Iodinated contrast: Therapy should be temporarily discontinued prior to or at the time of

intravascular administration of iodinated contrast media (potential for acute alteration in renal

function). Metformin should be withheld for 48 hours after the radiologic study and restarted only

after renal function has been confirmed as normal.

Surgical procedures: Therapy should be suspended for any surgical procedures (resume only

after normal oral intake resumed and normal renal function is verified).

Adverse Reactions


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>10%:

Gastrointestinal: Diarrhea (IR tablet: 12% to 53%; ER tablet: 10% to 17%), nausea/vomiting (IR

tablet: 7% to 26%; ER tablet: 7% to 9%), flatulence (12%)

Neuromuscular & skeletal: Weakness (9%)

1% to 10%:

Cardiovascular: Chest discomfort, flushing, palpitation

Central nervous system: Headache (6%), chills, dizziness, lightheadedness

Dermatologic: Rash

Endocrine & metabolic: Hypoglycemia

Gastrointestinal: Indigestion (7%), abdominal discomfort (6%), abdominal distention, abnormal

stools, constipation, dyspepsia/ heartburn, taste disorder

Neuromuscular & skeletal: Myalgia

Respiratory: Dyspnea, upper respiratory tract infection

Miscellaneous: Diaphoresis increased, vitamin B12 levels decreased (7%), flu-like syndrome, nail

disorder


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Cimetidine: May increase the serum concentration of MetFORMIN. Risk D: Consider therapy

modification

Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of Antidiabetic Agents. In

some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute

adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin

or other antidiabetic agent use. Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the hypoglycemic effect of Antidiabetic Agents. In some

instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal

crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other

antidiabetic agent use. Risk C: Monitor therapy

Dalfampridine: May increase the serum concentration of MetFORMIN. MetFORMIN may increase

the serum concentration of Dalfampridine. Risk C: Monitor therapy

Dofetilide: MetFORMIN may increase the serum concentration of Dofetilide. Risk C: Monitor therapy

Glycopyrrolate: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Iodinated Contrast Agents: May enhance the adverse/toxic effect of MetFORMIN. Renal dysfunction

that may be caused by iodinated contrast agents may lead to metformin-associated lactic acidosis.

Management: Withhold metformin from all patients receiving intravascular iodinated contrast agents

prior to or at the time of the procedure and for at least 48 hrs thereafter. Document adequate renalfunction before restarting metformin. Risk D: Consider therapy modification

LamoTRIgine: May increase the serum concentration of MetFORMIN. Management: The

lamotrigine Canadian product monograph states that coadministration of these drugs is not

recommended. Risk C: Monitor therapy

Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic effect of

Antidiabetic Agents. Risk C: Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy

modification

Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor

therapy


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Trospium: MetFORMIN may decrease the serum concentration of Trospium. Risk C: Monitor

therapy

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid or limit ethanol (incidence of lactic acidosis may be increased; may cause

hypoglycemia).

Food: Food decreases the extent and slightly delays the absorption. May decrease absorption of

vitamin B12 and/or folic acid.

Herb/Nutraceutical: Caution with chromium, garlic, gymnema (may cause hypoglycemia).

Storage

Oral solution: Store at 15C to 30C (59F to 86F).

Tablets: Store at 20C to 25C (68F to 77F); excursion permitted to 15C to 30C (59F to 86F).

Protect from light and moisture.

Mechanism of Action

Decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves

insulin sensitivity (increases peripheral glucose uptake and utilization)

Pharmacodynamics/Kinetics

Onset of action: Within days; maximum effects up to 2 weeks

Distribution: Vd: 654 358 L; partitions into erythrocytes

Protein binding: Negligible

Metabolism: Not metabolized by the liver

Bioavailability: Absolute: Fasting: 50% to 60%

Half-life elimination: Plasma: 4-9 hours

Time to peak, serum: Immediate release: 2-3 hours; Extended release: 7 hours (range: 4-8 hours)

Excretion: Urine (90% as unchanged drug; active secretion)

Dosage


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Type 2 diabetes management: Note: Allow 1-2 weeks between dose titrations: Generally, clinically

significant responses are not seen at doses 2000 mg/day is required, it may

be better tolerated in three divided doses. Maximum recommended dose 2550 mg/day.

Extended release tablet: Oral: Note: If glycemic control is not achieved at maximum dose, may

divide dose and administer twice daily.

Children 17 years and Adults:

Fortamet: Initial: 500-1000 mg once daily; dosage may be increased by 500 mg weekly; maximum

dose: 2500 mg once daily

Glucophage XR: Initial: 500 mg once daily; dosage may be increased by 500 mg weekly;

maximum dose: 2000 mg once daily

Adults: Glumetza: Initial: 1000 mg once daily; dosage may be increased by 500 mg weekly;

maximum dose: 2000 mg once daily

Elderly: The initial and maintenance dosing should be conservative, due to the potential for

decreased renal function. Generally, elderly patients should not be titrated to the maximum dose of

metformin. Do not use in patients 80 years of age unless normal renal function has been

established.

Transfer from other antidiabetic agents: No transition period is generally necessary except when

transferring from chlorpropamide. When transferring from chlorpropamide, care should be exercised

during the first 2 weeks because of the prolonged retention of chlorpropamide in the body, leading

to overlapping drug effects and possible hypoglycemia.


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Concomitant metformin and oral sulfonylurea therapy: If patients have not responded to 4

weeks of the maximum dose of metformin monotherapy, consider a gradual addition of an oral

sulfonylurea, even if prior primary or secondary failure to a sulfonylurea has occurred. Continue

metformin at the maximum dose. If adequate response has not occurred following 3 months of

metformin and sulfonylurea combination therapy, consider switching to insulin with or withoutmetformin.

Failed sulfonylurea therapy: Patients with prior failure on glyburide may be treated by gradual

addition of metformin. Initiate with glyburide 20 mg and metformin 500 mg daily. Metformin dosage

may be increased by 500 mg/day at weekly intervals, up to a maximum metformin dose (dosage of

glyburide maintained at 20 mg/day).

Concomitant metformin and insulin therapy: Initial: 500 mg metformin once daily, continue

current insulin dose; increase by 500 mg metformin weekly until adequate glycemic control is

achieved

Maximum daily dose: Immediate release and solution: 2550 mg metformin; Extended release: 2000-

2500 mg (varies by product)

Decrease insulin dose 10% to 25% when FPG


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Monitoring Parameters

Urine for glucose and ketones, fasting blood glucose, hemoglobin A 1c, and fructosamine. Initial and

periodic monitoring of hematologic parameters (eg, hemoglobin/hematocrit and red blood cell

indices) and renal function should be performed, at least annually. While megaloblastic anemia has

been rarely seen with metformin, if suspected, check vitamin B12and folate if anemia is present.

Reference Range

Recommendations for glycemic control in nonpregnant adults with diabetes (ADA, 2012):

Hb A1c:


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mortality, hypoglycemia requiring assistance, and weight gain in adult type 2 diabetes. How "tightly"

to control a geriatric patient's blood glucose needs to be individualized. Such a decision should be

based on several factors, including the patient's functional and cognitive status, how well he/she

recognizes hypoglycemic or hyperglycemic symptoms, and how to respond to them and other

disease states. An Hb A1c


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Assess for signs and symptoms of vitamin B12 and/or folic acid deficiency during therapy;

supplementation may be required. Refer patient to diabetes educator for instruction if needed.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific

product labeling.

Solution, oral, as hydrochloride:

Riomet: 100 mg/mL (118 mL, 473 mL) [dye free, ethanol free, sugar free; contains saccharin;

cherry flavor]

Tablet, oral, as hydrochloride: 500 mg, 850 mg, 1000 mg

Glucophage: 500 mg, 850 mg

Glucophage: 1000 mg [scored]

Tablet, extended release, oral, as hydrochloride: 500 mg, 750 mg, 1000 mg

Fortamet: 500 mg, 1000 mg

Glucophage XR: 500 mg, 750 mg

Glumetza: 500 mg, 1000 mg

Pricing: U.S. (www.drugstore.com)

Solution (Riomet)

500 mg/5 mL (473): $201.59

Tablet, 24-hour(Fortamet)

500 mg (60): $338.55

1000 mg (60): $683.99

Tablet, 24-hour(Glucophage XR)

500 mg (60): $69.99


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750 mg (30): $53.99

Tablet, 24-hour(Glumetza)

500 mg (100): $389.00

1000 mg (100): $859.97

Tablet, 24-hour(MetFORMIN HCl)

500 mg (90): $20.99

750 mg (30): $32.99

Tablets (Glucophage)

500 mg (60): $69.99

850 mg (60): $113.29

1000 mg (60): $141.08

Tablets (MetFORMIN HCl)

500 mg (60): $12.99

850 mg (90): $77.99

1000 mg (30): $17.99

La epidemia de la diabetes mellitus (DM) es reconocida por la Organizacin Mundialde la Salud (OMS) como una amenaza mundial. En 2005 se registraron 1.1 millones demuertes debidas a la diabetes, de las cuales alrededor de 80% ocurrieron en pasesde ingresos bajos o medios, que en su mayora se encuentran menos preparadospara enfrentar esta epidemia.

De conformidad con la informacin de la Encuesta Nacional de Salud y Nutricin2006 (ENSANUT) la prevalencia aument a 14%, lo que representa un total de 8millones de personas con diabetes; en la poblacin urbana, la prevalencia fuesignificativamente mayor.

En Mxico, la DM ocupa el primer lugar en nmero de defunciones por ao, tanto enhombres como en mujeres las tasas de mortalidad muestran una tendencia


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ascendente en ambos sexos con ms de 70 mil muertes y 400,000 casos nuevosanuales cabe sealar que segn la Direccin General de Informacin en Salud en el2007 hubo un nmero mayor de defunciones en el grupo de las mujeres (37,202muertes) comparado con el de los hombres (33,310), con una tasa 69.2 por 100,000habitantes en mujeres y de 64 en hombres, diferencias importantes a considerar en lasacciones preventivas, de deteccin, diagnstico y tratamiento de este

padecimiento. La diabetes no es un factor de riesgo cardiovascular.

Es un equivalente de enfermedad cardiovascular debido a que el riesgo de sufrir undesenlace cardiovascular es igual al de la cardiopata isqumica.

FUENTE: NORMA Oficial Mexicana NOM-015-SSA2-2010, Para la prevencin,tratamiento y control de la diabetes mellitus.

La diabetes mellitus es un factor de riesgo cardiovascular, se estima que entre 7 y 8 decada 10 personas con diabetes mueren por problema macrovascular.

Fuente: Secretaria deGobernacin,http://www.dof.gob.mx/documentos/3868/Salud/Salud.htm

Encuesta Nacional de Salud y Nutricin 2006 (ENSANUT)

ESTADSTICAS DIABETES

Cada hora se diagnostican 38 nuevos casos de diabetes

Cada dos horas mueren 5 personas a causa de complicaciones originadas por ladiabetes

De cada 100 pacientes con diabetes, 14 presenta alguna complicacin renal

El 30% de los problemas de pie diabtico termina en amputacin

De cada cinco pacientes con diabetes, 2 desarrollan ceguera

Mxico ocupa el dcimo lugar en diabetes mundial y se estima que para 2030 ocupeel sptimo puesto.

Fuente: Presentacin: Impacto de la Diabetes Mellitus desde la perspectivainstitucional. Dr. Ernesto Alcntar Luna

Prevalencia de diabetes tipo 1 en nios

2010Poblacin total infantil (0-14 aos, miles demillones)

1.9
http://www.dof.gob.mx/documentos/3868/Salud/Salud.htmhttp://www.dof.gob.mx/documentos/3868/Salud/Salud.htmhttp://www.dof.gob.mx/documentos/3868/Salud/Salud.htmhttp://www.dof.gob.mx/documentos/3868/Salud/Salud.htm


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ipo 1 en nios (0-14 aos)Nmero de nios con diabetes tipo 1 (miles) 479.6Nmero de casos de recin diagnostico por ao(miles)

75.8

Incremento anualincidencia(%) 3.0

IMSS Declar en octubre 2010: 400 mil nios diabetes tipo 1 y 2 son atendidospor esa institucin.

Datos sobre Diabetes en nios tipo 2

Hospital General: 600 pacientes menores de 18 aos Fuente: FederacinMexicana de Diabetes, A.C.

Hospital infantil: 150 pacientes. Fuente: Federacin Mexicana de Diabetes, A.C.

La diabetes tipo 1 se encuentra en rpido crecimiento en nios y adolescentes en

muchos pases, y las pruebas sugieren que hoy da se estn detectando casos dediabetes tipo 2 en nios en un nmero creciente de pases.Se calcula que, anualmente, alrededor de 76.000 nios de menos de 15 aosdesarrollan diabetes tipo 1 en el mundo. De los 480.000 nios que se calcula tienendiabetes tipo 1, el 24% procede de la regin del Sudeste Asitico, pero la reginEuropea se le aproxima estrechamente, ocupando el segundo lugar (23%).Fuente:http://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundial

*Obesidad y sobrepeso

Uno de cada tres adolescentes de entre 12 y 19 aos tiene obesidad u sobrepeso.Aproximadamente 5 millones 757mil 400 adolescentes

La prevalencia de sobrepeso fue ms alta en hombres mayores a 20 aos (42.5%) queen mujeres de ms de20 aos (37.4%), sin embargo la prevalencia de obesidad enmujeres fue de 34.5% y en hombres de 24.2%. Por la tanto, la prevalencia desobrepeso y obesidad a nivel nacional fue de 71.9% en mujeres mayores de 20 aos y66.7% en hombres mayores de 20 aos.

http://www.fmdiabetes.org/fmd/pag/diabetes_numeros.php

Distrito Federal

Prevalencia de diabetes en adultos de 20 aos o ms es de 8.9%, siendo ms

elevada en mujeres (9.1%) que en hombres (8.6%)

Factores de riesgo para enfermedades crnicas
http://archive.diabetesatlas.org/es/glossary/term/17http://archive.diabetesatlas.org/es/glossary/term/17http://archive.diabetesatlas.org/es/glossary/term/17http://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://www.fmdiabetes.org/fmd/pag/diabetes_numeros.phphttp://www.fmdiabetes.org/fmd/pag/diabetes_numeros.phphttp://www.fmdiabetes.org/fmd/pag/diabetes_numeros.phphttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/content/diabetes-en-j%C3%B3venes-una-perspectiva-mundialhttp://archive.diabetesatlas.org/es/glossary/term/17


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Se estima que ms del 27% de los adultos de 20 aos o ms fumaban y casi

14% haba fumado alguna vez hasta el momento de realizarse la Encuesta de

Nacional de Salud y Nutricin 2006

17.3% de los adultos reportaron haber consumido ms de cinco copas en un

mismo da por lo menos una vez al mes

32.2% de los adolescentes de 12 a 19 aos present exceso de peso

La prevalencia de obesidad y sobrepeso en adultos de 20 aos o ms fue de

73%, 75.4% en mujeres y 69.8% en hombres

La diabetes mellitus afecta aproximadamente 24 millones de personas en EstadosUnidos. De stas, 17.9 millones han sido diagnosticadas, pero unos 6 millonesdesconocen que tienen la enfermedad.

Esta poblacin de personas con diabetes mellitus afecta a grupos tnicos:

Indoamericanos y nativos de Alaska (16.5 %)

Negros (11.8 %)

Hispanos (10.4 %)

Los hispanos registran las siguientes tasas:

Puertorriqueos (12.6 %)

Mxicoamericanos (11.9 %)

Cubanos (8.2 %)

Complicaciones

La diabetes es la sptima causa principal de muerte, sin embargo puede provocardiscapacidad permanente a causa de las complicaciones. Como enfermedadescardacas y accidentes cerebrovasculares, ceguera, enfermedad renal crnica yamputaciones.

El riesgo de sufrir accidentes cerebrovasculares es de 2 a 4 veces ms alto en laspersonas con diabetes.

La diabetes es la causa principal de ceguera entre los adultos de 20 a 74 aos deedad.Adems en personas con diabetes se realizan ms del 60% de las amputaciones notraumticas de las extremidades inferiores.


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Biografia metformina

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